Linagliptin as Add on Therapy to Empagliflozin 10 mg or 25 mg With Japanese Patients With Type 2 Diabetes Mellitus

Diabetes Mellitus, Type 2 Clinical Trial

Official title:

A Phase III, Randomised, Double-blind, Parallel Group, 24-week Study to Evaluate Efficacy and Safety of Once Daily Empagliflozin 10 mg and Linagliptin 5 mg Fixed Dose Combination Compared With Empagliflozin 10 mg Plus Placebo and a 52-week Study to Evaluate Efficacy and Safety of Once Daily Empagliflozin 25 mg and Linagliptin 5 mg Fixed Dose Combination Compared With Empagliflozin 25 mg Plus Placebo in Patients With Type 2 Diabetes Mellitus and Insufficient Glycaemic Control After 16-week Treatment With Empagliflozin (10 mg or 25 mg) Alone Once Daily.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02489968
• Other study ID #: 1275.13
• Status: Completed
• Phase: Phase 3
• Start date: May 12, 2015
• Est. completion date: June 16, 2017

Study information

• Verified date: September 2018
• Source: Boehringer Ingelheim
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Two independent study parts (i.e. Part A and Part B) are included in this trial. Part A will evaluate empagliflozin 10 mg + linagliptin and Part B will evaluate empagliflozin 25 mg + linagliptin. All analyses will be carried out separately for these study parts. The objective of Part A is to investigate the efficacy, safety and tolerability of the fixed dose combination (FDC) of empagliflozin 10 mg / linagliptin 5 mg compared with empagliflozin 10 mg plus FDC matching placebo administered orally once daily for 24 weeks in Japanese patients with T2DM (Type 2 Diabetes Mellitus) who have insufficient glycaemic control after 16 weeks of treatment with empagliflozin 10 mg alone once daily. The study is designed to show superiority of the FDC of empagliflozin 10 mg / linagliptin 5 mg over empagliflozin 10 mg plus FDC matching placebo after 24 weeks of treatment. The objective of Part B is to investigate the efficacy, safety and tolerability of the FDC of empagliflozin 25 mg / linagliptin 5 mg compared with empagliflozin 25 mg plus FDC matching placebo administered orally once daily for 24 weeks in Japanese patients with T2DM who have insufficient glycaemic control after 16 weeks of treatment with empagliflozin 25 mg alone once daily. The study is designed to show superiority of the FDC of empagliflozin 25 mg / linagliptin 5 mg over empagliflozin 25 mg plus FDC matching placebo after 24 weeks of treatment. The 24 week treatment period will be followed by a 28 week extension treatment period to evaluate further efficacy and safety up to 52 weeks.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 880
• Est. completion date: June 16, 2017
• Est. primary completion date: November 18, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years and older

Eligibility

Inclusion criteria:

• Diagnosis of type 2 diabetes prior to informed consent

• Male and female patients on diet and exercise regimen for at least 12 weeks prior to informed consent who are:

• drug-naïve, defined as no antidiabetic drugs for at least 12 weeks prior to informed consent or,

• 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 the informed consent (for thiazolidinedione, therapy has to be unchanged for at least 18 weeks prior to the informed consent). Individual antidiabetic drug will have to be discontinued at Visit 1.

• haemoglobin A1c (HbA1c) at Visit 1 (screening)

• for patients without antidiabetic therapy : HbA1c >=8.0 to =<10.5%

• for patients with one oral antidiabetic drug : HbA1c >=7.5 to =<10.5%

• HbA1c >=7.5 to =<10.0% at Visit 4 for randomisation into the double blind treatment period

Exclusion criteria:

• Uncontrolled hyperglycaemia with a glucose level >270 mg/dL (>15.0 mmol/L) during the open label stabilisation period and placebo run in period

• Impaired renal function, defined as estimated glomerular filtration rate (eGFR) <45 mL/min/1.73m2 (modification of diet in renal disease (MDRD) formula)

• Acute coronary syndrome, stroke or transient ischemic attack (TIA) within 12 weeks prior to informed consent

• Indication of liver disease, defined by serum levels of either alanine transaminase (ALT), aspartate transaminase (AST), or alkaline phosphatase (ALP) above 3 x upper limit of normal (ULN)

