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OpenTrials
Completed

NCT Number: NCT04604795

Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of GSK3915393 in Healthy Participants and to Evaluate the Interaction Between GSK3915393 and Grapefruit Juice and Itraconazole

This is a 3-part first time into human study (FTIH) study for GSK3915393. Parts A and B of the study will evaluate the safety, tolerability and pharmacokinetics (PK) of single ascending and repeat oral doses of GSK3915393 in healthy adult participants. Part C will evaluate the impact of co-administration of GSK3915393 with grapefruit juice and itraconazole on the PK of GSK3915393.

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Key information

Conditions

Celiac Disease Coeliac Disease Digestive System Diseases Gastrointestinal Diseases Intestinal Diseases Malabsorption Syndromes Metabolic Diseases Nutritional and Metabolic Diseases

Age range

18 year–50 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

GSK Investigational Site

London, NW10 7EW, United Kingdom

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Between 18 and 50 years of age inclusive, at the time of signing the informed consent.
  • Healthy participants who are overtly healthy as determined by medical evaluation including medical history, physical examination, laboratory tests, and cardiac monitoring.
  • Negative coronavirus disease of 2019 (COVID-19) test on admission.
  • Body weight >=40 kilograms (kg) and body mass index (BMI) within the range 18.5-29.9 kilograms per square meter (kg/m^2) (inclusive).
  • Male or females: No restrictions for male participants. A female participant is eligible to participate if she is not pregnant or breastfeeding, and one of the following conditions applies: Is a woman of non-childbearing potential (WONCBP) OR Is a woman of childbearing potential (WOCBP) and using an acceptable contraceptive method from 30 days prior to first dose until follow up visit. The investigator should evaluate the potential for contraceptive method failure (e.g., noncompliance, recently initiated in relationship to the first dose of study intervention). A WOCBP must have a negative highly sensitive pregnancy test (serum) at screening and on admission to the clinical unit. The investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a woman with an early undetected pregnancy.
  • Capable of giving signed informed consent.

Exclusion criteria

  • History or current evidence of cardiovascular, respiratory, hepatic, renal, gastrointestinal (Irritable bowel syndrome [IBS], Gastroesophageal reflux disease [GERD], nausea, vomiting or dysphagia), endocrine, hematological, neurological, or psychiatric disorders capable of significantly altering the absorption, metabolism, or elimination of drugs; constituting a risk when taking the study treatment; or interfering with the interpretation of data.
  • Current evidence of active infection.
  • Participants with signs/symptoms suggestive of COVID-19 (i.e. fever, cough, etc) within the past 14 days prior to screening and admission to clinical unit.
  • Participants with known COVID-19 positive contacts in the past 14 days prior to screening and admission to clinical unit.
  • Any history of suicidal behavior within the past 6 months or any history of attempted suicide in a participant's lifetime.
  • Alanine transaminase (ALT) >1.5 times upper limit of normal (ULN).
  • Bilirubin >1.5 times ULN (isolated bilirubin >1.5 times ULN is acceptable if bilirubin is fractionated and direct bilirubin <35 percent).
  • Current or chronic history of liver disease or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
  • History of gastrointestinal (GI) surgery (with exception of appendectomy).
  • Average QT interval corrected using Fridericia's formula (QTcF) >450 milliseconds (msec) at screening.
  • Any clinically relevant abnormality on the screening medical assessment, laboratory examination, or electrocardiogram.
  • History of QTc prolongation, symptomatic cardiac arrhythmias or cardiac arrest.
  • For Part C only, history of liver toxicity resulting from drug administration.
  • For Part C only, history of intolerance to itraconazole.
  • History of sensitivity to any of the study medication, or components thereof or a history of drug or other allergy that, in the opinion of the investigator or GlaxoSmithKline Medical Monitor, contraindicates their participation.
  • Use of any immunosuppressive medications within 6 months prior to entry.
  • Unable to refrain from the use of prescription or non-prescription drugs, including vitamins, probiotics, antacids, herbal and dietary supplements (including Saint [St] John's Wort) within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half- lives (whichever is longer) prior to the first dose of study medication for each dosing, unless in the opinion of the Investigator and GlaxoSmithKline Medical Monitor the medication will not interfere with the study procedures or compromise participant safety. (Paracetamol is acceptable at a dose of no more than 500 milligrams [mg] at a time and no more than 2 grams [g] per day).
  • Participants who have received a COVID-19 vaccine within 7 days of admission (or readmission) to the clinical unit or who are demonstrating signs/symptoms attributed to a COVID-19 vaccination that occurred greater than 7 days earlier.
  • Recent donation of blood or blood products such that participation in the study would result in loss of blood in excess of 500 milliliter (mL) within 56 days.
  • The participant has participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day in the current study: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer).
  • Exposure to more than 4 investigational medicinal products within 12 months prior to the first dosing day.
  • Unwillingness or inability to follow the procedures outlined in the protocol or any other type of medical research within 30 days of randomization.
  • Presence of hepatitis B surface antigen (HBsAg) at screening or within 3 months prior to first dose of study treatment.
  • Positive hepatitis C antibody test result at screening or within 3 months prior to first dose of study treatment.
  • Positive Hepatitis C ribonucleic acid (RNA) test result at screening or within 3 months prior to first dose of study treatment.
  • A positive pre-study drug/alcohol screen.
  • Positive human immunodeficiency virus (HIV) antibody test.
  • History of drug abuse (as defined by the current version of the Diagnostic and Statistical Manual [DSM]) within 2 years before dosing, or a positive drug screen reflecting consumption of illicit drugs.
  • Regular alcohol consumption within 6 months prior to screening: An average weekly intake of >21 units for males or >14 units for females. One unit is equivalent to 8 g of alcohol: a half-pint (approximately 240 mL) of beer, 1 glass (125 mL) of wine or 1 (25 mL) measure of spirits.
  • Urinary cotinine levels indicative of smoking or use of tobacco or nicotine-containing products (e.g. nicotine patches or vaporizing devices) at screening or on admission to the unit.

