A Dose-escalating Clinical Trial With KH176

Primary outcomes

1. SAD: Change From Baseline in ECG Results by Timepoint: Corrected QT Interval According to Fridericia's Formula (QTcF)

   Time frame: Baseline, 1, 2, 4, 6, 8, 12, 24 hours, 7 day follow up

   The baseline ECG recording consists of a triplicate recording (3 recordings of a least 3 complexes within a 5 minute window) prior to dosing on Day 1. For the evaluation of the corrected QT intervals the average of the 3 recordings will be taken as baseline. Other ECG recordings will be singlet (one recording of at least 3 complexes) prior to dosing. QTcF is calculated as the quotient between the QT interval in milliseconds and the cube root of the RR interval in seconds, according to Fridericia's formula.

2. Pharmacodynamics of KH176

   Time frame: Day 1, day 7

   Change from baseline in biochemistry related to Oxidative Phosphorylation (OXPHOS) (glutathione, lactate); MAD group

3. Relationship to Study Drug and Severity of Treatment-emergent Adverse Events

   Time frame: 4 months

4. Change From Baseline in Hematology Laboratory Test Results by Timepoint: Red Blood Cell Count. SAD Group

   Time frame: Baseline (pre-dose Day 1), 24h post dose, FU (7 days after last dosing)

   Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.

5. Change From Baseline in Hematology Laboratory Test Results by Timepoint: Erythrocyte Sedimentation Rate (SAD Group)

   Time frame: Baseline (pre-dose Day1), 24h post dose, FU (7 days after last dosing)

6. Change From Baseline in Hematology Laboratory Test Results by Timepoint: Erythrocyte Sedimentation Rate MAD Group

   Time frame: Baseline (pre-dose Day 1), Day 3, Day 8, FU (7 days after last dosing)

7. Change From Baseline in Hematology Laboratory Test Results by Timepoint: Hematocrit SAD Group

   Time frame: Baseline (pre-dose Day 1), 24 h postdose, FU (7 days after last dosing)

   Hematocrit is a measure of the ratio of red blood cells (RBCs) in the blood by volume. Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.

8. Change From Baseline in Hematology Laboratory Test Results by Timepoint: Mean Corpuscular Haemoglobin. SAD

   Time frame: Baseline (pre-dose Day 1), 24 h post dose, FU (7 days after last dosing)

   Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.

9. Change From Baseline in Hematology Laboratory Test Results by Timepoint: Mean Corpuscular Hemoglobin Concentration - SAD

   Time frame: Baseline (pre-dose Day 1), 24 h post dose, FU (7 days after last dosing)

   Erythrocyte mean corpuscular hemoglobin concentration (MCHC) is a measure of the average concentration of hemoglobin per red blood cell. Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.

10. Change From Baseline in Hematology Laboratory Test Results by Timepoint: Mean Corpuscular Volume - SAD

    Time frame: Baseline (pre-dose Day 1), 24 h post dose, FU (7 days after last dosing)

    Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.

11. MAD: Change From Baseline in ECG Results by Time Point: QTcF

    Time frame: Baseline, Day1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7

    The baseline ECG recording consists of a triplicate recording (3 recordings of a least 3 complexes within a 5 minute window) prior to dosing on Day 1. For the evaluation of the corrected QT intervals the average of the 3 recordings will be taken as baseline. Other ECG recordings will be singlet (one recording of at least 3 complexes) prior to dosing, or around the expected Cmax on Day 1 or 7 for the multiple-dose part.

    QTcF is calculated as the quotient between the QT interval in milliseconds and the cube root of the RR interval in seconds, according to Fridericia's formula.

12. Change From Baseline in Hematology Laboratory Test Results by Timepoint: White Blood Cell Count. SAD Group

    Time frame: Baseline (pre-dose Day 1), 24h post dose, FU (7 days after last dosing)

    Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.

13. Change From Baseline in Hematology Laboratory Test Results by Timepoint: Lymphocytes. SAD Group

    Time frame: Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose)

    Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.

14. Change From Baseline in Hematology Laboratory Test Results by Timepoint: Neutrophils. SAD Group

    Time frame: Baseline (pre-dose Day 1), 24h post dose, FU (7 days after last dosing)

    Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.