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2

Intervention

Drug:
• empagliflozin 10 mg + linagliptin 5 mg
empagliflozin low dose + linagliptin once daily
• empagliflozin 10 mg
empagliflozin low dose once daily
• empagliflozin 25 mg + linagliptin 5 mg
empagliflozin high dose + linagliptin once daily
• empagliflozin 25 mg
empagliflozin high dose once daily
• Placebo

Locations

Country	Name	City	State
Japan	Tokai Memorial Hospital	Aichi, Kasugai
Japan	Japan Organization of Occupational Health and Safety Chubu Rosai Hospital	Aichi, Nagoya
Japan	Tokuyama Clinic	Chiba, Chiba
Japan	Matsuyama Shimin Hospital	Ehime, Matsuyama
Japan	Tanaka Int. Clinic, Ehime, DIA Med.,CV Med.	Ehime, Niihama
Japan	Murakami Memorial Hp., Ehime, I.M.	Ehime, Saijo
Japan	Kunisaki Makoto Clinic, Fukuoka, I.M./CV Med.	Fukuoka, Fukuoka
Japan	Fukuoka Shin Mizumaki Hospital	Fukuoka, Onga
Japan	Shin Yukuhashi Hospital	Fukuoka, Yukuhashi
Japan	Hashimoto I.M., Gifu, I.M.	Gifu, Gifu
Japan	Kikuchi Naika Clinic, Gunma, I.M.	Gunma, Maebashi
Japan	Hasegawa Internal Medicine Clinic	Hokkaido, Chitose
Japan	Ebetsu Internal Medicine Clinic	Hokkaido, Ebetsu
Japan	Hakodate Koseiin Hakodate Central General Hospital	Hokkaido, Hakodate
Japan	Iida Medical Clinic	Hokkaido, Hakodate
Japan	Japan Community Health Care Organization Hokkaido Hospital	Hokkaido, Sapporo
Japan	Kurihara Clinic	Hokkaido, Sapporo
Japan	Manda Memorial Hospital	Hokkaido, Sapporo
Japan	Sapporo Diabetes, Thyroid Clinic	Hokkaido, Sapporo
Japan	Uehara Clinic	Hokkaido, Sapporo
Japan	Ashiya Municipal Hospital	Hyogo, Ashiya
Japan	Itabashi DIA Med. and DERM Clinic, Ibaraki, I.M.	Ibaraki, Koga
Japan	Namegata District General Hospital	Ibaraki, Namegata
Japan	Hokuriku Hp., Ishikawa, I.M.	Ishikawa, Kanazawa
Japan	Hirano Medical Clinic	Iwate, Morioka
Japan	Oikawa Clinic	Iwate, Morioka
Japan	Iwamoto Clinic, Kagawa, DIAB I.M.	Kagawa, Zentsuji
Japan	Tenpozan Clinic of I.M., Kagoshima, I.M.	Kagoshima, Kagoshima
Japan	Hayashi DIA Clinic, Kanagawa, DIA Tract Med.·I.M.	Kanagawa, Chigasaki
Japan	Takai Naika Clinic	Kanagawa, Kamakura
Japan	Motomachi Takatsuka Naika Clinic, Kanagawa, I.M.	Kanagawa, Yokohama
Japan	Nagatsuta Family Clinic, Kanagawa, I.M.	Kanagawa, Yokohama
Japan	Yokohama Minoru Clinic	Kanagawa, Yokohama
Japan	Jinnouchi Clinic Diabetes Care Center	Kumamoto, Kumamoto
Japan	Kumamoto University Hospital	Kumamoto, Kumamoto
Japan	Morinagaueno clinic, Kumamoto, Digestive Tract I.M.	Kumamoto, Kumamoto
Japan	Kajiyama Clinic, Kyoto, I.M.	Kyoto, Kyoto
Japan	Matsumoto Nakagawa Hospital	Nagano, Matsumoto
Japan	Ota DIA I.M. Clinic, Nagano, I.M.	Nagano, Nagano
Japan	Saiseikai Niigata Daini Hp., Niigata, METAB ENDO	Niigata, Niigata
Japan	Tsuyama Chuo Hospital	Okayama, Tsuyama
Japan	Yaesu Clinic, Okinawa, I.M.	Okinawa, Naha
Japan	Tanaka Clinic, Okinawa, I.M.	Okinawa, Tomigusuku
Japan	AMC Nishi-umeda Clinic	Osaka
Japan	Shiraiwa Medical Clinic, Osaka, I.M.	Osaka
Japan	Ikeoka Clinic, Osaka, I.M.	Osaka, Osaka
Japan	Kinugawa CARDIOL Clinic, Osaka, I.M.	Osaka, Osaka