Treatment and study plan

GSK3915393 Capsules

Drug

GSK3915393 capsules will be given orally.

GSK3915393 Solution for Infusion

Drug

GSK3915393 solution for infusion will be administered intravenously.

placebo capsules

Drug

Placebo matching GSK3915393 capsules will be given orally.

Itraconazole

Drug

Participants will be administered with GSK3915393 along with ITZ orally

Water

Other

Participants will be administered with GSK3915393 along with water orally

Grape fruit juice

Other

Participants will be administered with GSK3915393 along with GFJ orally

Primary outcomes

  1. Part A: Number of Participants With All Non-serious Adverse Events (AEs) and Serious AEs (SAEs) Following Administration of Oral Dose

    Time frame: Up to 70 days

    An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. SAE is defined as any serious adverse event that, at any dose which results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, other situations as per investigator's medical or scientific judgment.

  2. Part A: Number of Participants With Treatment-related AEs Following Administration of Oral Dose

    Time frame: Up to 70 days

    An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. Number of participants with treatment related AEs were presented.

  3. Part B: Number of Participants With All Non-serious AEs and SAEs

    Time frame: Up to 28 days

    An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. SAE is defined as any serious adverse event that, at any dose which results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, other situations as per investigator's medical or scientific judgment.

  4. Part B: Number of Participants With Treatment-related AEs

    Time frame: Up to 28 days

    An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. Number of participants with treatment related AEs are presented.

  5. Part A: Number of Participants With Worst Case Chemistry Results by Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline Following Administration of Oral Dose

    Time frame: Up to 70 days

    Blood samples were collected for analysis of chemistry parameters. PCI ranges were >=2*Upper limit of normal (ULN) units per liter (U/L)(Alanine Aminotransferase [ALT]), >=2*ULN (U/L) (Aspartate Aminotransferase ([AST]), >=2*ULN (Alkaline Phosphatase [ALP]) (U/L), >=1.5*ULN (micromoles per liter) (bilirubin), <2 or >2.75 millimoles/liter (L) (mmol/L)(calcium), <3 or >11 mmol/L (glucose), <3 or >5.5 mmol/L (potassium), <130 or >150 mmol/L (sodium),<50 or >85 grams/liter (protein). Participants were counted in worst case category that their value changes to (low, within [w/in] range or no change [NC], or high), unless there is no change in their category. Participants whose laboratory value category was unchanged (e.g., High to High), or whose value became within range, are recorded in 'To within Range No Change' category. Participants were counted twice if participant had values that changed 'To Low' and 'To High', so percentages may not add to 100 percentage (%).

  6. Part A: Number of Participants With Worst Case Chemistry Results-creatinine by PCI Criteria Post-Baseline Relative to Baseline Following Administration of Oral Dose

    Time frame: Up to 70 days

    Blood samples were collected for analysis of creatinine. Participants were counted under increase of PCI if they had change from Baseline > 44.2 micromoles per Liter for any post Baseline assessment. Participants who did not meet this PCI criteria are counted as within (w/in) range.

  7. Part A: Number of Participants With Worst Case Chemistry Results-urea by PCI Criteria Post-Baseline Relative to Baseline Following Administration of Oral Dose

    Time frame: Up to 70 days

    Blood samples were collected for analysis of chemistry parameters. PCI range for Urea: High >10.5 mmol/L. Participants were counted in worst case category that their value changes to (within [w/in] range or no change [NC], or high), unless there is no change in their category. Participants whose laboratory value category was unchanged (e.g., High to High), or whose value became within range, are recorded in 'To within Range No Change' category.

  8. Part A: Number of Participants With Worst Case Hematology Results by PCI Criteria Post-Baseline Relative to Baseline Following Administration of Oral Dose

    Time frame: Up to 70 days

    Blood samples were collected for analysis of hematology parameters. PCI ranges were >1*10^9 cell per liter (cells/L) (eosinophils), <0.2 or >0.54 proportion of red blood cells in blood (hematocrit), <80 or >180 grams per liter(g/L) (hemoglobin), <3 or >20 x10^9 cells/L (leukocytes), <0.8*10^9 cells/L (lymphocytes), <1.5 or >16*10^9 cells/L (neutrophils) and <100 or >550*10^9 cells/L (platelets). Participants were counted in worst case category that their value changes to (low, within range or no change or high), unless there is no change in their category. Participants whose laboratory value category was unchanged (for example [e.g.], High to High), or whose value became within range, were recorded in "To within Range or No Change" category. Participants were counted twice if participant has values that changed 'To Low' & 'To High', so the percentages may not add to 100%.

  9. Part A: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline Following Administration of Oral Dose

    Time frame: Up to 70 days

    Vital signs included diastolic blood pressure (DBP), systolic blood pressure (SBP), pulse rate (PR), body temperature, respiratory rate (RR) and were measured after resting for at least 5 minutes in semi-supine position. PCI ranges were, SBP (millimeters of mercury[mmHg]): <85 (low) or >160 (high), DBP (mmHg): <45 (low) or >100 (high), heart rate (beats per minute): <40 (low) or >110 (high), respiration rate (breaths per minute):<=8 (low) or >20 (high) and body temperature (degrees Celsius) <=35.5 (low) or >38.0 (high). Participants were counted in worst case category that their value changes to (low, within range or no change, or high), unless there is no change in their category. Participants whose laboratory value category was unchanged (e.g., High to High), or whose value became within range, are recorded in 'To W/in Range No Change' category. Participants were counted twice if participant had values that changed 'To Low' and 'To High', so percentages may not add to 100%.