15. Change From Baseline in Hematology Laboratory Test Results by Timepoint: Hematocrit MAD Group

    Time frame: Baseline (pre-dose Day 1), Day 3, Day 8, FU (7 days post dose)

    Hematocrit is a measure of the ratio of red blood cells (RBCs) in the blood by volume. Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value

16. Change From Baseline in Hematology Laboratory Test Results by Timepoint: Eosinophils. SAD Group

    Time frame: Baseline (pre-dose Day 1), 24h post dose, FU (7 days after last dosing)

    Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.

17. Change From Baseline in Hematology Laboratory Test Results by Timepoint: Thrombocytes. SAD Group

    Time frame: Baseline (pre-dose Day 1), 24h, FU (7 days post-dose)

    Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.

18. Change From Baseline in Hematology Laboratory Test Results by Timepoint: Basophils. SAD Group

    Time frame: Baseline (pre-dose Day 1), 24h post dose, FU (7 days post-dose)

    Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value ateach timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.

19. Change From Baseline in Hematology Laboratory Test Results by Timepoint: Monocytes. SAD Group

    Time frame: Baseline (pre-dose Day 1), 24h post dose, FU (7 days post-dose)

    Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.

20. Change From Baseline in Hematology Laboratory Test Results by Timepoint: Mean Corpuscular Volume. MAD Group

    Time frame: Baseline (pre-dose Day 1), Day 3, Day 8, FU (7 days post dose)

    Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.

21. Change From Baseline in Hematology Laboratory Test Results by Timepoint: Hemoglobin. MAD Group

    Time frame: Baseline (pre-dose Day 1), Day 3, Day 8, FU (7 days post dose)

    Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.

22. Change From Baseline in Hematology Laboratory Test Results by Timepoint: White Blood Cell Count. MAD

    Time frame: Baseline (pre-dose Day 1), Day 3, Day 8, FU (7 days post dose)

    Blood samples were collected from participants at the indicated time points for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each time point are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.

23. Change From Baseline in Hematology Laboratory Test Results by Timepoint: Neutrophils. MAD Group

    Time frame: Baseline (pre-dose Day 1), Day 3, Day 8, FU (7 days post dose)

    Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.

24. Change From Baseline in Hematology Laboratory Test Results by Timepoint: Mean Corpuscular Haemoglobin Concentration. MAD Group

    Time frame: Baseline (pre-dose Day 1), Day 3, Day 8, FU (7 days post dose)

    Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.

25. Change From Baseline in Hematology Laboratory Test Results by Timepoint: Lymphocytes. MAD Group

    Time frame: Baseline (pre-dose Day 1), Day 3, Day 8, FU (7 days post dose)

    Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.

26. Change From Baseline in Hematology Laboratory Test Results by Timepoint: Mean Corpuscular Hemoglobin. MAD Group

    Time frame: Baseline (pre-dose Day 1), Day 3, Day 8, FU (7 days post dose)

    Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.

27. Change From Baseline in Hematology Laboratory Test Results by Timepoint: Red Blood Cell Count. MAD Group

    Time frame: Baseline (pre-dose Day 1), Day 3, Day 8, FU (7 days post dose)

    Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.

28. Change From Baseline in Hematology Laboratory Test Results by Timepoint: Eosinophils. MAD Group

    Time frame: Baseline (pre-dose Day 1), Day 3, Day 8, FU (7 days post dose)

    Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.

29. Change From Baseline in Hematology Laboratory Test Results by Timepoint: Monocytes. MAD Group

    Time frame: Baseline (pre-dose Day 1), Day 3, Day 8, FU (7 days post dose)

    Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.

30. Change From Baseline in Hematology Laboratory Test Results by Timepoint: Thrombocytes. MAD Group

    Time frame: Baseline (pre-dose Day 1), Day 3, Day 8, FU (7 days post dose)

    Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.

31. Change From Baseline in Hematology Laboratory Test Results by Timepoint: Basophils. MAD Group

    Time frame: Baseline (pre-dose Day 1), Day 3, Day 8, FU (7 days post dose)

    Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.

32. Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Aspartate Aminotransferase. SAD Group

    Time frame: Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose)

    Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.

33. Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Total Protein. SAD Group

    Time frame: Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose)

    Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.

34. Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Gamma-GT. SAD Group

    Time frame: Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose)

    Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value

35. Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Alkaline Phosphatase. SAD Group

    Time frame: Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose)

    Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.

36. Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Creatinine. SAD Group

    Time frame: Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose)

    Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.

37. Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Chloride. SAD Group

    Time frame: Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose)

    Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.

38. Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Total Bilirubin. SAD Group

    Time frame: Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose)

    Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.

39. Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Alanine Aminotransferase. SAD Group

    Time frame: Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose)

    Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.

40. Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Creatinine Kinase. SAD Group

    Time frame: Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose)

    Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.

41. Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Urea. SAD Group

    Time frame: Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose)

    Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.

42. Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Sodium. SAD Group

    Time frame: Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose)

    Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.

43. Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Potassium. SAD Group

    Time frame: Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose)

    Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.

44. Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Phosphate. SAD Group

    Time frame: Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose)

    Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.

45. Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Calcium (Corrected for Albumin). SAD Group

    Time frame: Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose)

    Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.

46. Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Uric Acid. SAD Group

    Time frame: Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose)

    Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.

47. Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Triiodothyronine (T3). SAD Group

    Time frame: Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose)

    Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.

48. Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Lipase. SAD Group

    Time frame: Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose)

    Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.

49. Change From Baseline in Chemistry Laboratory Test Results by Timepoint: (Fasting) Glucose. SAD Group

    Time frame: Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose)

    Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.

50. Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Human Serum Albumin. SAD Group

    Time frame: Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose)

    Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.

51. Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Cholesterol. SAD Group

    Time frame: Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose)

    Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.

52. Change From Baseline in Chemistry Laboratory Test Results by Timepoint: High Density Lipoproteins. SAD Group

    Time frame: Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose)

    Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.

53. Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Triglycerides. SAD Group

    Time frame: Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose)

    Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.

54. Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Low Density Lipoproteins. SAD Group

    Time frame: Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose)

    Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.

55. Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Bicarbonate. SAD Group

    Time frame: Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose)

    Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.

56. Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Thyroid-stimulating Hormone. SAD Group

    Time frame: Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose)

    Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.

57. Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Thyroxine (T4). SAD Group

    Time frame: Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose)

    Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.

58. Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Lactate. SAD Group

    Time frame: Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose)

    Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.

59. Change From Baseline in Chemistry Laboratory Test Results by Time Point: Total Protein. MAD Group

    Time frame: Baseline (pre-dose Day1), Day 3, Day 8, FU (one week after last dosing)

    Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.

60. Change From Baseline in Chemistry Laboratory Test Results by Time Point: Alkaline Phosphatase. MAD Group

    Time frame: Baseline, Day 3, Day 8, FU (one week after last dosing)

    Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.

61. Change From Baseline in Chemistry Laboratory Test Results by Time Point: Aspartate Aminotransferase. MAD Group

    Time frame: Baseline, Day 3, Day 8, FU (one week after last dosing)

    Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.

62. Change From Baseline in Chemistry Laboratory Test Results by Time Point: Creatine Kinase. MAD Group

    Time frame: Baseline, Day 3, Day 8, FU (one week after last dosing)

    Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.

63. Change From Baseline in Chemistry Laboratory Test Results by Time Point: Gamma GT. MAD Group

    Time frame: Baseline, Day 3, Day 8, FU (one week after last dosing)

    Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.

64. Change From Baseline in Chemistry Laboratory Test Results by Time Point: Total Bilirubin. MAD Group

    Time frame: Baseline, Day 3, Day 8, FU (one week after last dosing)

    Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.

65. Change From Baseline in Chemistry Laboratory Test Results by Time Point: Urea. MAD Group

    Time frame: Baseline, Day 3, Day 8, FU (one week after last dosing)

    Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.

66. Change From Baseline in Chemistry Laboratory Test Results by Time Point: Creatinine. MAD Group

    Time frame: Baseline, Day 3, Day 8, FU (one week after last dosing)

    Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.

67. Change From Baseline in Chemistry Laboratory Test Results by Time Point: Sodium. MAD Group

    Time frame: Baseline, Day 3, Day 8, FU (one week after last dosing)

    Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.

