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

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified July 2014 by Janssen Research & Development, LLC
Sponsor:
Information provided by (Responsible Party):
Janssen Research & Development, LLC
ClinicalTrials.gov Identifier:
NCT02009488
First received: December 9, 2013
Last updated: July 4, 2014
Last verified: July 2014
  Purpose

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.


Condition Intervention Phase
Diabetes Mellitus, Type 2
Drug: Canagliflozin, 100 mg
Drug: Canagliflozin, 300 mg
Drug: Placebo
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver)
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Janssen Research & Development, LLC:

Primary Outcome Measures:
  • Change from baseline in hepatic insulin sensitivity [ Time Frame: Baseline, 25 weeks ] [ Designated as safety issue: No ]
  • Change from baseline in peripheral tissue insulin sensitivity [ Time Frame: Baseline, 25 weeks ] [ Designated as safety issue: No ]
  • Change from baseline in liver fat content, determined using magnetic resonance spectroscopy (MRS) [ Time Frame: Baseline, 25 weeks ] [ Designated as safety issue: No ]
  • Change from baseline in insulin secretion rate (ISR) during mixed-meal tolerance test (MMTT) [ Time Frame: Baseline, 25 weeks ] [ Designated as safety issue: No ]
  • Change from baseline in beta-cell glucose sensitivity, determined as a slope of ISR vs. plasma glucose concentration during MMTT [ Time Frame: Baseline, 25 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Changes from baseline in substrate oxidation and energy production rates during MMTT and euglycemic clamp [ Time Frame: Baseline, 25 weeks ] [ Designated as safety issue: No ]
  • Changes from baseline in insulin clearance during MMTT and euglycemic clamp [ Time Frame: Baseline, 25 weeks ] [ Designated as safety issue: No ]
  • Change from baseline in suppression of free fatty acids (FFAs) during euglycemic clamp [ Time Frame: Baseline, 25 weeks ] [ Designated as safety issue: No ]
  • Changes from baseline in basal and postprandial plasma glucagon, FFAs and β-hydroxybutyrate during MMTT [ Time Frame: Baseline, 25 weeks ] [ Designated as safety issue: No ]
  • Change from baseline in renal threshold for glucose (RTG), estimated using an MMTT-based method [ Time Frame: Baseline, 25 weeks ] [ Designated as safety issue: No ]

Estimated Enrollment: 56
Study Start Date: July 2014
Estimated Study Completion Date: December 2015
Estimated Primary Completion Date: February 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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.
Drug: Canagliflozin, 100 mg
One 100 mg capsule taken orally (by mouth) once daily
Drug: Canagliflozin, 300 mg
One 300 mg capsule taken orally (by mouth) once daily
Placebo Comparator: 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).
Drug: Placebo
One placebo capsule (inactive medication) once daily.

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.

  Eligibility

Ages Eligible for Study:   25 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02009488

Contacts
Contact: This study is not yet recruiting patients. Please check back for future recruiting sites, or email JNJ.CT@sylogent.com

Locations
United States, California
Not yet recruiting
San Diego, La Jolla, California, United States
United States, Florida
Not yet recruiting
Gainesville, Florida, United States
Sponsors and Collaborators
Janssen Research & Development, LLC
Investigators
Study Director: Janssen Research & Development, LLC Clinical Trial Janssen Research & Development, LLC
  More Information

No publications provided

Responsible Party: Janssen Research & Development, LLC
ClinicalTrials.gov Identifier: NCT02009488     History of Changes
Other Study ID Numbers: CR103062, 28431754DIA1054
Study First Received: December 9, 2013
Last Updated: July 4, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Janssen Research & Development, LLC:
Diabetes Mellitus, Type 2
Metformin
Canagliflozin
INVOKANA®
Insulin sensitivity
DPP-4 inhibitor
dipeptidyl peptidase-4

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Insulin Resistance
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Hyperinsulinism
Insulin
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 28, 2014