  10. Part A: Number of Participants With Worst Case Post-Baseline Abnormal Electrocardiogram (ECG) Findings Following Administration of Oral Dose

    Time frame: Up to 70 days

    Twelve lead ECG was obtained using an ECG machine that automatically calculated the heart rate and measured QTc, PR, QRS intervals. Abnormal findings were categorized as clinically significant and not clinically significant. Clinically significant abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition. Data for number of participants with worst case post-Baseline abnormal ECG findings have been presented.

  11. Part A: Number of Participants With Abnormal Physical Examination Findings Following Administration of Oral Dose

    Time frame: Up to 70 days

    A full physical examination was performed which included, at a minimum, assessments of the Skin, Cardiovascular, Respiratory, Gastrointestinal and Neurological systems.

  12. Part B: Number of Participants With Worst Case Chemistry Results by PCI Criteria Post-Baseline Relative to Baseline Following Administration of Repeat Oral Dose of GSK3915393

    Time frame: Up to 28 days

    Blood samples were collected for analysis of chemistry parameters. PCI ranges were >=2*ULN (U/L)(ALT), >=2*ULN (U/L) (AST), >=2*ULN (ALP) (U/L), >=1.5*ULN (micromoles per liter) (bilirubin), <2 or >2.75 millimoles/liter (L) (mmol/L)(calcium), <3 or >11 mmol/L (glucose), <3 or >5.5 mmol/L (potassium), <130 or >150 mmol/L (sodium),<50 or >85 grams/liter (protein). Participants were counted in worst case category that their value changes to (low, within [w/in] range or no change [NC], or high), unless there is no change in their category. Participants whose laboratory value category was unchanged (e.g., High to High), or whose value became within range, are recorded in 'To within Range No Change' category. Participants were counted twice if participant had values that changed 'To Low' and 'To High', so percentages may not add to 100 percentage (%).

  13. Part B: Number of Participants With Worst Case Chemistry Results-urea by PCI Criteria Post-Baseline Relative to Baseline Following Administration of Repeat Oral Dose of GSK3915393

    Time frame: Up to 28 days

    Blood samples were collected for analysis of chemistry parameters. PCI range for Urea: High >10.5 mmol/L. Participants were counted in worst case category that their value changes to (within [w/in] range or NC, or high), unless there is no change in their category. Participants whose laboratory value category was unchanged (e.g., High to High), or whose value became within range, are recorded in 'To within Range No Change' category.

  14. Part B: Number of Participants With Worst Case Chemistry Results-creatinine by PCI Criteria Post-Baseline Relative to Baseline Following Administration of Repeat Oral Dose

    Time frame: Up to 28 days

    Blood samples were collected for analysis of creatinine. Participants were counted under increase of PCI if they had change from Baseline > 44.2 micromoles per Liter for any post Baseline assessment. Participants who did not meet this PCI criteria are counted as w/in range. Participants whose laboratory value became within range, were recorded in 'To within Range' category.

  15. Part B: Number of Participants With Worst Case Hematology Results by PCI Criteria Post-Baseline Relative to Baseline Following Repeat Oral Dose of GSK3915393

    Time frame: Up to 28 days

    Blood samples were collected for analysis of hematology parameters. PCI ranges were 1*10^9 cell per liter (cells/L) (eosinophils), <0.2 or >0.54 proportion of red blood cells in blood (hematocrit), <80 or >180 grams per liter(g/L) (hemoglobin), <3 or >20 x10^9 cells/L (leukocytes), <0.8*10^9 cells/L (lymphocytes), <1.5 or >16*10^9 cells/L (neutrophils) and <100 or >550*10^9 cells/L (platelets). Participants were counted in worst case category that their value changes to (low, within range or no change or high), unless there is no change in their category. Participants whose laboratory value category was unchanged (for example [e.g.], High to High), or whose value became within range, were recorded in "To within Range or No Change" category. Participants were counted twice if participant has values that changed 'To Low' & 'To High', so the percentages may not add to 100%.

  16. Part B: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline Following Repeat Oral Dose of GSK3915393

    Time frame: Up to 28 days

    Vital signs included DBP, SBP, PR, body temperature, RR and were measured after resting for at least 5 minutes in semi-supine position. PCI ranges were, SBP (mmHg): <85 (low) or >160 (high), DBP (mmHg): <45 (low) or >100 (high), heart rate (beats per minute): <40 (low) or >110 (high), respiration rate (breaths per minute):<=8 (low) or >20 (high) and body temperature (degrees Celsius) <=35.5 (low) or >38.0 (high). Participants were counted in worst case category that their value changes to (low, within range or no change, or high), unless there is no change in their category. Participants whose laboratory value category was unchanged (e.g., High to High), or whose value became within range, are recorded in 'To W/in Range No Change' category. Participants were counted twice if participant had values that changed 'To Low' and 'To High', so percentages may not add to 100%.

  17. Part B: Number of Participants With Worst Case Post-Baseline Abnormal ECG Findings Following Repeat Oral Dose of GSK3915393

    Time frame: Up to 28 days

    Twelve lead ECG was obtained using an ECG machine that automatically calculated the heart rate and measured QTc, PR, QRS intervals. Abnormal findings were categorized as clinically significant and not clinically significant. Clinically significant abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition. Data for number of participants with worst case post-Baseline abnormal ECG findings have been presented.

  18. Part B: Number of Participants With Abnormal Physical Examination Findings Following Administration of Repeat Oral Dose of GSK3915393

    Time frame: Up to 28 days

    A full physical examination was performed which included, at a minimum, assessments of the Skin, Cardiovascular, Respiratory, Gastrointestinal and Neurological systems.

  19. Part C: Maximum Observed Plasma Drug Concentration (Cmax) Following IV Dose of GSK3915393

    Time frame: Pre-dose and at 20, 40 minutes, 1, 1 hour 5 minutes, 1 hour 10 minutes, 1 hours 20 minutes, 1 hour 40 minutes, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, and 10 hours post-dose

    Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3915393.

