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Completed

NCT Number: NCT01619332

Clinical Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of LEZ763

This study is a three part study to assess the safety and efficacy of LEZ763 on normal healthy volunteers and patients with Type 2 Diabetes.

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Key information

Conditions

Type II Diabetes Diabetes Mellitus Diabetes Mellitus, Type 2 Endocrine System Diseases Glucose Metabolism Disorders Metabolic Diseases Nutritional and Metabolic Diseases

Age range

18 year–65 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1 / Phase 2

Primary location

Novartis Investigative Site, Chula Vista, California, United States

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Who can participate

Healthy volunteers accepted: Yes

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

Inclusion criteria

  • All subjects: (suggest this will reduce duplication)
  • Male or female aged 18-65 yr,
  • Subjects must weigh at least 50 kg to participate in the study. Body mass index (BMI) must be within the range of 18-37 kg/m2 (inclusive
  • Only postmenopausal females or female subjects who report surgical sterilization (women without child bearing potential) will be allowed in this study.
  • Subjects with stable conventional sleep-wake cycle

Normal Healthy Volunteers

  • Healthy male or female subjects,
  • must be in good health (as determined by past medical history, physical examination, vital signs, electrocardiogram, and laboratory tests at Screening).

Type II Diabetic Patients

  • Type 2 diabetes diagnosed by American Diabetes Association criteria for at least 3 months prior to screening.
  • Patients either drug naïve or on stable dose of metformin (stable dose for at least 4 weeks prior to Screening). The metformin dose should remain constant during the course of the study.
  • HbA1c 6.5 to 9.5 % inclusive at screening

Exclusion criteria

All subjects:

  • Smokers (use of tobacco products in the previous 3 months).
  • Donation or loss of 400 mL or more of blood within 8 weeks prior to first dosing, or longer if required by local regulation.
  • Significant illness within two weeks prior to dosing.
  • Have (or have history of) drug or alcohol abuse within the 12 months prior to dosing or evidence of such abuse as indicated by the laboratory assays conducted during the screening or baseline evaluations

Normal Healthy Volunteers

  • History of diabetes, or adrenal disorders.

Type II Diabetic Patients

  • Type 1 diabetes mellitus; positive anti-GAD antibodies; acquired or secondary forms of diabetes such as those resulting from pancreatic surgery/injury, cystic fibrosis related diabetes
  • Evidence of clinically significant diabetic complications (such nephropathy, retinopathy, neuropathy) Other protocol defined inclusion/exclusion criteria may apply

Treatment and study plan

Placebo

Drug

Placebo will be given orally once daily for 28 days to patients assigned to placebo in a randomized and blinded manner

Sitagliptin

Drug

Sitaglitpin will be given orally once daily for 28 days to patients assigned to this treatment in a randomized and blinded manner

LEZ763

Drug

LEZ763 will be given orally once daily for 28 days in a randomized and blinded manner

Primary outcomes

  1. Number of Patients with adverse events, serious adverse events and death

    Time frame: Day 28

    An adverse event is the appearance or worsening of any undesirable sign, symptom, or medical condition occurring after starting the study drug even if the event is not considered to be related to study drug. Adverse events will also be determined on the basis of clinical laboratory assessments, electrocardiographic evaluations and vital signs determinations.

  2. Pharmacokinetics of LEZ763 (Part I): area under the plasma concentration-time curve from time zero to infinity (AUCinf)

    Time frame: pre-dose, and 0.5, 0.66, 0.75, 1, 1.5, 2, 2.5, 3, 3.5 4, 6, 8, 12 hours post-dose on Day 1; 24 and 36 hours Day 2; Day 3, Day 4

    Blood will be collected at multiple timepoints and will be analyzed for LEZ736 concentrations after single dose

  3. Pharmacokinetics of LEZ763 (Part I): area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration (AUClast)

    Time frame: pre-dose, and 0.5, 0.66, 0.75, 1, 1.5, 2, 2.5, 3, 3.5 4, 6, 8, 12 hours post-dose on Day 1; 24 and 36 hours Day 2; Day 3, Day 4

    Blood will be collected at multiple timepoints and will be analyzed for LEZ736 concentrations after single dose

