Empagliflozin Add on to Linagliptin Study in Japanese Patient With Type 2 Diabetes Mellitus
24 septembre 2018 mis à jour par: 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
Aperçu de l'étude
Statut
Complété
Les conditions
Type d'étude
Interventionnel
Inscription (Réel)
275
Phase
- Phase 3
Contacts et emplacements
Cette section fournit les coordonnées de ceux qui mènent l'étude et des informations sur le lieu où cette étude est menée.
Lieux d'étude
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Aichi, Nagoya, Japon, 454-0933
- Nagoya Kyoritsu Hospital
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Chiba, Kashiwa, Japon, 277-0825
- Kashiwa City Hospital
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Fukuoka, Fukuoka, Japon, 811-1346
- Otabe internal medicine clinic
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Fukuoka, Itoshima, Japon, 819-1104
- Nakamura Cardiovascular Clinic
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Fukuoka, Kurume, Japon, 830-0023
- Tanaka I.M. Clinic, Fukuoka, I.M.
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Fukushima, Koriyama, Japon, 963-8851
- Seino I.M. Clinic, Fukushima, I.M.
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Hiroshima, Hiroshima, Japon, 733-0011
- Hiraoka Naika Clinic, Hiroshima, I.M.
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Hokkaido, Sapporo, Japon, 003-0026
- Matsuda Cardiovascular Clinic
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Hokkaido, Sapporo, Japon, 006-0811
- Teine Keijinkai Clinic
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Hokkaido, Sapporo, Japon, 006-0852
- Mita Internal Medicine Cardiology Clinic
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Hokkaido, Sapporo, Japon, 063-0826
- Miyanosawa Clinic of Internal Medicine and Cardiology
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Ibaraki, Koga, Japon, 306-0232
- Itabashi Diabetic medicine and Dermatology Clinic
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Ibaraki, Naka, Japon, 311-0113
- Nakakinen clinic
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Kanagawa, Kawasaki, Japon, 214-0014
- Kubota Clinic
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Kanagawa, Sagamihara, Japon, 252-0375
- Kitasato University Hospital
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Kanagawa, Yokohama, Japon, 235-0045
- H.E.C Science Clinic
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Kyoto, Kyoto, Japon, 604-8151
- Yoshimasa Diabetes & Endocrine Clinic
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Kyoto, Kyoto, Japon, 615-8125
- Medical Corporation Hayashi Katagihara Clinic
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Kyoto, Kyoto, Japon, 607-8062
- Rakuwakai Otowa Hospital
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Nagano, Matsumoto, Japon, 390-0848
- Miyamoto Naika Clinic, Nagano, I.M.
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Nagano, Matsumoto, Japon, 399-0036
- Gibo Hepatology Clinic, Nagano, Digestive Tract I.M.
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Osaka, Higashi-Osaka, Japon, 577-0803
- Takekawa Clinic, Osaka, I.M.
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Osaka, Osaka, Japon, 532-0003
- Medical Corporation Koseikai Fukuda Naika Clinic
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Osaka, Osaka, Japon, 532-0026
- Kinugawa Cardiovascular Internal Medicine clinic
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Osaka, Osaka, Japon, 536-0023
- Sato Hospital
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Osaka, Osaka, Japon, 555-0032
- Nakaoka Clinic
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Osaka, Suita, Japon, 565-0853
- OCROM Clinic
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Osaka, Takatsuki, Japon, 569-1123
- Miyauchi Medical Center
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Saitama, Hanno, Japon, 357-0024
- Medical Corporation Shinseikai Mashiba Clinic
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Saitama, Kawagoe, Japon, 350-0851
- Asano Clinic
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Saitama, Saitama, Japon, 336-0963
- Medical Corporation Fusa Shimizu Clinic Fusa
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Saitama, Tokorozawa, Japon, 359-1161
- Ogino Clinic
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Tokyo, Chiyoda-ku, Japon, 101-0047
- Kanda Clinic
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Tokyo, Chuo-ku, Japon, 103-0027
- Fukuwa Clinic
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Tokyo, Chuo-ku, Japon, 103-0027
- Tokyo-Eki Center-building Clinic
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Tokyo, Hachioji, Japon, 192-0046
- Myojin Tou Clinic
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Tokyo, Koto-ku, Japon, 136-0073
- Sawai Medical Clinic
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Tokyo, Meguro-ku, Japon, 153-0051
- Mishuku Hospital
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Tokyo, Shinagawa-ku, Japon, 140-8522
- Toshiba General Hospital
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Tokyo, Shinjuku-ku, Japon, 160-0022
- ToCROM Clinic
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Critères de participation
Les chercheurs recherchent des personnes qui correspondent à une certaine description, appelée critères d'éligibilité. Certains exemples de ces critères sont l'état de santé général d'une personne ou des traitements antérieurs.
