Empagliflozin Add on to Linagliptin Study in Japanese Patient With Type 2 Diabetes Mellitus
2018年9月24日 更新者：Boehringer Ingelheim
A Phase III, Randomised, Double-blind, Parallel Group, 52 Week Study to Evaluate Efficacy and Safety of Once Daily Empagliflozin and Linagliptin Fixed Dose Combination Compared With Linagliptin Plus Placebo in Japanese Type 2 Diabetes Mellitus Patients With Insufficient Glycaemic Control After 16 Weeks Treatment With Once Daily Linagliptin 5 mg.
This trial will compare the use of fixed dose combination of empagliflozin and linagliptin to linagliptin alone in patient with type 2 diabetes mellitus
調査の概要
状態
完了
条件
研究の種類
介入
入学 (実際)
275
段階
- フェーズ 3
連絡先と場所
このセクションには、調査を実施する担当者の連絡先の詳細と、この調査が実施されている場所に関する情報が記載されています。
研究場所
-
-
-
Aichi, Nagoya、日本、454-0933
- Nagoya Kyoritsu Hospital
-
Chiba, Kashiwa、日本、277-0825
- Kashiwa City Hospital
-
Fukuoka, Fukuoka、日本、811-1346
- Otabe internal medicine clinic
-
Fukuoka, Itoshima、日本、819-1104
- Nakamura Cardiovascular Clinic
-
Fukuoka, Kurume、日本、830-0023
- Tanaka I.M. Clinic, Fukuoka, I.M.
-
Fukushima, Koriyama、日本、963-8851
- Seino I.M. Clinic, Fukushima, I.M.
-
Hiroshima, Hiroshima、日本、733-0011
- Hiraoka Naika Clinic, Hiroshima, I.M.
-
Hokkaido, Sapporo、日本、003-0026
- Matsuda Cardiovascular Clinic
-
Hokkaido, Sapporo、日本、006-0811
- Teine Keijinkai Clinic
-
Hokkaido, Sapporo、日本、006-0852
- Mita Internal Medicine Cardiology Clinic
-
Hokkaido, Sapporo、日本、063-0826
- Miyanosawa Clinic of Internal Medicine and Cardiology
-
Ibaraki, Koga、日本、306-0232
- Itabashi Diabetic medicine and Dermatology Clinic
-
Ibaraki, Naka、日本、311-0113
- Nakakinen clinic
-
Kanagawa, Kawasaki、日本、214-0014
- Kubota Clinic
-
Kanagawa, Sagamihara、日本、252-0375
- Kitasato University Hospital
-
Kanagawa, Yokohama、日本、235-0045
- H.E.C Science Clinic
-
Kyoto, Kyoto、日本、604-8151
- Yoshimasa Diabetes & Endocrine Clinic
-
Kyoto, Kyoto、日本、615-8125
- Medical Corporation Hayashi Katagihara Clinic
-
Kyoto, Kyoto、日本、607-8062
- Rakuwakai Otowa Hospital
-
Nagano, Matsumoto、日本、390-0848
- Miyamoto Naika Clinic, Nagano, I.M.
-
Nagano, Matsumoto、日本、399-0036
- Gibo Hepatology Clinic, Nagano, Digestive Tract I.M.
-
Osaka, Higashi-Osaka、日本、577-0803
- Takekawa Clinic, Osaka, I.M.
-
Osaka, Osaka、日本、532-0003
- Medical Corporation Koseikai Fukuda Naika Clinic
-
Osaka, Osaka、日本、532-0026
- Kinugawa Cardiovascular Internal Medicine clinic
-
Osaka, Osaka、日本、536-0023
- Sato Hospital
-
Osaka, Osaka、日本、555-0032
- Nakaoka Clinic
-
Osaka, Suita、日本、565-0853
- OCROM Clinic
-
Osaka, Takatsuki、日本、569-1123
- Miyauchi Medical Center
-
Saitama, Hanno、日本、357-0024
- Medical Corporation Shinseikai Mashiba Clinic
-
Saitama, Kawagoe、日本、350-0851
- Asano Clinic
-
Saitama, Saitama、日本、336-0963
- Medical Corporation Fusa Shimizu Clinic Fusa
-
Saitama, Tokorozawa、日本、359-1161
- Ogino Clinic
-
Tokyo, Chiyoda-ku、日本、101-0047
- Kanda Clinic
-
Tokyo, Chuo-ku、日本、103-0027
- Fukuwa Clinic
-
Tokyo, Chuo-ku、日本、103-0027
- Tokyo-Eki Center-building Clinic
-
Tokyo, Hachioji、日本、192-0046
- Myojin Tou Clinic
-
Tokyo, Koto-ku、日本、136-0073
- Sawai Medical Clinic
-
Tokyo, Meguro-ku、日本、153-0051
- Mishuku Hospital
-
Tokyo, Shinagawa-ku、日本、140-8522
- Toshiba General Hospital
-
Tokyo, Shinjuku-ku、日本、160-0022
- ToCROM Clinic
-
-
参加基準
研究者は、適格基準と呼ばれる特定の説明に適合する人を探します。これらの基準のいくつかの例は、人の一般的な健康状態または以前の治療です。
適格基準
就学可能な年齢
20年歳以上 (大人、高齢者)
健康ボランティアの受け入れ
いいえ
受講資格のある性別
全て
説明
Inclusion criteria:
- Diagnosis of Type-2 Diabetes Mellitus (T2DM) prior to informed consent
Male and female patients on diet and exercise regimen for at least 12 weeks prior to informed consent who are:
- 1 drug-naïve, defined as no antidiabetic drugs for at least 12 weeks prior to informed consent, or
- 2 pre-treated with one oral antidiabetic drug (for sulfonylurea, with up to half of the maximum approved dose) on stable dosage for at least 12 weeks prior to informed consent (for thiazolidinedione, therapy has to be unchanged for at least 18 weeks prior to the informed consent, for linagliptin 5 mg at least 16 weeks prior to Visit 1). Individual antidiabetic drug (except linagliptin) will have to be discontinued at Visit 1.