  20. Part C: Cmax of GSK3915393 Following IV Dose of GSK3915393+ITZ

    Time frame: Pre-dose and at 20, 40 minutes, 1, 1 hour 5 minutes, 1 hour 10 minutes, 1 hours 20 minutes, 1 hour 40 minutes, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 10, 12, 24, 36, 48, and 60 hours post-dose

    Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3915393.

  21. Part C: Cmax Following Oral Dose of GSK3915393 in Combination With Water, GFJ and ITZ

    Time frame: Pre-dose and at 20, 40 minutes, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 24, 36, 48 and 60 hours post-dose

    Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3915393. For Part C: GSK3915393 20 mg+ Water and Part C: GSK3915393 20 mg+ GFJ, concentrations after 24 hours post-dose were expected to be non-quantifiable. Cmax was derived based on collected assessments (up to 24 hours for Part C: GSK3915393 20 mg+ Water and Part C: GSK3915393 20 mg+ GFJ, up to 60 hours for Part C: GSK3915393 20 mg+ ITZ). Only the quantifiable concentration time points were to be considered for assessment of pharmacokinetic parameters.

  22. Part C: Time to Maximum Observed Plasma Drug Concentration (Tmax) Following IV Dose of GSK3915393

    Time frame: Pre-dose and at 20, 40 minutes, 1, 1 hour 5 minutes, 1 hour 10 minutes, 1 hours 20 minutes, 1 hour 40 minutes, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, and 10 hours post-dose

    Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3915393.

  23. Part C: Tmax of GSK3915393 Following IV Dose of GSK3915393+ITZ

    Time frame: Pre-dose and at 20, 40 minutes, 1, 1 hour 5 minutes, 1 hour 10 minutes, 1 hours 20 minutes, 1 hour 40 minutes, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 10, 12, 24, 36, 48, and 60 hours post-dose

    Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3915393.

  24. Part C: Tmax of GSK3915393 Following Oral Dose of GSK3915393 in Combination With Water, GFJ and ITZ

    Time frame: Pre-dose and at 20, 40 minutes, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 24, 36, 48 and 60 hours post-dose

    Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3915393. For Part C: GSK3915393 20 mg+ Water and Part C: GSK3915393 20 mg+ GFJ, concentrations after 24 hours post-dose were expected to be non-quantifiable. Tmax was derived based on collected assessments (up to 24 hours for Part C: GSK3915393 20 mg+ Water and Part C: GSK3915393 20 mg+ GFJ, up to 60 hours for Part C: GSK3915393 20 mg+ ITZ). Only the quantifiable concentration time points were to be considered for assessment of pharmacokinetic parameters.

  25. Part C: Area Under Curve up to the Last Measurable Concentration (AUCLST[0-10]) Following IV Dose of GSK3915393

    Time frame: Pre-dose and at 20, 40 minutes, 1, 1 hour 5 minutes, 1 hour 10 minutes, 1 hours 20 minutes, 1 hour 40 minutes, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, and 10 hours post-dose

    Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3915393.

  26. Part C: AUCLST(0-24) of GSK3915393 Following IV Dose of GSK3915393+ITZ

    Time frame: Pre-dose and at 20, 40 minutes, 1, 1 hour 5 minutes, 1 hour 10 minutes, 1 hours 20 minutes, 1 hour 40 minutes, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 10, 12, and 24 hours post-dose

    Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3915393.

  27. Part C: AUCLST(0-24) of GSK3915393 Following Oral Dose of GSK3915393 in Combination With Water, GFJ and ITZ

    Time frame: Pre-dose and at 20, 40 minutes, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14 and 24 hours post-dose

    Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3915393.

  28. Part C: AUC From Time Zero to Infinity (AUC[0-inf]) Following IV Dose of GSK3915393

    Time frame: Pre-dose and at 20, 40 minutes, 1, 1 hour 5 minutes, 1 hour 10 minutes, 1 hours 20 minutes, 1 hour 40 minutes, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, and 10 hours post-dose

    Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3915393.

  29. Part C: AUC(0-inf) of GSK3915393 Following IV Dose of GSK3915393+ITZ

    Time frame: Pre-dose and at 20, 40 minutes, 1, 1 hour 5 minutes, 1 hour 10 minutes, 1 hours 20 minutes, 1 hour 40 minutes, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 10, 12, 24, 36, 48, and 60 hours post-dose

    Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3915393.

  30. Part C: AUC(0-inf) of GSK3915393 Following Oral Dose of GSK3915393 in Combination With Water, GFJ and ITZ

    Time frame: Pre-dose and at 20, 40 minutes, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 24, 36, 48 and 60 hours post-dose

    Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3915393. For Part C: GSK3915393 20 mg+ Water and Part C: GSK3915393 20 mg+ GFJ, concentrations after 24 hours post-dose were expected to be non-quantifiable. AUC(0-inf) was derived based on collected assessments (up to 24 hours for Part C: GSK3915393 20 mg+ Water and Part C: GSK3915393 20 mg+ GFJ, up to 60 hours for Part C: GSK3915393 20 mg+ ITZ). Only the quantifiable concentration time points were to be considered for assessment of pharmacokinetic parameters.

  31. Part C: Apparent Terminal Half-life (t1/2) of GSK3915393 Following IV Dose of GSK3915393

    Time frame: Pre-dose and at 20, 40 minutes, 1, 1 hour 5 minutes, 1 hour 10 minutes, 1 hours 20 minutes, 1 hour 40 minutes, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, and 10 hours post-dose

    Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3915393.

  32. Part C: t1/2 of GSK3915393 Following IV Dose of GSK3915393+ITZ

    Time frame: Pre-dose and at 20, 40 minutes, 1, 1 hour 5 minutes, 1 hour 10 minutes, 1 hours 20 minutes, 1 hour 40 minutes, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 10, 12, 24, 36, 48, and 60 hours post-dose

    Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3915393.