Critère d'éligibilité
Âges éligibles pour étudier
20 ans et plus (Adulte, Adulte plus âgé)
Accepte les volontaires sains
Non
Sexes éligibles pour l'étude
Tout
La description
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
Plan d'étude
Cette section fournit des détails sur le plan d'étude, y compris la façon dont l'étude est conçue et ce que l'étude mesure.
Comment l'étude est-elle conçue ?
Détails de conception
- Objectif principal: Traitement
- Répartition: Randomisé
- Modèle interventionnel: Affectation parallèle
- Masquage: Double
Armes et Interventions
Groupe de participants / Bras |
Intervention / Traitement |
|---|---|
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Comparateur actif: Linagliptin
patient to receive 5 mg linagliptin once daily
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Autres noms:
Matching placebo empagliflozin + linagliptin
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Expérimental: Empagliflozin + linagliptin low dose
patient to receive one tablet once daily
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tablet
Matching placebo linagliptin
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Expérimental: Empagliflozin + linagliptin high dose
patient to receive one tablet once daily
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Matching placebo linagliptin
tablet
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Comparateur placebo: Linagliptin placebo
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tablet
Matching placebo linagliptin
tablet
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Comparateur placebo: Empagliflozin + linagliptin high dose placebo
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Autres noms:
|
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Comparateur placebo: Empagliflozin + linagliptin low dose placebo
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Autres noms:
Matching placebo empagliflozin + linagliptin
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Que mesure l'étude ?
Principaux critères de jugement
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
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Change of Glycosylated Haemoglobin A1c (Glycosylated Haemoglobin A1c After 24 Weeks of Double-blind Treatment From Baseline)
Délai: 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
|
Mesures de résultats secondaires
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
|
Change in HbA1c From Week 28 at Week 52 (Empagliflozin 25 mg/Linagliptin 5 mg Only)
Délai: 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
|
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Change in HbA1c From Baseline at Week 52 (All Empagliflozin Versus All Placebo)
Délai: 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
|
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Change in HbA1c From Baseline at Week 52 (Empagliflozin 25 mg/Linagliptin 5 mg Versus Linagliptin 5 mg + Placebo 25 mg)
Délai: 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)
Délai: 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
|
Collaborateurs et enquêteurs
C'est ici que vous trouverez les personnes et les organisations impliquées dans cette étude.
Parrainer
Collaborateurs
Publications et liens utiles
La personne responsable de la saisie des informations sur l'étude fournit volontairement ces publications. Il peut s'agir de tout ce qui concerne l'étude.
Liens utiles
Dates d'enregistrement des études
Ces dates suivent la progression des dossiers d'étude et des soumissions de résultats sommaires à ClinicalTrials.gov. Les dossiers d'étude et les résultats rapportés sont examinés par la Bibliothèque nationale de médecine (NLM) pour s'assurer qu'ils répondent à des normes de contrôle de qualité spécifiques avant d'être publiés sur le site Web public.
Dates principales de l'étude
Début de l'étude (Réel)
14 mai 2015
Achèvement primaire (Réel)
26 août 2016
Achèvement de l'étude (Réel)
27 mars 2017
Dates d'inscription aux études
Première soumission
21 mai 2015
Première soumission répondant aux critères de contrôle qualité
21 mai 2015
Première publication (Estimation)
25 mai 2015
Mises à jour des dossiers d'étude
Dernière mise à jour publiée (Réel)
15 février 2019
Dernière mise à jour soumise répondant aux critères de contrôle qualité
24 septembre 2018
Dernière vérification
1 septembre 2018
Plus d'information
Termes liés à cette étude
Termes MeSH pertinents supplémentaires
- Troubles du métabolisme du glucose
- Maladies métaboliques
- Maladies du système endocrinien
- Diabète sucré
- Diabète sucré, Type 2
- Agents hypoglycémiants
- Effets physiologiques des médicaments
- Mécanismes moléculaires de l'action pharmacologique
- Inhibiteurs d'enzymes
- Les hormones
- Hormones, substituts hormonaux et antagonistes hormonaux
- Inhibiteurs de protéase
- Incrétines
- Inhibiteurs du transporteur sodium-glucose 2
- Inhibiteurs de dipeptidyl-peptidase IV
- Empagliflozine
- Linagliptine
Autres numéros d'identification d'étude
- 1275.19
Ces informations ont été extraites directement du site Web clinicaltrials.gov sans aucune modification. Si vous avez des demandes de modification, de suppression ou de mise à jour des détails de votre étude, veuillez contacter register@clinicaltrials.gov. Dès qu'un changement est mis en œuvre sur clinicaltrials.gov, il sera également mis à jour automatiquement sur notre site Web .