HbA1c at Visit 1
- 1 HbA1c =8.0% and =10.5% for patients who are drug-naïve, or
- 2 HbA1c =7.5% and =10.5% for patients with one oral antidiabetic drug (except linagliptin), or
- 3 HbA1c =7.5% and =10.0% for patients with linagliptin 5 mg
- HbA1c =7.5% and =10.0% at Visit 4 for randomisation into the double-blind treatment period. Patient who are pre-treated with linagliptin 5 mg for 16 weeks or more prior to Visit 1 and meet the criteria of HbA1c can directly move on to the run-in (Visit 4).
- Age =20 years at informed consent
- BMI =40.0 kg/m2 at Visit 1 (screening)
- Signed and dated written informed consent by date of Visit 1 in accordance with Good Clinical Practice (GCP) and local legislation
Exclusion criteria:
- Uncontrolled hyperglycemia with a glucose level >270 mg/dL (>15.0 mmol/L) after an overnight fast during the open-label stabilisation period (from Visit 2 to Visit 4) and run-in period (from Visit 4 to Visit 5) , confirmed by a second measurement (not on the same day and done either at the central or at local laboratory).
- Acute coronary syndrome (ST-elevation myocardial infarction [STEMI], non-STEMI, and unstable angina pectoris), stroke or transient ischemic attack within 12 weeks prior to informed consent
- Indication of liver disease, defined by serum levels of either alanine aminotransferase (ALT Serum glutamic pyruvate transaminase [SGPT]), aspartate aminotransferase (AST, Serum glutamic oxaloacetic transaminase [SGOT]), or alkaline phosphatase (ALP) above 3 x upper limit of normal (ULN) as determined during screening, open-label stabilisation period and/or run-in period
- Impaired renal function, defined as estimated glomerular filtration rate (eGFR) <45 mL/min/1.73 m2 (MDRD formula) as determined during screening, open-label stabilisation period and/or run-in period
- Known hereditary galactose intolerance
- Known contraindications to linagliptin and empagliflozin according to the Japanese label
- Any previous (within 2 years prior to informed consent) or planned bariatric surgery (or any other weight loss surgery) or other gastrointestinal surgery that induce chronic malabsorption
- Medical history of cancer (except for resected non-invasive basal cell or squamous carcinoma) and/or treatment for cancer within the last 5 years
- Known blood dyscrasias or any disorders causing haemolysis or unstable red blood cell (RBC) count (e.g. malaria, babesiosis, haemolytic anaemia).
- Treatment with insulin, Glucagon-like peptide-1 agonists, within 12 weeks prior to informed consent
- Treatment with anti-obesity drugs within 12 weeks prior to informed consent or any other treatment at the time of screening (i.e., surgery, aggressive diet regimen, etc.) leading to unstable body weight
- Current treatment with systemic steroids (other than inhaled or topical steroids) at informed consent or change in dosage of thyroid hormones within 6 weeks prior to informed consent or any other uncontrolled endocrine disorder except T2DM
Pre-menopausal women (last menstruation =1 year prior to informed consent) who:
- 1 are nursing or pregnant or
- 2 are of child-bearing potential and are not practicing an acceptable method of birth control, or do not plan to continue using this method throughout the trial and do not agree to submit to periodic pregnancy testing during participation in the trial. Acceptable methods of birth control include tubal ligation, intra uterine devices/systems, oral contraceptives, complete sexual abstinence, double barrier method and vasectomised partner
- Known or suspected allergy or hypersensitivity to trial products or related products (e.g., Dipeptidyl-peptidase-4 inhibitors or Sodium-glucose co-transporter-2 inhibitors)
- Alcohol or drug abuse within the 12 weeks prior to informed consent that would interfere with trial participation or any ongoing condition leading to a decreased compliance to trial procedures or trial drug intake, by the judgment of the investigator
- Intake of an investigational drug in another trial within 30 days prior to Visit 1 or participation in the follow-up period of another trial (participation in observational studies is permitted)
- Any other clinical condition that, in the opinion of the investigator, would jeopardize patient's safety while participating in this clinical trial
研究計画
このセクションでは、研究がどのように設計され、研究が何を測定しているかなど、研究計画の詳細を提供します。
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 |
|---|---|
|
アクティブコンパレータ：Linagliptin
patient to receive 5 mg linagliptin once daily
|
他の名前：
Matching placebo empagliflozin + linagliptin
|
|
実験的：Empagliflozin + linagliptin low dose
patient to receive one tablet once daily
|
tablet
Matching placebo linagliptin
|
|
実験的：Empagliflozin + linagliptin high dose
patient to receive one tablet once daily
|
Matching placebo linagliptin
tablet
|
|
プラセボコンパレーター：Linagliptin placebo
|
tablet
Matching placebo linagliptin
tablet
|
|
プラセボコンパレーター：Empagliflozin + linagliptin high dose placebo
|
他の名前：
|
|
プラセボコンパレーター：Empagliflozin + linagliptin low dose placebo
|
他の名前：
Matching placebo empagliflozin + linagliptin
|
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 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Change of Glycosylated Haemoglobin A1c (Glycosylated Haemoglobin A1c After 24 Weeks of Double-blind Treatment From Baseline)
時間枠：Baseline and 24 week
|
Change from baseline in Glycosylated haemoglobin A1c (HbA1c) at Week 24 was calculated as: HbA1c at Week 24 - HbA1c at baseline.
