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

NCT02009488 | Completed Phase 1 FDA Drug

• 2 other identifiers: CR10306228431754DIA1054
• Study Type: interventional
• Target: 59
• Locations: 1 country
• Sites: 2

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.

Conditions

Diabetes Mellitus, Type 2

Keywords

Diabetes Mellitus, Type 2; Metformin; Canagliflozin; INVOKANA®; Insulin sensitivity; DPP-4 inhibitor; dipeptidyl peptidase-4

Outcome Measures

Primary Outcomes (5)

• Change from baseline in hepatic insulin sensitivity

  Baseline, 25 weeks

• Change from baseline in peripheral tissue insulin sensitivity

  Baseline, 25 weeks

• Change from baseline in liver fat content, determined using magnetic resonance spectroscopy (MRS)

  Baseline, 25 weeks

• Change from baseline in insulin secretion rate (ISR) during mixed-meal tolerance test (MMTT)

  Baseline, 25 weeks

• Change from baseline in beta-cell glucose sensitivity, determined as a slope of ISR vs. plasma glucose concentration during MMTT

  Baseline, 25 weeks

Secondary Outcomes (5)

• Changes from baseline in substrate oxidation and energy production rates during MMTT and euglycemic clamp

  Baseline, 25 weeks

• Changes from baseline in insulin clearance during MMTT and euglycemic clamp

  Baseline, 25 weeks

• Change from baseline in suppression of free fatty acids (FFAs) during euglycemic clamp

  Baseline, 25 weeks

• Changes from baseline in basal and postprandial plasma glucagon, FFAs and β-hydroxybutyrate during MMTT

  Baseline, 25 weeks

• Change from baseline in renal threshold for glucose (RTG), estimated using an MMTT-based method

  Baseline, 25 weeks

Study Arms (2)

Canagliflozin (JNJ-28431754)

EXPERIMENTAL

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; Drug: Canagliflozin, 300 mg

Placebo

PLACEBO COMPARATOR

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

Interventions

Canagliflozin, 100 mg DRUG

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

Canagliflozin (JNJ-28431754)

Canagliflozin, 300 mg DRUG

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

Canagliflozin (JNJ-28431754)

Placebo DRUG

One placebo capsule (inactive medication) once daily.

Placebo

Eligibility Criteria

• Age: 25 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Janssen Research & Development, LLC: lead

Study Sites (2)

Unknown Facility

San Diego, La Jolla, California, United States

Location

Unknown Facility

Gainesville, Florida, United States

Location

Related Links

• 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

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Insulin Resistance

Interventions

Canagliflozin

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Hyperinsulinism

Intervention Hierarchy (Ancestors)

Thiophenes; Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Glucosides; Glycosides; Carbohydrates

Study Officials

• Janssen Research & Development, LLC Clinical Trial

  Janssen Research & Development, LLC

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 9, 2013
• First Posted: December 12, 2013
• Study Start: September 8, 2014
• Primary Completion: January 3, 2017
• Study Completion: January 3, 2017
• Last Updated: January 4, 2018

Record last verified: 2018-01

Locations

US (2)