  33. Part C: t1/2 of GSK3915393 Following Oral Dose of GSK3915393 in Combination With Water, GFJ and ITZ

    Time frame: Pre-dose and at 20, 40 minutes, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 24, 36, 48 and 60 hours post-dose

    Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3915393. For Part C: GSK3915393 20 mg+ Water and Part C: GSK3915393 20 mg+ GFJ, concentrations after 24 hours post-dose were expected to be non-quantifiable. t1/2 was derived based on collected assessments (up to 24 hours for Part C: GSK3915393 20 mg+ Water and Part C: GSK3915393 20 mg+ GFJ, up to 60 hours for Part C: GSK3915393 20 mg+ ITZ). Only the quantifiable concentration time points were to be considered for assessment of pharmacokinetic parameters.

Secondary outcomes

  1. Part A: Cmax Following Single Oral Dose of GSK3915393

    Time frame: Pre-dose and at 20, 40 minutes, 1, 1.5, 2, 3, 4, 6, 10, 12, 14, 24 and 36 hours post-dose

    Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3915393.

  2. Part A: Cmax Following Single IV Dose of GSK3915393

    Time frame: Pre-dose and at 20, 40 minutes, 1, 1 hour 5 minutes, 1 hour 10 minutes, 1 hours 20 minutes, 1 hour 40 minutes, 2, 2.5, 3, 3.5, 4, 5 and 6 hours post-dose

    Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3915393.

  3. Part A: Tmax Following Single Oral Dose of GSK3915393

    Time frame: Pre-dose and at 20, 40 minutes, 1, 1.5, 2, 3, 4, 6, 10, 12, 14, 24 and 36 hours post-dose

    Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3915393.

  4. Part A: Tmax Following IV Dose of GSK3915393

    Time frame: Pre-dose and at 20, 40 minutes, 1, 1 hour 5 minutes, 1 hour 10 minutes, 1 hours 20 minutes, 1 hour 40 minutes, 2, 2.5, 3, 3.5, 4, 5 and 6 hours post-dose

    Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3915393.

  5. Part A: AUCLST(0-24) Following Single Oral Dose of GSK3915393

    Time frame: Pre-dose and at 20, 40 minutes, 1, 1.5, 2, 3, 4, 6, 10, 12, 14, and 24 hours post-dose

    Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3915393.

  6. Part A: AUCLST(0-6) Following Single IV Dose of GSK3915393

    Time frame: Pre-dose and at 20, 40 minutes, 1, 1 hour 5 minutes, 1 hour 10 minutes, 1 hours 20 minutes, 1 hour 40 minutes, 2, 2.5, 3, 3.5, 4, 5 and 6 hours post-dose

    Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3915393.

  7. Part A: AUC(0-inf) Following Single Oral Dose of GSK3915393

    Time frame: Pre-dose and at 20, 40 minutes, 1, 1.5, 2, 3, 4, 6, 10, 12, 14, 24 and 36 hours post-dose

    Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3915393.

  8. Part A: AUC(0-inf) Following Single IV Dose of GSK3915393

    Time frame: Pre-dose and at 20, 40 minutes, 1, 1 hour 5 minutes, 1 hour 10 minutes, 1 hours 20 minutes, 1 hour 40 minutes, 2, 2.5, 3, 3.5, 4, 5 and 6 hours post-dose

    Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3915393.

  9. Part A: t1/2 Following Single IV Dose of GSK3915393 100 mcg IV

    Time frame: Pre-dose and at 20, 40 minutes, 1, 1 hour 5 minutes, 1 hour 10 minutes, 1 hours 20 minutes, 1 hour 40 minutes, 2, 2.5, 3, 3.5, 4, 5 and 6 hours post-dose

    Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3915393.

  10. Part A: Clearance (CL) Following Single IV Dose of GSK3915393

    Time frame: Pre-dose and at 20, 40 minutes, 1, 1 hour 5 minutes, 1 hour 10 minutes, 1 hours 20 minutes, 1 hour 40 minutes, 2, 2.5, 3, 3.5, 4, 5 and 6 hours post-dose

    Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3915393.

  11. Part A: Volume of Distribution (Vd) Following Single IV Dose of GSK3915393

    Time frame: Pre-dose and at 20, 40 minutes, 1, 1 hour 5 minutes, 1 hour 10 minutes, 1 hours 20 minutes, 1 hour 40 minutes, 2, 2.5, 3, 3.5, 4, 5 and 6 hours post-dose

    Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3915393.

  12. Part A: Absolute Bioavailability (F) Following Single Oral Dose of GSK3915393

    Time frame: Pre-dose and at 20, 40 minutes, 1, 1.5, 2, 3, 4, 6, 10, 12, 14, 24 and 36 hours post-dose

    Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3915393. Absolute bioavailability is the amount of drug from a formulation that reaches the systemic circulation relative to an IV dose. It was expressed as ratio was calculated as (AUC[0-inf] for oral divided by oral dose) divided by (AUC[0-inf] for IV/dose given as IV).

  13. Part A: Fraction of Drug Escaping Hepatic Metabolism (FH) Following Single Oral Dose of GSK3915393

    Time frame: Pre-dose and at 20, 40 minutes, 1, 1.5, 2, 3, 4, 6, 10, 12, 14, 24 and 36 hours post-dose

    Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3915393. FH was expressed as ratio and was calculated as: 1 minus hepatic extraction ratio. Hepatic extraction ratio=hepatic blood clearance (milliliters per minute)/hepatic blood flow (milliliters per minute).

  14. Part A: Product of Fraction of Drug Absorbed and Fraction of Drug Escaping Gut Metabolism (FA*FG) Following Oral Dose of GSK3915393

    Time frame: Pre-dose and at 20, 40 minutes, 1, 1.5, 2, 3, 4, 6, 10, 12, 14, 24 and 36 hours post-dose

    Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3915393. Product of FA*FG was calculated as: (absolute bioavailability [F] divided by fraction of drug escaping hepatic metabolism [FH]).

  15. Part A: Number of Participants With All Non-serious AEs and SAEs Following Administration Administration of IV Dose of GSK3915393

    Time frame: Up to 21 days

    An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. SAE is defined as any serious adverse event that, at any dose which results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, other situations as per investigator's medical or scientific judgment.

  16. Part A: Number of Participants With Worst Case Chemistry Results by PCI Criteria Post-Baseline Relative to Baseline Following Administration Administration of IV Dose of GSK3915393

    Time frame: Up to 21 days

    Blood samples were collected for analysis of chemistry parameters. PCI ranges were >=2*ULN (U/L)(ALT), >=2*ULN (U/L) (AST), >=2*ULN (ALP) (U/L), >=1.5*ULN (micromoles per liter) (bilirubin), <2 or >2.75 millimoles/liter (L) (mmol/L)(calcium), <3 or >11 mmol/L (glucose), <3 or >5.5 mmol/L (potassium), <130 or >150 mmol/L (sodium),<50 or >85 grams/liter (protein). Participants were counted in worst case category that their value changes to (low, within [w/in] range or no change [NC], or high), unless there is no change in their category. Participants whose laboratory value category was unchanged (e.g., High to High), or whose value became within range, are recorded in 'To within Range No Change' category. Participants were counted twice if participant had values that changed 'To Low' and 'To High', so percentages may not add to 100 percentage (%).

  17. Part A: Number of Participants With Worst Case Chemistry Results-creatinine by PCI Criteria Post-Baseline Relative to Baseline Following Administration Administration of IV Dose of GSK3915393

    Time frame: Up to 21 days

    Blood samples were collected for analysis of creatinine. Participants were counted under increase of PCI if they had change from Baseline >44.2 micromoles per Liter for any post Baseline assessment. Participants who did not meet this PCI criteria are counted as w/in range.

  18. Part A: Number of Participants With Worst Case Chemistry Results-urea by PCI Criteria Post-Baseline Relative to Baseline Following Administration of IV Dose of GSK3915393

    Time frame: Up to 21 days

    Blood samples were collected for analysis of chemistry parameters. PCI range for Urea: High >10.5 mmol/L. Participants were counted in worst case category that their value changes to (within [w/in] range or no change [NC], or high), unless there is no change in their category. Participants whose laboratory value category was unchanged (e.g., High to High), or whose value became within range, are recorded in 'To within Range No Change' category.

  19. Part A: Number of Participants With Worst Case Hematology Results by PCI Criteria Post-Baseline Relative to Baseline Following Administration of IV Dose of GSK3915393

    Time frame: Up to 21 days

    Blood samples were collected for analysis of hematology parameters. PCI ranges were >1*10^9 cell per liter (cells/L) (eosinophils), <0.2 or >0.54 proportion of red blood cells in blood (hematocrit), <80 or >180 grams per liter(g/L) (hemoglobin), <3 or >20 x10^9 cells/L (leukocytes), <0.8*10^9 cells/L (lymphocytes), <1.5 or >16*10^9 cells/L (neutrophils) and <100 or >550*10^9 cells/L (platelets). Participants were counted in worst case category that their value changes to (low, within range or no change or high), unless there is no change in their category. Participants whose laboratory value category was unchanged (for example [e.g.], High to High), or whose value became within range, were recorded in "To within Range or No Change" category. Participants were counted twice if participant has values that changed 'To Low' & 'To High', so the percentages may not add to 100%.

  20. Part A: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline Following IV Dose of GSK3915393

    Time frame: Up to 21 days

    Vital signs included DBP, SBP, PR, body temperature, RR and were measured after resting for at least 5 minutes in semi-supine position. PCI ranges were, SBP (mmHg): <85 (low) or >160 (high), DBP (mmHg): <45 (low) or >100 (high), heart rate (beats per minute): <40 (low) or >110 (high), respiration rate (breaths per minute):<=8 (low) or >20 (high) and body temperature (degrees Celsius) <=35.5 (low) or >38.0 (high). Participants were counted in worst case category that their value changes to (low, within range or no change, or high), unless there is no change in their category. Participants whose laboratory value category was unchanged (e.g., High to High), or whose value became within range, are recorded in 'To W/in Range No Change' category. Participants were counted twice if participant had values that changed 'To Low' and 'To High', so percentages may not add to 100%.

  21. Part A: Number of Participants With Worst Case Post-Baseline Abnormal ECG Findings Following Administration of IV Dose of GSK3915393

    Time frame: Up to 21 days

    Twelve lead ECG was obtained using an ECG machine that automatically calculated the heart rate and measured QTc, PR, QRS intervals. Abnormal findings were categorized as clinically significant and not clinically significant. Clinically significant abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition. Data for number of participants with worst case post-Baseline abnormal ECG findings have been presented.

  22. Part A: Number of Participants With Abnormal Physical Examination Findings Following Administration of IV Dose of GSK3915393

    Time frame: Up to 21 days

    A full physical examination was performed which included, at a minimum, assessments of the Skin, Cardiovascular, Respiratory, Gastrointestinal and Neurological systems.

  23. Part B: Cmax(0-10) Following Dosing of GSK3915393 on Days 1 and 14

    Time frame: Days 1 and 14: Pre-dose, 20, 40 minutes, 1, 1.5, 2, 3, 4, 6, and 10 hours post-dose

    Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3915393.

  24. Part B: Cmax(10-24) Following Repeat Dose 20 mg and 80 mg of GSK3915393

    Time frame: Days 1 and 14: 10 hours, 10 hours 20 minutes, 10 hours 40 minutes, 12, 12.5 ,13, 14, 16, and 24 hours post-dose

    Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3915393.

  25. Part B: Cmax(10-24) Following Dose 160 mg (QD) of GSK3915393

    Time frame: Days 1 and 14: 10, 24 hours post-dose

    Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3915393.