Baseline is referred to the last observed measurement prior to the administration of randomized trial medication.
Adjusted mean (Least square mean) and its standard error (SE) is presented.
|
Baseline and 24 week
|
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Change in HbA1c From Week 28 at Week 52 (Empagliflozin 25 mg/Linagliptin 5 mg Only)
時間枠：28 Week (pre up-titration) and 52 Week
|
Change from Week 28 in HbA1c at Week 52 was calculated as: HbA1c at Week 52 - HbA1c at Week 28. Week 28 (pre up-titration) is referred to the last observed measurement prior to the first administration of any double-blind randomized trial medication in the up-titration period. Adjusted mean (Least square mean) and its standard error (SE) is presented. This endpoint was based on 1 group of the Full analysis set with up-titration (FASUT-II) whose dose was up-titrated to Empagliflozin 25 mg/Linagliptin 5 mg fixed dose combination thus there is no comparison group. Hence, no comparison is made. A restricted maximum likelihood (REML)-based mixed model repeated measures (MMRM) approach was used with baseline HbA1c as linear covariate and baseline eGFR, prior use of antidiabetic drug, visit as fixed effect(s). The covariance used to fit the model was unstructured. |
28 Week (pre up-titration) and 52 Week
|
|
Change in HbA1c From Baseline at Week 52 (All Empagliflozin Versus All Placebo)
時間枠：Baseline and 52 week
|
Change from baseline in HbA1c at Week 52 was calculated as: HbA1c at Week 52 - HbA1c at baseline.
Baseline is referred to the last observed measurement prior to the administration of randomized trial medication.
Adjusted mean (Least square mean) and its standard error (SE) is presented.
|
Baseline and 52 week
|
|
Change in HbA1c From Baseline at Week 52 (Empagliflozin 25 mg/Linagliptin 5 mg Versus Linagliptin 5 mg + Placebo 25 mg)
時間枠：Baseline and 52 week
|
Change from baseline in HbA1c at Week 52 was calculated as: HbA1c at Week 52 - HbA1c at baseline.
Baseline is referred to the last observed measurement prior to the administration of randomized trial medication.
Adjusted mean (Least square mean) and its standard error (SE) is presented.
|
Baseline and 52 week
|
|
Change in HbA1c From Baseline at Week 52 (Empagliflozin 25 mg/Linagliptin 5 mg Versus All Placebo)
時間枠：Baseline and 52 week
|
Change from baseline in HbA1c at Week 52 was calculated as: HbA1c at Week 52 - HbA1c at baseline.
Baseline is referred to the last observed measurement prior to the administration of randomized trial medication.
Adjusted mean (Least square mean) and its standard error (SE) is presented.
|
Baseline and 52 week
|
協力者と研究者
ここでは、この調査に関係する人々や組織を見つけることができます。
スポンサー
出版物と役立つリンク
研究に関する情報を入力する責任者は、自発的にこれらの出版物を提供します。これらは、研究に関連するあらゆるものに関するものである可能性があります。
便利なリンク
研究記録日
これらの日付は、ClinicalTrials.gov への研究記録と要約結果の提出の進捗状況を追跡します。研究記録と報告された結果は、国立医学図書館 (NLM) によって審査され、公開 Web サイトに掲載される前に、特定の品質管理基準を満たしていることが確認されます。
主要日程の研究
研究開始 (実際)
2015年5月14日
一次修了 (実際)
2016年8月26日
研究の完了 (実際)
2017年3月27日
試験登録日
最初に提出
2015年5月21日
QC基準を満たした最初の提出物
2015年5月21日
最初の投稿 (見積もり)
2015年5月25日
学習記録の更新
投稿された最後の更新 (実際)
2019年2月15日
QC基準を満たした最後の更新が送信されました
2018年9月24日
最終確認日
2018年9月1日
詳しくは
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。