68. Change From Baseline in Chemistry Laboratory Test Results by Time Point: Potassium. MAD Group

    Time frame: Baseline, Day 3, Day 8, FU (one week after last dosing)

    Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.

69. Change From Baseline in Chemistry Laboratory Test Results by Time Point: Chloride. MAD Group

    Time frame: Baseline, Day 3, Day 8, FU (one week after last dosing)

    Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.

70. Change From Baseline in Chemistry Laboratory Test Results by Time Point: Calcium (Corrected for Albumin). MAD Group

    Time frame: Baseline, Day 3, Day 8, FU (one week after last dosing)

    Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.

71. Change From Baseline in Chemistry Laboratory Test Results by Time Point: Uric Acid. MAD Group

    Time frame: Baseline, Day 3, Day 8, FU (one week after last dosing)

    Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.

72. Change From Baseline in Chemistry Laboratory Test Results by Time Point: Lipase. MAD Group

    Time frame: Baseline, Day 3, Day 8, FU (one week after last dosing)

    Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.

73. Change From Baseline in Chemistry Laboratory Test Results by Time Point: Alanine Aminotransferase. MAD Group

    Time frame: Baseline, Day 3, Day 8, FU (one week after last dosing)

    Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.

74. Change From Baseline in Chemistry Laboratory Test Results by Time Point: Phosphate. MAD Group

    Time frame: Baseline, Day 3, Day 8, FU (one week after last dosing)

    Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.

75. Change From Baseline in Chemistry Laboratory Test Results by Time Point: Human Serum Albumin. MAD Group

    Time frame: Baseline, Day 3, Day 8, FU (one week after last dosing)

    Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.

76. Change From Baseline in Chemistry Laboratory Test Results by Time Point: Fasting Glucose. MAD Group

    Time frame: Baseline, Day 3, Day 8, FU (one week after last dosing)

    Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.

77. Change From Baseline in Chemistry Laboratory Test Results by Time Point: Cholesterol. MAD Group

    Time frame: Baseline, Day 3, Day 8, FU (one week after last dosing)

    Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.

78. Change From Baseline in Chemistry Laboratory Test Results by Time Point: Triglycerides. MAD Group

    Time frame: Baseline, Day 3, Day 8, FU (one week after last dosing)

    Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.

79. Change From Baseline in Chemistry Laboratory Test Results by Time Point: Low Density Lipoproteins. MAD Group

    Time frame: Baseline, Day 3, Day 8, FU (one week after last dosing)

    Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.

80. Change From Baseline in Chemistry Laboratory Test Results by Time Point: High Density Lipoproteins. MAD Group

    Time frame: Baseline, Day 3, Day 8, FU (one week after last dosing)

    Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.

81. Change From Baseline in Chemistry Laboratory Test Results by Time Point: Thyroid-stimulating Hormone. MAD Group

    Time frame: Baseline, Day 3, Day 8, FU (one week after last dosing)

    Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.

82. Change From Baseline in Chemistry Laboratory Test Results by Time Point: Trilodothyronine (T3). MAD Group

    Time frame: Baseline, Day 3, Day 8, FU (one week after last dosing)

    Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.

83. Change From Baseline in Chemistry Laboratory Test Results by Time Point: Thyroxine (T4). MAD Group

    Time frame: Baseline, Day 3, Day 8, FU (one week after last dosing)

    Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.

84. Change From Baseline in Chemistry Laboratory Test Results by Time Point: Bicarbonate. MAD Group

    Time frame: Baseline, Day 3, Day 8, FU (one week after last dosing)

    Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.

85. Change From Baseline in Chemistry Laboratory Test Results by Time Point: Lactate. MAD Group

    Time frame: Baseline, Day 3, Day 8, FU (one week after last dosing)

    Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.

86. Phospholipidosis

    Time frame: Day 1, Day 7

    Change from Day 1 to Day 7 in di-docosahexaenoyl (22:6)-bis(monoacylglycerol) phosphate (di-22:6-BMP) and normalized di-22:6-BMP (urine) - MAD

87. MAD: Change From Baseline in ECG Results by Time Point: Corrected QT Interval According to Barret's Formaula (QTcB)

    Time frame: Baseline (pre-dose Day 1), Day1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Follow-up

    The baseline ECG recording consists of a triplicate recording (3 recordings of a least 3 complexes within a 5 minute window) prior to dosing on Day 1. For the evaluation the average of the 3 recordings will be taken as baseline. Other ECG recordings will be singlet (one recording of at least 3 complexes) prior to dosing, or around the expected Cmax on Day 1 or 7 for the multiple- dose part.

88. MAD: Change From Baseline in ECG Results by Time Point: P Wave-Q Wave Interval (PQ Interval)

    Time frame: Baseline (pre-dose Day 1), Day1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Follow-up

    The baseline ECG recording consists of a triplicate recording (3 recordings of a least 3 complexes within a 5 minute window) prior to dosing on Day 1. For the evaluation of the PQ interval the average of the 3 recordings will be taken as baseline.

89. MAD: Change From Baseline in ECG Results by Time Point: the Interval That Denotes Depolarization of the Ventricles, Between the Beginning of the Q Wave and the End of the S Wave (QRS Interval)

    Time frame: Baseline (pre-dose Day 1), Day1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Follow-up

    The baseline ECG recording consists of a triplicate recording (3 recordings of a least 3 complexes within a 5 minute window) prior to dosing on Day 1. For the evaluation the average of the 3 recordings will be taken as baseline. Other ECG recordings will be singlet (one recording of at least 3 complexes) prior to dosing, or around the expected Cmax on Day 1 or 7 for the multiple- dose part.

90. MAD: Change From Baseline in ECG Results by Time Point: QT Interval

    Time frame: Baseline (pre-dose Day 1), Day1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Follow-up

    The baseline ECG recording consists of a triplicate recording (3 recordings of a least 3 complexes within a 5 minute window) prior to dosing on Day 1. For the evaluation the average of the 3 recordings will be taken as baseline. Other ECG recordings will be singlet (one recording of at least 3 complexes) prior to dosing, or around the expected Cmax on Day 1 or 7 for the multiple- dose part.

91. SAD: Change From Baseline in ECG Results by Time Point: PQ Interval

    Time frame: Pre-dose, Day 1, Day 7

    The baseline ECG recording consists of a triplicate recording (3 recordings of a least 3 complexes within a 5 minute window) prior to dosing on Day 1. For the evaluation the average of the 3 recordings will be taken as baseline.

92. SAD: Change From Baseline in ECG Results by Time Point: QRS Interval

    Time frame: Pre-dose, Day 1, Day 7

    The baseline ECG recording consists of a triplicate recording (3 recordings of a least 3 complexes within a 5 minute window) prior to dosing on Day 1. For the evaluation the average of the 3 recordings will be taken as baseline.

93. SAD: Change From Baseline in ECG Results by Time Point: QT Interval

    Time frame: Pre-dose, Day 1, Day 7

    The baseline ECG recording consists of a triplicate recording (3 recordings of a least 3 complexes within a 5 minute window) prior to dosing on Day 1. For the evaluation the average of the 3 recordings will be taken as baseline.

94. SAD: Change From Baseline in ECG Results by Time Point: QTcB Interval

    Time frame: Pre-dose, Day1, Day 7

    The baseline ECG recording consists of a triplicate recording (3 recordings of a least 3 complexes within a 5 minute window) prior to dosing on Day 1. For the evaluation the average of the 3 recordings will be taken as baseline.

95. Terminal Elimination Half-life (T1/2) of KH176 Over 24 Hours: SAD

    Time frame: Pre-dose (5 min before dosing) and 0.5, 1, 1.5, 2, 3, 6, 8, 12, and 24 hours post-dose

    Plasma concentrations of KH176 were analysed after single dose administration of doses 10mg, 30mg, 100mg (with and without food), 300mg, 800mg, 2000mg b.i.d.

96. Terminal Elimination Half-life (T1/2) of KH183: SAD

    Time frame: Pre-dose (5 min before dosing) and 0.5, 1, 1.5, 2, 3, 6, 8, 12, and 24 hours post-dose

    Plasma concentrations of KH183 were analysed after single dose administration of doses 10mg, 30mg, 100mg (with and without food) , 300mg, 800mg, 2000mg b.i.d.