  26. Part B: Tmax(0-10) Following Dosing of GSK3915393 on Days 1 and 14

    Time frame: Days 1 and 14: Pre-dose, 20, 40 minutes, 1, 1.5, 2, 3, 4, 6, and 10 hours post-dose

    Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3915393.

  27. Part B: Tmax(10-24) Following Repeat Dose 20 mg BID and 80 mg BID of GSK3915393

    Time frame: Days 1 and 14: 10 hours, 10 hours 20 minutes, 10 hours 40 minutes, 12, 12.5 ,13, 14, 16, and 24 hours post-dose

    Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3915393.

  28. Part B: Tmax(10-24) Following Dose 160 mg (QD) of GSK3915393

    Time frame: Days 1 and 14: 10, 24 hours post-dose

    Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3915393.

  29. Part B: AUCLST(0-10) Following Dosing of GSK3915393

    Time frame: Days 1 and 14: Pre-dose, 20, 40 minutes, 1, 1.5, 2, 3, 4, 6, and 10 hours post-dose

    Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3915393.

  30. Part B: AUCLST(0-24) Following Repeat Dose 20 mg BID and 80 mg BID of GSK3915393

    Time frame: Days 1 and 14: Pre-dose, 20 minutes, 40 minutes, 1, 1.5, 2, 3, 4, 6, 10, 10 hours 20 minutes, 10 hours 40 minutes, 12, 12.5 ,13, 14, 16, and 24 hours post-dose

    Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3915393.

  31. Part B: AUCLST(0-24) Following Dose of GSK3915393 160 mg (QD)

    Time frame: Days 1 and 14: Pre-dose, 20 minutes, 40 minutess, 1, 1.5, 2, 3 ,4, 6, 10 and 24 hours post-dose

    Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3915393.

  32. Part B: AUC(10-24) Following Repeat Dose 20 mg BID and 80 mg BID of GSK3915393

    Time frame: Days 1 and 14: 10 hours, 10 hours 20 minutes, 10 hours 40 minutes, 12, 12.5 ,13, 14, 16, and 24 hours post-dose

    Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3915393.

  33. Part B: AUC(10-24) Following Repeat Dose of GSK3915393 160 mg (QD)

    Time frame: Days 1 and 14: 10 and 24 hours post-dose

    Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3915393.

  34. Part B: Cmax(0-10) Following First Dosing of GSK3915393 on Days 3, 5 and 7 (for Food-effect Assessment)

    Time frame: Days 3, 5 and 7: Pre-dose, 20, 40 minutes, 1, 1.5, 2, 3, 4, 6 and 10 hours post-dose

    Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3915393.

  35. Part B: Tmax(0-10) Following First Dosing of GSK3915393 on Days 3, 5 and 7 (for Food-effect Assessment)

    Time frame: Days 3, 5 and 7: Pre-dose, 20, 40 minutes, 1, 1.5, 2, 3, 4, 6 and 10 hours post-dose

    Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3915393.

  36. Part B: AUCLST(0-10) Following First Dosing of GSK3915393 on Days 3, 5 and 7 (for Food-effect Assessment)

    Time frame: Days 3, 5 and 7: Pre-dose, 20, 40 minutes, 1, 1.5 ,2, 3, 4, 6 and 10 hours post-dose

    Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3915393.

  37. Part B: Trough Concentration (Ctau) Following Dose of 20 mg BID and 80 mg BID of GSK3915393 on Day 14

    Time frame: Day 14: Pre-dose, 20, 40 minutes, 1, 1.5 ,2, 3, 4, 6, 10, 10 hour 20 minutes, 10 hours 40 minutes, 12, 12.5, 13, 14, 16 and 24 hours post-dose

    Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3915393.

  38. Part B: Trough Concentration (Ctau) Following Dose of 160 mg of GSK3915393 on Day 14

    Time frame: Day 14: Pre-dose, 20, 40 minutes, 1, 1.5 ,2, 3, 4, 6, 10, and 24 hours post-dose

    Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3915393.

  39. Part C: Number of Participants With All Non-serious AEs and SAEs

    Time frame: Up to 72 days

    An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. SAE is defined as any serious adverse event that, at any dose which results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, other situations as per investigator's medical or scientific judgment.

  40. Part C: Number of Participants With Treatment-related AEs Following Dose of GSK3915393

    Time frame: Up to 72 days

    An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. Number of participants with treatment related AEs are presented.

  41. Part C: Number of Participants With Worst Case Chemistry Results by PCI Criteria Post-Baseline Relative to Baseline Following Dose Administration of GSK3915393

    Time frame: Up to 72 days

    Blood samples were collected for analysis of chemistry parameters. PCI ranges were >=2*ULN (U/L)(ALT), >=2*ULN (U/L) (AST), >=2*ULN (ALP) (U/L), >=1.5*ULN (micromoles per liter) (bilirubin), <2 or >2.75 millimoles/liter (L) (mmol/L)(calcium), <3 or >11 mmol/L (glucose), <3 or >5.5 mmol/L (potassium), <130 or >150 mmol/L (sodium),<50 or >85 grams/liter (protein). Participants were counted in worst case category that their value changes to (low, within [w/in] range or no change [NC], or high), unless there is no change in their category. Participants whose laboratory value category was unchanged (e.g., High to High), or whose value became within range, are recorded in 'To within Range No Change' category. Participants were counted twice if participant had values that changed 'To Low' and 'To High', so percentages may not add to 100 percentage (%).

  42. Part C: Number of Participants With Worst Case Chemistry Results: Creatinine by PCI Criteria Post-Baseline Relative to Baseline Following Dose Administration of GSK3915393

    Time frame: Up to 72 days

    Blood samples were collected for analysis of creatinine. Participants were counted under increase of PCI if they had change from Baseline > 44.2 micromoles per Liter for any post Baseline assessment. Participants who did not meet this PCI criteria are counted as w/in range. Participants whose laboratory value became within range, were recorded in 'To within Range' category.