Japan	Nanko Clinic, Osaka, I.M.	Osaka, Osaka
Japan	Umeda Oak Clinic, Osaka, I.M.	Osaka, Osaka
Japan	OCROM Clinic	Osaka, Suita
Japan	Saga Memorial Hospital	Saga, Saga
Japan	Odayaka Life Naika Clinic, Saitama, I.M.	Saitama, Koshigaya
Japan	Medical corporation Chisei-kai Watanabe clinic	Saitama, Okegawa
Japan	Medical Corporation Toujinkai Sakado Central Hospital	Saitama, Sakado
Japan	SAINO Clinic,	Saitama, Tokorozawa
Japan	Hamamatsu Rosai Hospital	Shizuoka, Hamamatsu
Japan	Plumeria Clinic, Shizuoka, I.M.	Shizuoka, Shizuoka
Japan	Wakakusa Clinic, Tochigi, I.M.	Tochigi, Shimotsuke
Japan	Kanda Clinic, Tokyo, I.M.	Tokyo
Japan	AGE Makita Medical Clinic	Tokyo, Chuo-ku
Japan	Fukuwa Clinic	Tokyo, Chuo-ku
Japan	Hosono Clinic	Tokyo, Chuo-ku
Japan	Nihonbashi Enomoto Internal Medicine	Tokyo, Chuo-ku
Japan	Nihonbashi Sakura Clinic	Tokyo, Chuo-ku
Japan	Tokyo Center Clinic	Tokyo, Chuo-ku
Japan	Tokyo-Eki Center-building Clinic	Tokyo, Chuo-ku
Japan	Kasai Diabetes Clinic	Tokyo, Edogawa-ku
Japan	Medical Corporation Keikokai P1-Clinic	Tokyo, Hachioji
Japan	Minamino Heart Clinic	Tokyo, Hachioji
Japan	New Medical Research System Clinic	Tokyo, Hachioji
Japan	Shinkoiwa Ekimae Sougou Clinic	Tokyo, Katushika-ku
Japan	Musashino Polyclinic	Tokyo, Kiyose
Japan	Pedi Shiodome Clinic	Tokyo, Minato-ku
Japan	Shinagawa East one Medical Clinic	Tokyo, Minato-ku
Japan	Shimamura Kinen Hospital	Tokyo, Nerima-ku
Japan	Honda Hidehiko Clinic	Tokyo, Ota-ku
Japan	Kenkoukan Suzuki Clinic	Tokyo, Ota-ku
Japan	Miho Clinic	Tokyo, Shinagawa-ku
Japan	Sakayori Clinic	Tokyo, Shinagawa-ku
Japan	ToCROM Clinic	Tokyo, Shinjuku-ku
Japan	Ikebukuro Metropolitan Clinic	Tokyo, Toshima-ku
Japan	Fujikoshi Hp., Toyama, I.M.	Toyama, Toyama
Japan	Clinic Sugiyama, Yamagata, I.M.	Yamagata, Yamagata

Sponsors (2)

Lead Sponsor	Collaborator
Boehringer Ingelheim	Eli Lilly and Company

Country where clinical trial is conducted

Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Glycated Haemoglobin A1c (HbA1c) (%) From Baseline After 24 Weeks of Treatment	Change from baseline in HbA1c (%) after 24 weeks of treatment with double-blind trial medication. Change was calculated as: HbA1c value at 24-week - HbA1c value at baseline, for each patient. Baseline was defined as the last observation before the first intake of double-blind randomised trial medication. Statistical analysis presented is based on a restricted maximum likelihood (REML)-based mixed model repeated measures (MMRM) approach. Full Analysis Set (Observed Cases) [FAS (OC)]: This analysis set consisted of all patients who were randomised and treated with at least 1 dose of trial drug during the double-blind part of the trial and who had a baseline HbA1c assessment and at least 1 on-treatment HbA1c assessment during the 24-week double-blind part of the trial. Observed cases analysis included only the available data that were observed while patients were on treatment, i.e., excluding the missing data.	Baseline and 24 week

External Links

•   Synopsis Link