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

3 januari 2018 uppdaterad av: Janssen Research & Development, LLC

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

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.

Studieöversikt

Status

Avslutad

Betingelser

Intervention / Behandling

Detaljerad beskrivning

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.

Studietyp

Interventionell

Inskrivning (Faktisk)

59

Fas

  • Fas 1

Kontakter och platser

Det här avsnittet innehåller kontaktuppgifter för dem som genomför studien och information om var denna studie genomförs.

Studieorter

  • Förenta staterna
    • California
      • San Diego, La Jolla, California, Förenta staterna
    • Florida
      • Gainesville, Florida, Förenta staterna

Deltagandekriterier

Forskare letar efter personer som passar en viss beskrivning, så kallade behörighetskriterier. Några exempel på dessa kriterier är en persons allmänna hälsotillstånd eller tidigare behandlingar.

Urvalskriterier

Åldrar som är berättigade till studier

25 år till 70 år (Vuxen, Äldre vuxen)

Tar emot friska volontärer

Nej

Kön som är behöriga för studier

Allt

Beskrivning

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.

Studieplan

Det här avsnittet ger detaljer om studieplanen, inklusive hur studien är utformad och vad studien mäter.

Hur är studien utformad?

Designdetaljer

  • Primärt syfte: Behandling
  • Tilldelning: Randomiserad
  • Interventionsmodell: Parallellt uppdrag
  • Maskning: Dubbel

Vapen och interventioner

Deltagargrupp / Arm
Intervention / Behandling
Experimentell: 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.
Läkemedel: Canagliflozin, 100 mg
En 100 mg kapsel tas oralt (genom munnen) en gång dagligen
Läkemedel: Canagliflozin, 300 mg
En 300 mg kapsel tas oralt (genom munnen) en gång dagligen
Placebo-jämförare: 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).
Läkemedel: Placebo
One placebo capsule (inactive medication) once daily.

Vad mäter studien?

Primära resultatmått

Resultatmått
Tidsram
Change from baseline in hepatic insulin sensitivity
Tidsram: Baseline, 25 weeks
Baseline, 25 weeks
Change from baseline in peripheral tissue insulin sensitivity
Tidsram: Baseline, 25 weeks
Baseline, 25 weeks
Change from baseline in liver fat content, determined using magnetic resonance spectroscopy (MRS)
Tidsram: Baseline, 25 weeks
Baseline, 25 weeks
Change from baseline in insulin secretion rate (ISR) during mixed-meal tolerance test (MMTT)
Tidsram: Baseline, 25 weeks
Baseline, 25 weeks
Change from baseline in beta-cell glucose sensitivity, determined as a slope of ISR vs. plasma glucose concentration during MMTT
Tidsram: Baseline, 25 weeks
Baseline, 25 weeks

Sekundära resultatmått

Resultatmått
Tidsram
Changes from baseline in substrate oxidation and energy production rates during MMTT and euglycemic clamp
Tidsram: Baseline, 25 weeks
Baseline, 25 weeks
Changes from baseline in insulin clearance during MMTT and euglycemic clamp
Tidsram: Baseline, 25 weeks
Baseline, 25 weeks
Change from baseline in suppression of free fatty acids (FFAs) during euglycemic clamp
Tidsram: Baseline, 25 weeks
Baseline, 25 weeks
Changes from baseline in basal and postprandial plasma glucagon, FFAs and β-hydroxybutyrate during MMTT
Tidsram: Baseline, 25 weeks
Baseline, 25 weeks
Change from baseline in renal threshold for glucose (RTG), estimated using an MMTT-based method
Tidsram: Baseline, 25 weeks
Baseline, 25 weeks

Samarbetspartners och utredare

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Sponsor

Janssen Research & Development, LLC

Publikationer och användbara länkar

Den som ansvarar för att lägga in information om studien tillhandahåller frivilligt dessa publikationer. Dessa kan handla om allt som har med studien att göra.

Användbara länkar

Studieavstämningsdatum

Dessa datum spårar framstegen för inlämningar av studieposter och sammanfattande resultat till ClinicalTrials.gov. Studieposter och rapporterade resultat granskas av National Library of Medicine (NLM) för att säkerställa att de uppfyller specifika kvalitetskontrollstandarder innan de publiceras på den offentliga webbplatsen.

Studera stora datum

Studiestart (Faktisk)

8 september 2014

Primärt slutförande (Faktisk)

3 januari 2017

Avslutad studie (Faktisk)

3 januari 2017

Studieregistreringsdatum

Först inskickad

9 december 2013

Först inskickad som uppfyllde QC-kriterierna

9 december 2013

Första postat (Uppskatta)

12 december 2013

Uppdateringar av studier

Senaste uppdatering publicerad (Faktisk)

4 januari 2018

Senaste inskickade uppdateringen som uppfyllde QC-kriterierna

3 januari 2018

Senast verifierad

1 januari 2018

Mer information

Termer relaterade till denna studie

Nyckelord

Ytterligare relevanta MeSH-villkor

Andra studie-ID-nummer

  • CR103062
  • 28431754DIA1054 (Annan identifierare: Janssen Research & Development, LLC)

Läkemedels- och apparatinformation, studiedokument

Studerar en amerikansk FDA-reglerad läkemedelsprodukt

Ja

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