Treatment Differences Between Canagliflozin and Placebo in Insulin Secretion in Subjects With Type 2 Diabetes Mellitus (T2DM)

NCT ID: NCT02009488

Last Updated: 2018-01-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 59 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-09-08
• Study Completion Date: 2017-01-03

Brief Summary

The purpose of this study is to assess changes from baseline in insulin sensitivity, hepatic fat content and beta cell function after approximately 24-25 weeks of treatment with canagliflozin compared to placebo in participants with type 2 diabetes mellitus (T2DM) with inadequate glycemic (blood sugar) control on metformin monotherapy or on combination therapy with metformin and a dipeptidyl peptidase-4 (DPP-4) inhibitor.

Detailed Description

This is a double-blind (neither physician nor participants knows the treatment that the participant receives), randomized (the study medication is assigned by chance), placebo-controlled (an inactive substance is compared with a medication to test whether the medication has a real effect in a clinical study), parallel-groups study which will be conducted at 2 clinical research centers (CRC) in the US. Approximately 56 participants, ages 25-70 years, with T2DM inadequately controlled on either metformin monotherapy or combination therapy with metformin and a DPP-4 inhibitor, will be enrolled. The study has 3 phases: pre-treatment, double-blind treatment, and post-treatment.

Pre-Treatment Phase will consist of a screening visit (Week -5), 14 days Single- Blind Placebo Run-in period, followed by 14 days of Single-Blind Placebo Baseline Period, during which participants will be randomized (1:1) to one of 2 treatment groups, either canagliflozin or placebo. Double-Blind Treatment Phase begins on Day 1, and ends at approximately Week 25, during which participants will be assessed at least biweekly at outpatient visits or by telephone contact. Canagliflozin treatment will be initiated at 100 mg/day, with up-titration to 300 mg/day, consistent with the approved INVOKANA® US Prescribing Information 2013. During post-treatment phase, a follow-up visit will occur within approximately 28 days after the last dose of study drug.

At baseline and after 24 weeks of treatment with canagliflozin, hepatic and peripheral insulin sensitivity will be assessed using tracer labeled euglycemic clamp technique; hepatic fat content will be determined using 1H nuclear magnetic resonance spectroscopy (MRS); beta cell function (insulin secretion rate and beta cell glucose sensitivity) will be assessed during mixed meal tolerance test (MMTT); substrate oxidation and energy production rates will be measured using indirect calorimetry during euglycemic clamp and MMTT.

During the study, participants will remain on their stable dose regimens of metformin or combination metformin DPP-4 inhibitor therapy, unless the investigator considers dose modification to be medically necessary. The total study duration for each participant participating in this study will be up to approximately 34 weeks.

Conditions

Diabetes Mellitus, Type 2

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Canagliflozin (JNJ-28431754)

Each patient will receive canagliflozin 100 mg once daily during the first 4 weeks of the 25 weeks double-blind period, then the dose may be increased to 300 mg once daily, till the end of the period.

Group Type: EXPERIMENTAL

Canagliflozin, 100 mg

Intervention Type: DRUG

One 100 mg capsule taken orally (by mouth) once daily

Canagliflozin, 300 mg

Intervention Type: DRUG

One 300 mg capsule taken orally (by mouth) once daily

Placebo

One placebo capsule taken orally (by mouth) once daily for approximately 28 days during the Pre-Treatment Run-In and the Baseline Periods, then during double-blind study for 178 days (approximately 24-25 weeks).

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

One placebo capsule (inactive medication) once daily.

Interventions

Canagliflozin, 100 mg

One 100 mg capsule taken orally (by mouth) once daily

Intervention Type: DRUG

Canagliflozin, 300 mg

One 300 mg capsule taken orally (by mouth) once daily

Intervention Type: DRUG

Placebo

One placebo capsule (inactive medication) once daily.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Must have a diagnosis of T2DM for at least 3 months and be on either metformin monotherapy at a stable dose of >=1,000 mg per day or on combination therapy of metformin >=1,000 mg per day and a DPP-4 inhibitor at stable daily doses for at least 12 weeks prior to screening with an HbA1c of >=7.0% and <= 9.5% at Screening
• Fasting plasma glucose >=120 mg/dL and <=240 mg/dL at the Week -4 visit
• Fasting fingerstick glucose >=120 mg/dL and <=240 mg/dL performed at clinical research center on Day -14
• Must be medically stable on the basis of clinical laboratory tests performed at screening

Exclusion Criteria

• Has a history of diabetic ketoacidosis, type 1 diabetes mellitus (T1DM), pancreas or β-cell transplantation, or diabetes secondary to pancreatitis or pancreatectomy
• Has claustrophobia or anxiety, related to previous negative experiences with magnetic resonance imaging procedures which cannot be managed with an anxiolytic drug
• Has a history of brittle or labile glycemic control, with widely varying glucose measurements
• Has proliferative diabetic retinopathy (based on an eye examination within one year prior to Screening), currently receiving or requiring treatment
• Has a history of 1 or more severe hypoglycemic episodes within 6 months before screening
• Has history of hereditary glucose-galactose malabsorption or primary renal glucosuria.

• Minimum Eligible Age: 25 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Janssen Research & Development, LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Janssen Research & Development, LLC Clinical Trial

Role: STUDY_DIRECTOR

Janssen Research & Development, LLC

Locations

San Diego, La Jolla, California, United States

Gainesville, Florida, United States

Countries

United States

Related Links

http://filehosting.pharmacm.com/DownloadService.ashx?client=CTR_JNJ_7051&studyid=5730&filename=CR103062_CSR.pdf

A Double-Blind, Placebo-Controlled, Randomized, Parallel Groups, Multicenter Study to Investigate the Effects of Canagliflozin on Insulin Sensitivity, Hepatic Fat Content and Beta Cell Function in Subjects with Type 2 Diabetes Mellitus

Other Identifiers

28431754DIA1054

Identifier Type: OTHER

Identifier Source: secondary_id

CR103062

Identifier Type: -

Identifier Source: org_study_id