  4. Pharmacokinetics of LEZ763 (Part I): Terminal elimination half-life (T1/2)

    Time frame: pre-dose, and 0.5, 0.66, 0.75, 1, 1.5, 2, 2.5, 3, 3.5 4, 6, 8, 12 hours post-dose on Day 1; 24 and 36 hours Day 2; Day 3, Day 4

    Blood will be collected at multiple timepoints and will be analyzed for LEZ736 concentrations after single dose

  5. Pharmacokinetics of LEZ763 (Part I): Apparent systemic (or total body) clearance from plasma following extravascular administration (CL/F)

    Time frame: pre-dose, and 0.5, 0.66, 0.75, 1, 1.5, 2, 2.5, 3, 3.5 4, 6, 8, 12 hours post-dose on Day 1; 24 and 36 hours Day 2; Day 3, Day 4

    Blood will be collected at multiple timepoints and will be analyzed for LEZ736 concentrations after single dose

  6. Pharmacokinetics of LEZ763 (Part I) : Observed maximum plasma concentration (Cmax) following drug administration

    Time frame: pre-dose, and 0.5, 0.66, 0.75, 1, 1.5, 2, 2.5, 3, 3.5 4, 6, 8, 12 hours post-dose on Day 1; 24 and 36 hours Day 2; Day 3, Day 4

    Blood will be collected at multiple timepoints and will be analyzed for LEZ736 concentrations after single and multiple doses

  7. Pharmacokinetics of LEZ763 (Part I): time to reach the maximum concentration after drug administration (Tmax)

    Time frame: pre-dose, and 0.5, 0.66, 0.75, 1, 1.5, 2, 2.5, 3, 3.5 4, 6, 8, 12 hours post-dose on Day 1; 24 and 36 hours Day 2; Day 3, Day 4

    Blood will be collected at multiple timepoints and will be analyzed for LEZ736 concentrations after single dose

  8. Pharmacokinetics of LEZ763 (Part II) : Observed maximum plasma concentration (Cmax) following drug administration

    Time frame: pre-dose, and 0.5, 0.66, 0.75, 1, 1.5, 2, 2.5, 3, 3.5 4, 6, 8, 12 hours post-dose on Day 1 and Day 10

    Blood will be collected at multiple timepoints and will be analyzed for LEZ736 concentrations after multiple doses

  9. Pharmacokinetics of LEZ763 (Part II): time to reach the maximum concentration after drug administration (Tmax)

    Time frame: pre-dose, and 0.5, 0.66, 0.75, 1, 1.5, 2, 2.5, 3, 3.5 4, 6, 8, 12 hours post-dose on Day 1 and Day 10

    Blood will be collected at multiple timepoints and will be analyzed for LEZ736 concentrations after multiple doses

  10. Pharmacokinetics of LEZ763 (Part II): Accumulation ratio(Racc)

    Time frame: pre-dose, and 0.5, 0.66, 0.75, 1, 1.5, 2, 2.5, 3, 3.5 4, 6, 8, 12 hours post-dose on Day 1 and Day 27

    Blood will be collected at multiple timepoints and will be analyzed for LEZ736 concentrations after multiple doses

  11. Pharmacokinetics of LEZ763 (Part III) : Observed maximum plasma concentration (Cmax) following drug administration

    Time frame: pre-dose, and 0.5, 0.66, 0.75, 1, 1.5, 2, 2.5, 3, 3.5 4, 6, 8, 12 hours post-dose on Day 1 and Day 27

    Blood will be collected at multiple timepoints and will be analyzed for LEZ736 concentrations after multiple doses

  12. Pharmacokinetics of LEZ763 (Part III): time to reach the maximum concentration after drug administration (Tmax)

    Time frame: pre-dose, and 0.5, 0.66, 0.75, 1, 1.5, 2, 2.5, 3, 3.5 4, 6, 8, 12 hours post-dose on Day 1 and Day 27

    Blood will be collected at multiple timepoints and will be analyzed for LEZ736 concentrations after multiple doses

  13. Pharmacokinetics of LEZ763 (Part III): Area under the plasma concentration-time curve from time zero to the end of the dosing interval tau (AUCtau)