97. Maximum Concentration (Cmax) of KH176: SAD Group

    Time frame: Pre-dose (5 min before dosing) and 0.5, 1, 1.5, 2, 3, 6, 8, 12, and 24 hours post-dose

    Plasma concentrations of KH176 were analysed after single dose administration of doses 10mg, 30mg, 100mg (with and without food), 300mg, 800mg, 2000mg b.i.d.

98. Maximum Concentration (Cmax) of KH183 Over 24 Hours: SAD

    Time frame: Pre-dose (5 min before dosing) and 0.5, 1, 1.5, 2, 3, 6, 8, 12, and 24 hours post-dose

    Plasma concentrations of KH183 were analysed after single dose administration of doses 10mg, 30mg, 100mg (with and without food) , 300mg, 800mg, 2000mg b.i.d.

99. Maximum Concentration (Cmax) of KH183 (Active Metabolite of KH176): MAD Group

    Time frame: Predose at Day 1, 2, 4, 7, and post-dose at Day 1 and Day 7 at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hours

    Plasma concentrations of KH183 were analysed after multiple-dose administration of doses of 100, 200 and 400 mg b.i.d.: Cmax was obtained directly from the concentration-time data.

100. Maximum Concentration (Cmax) of KH176: MAD

     Time frame: pre-dose at Day 1, 2, 4, 7, and post-dose at Day 1 and Day 7 at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hours

     Plasma concentrations of KH176 were analysed after multiple-dose administration of doses of 100, 200 and 400 mg b.i.d.

101. Time to Maximum Concentration (Tmax) of KH176 Over 24 Hours: SAD

     Time frame: Pre-dose (5 min before dosing) and 0.5, 1, 1.5, 2, 3, 6, 8, 12, and 24 hours post-dose

     Plasma concentrations of KH176 were analysed after single dose administration of doses 10mg, 30mg, 100mg (with and without food), 300mg, 800mg, 2000mg b.i.d.

102. Time to Reach Peak Plasma Concentration (Tmax) of KH183: SAD

     Time frame: Pre-dose (5 min before dosing) and 0.5, 1, 1.5, 2, 3, 6, 8, 12, and 24 hours post-dose

     Plasma concentrations of KH183 were analysed after single dose administration of doses 10mg, 30mg, 100mg (with and without food), 300mg, 800mg, 2000mg b.i.d.

103. Time to Maximum Concentration (Tmax) of KH176 at Day 1, Day 7: MAD Group

     Time frame: pre-dose at Day 1, 2, 4, 7, and post-dose at Day 1 and Day 7 at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hours

     Plasma concentrations of KH176 were analysed after multiple-dose administration of doses of 100, 200 and 400 mg b.i.d.

104. Time to Maximum Concentration (Tmax) of KH183 (Active Metabolite of KH176): MAD Group

     Time frame: Predose at Day 1, 2, 4, 7, and post-dose at Day 1 and Day 7 at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hours

     Plasma concentrations of KH183 were analysed after multiple-dose administration of doses of 100, 200 and 400 mg b.i.d.. tmax was obtained directly from the concentration-time data.

105. Accumulation Factor (Racc) of KH176 Over 7 Days: MAD Group

     Time frame: Pre-dose at Day 1, 2, 4, 7, and post-dose at Day 1 and Day 7 at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hours

     Plasma concentrations of KH176 were analysed after multiple-dose administration of doses of 100, 200 and 400 mg b.i.d.. Racc was calculated as follows: AUCtau day 7/ AUCtau day 1.

106. Accumulation Factor (Racc) of KH183 (Active Metabolite of KH176): MAD Group

     Time frame: Predose at Day 1, 2, 4, 7, and post-dose at Day 1 and Day 7 at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hours

     Plasma concentrations of KH183 were analysed after multiple-dose administration of doses of 100, 200 and 400 mg b.i.d.: Accumulation factor was calculated as follows: AUCtau day 7/ AUCtau day 1.

