A Clinical Trial to Study the Efficacy, Safety, Tolerability and Pharmacokinetics of P2202 in Patients of Type 2 Diabetes

A Phase II, Randomized, Double-blind, Placebo-controlled, Dose-ranging, Two-staged, Fixed Design Study to Evaluate the Efficacy, Safety, Tolerability and Pharmacokinetics of P2202 in Overweight/Obese Patients of Type 2 Diabetes Mellitus Inadequately Controlled on Metformin, Sulphonylurea, or Both.

It is a phase II, randomized, double-blind, placebo-controlled study of P2202 in patients of type 2 diabetes mellitus, inadequately controlled with a stable dose of metformin or sulfonylurea or both.

Study Overview

• Status: Terminated
• Conditions: Type 2 Diabetes Mellitus
• Intervention / Treatment: Drug: Placebo; Drug: P2202

Detailed Description

It is a phase II, prospective, randomized, double-blind, placebo-controlled, dose-ranging, multi-centre, two-staged, fixed-design study of P2202 in patients of type 2 diabetes mellitus, inadequately controlled with a stable dose of metformin or sulfonylurea or both. This study will consist of accrual in Stage I (n=56/arm, which is 70% of the total sample size required), followed by an interim analysis on completion of the treatment period, to aid further decisions on accrual and dose selection in Stage II of the study, and completion of Stage I.

• Study Type: Interventional
• Enrollment (Actual): 48
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M4G 3E8
      • LMC Endocrinolgy Centres Ltd

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Subjects who understand and are willing to give informed consent to participate in the trial.
• Adult male and female subjects between 18 years to 65 years of age with a BMI ≥ 27 kg/m2 ≤ 40 kg/m2, inclusively.
• Subjects with established type 2 diabetes mellitus of at least 3 months duration at the time of screening.
• Subjects with an inadequate glycemic control defined by an HbA1c level of ≥ 7.5% and ≥10% at screening.

• Subjects who are on a stable dose of:

  • Metformin (up to 2.55 gm/day or maximum tolerated dose of at least 1 gm/day) and/or
  • Sulfonylurea (glimepiride ≤ 4 mg/day, gliclazide ≤ 160 mg, glibenclamide or glyburide ≤ 10 mg and glipizide ≤ 10 mg), for ≤ 2 months prior to the screening visit.
• Subjects with fasting plasma glucose of ≤14.4 mmol/L (260 mg/dL) and at least 5.5 mmol/L or 100 mg/dL.

Exclusion Criteria:

• Subjects who have type 1 diabetes mellitus, maturity-onset diabetes of the young or any rare form of diabetes. Subjects with hyperglycemia due to secondary causes.
• Subjects who have had more than 4 episodes of severe hypoglycemia in the 6 months prior to screening.
• Subjects with a history of acute diabetic complications
• Subjects who have been treated with insulin (except for use of insulin for short term management of acute conditions), thiazolidinediones, dual proliferator activated receptors agonists, glucagon-like peptide analogues, dipeptidyl peptidase inhibitors or 11bHSD-1 inhibitors in any form, in the 3 months prior to screening.
• Subjects who are receiving systemic glucocorticoids (≥14 days)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: P2202; Two treatment arms in Stage I- P2202 (1000 mg) and placebo Four treatment arms in stage II- P2202 (suggested dose levels 750 mg, 500 mg or 250 mg) or placebo	Drug: P2202; Novel oral drug with potent and selective 11 beta-hydroxysteroid dehydrogenase type 1 (11b-HSD1) inhibitory properties, being developed for the management of type 2 diabetes mellitus
Placebo Comparator: Placebo; Two treatment arms in Stage I- P2202 (1000 mg) and placebo Four treatment arms in stage II- P2202 (suggested dose levels 750 mg, 500 mg or 250 mg) or placebo	Drug: Placebo; Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in HbA1c from baseline	The change in HbA1c from baseline till end of 12 weeks in patients of type 2 diabetes mellitus, in the P2202 arms as compared to placebo.	From baseline till end of 12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of subjects with adverse events	Safety assessment will be done by eliciting information regarding AEs including evaluation of hypoglycemic events, physical examination, vital signs assessment, 12-lead ECGs, clinical laboratory tests, markers of HPA axis function, plasma ACTH and free testosterone, plasma rennin and serum aldosterone and self-monitoring of blood glucose profiles.	From screening to 3 weeks (± 1 week) after the last visit at the end of Week 12 or early exit visit

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetic profile (Cmax, Tmax and AUC)	PK parameters derived will be maximum plasma concentration (Cmax), time at which Cmax is reached (Tmax), area under the plasma concentration curve calculated up to 24 hours (AUC 0-24h), area under the curve extrapolated to infinity (AUC 0-inf), elimination rate constant (Kel), volume of distribution (Vz), terminal elimination half life (t1/2) and protein binding.	Pre dose at Day 1 Week 1 till Week 12

Collaborators and Investigators

• Sponsor: Piramal Enterprises Limited
• Investigators: Principal Investigator: Dr. Ronnie Aronson, M.D., Health Canada; Principal Investigator: Dr. Robert Petrella, M.D., Health Canada; Principal Investigator: Dr. Naresh Aggarwal, M.D., Health Canada

Study record dates

Study Major Dates

• Study Start: April 1, 2011
• Primary Completion (Actual): December 1, 2012
• Study Completion (Actual): July 1, 2013

Study Registration Dates

• First Submitted: August 21, 2012
• First Submitted That Met QC Criteria: August 27, 2012
• First Posted (Estimate): August 28, 2012

Study Record Updates

• Last Update Posted (Estimate): August 5, 2013
• Last Update Submitted That Met QC Criteria: August 2, 2013
• Last Verified: August 1, 2013

More Information

Terms related to this study

• Keywords: Diabetes Mellitus
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2
• Other Study ID Numbers: P2202/47/10