    Time frame: pre-dose, and 0.5, 0.66, 0.75, 1, 1.5, 2, 2.5, 3, 3.5 4, 6, 8, 12 hours post-dose on Day 1 and Day 27

    Blood will be collected at multiple timepoints and will be analyzed for LEZ736 concentrations after single and multiple doses

  14. Pharmacokinetics of LEZ763 (Part III): Accumulation ratio(Racc)

    Time frame: pre-dose, and 0.5, 0.66, 0.75, 1, 1.5, 2, 2.5, 3, 3.5 4, 6, 8, 12 hours post-dose on Day 1 and Day 27

    Blood will be collected at multiple timepoints and will be analyzed for LEZ736 concentrations after single and multiple doses

  15. Pharmacokinetics of LEZ763 and Sitagliptin (Part III): Observed maximum plasma concentration (Cmax) following drug administration

    Time frame: pre-dose, and 0.5, 0.66, 0.75, 1, 1.5, 2, 2.5, 3, 3.5 and 4 hours post-dose on Day 28

    Blood will be collected at multiple timepoints and will be analyzed for LEZ736 concentrations after multiple doses

  16. Pharmacokinetics of LEZ763 and Sitagliptin (Part III): Area under the plasma concentration-time curve from time zero to the end of the dosing interval tau (AUCtau)

    Time frame: pre-dose, and 0.5, 0.66, 0.75, 1, 1.5, 2, 2.5, 3, 3.5 and 4 hours post-dose on Day 28

    Blood will be collected at multiple timepoints and will be analyzed for LEZ736 concentrations after multiple doses

  17. Pharmacokinetics of LEZ763 and Sitagliptin (Part III): Time to reach the maximum concentration after drug administration (Tmax)

    Time frame: pre-dose, and 0.5, 0.66, 0.75, 1, 1.5, 2, 2.5, 3, 3.5 and 4 hours post-dose on Day 28

    Blood will be collected at multiple timepoints and will be analyzed for LEZ736 concentrations after multiple doses

  18. Area under the effect curve (AUC0-4h) over the 4-hour post-dose period to measure glucose response following a standard mixed meal test

    Time frame: 4 hour post-dose Day 27

Secondary outcomes

  1. Area under the serum Glucagon-like-peptide 1 (GLP-1) curve (AUC0-24 hours)

    Time frame: Pre-dose, and 0.5, 0.66, 0.75, 1, 1.5, 2, 2.5, 3, 3.5 and 4 hours post-dose on Day -1, Day 1, Day 27, and Day 28

    GLP-1 Biomarker measures will be evaluated at pre-dose, and 0.5, 0.66, 0.75, 1, 1.5, 2, 2.5, 3, 3.5 and 4 hours post-dose

  2. 2-hour value of post-prandial glucose

    Time frame: Day 1 of Part I, Day 1 and day 10 of Part II

  3. Change from baseline in Fasting C-peptide at Day 27 (Part III)

    Time frame: Baseline, Day 27

  4. Change from baseline in Fasting Insulin at Day 27 (Part III)

    Time frame: Baseline , Day 27

  5. Change from baseline in fasting plasma glucose at Day 27 (Part III)

    Time frame: Baseline , Day 27

  6. Change From Baseline in peak glucose level following meal Test at Day 27 (Part III)

    Time frame: Baseline , Day 27

  7. Peak effect (Emax) on postprandial GLP-1 (Part III)

    Time frame: Baseline , Day 27

  8. Change from baseline in Peptide YY (PYY) (Part III)

    Time frame: Baseline , Day 27

  9. Change from baseine in Gastric inhibit polypeptide (GIP) (Part III)

    Time frame: Baseline , Day 27

Sponsors and collaborators

Lead sponsor

Novartis Pharmaceuticals

Industry

Registry information

Official study title

A Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of LEZ763 Following Single and Multiple Ascending Doses in Healthy Subjects and Patients With Type 2 Diabetes

Important dates

Study start
2012
Primary completion
2013
Study completion
2013
First posted
Jun 14, 2012
Registry last updated
Dec 17, 2020

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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