  43. Part C: Number of Participants With Worst Case Chemistry Results: Urea by PCI Criteria Post-Baseline Relative to Baseline Following Dose Administration of GSK3915393

    Time frame: Up to 72 days

    Blood samples were collected for analysis of chemistry parameters. PCI range for Urea: High >10.5 mmol/L. Participants were counted in worst case category that their value changes to ( within [w/in] range or no change [NC], or high), unless there is no change in their category. Participants whose laboratory value category was unchanged (e.g., High to High), or whose value became within range, are recorded in 'To within Range No Change' category.

  44. Part C: Number of Participants With Worst Case Hematology Results by PCI Criteria Post-Baseline Relative to Baseline Following Dose Administration of GSK3915393

    Time frame: Up to 72 days

    Blood samples were collected for analysis of hematology parameters. PCI ranges were 1*10^9 cell per liter (cells/L) (eosinophils), <0.2 or >0.54 proportion of red blood cells in blood (hematocrit), <80 or >180 grams per liter(g/L) (hemoglobin), <3 or >20 x10^9 cells/L (leukocytes), <0.8*10^9 cells/L (lymphocytes), <1.5 or >16*10^9 cells/L (neutrophils) and <100 or >550*10^9 cells/L (platelets). Participants were counted in worst case category that their value changes to (low, within range or no change or high), unless there is no change in their category. Participants whose laboratory value category was unchanged (for example [e.g.], High to High), or whose value became within range, were recorded in "To within Range or No Change" category. Participants were counted twice if participant has values that changed 'To Low' & 'To High', so the percentages may not add to 100%.

  45. Part C: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline Following Dose Administration of GSK3915393

    Time frame: Up to 72 days

    Vital signs included DBP, SBP, PR, body temperature, RR and were measured after resting for at least 5 minutes in semi-supine position. PCI ranges were, SBP (mmHg): <85 (low) or >160 (high), DBP (mmHg): <45 (low) or >100 (high), heart rate (beats per minute): <40 (low) or >110 (high), respiration rate (breaths per minute):<=8 (low) or >20 (high) and body temperature (degrees Celsius) <=35.5 (low) or >38.0 (high). Participants were counted in worst case category that their value changes to (low, within range or no change, or high), unless there is no change in their category. Participants whose laboratory value category was unchanged (e.g., High to High), or whose value became within range, are recorded in 'To W/in Range No Change' category. Participants were counted twice if participant had values that changed 'To Low' and 'To High', so percentages may not add to 100%.

  46. Part C: Number of Participants With Worst Case Post-Baseline Abnormal ECG Findings Following Administration of GSK3915393

    Time frame: Up to 72 days

    Twelve lead ECG was obtained using an ECG machine that automatically calculated the heart rate and measured QTc, PR, QRS intervals. Abnormal findings were categorized as clinically significant and not clinically significant. Clinically significant abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition. Data for number of participants with worst case post-Baseline abnormal ECG findings have been presented.

  47. Part C: Number of Participants With Abnormal Physical Examination Findings Following Administration of GSK3915393

    Time frame: Up to 72 days

    A full physical examination was performed which included, at a minimum, assessments of the Skin, Cardiovascular, Respiratory, Gastrointestinal and Neurological systems.

  48. Part C: Fraction of Drug Escaping Hepatic Metabolism (FH) Following IV Dose of GSK3915393

    Time frame: Pre-dose and at 20, 40 minutes, 1, 1 hour 5 minutes, 1 hour 10 minutes, 1 hour 20 minutes, 1 hour 40 minutes, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 36, 48, and 60 hours post-dose

    Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3915393. FH was expressed as ratio and was calculated as: 1 minus hepatic extraction ratio. Hepatic extraction ratio=hepatic blood clearance (milliliters per minute)/hepatic blood flow (milliliters per minute)

  49. Part C: FH Following IV Administration of GSK3915393+ITZ

    Time frame: Pre-dose and at 20, 40 minutes, 1, 1 hour 5 minutes, 1 hour 10 minutes, 1 hour 20 minutes, 1 hour 40 minutes, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 10, 12, 24, 36, 48, and 60 hours post-dose

    Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3915393. FH was expressed as ratio and was calculated as: 1 minus Hepatic extraction ratio. Hepatic extraction ratio=hepatic blood clearance (milliliters per minute)/hepatic blood flow (milliliters per minute)

  50. Part C: Fraction of Drug Escaping Gut Metabolism (FG) Following Oral Administration of GSK3915393+Water

    Time frame: Pre-dose and at 20, 40 minutes, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, and 24 hours post-dose

    Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3915393. FG was expressed as ratio and calculated as: AUC of GSK3915393+water divided by AUC of GSK3915393+GFJ.

  51. Part C: Fraction of Drug Absorbed (FA) Following Oral Administration of GSK3915393+Water

    Time frame: Pre-dose and at 20, 40 minutes, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, and 24 hours post-dose

    Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3915393. FA was expressed as ratio was calculated as absolute bioavailability (F) divided by the product of fraction of drug escaping hepatic metabolism (FH) and fraction of drug escaping gut metabolism (FG).

Sponsors and collaborators

Lead sponsor

GlaxoSmithKline

Industry

Registry information

Official study title

A Randomized, Placebo Controlled, Double Blind, Single and Repeat Dose Escalation Phase 1 Study to Evaluate Safety, Tolerability, and Pharmacokinetics of GSK3915393 in Healthy Participants and Open Label Assessment of Coadministration of GSK3915393 With Grapefruit Juice and Itraconazole on the Pharmacokinetics of GSK3915393

Important dates

Study start
2020
Primary completion
2021
Study completion
2021
First posted
Oct 27, 2020
Registry last updated
May 9, 2023

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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