Clinical Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of LEZ763
- Registration Number
- NCT01619332
- Lead Sponsor
- Novartis Pharmaceuticals
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 220
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Placebo Part I : Healthy volunteers enrolled in 6 single ascending dose cohorts to receive matching placebo of LEZ763. Part II: Healthy volunteers enrolled in 5 multiple ascending dose cohorts to receive matching placebo of LEZ763. Part III- Placebo will be given orally once daily for 28 days to patients assigned to placebo in a randomized and blinded manner LEZ763 LEZ763 Part I- Healthy volunteers enrolled into 6 single-ascending dose cohorts Part II- Healthy volunteers enrolled into 5 multiple-ascending dose cohorts. Part III- LEZ763 will be given orally once daily for 28 days in a randomized and blinded manner Sitagliptin Sitagliptin Sitaglitpin will be given orally once daily for 28 days to patients assigned to this treatment in a randomized and blinded manner
- Primary Outcome Measures
Name Time Method Number of Patients with adverse events, serious adverse events and death 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.
Pharmacokinetics of LEZ763 (Part I): area under the plasma concentration-time curve from time zero to infinity (AUCinf) 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
Pharmacokinetics of LEZ763 (Part I): area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration (AUClast) 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
Pharmacokinetics of LEZ763 (Part I): Terminal elimination half-life (T1/2) 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
Pharmacokinetics of LEZ763 (Part I): Apparent systemic (or total body) clearance from plasma following extravascular administration (CL/F) 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
Pharmacokinetics of LEZ763 (Part I) : Observed maximum plasma concentration (Cmax) following drug administration 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
Pharmacokinetics of LEZ763 (Part I): time to reach the maximum concentration after drug administration (Tmax) 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
Pharmacokinetics of LEZ763 (Part II) : Observed maximum plasma concentration (Cmax) following drug administration 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
Pharmacokinetics of LEZ763 (Part II): time to reach the maximum concentration after drug administration (Tmax) 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
Pharmacokinetics of LEZ763 (Part II): Accumulation ratio(Racc) 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
Pharmacokinetics of LEZ763 (Part III) : Observed maximum plasma concentration (Cmax) following drug administration 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
Pharmacokinetics of LEZ763 (Part III): time to reach the maximum concentration after drug administration (Tmax) 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
Pharmacokinetics of LEZ763 (Part III): Area under the plasma concentration-time curve from time zero to the end of the dosing interval tau (AUCtau) 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
Pharmacokinetics of LEZ763 (Part III): Accumulation ratio(Racc) 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
Pharmacokinetics of LEZ763 and Sitagliptin (Part III): Observed maximum plasma concentration (Cmax) following drug administration 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
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) 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
Pharmacokinetics of LEZ763 and Sitagliptin (Part III): Time to reach the maximum concentration after drug administration (Tmax) 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
Area under the effect curve (AUC0-4h) over the 4-hour post-dose period to measure glucose response following a standard mixed meal test 4 hour post-dose Day 27
- Secondary Outcome Measures
Name Time Method Change from baseine in Gastric inhibit polypeptide (GIP) (Part III) Baseline , Day 27 Change From Baseline in peak glucose level following meal Test at Day 27 (Part III) Baseline , Day 27 Peak effect (Emax) on postprandial GLP-1 (Part III) Baseline , Day 27 Area under the serum Glucagon-like-peptide 1 (GLP-1) curve (AUC0-24 hours) 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-hour value of post-prandial glucose Day 1 of Part I, Day 1 and day 10 of Part II Change from baseline in Fasting C-peptide at Day 27 (Part III) Baseline, Day 27 Change from baseline in Fasting Insulin at Day 27 (Part III) Baseline , Day 27 Change from baseline in fasting plasma glucose at Day 27 (Part III) Baseline , Day 27 Change from baseline in Peptide YY (PYY) (Part III) Baseline , Day 27
Trial Locations
- Locations (1)
Novartis Investigative Site
🇺🇸San Antonio, Texas, United States