107. Area Under the Plasma Concentration Versus Time Curve (AUClast) of KH183: SAD Group

     Time frame: Pre-dose (5 min before dosing) and 0.5, 1, 1.5, 2, 3, 6, 8, 12, and 24 hours post-dose

     Plasma concentrations of KH183 were analysed after single dose administration of doses 10mg, 30mg, 100mg (with and without food) , 300mg, 800mg, 2000mg b.i.d.

108. Area Under the Plasma Concentration Versus Time Curve (AUClast) of KH176: SAD Group

     Time frame: pre-dose (5 min before dosing) and 0.5, 1, 1.5, 2, 3, 6, 8, 12, and 24 hours post-dose

     Plasma concentrations of KH176 were analysed after single dose administration of doses 10mg, 30mg, 100mg (with and without food), 300mg, 800mg, 2000mg b.i.d.

109. Area Under the Plasma Concentration-time Curve (AUCtau) of KH176: MAD Group:

     Time frame: Pre-dose at Day 1, 2, 4, 7, and post-dose at Day 1 and Day 7 at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hours

     Plasma concentrations of KH176 were analysed after multiple-dose administration of doses of 100, 200 and 400 mg b.i.d.

110. Area Under the Plasma Concentration-time Curve During a Dose Interval (AUCtau) of KH183 (Active Metabolite of KH176): MAD Group

     Time frame: Predose at Day 1, 2, 4, 7, and post-dose at Day 1 and Day 7 at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hours

     Plasma concentrations of KH183 were analysed after multiple-dose administration of doses of 100, 200 and 400 mg b.i.d.

111. Area Under the Plasma Concentration-time Curve From Time Zero Until Infinity (AUCl0-inf) of KH183: SAD

     Time frame: Pre-dose (5 min before dosing) and 0.5, 1, 1.5, 2, 3, 6, 8, 12, and 24 hours post-dose

     Plasma concentrations of KH183 were analysed after single dose administration of doses 10mg, 30mg, 100mg (with and without food) , 300mg, 800mg, 2000mg b.i.d.

112. Area Under the Plasma Concentration-time Curve From Time Zero Until Infinity (AUCl0-inf) of KH176: SAD

     Time frame: Pre-dose (5 min before dosing) and 0.5, 1, 1.5, 2, 3, 6, 8, 12, and 24 hours post-dose

     Plasma concentrations of KH176 were analysed after single dose administration of doses 10mg, 30mg, 100mg (with and without food) , 300mg, 800mg, 2000mg b.i.d.

113. KH176: Percentage of Administered Dose Excreted in Urine: SAD

     Time frame: 24 hours post-dose

     Urine concentrations of KH176 were analysed after single dose administration of doses 10mg, 30mg, 100mg (with and without food), 300mg, 800mg, 2000mg b.i.d.

114. KH183: Percentage of Administered Dose Excreted in Urine: SAD

     Time frame: 24 hours post-dose

     Urine concentrations of KH176 were analysed after single dose administration of doses 10mg, 30mg, 100mg (with and without food), 300mg, 800mg, 2000mg b.i.d.

115. KH176 + KH183: Percentage of Administered Dose Excreted in Urine: SAD

     Time frame: 24 hours post-dose

     Urine concentrations of KH176 were analysed after single dose administration of doses 10mg, 30mg, 100mg (with and without food), 300mg, 800mg, 2000mg b.i.d.

116. KH176: Percentage of Administered Dose Excreted in Urine: MAD

     Time frame: Day 7 post dose

     Urine concentrations of KH176 were analysed after multiple-dose administration of doses of 100, 200 and 400 mg b.i.d.

117. KH183: Percentage of Administered Dose Excreted in Urine: MAD

     Time frame: Post dose Day 7

     Urine concentrations of KH183 were analysed after multiple-dose administration of doses of 100, 200 and 400 mg b.i.d.

118. KH173 + KH183: Percentage of Administered Dose Excreted in Urine: MAD

     Time frame: Day 7 Post dose

     Urine concentrations of KH176 and KH183 were analysed after multiple-dose administration of doses of 100, 200 and 400 mg b.i.d.