Clinical Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of LEZ763

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01619332
First received: June 12, 2012
Last updated: September 2, 2014
Last verified: September 2014

June 12, 2012
September 2, 2014
March 2012
September 2013   (final data collection date for primary outcome measure)
  • Number of Patients with adverse events, serious adverse events and death [ Time Frame: Day 28 ] [ Designated as safety issue: No ]
    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) [ 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 ] [ Designated as safety issue: No ]
    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) [ 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 ] [ Designated as safety issue: No ]
    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) [ 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 ] [ Designated as safety issue: No ]
    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) [ 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 ] [ Designated as safety issue: No ]
    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 [ 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 ] [ Designated as safety issue: No ]
    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) [ 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 ] [ Designated as safety issue: No ]
    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 [ 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 ] [ Designated as safety issue: No ]
    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) [ 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 ] [ Designated as safety issue: No ]
    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) [ 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 ] [ Designated as safety issue: No ]
    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 [ 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 ] [ Designated as safety issue: No ]
    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) [ 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 ] [ Designated as safety issue: No ]
    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) [ 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 ] [ Designated as safety issue: No ]
    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) [ 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 ] [ Designated as safety issue: No ]
    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 [ 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 ] [ Designated as safety issue: No ]
    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) [ 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 ] [ Designated as safety issue: No ]
    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) [ 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 ] [ Designated as safety issue: No ]
    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 [ Time Frame: 4 hour post-dose Day 27 ] [ Designated as safety issue: No ]
Same as current
Complete list of historical versions of study NCT01619332 on ClinicalTrials.gov Archive Site
  • 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 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Day 1 of Part I, Day 1 and day 10 of Part II ] [ Designated as safety issue: No ]
  • Change from baseline in Fasting C-peptide at Day 27 (Part III) [ Time Frame: Baseline, Day 27 ] [ Designated as safety issue: No ]
  • Change from baseline in Fasting Insulin at Day 27 (Part III) [ Time Frame: Baseline , Day 27 ] [ Designated as safety issue: No ]
  • Change from baseline in fasting plasma glucose at Day 27 (Part III) [ Time Frame: Baseline , Day 27 ] [ Designated as safety issue: No ]
  • Change From Baseline in peak glucose level following meal Test at Day 27 (Part III) [ Time Frame: Baseline , Day 27 ] [ Designated as safety issue: No ]
  • Peak effect (Emax) on postprandial GLP-1 (Part III) [ Time Frame: Baseline , Day 27 ] [ Designated as safety issue: No ]
  • Change from baseline in Peptide YY (PYY) (Part III) [ Time Frame: Baseline , Day 27 ] [ Designated as safety issue: No ]
  • Change from baseine in Gastric inhibit polypeptide (GIP) (Part III) [ Time Frame: Baseline , Day 27 ] [ Designated as safety issue: No ]
Same as current
Not Provided
Not Provided
 
Clinical Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of LEZ763
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

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.

Not Provided
Interventional
Phase 1
Phase 2
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Type II Diabetes
  • Drug: Placebo
    Placebo will be given orally once daily for 28 days to patients assigned to placebo in a randomized and blinded manner
  • Drug: Sitagliptin
    Sitaglitpin will be given orally once daily for 28 days to patients assigned to this treatment in a randomized and blinded manner
  • Drug: LEZ763
    LEZ763 will be given orally once daily for 28 days in a randomized and blinded manner
  • Experimental: 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
    Intervention: Drug: LEZ763
  • Placebo Comparator: 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
    Intervention: Drug: Placebo
  • Active Comparator: Sitagliptin
    Sitaglitpin will be given orally once daily for 28 days to patients assigned to this treatment in a randomized and blinded manner
    Intervention: Drug: Sitagliptin
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
220
September 2013
September 2013   (final data collection date for primary outcome measure)

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
Both
18 Years to 65 Years
Yes
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT01619332
CLEZ763X2201
No
Novartis ( Novartis Pharmaceuticals )
Novartis Pharmaceuticals
Not Provided
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
Novartis
September 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP