Treatment Differences Between Canagliflozin and Placebo in Insulin Secretion in Subjects With Type 2 Diabetes Mellitus (T2DM)
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
調査の概要
詳細な説明
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.
研究の種類
入学 (実際)
段階
- フェーズ 1
連絡先と場所
研究場所
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California
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San Diego, La Jolla、California、アメリカ
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Florida
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Gainesville、Florida、アメリカ
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-
参加基準
適格基準
就学可能な年齢
健康ボランティアの受け入れ
受講資格のある性別
説明
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.
研究計画
研究はどのように設計されていますか？
デザインの詳細
- 主な目的：処理
- 割り当て：ランダム化
- 介入モデル：並列代入
- マスキング：ダブル
武器と介入
参加者グループ / アーム |
介入・治療 |
|---|---|
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実験的：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.
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100 mg カプセルを 1 日 1 回経口摂取します。
300 mg カプセル 1 個を 1 日 1 回経口摂取します
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プラセボコンパレーター：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).
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One placebo capsule (inactive medication) once daily.
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この研究は何を測定していますか？
主要な結果の測定
結果測定 |
時間枠 |
|---|---|
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Change from baseline in hepatic insulin sensitivity
時間枠：Baseline, 25 weeks
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Baseline, 25 weeks
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Change from baseline in peripheral tissue insulin sensitivity
時間枠：Baseline, 25 weeks
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Baseline, 25 weeks
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Change from baseline in liver fat content, determined using magnetic resonance spectroscopy (MRS)
時間枠：Baseline, 25 weeks
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Baseline, 25 weeks
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Change from baseline in insulin secretion rate (ISR) during mixed-meal tolerance test (MMTT)
時間枠：Baseline, 25 weeks
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Baseline, 25 weeks
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Change from baseline in beta-cell glucose sensitivity, determined as a slope of ISR vs. plasma glucose concentration during MMTT
時間枠：Baseline, 25 weeks
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Baseline, 25 weeks
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二次結果の測定
結果測定 |
時間枠 |
|---|---|
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Changes from baseline in substrate oxidation and energy production rates during MMTT and euglycemic clamp
時間枠：Baseline, 25 weeks
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Baseline, 25 weeks
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Changes from baseline in insulin clearance during MMTT and euglycemic clamp
時間枠：Baseline, 25 weeks
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Baseline, 25 weeks
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Change from baseline in suppression of free fatty acids (FFAs) during euglycemic clamp
時間枠：Baseline, 25 weeks
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Baseline, 25 weeks
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Changes from baseline in basal and postprandial plasma glucagon, FFAs and β-hydroxybutyrate during MMTT
時間枠：Baseline, 25 weeks
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Baseline, 25 weeks
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Change from baseline in renal threshold for glucose (RTG), estimated using an MMTT-based method
時間枠：Baseline, 25 weeks
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Baseline, 25 weeks
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協力者と研究者
出版物と役立つリンク
研究記録日
主要日程の研究
研究開始 (実際)
一次修了 (実際)
研究の完了 (実際)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (見積もり)
学習記録の更新
投稿された最後の更新 (実際)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
本研究に関する用語
その他の研究ID番号
- CR103062
- 28431754DIA1054 (その他の識別子：Janssen Research & Development, LLC)
医薬品およびデバイス情報、研究文書
米国FDA規制医薬品の研究
この情報は、Web サイト clinicaltrials.gov から変更なしで直接取得したものです。研究の詳細を変更、削除、または更新するリクエストがある場合は、register@clinicaltrials.gov。 までご連絡ください。 clinicaltrials.gov に変更が加えられるとすぐに、ウェブサイトでも自動的に更新されます。