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

NCT ID: NCT02489968

Last Updated: 2018-09-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 880 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-05-12
• Study Completion Date: 2017-06-16

Brief 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.

Conditions

Diabetes Mellitus, Type 2

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

empagliflozin 10 mg + linagliptin 5 mg

patient to receive a tablet containing low dose empagliflozin and linagliptin once daily

Group Type: EXPERIMENTAL

empagliflozin 10 mg + linagliptin 5 mg

Intervention Type: DRUG

empagliflozin low dose + linagliptin once daily

empagliflozin 10 mg

patient to receive a tablet containing low dose empagliflozin once daily

Group Type: EXPERIMENTAL

empagliflozin 10 mg

Intervention Type: DRUG

empagliflozin low dose once daily

Placebo

Intervention Type: DRUG

empagliflozin 25 mg + linagliptin 5 mg

patient to receive a tablet containing high dose empagliflozin and linagliptin once daily

Group Type: EXPERIMENTAL

empagliflozin 25 mg + linagliptin 5 mg

Intervention Type: DRUG

empagliflozin high dose + linagliptin once daily

empagliflozin 25 mg

patients to receive a tablet containing high dose empagliflozin once daily

Group Type: EXPERIMENTAL

empagliflozin 25 mg

Intervention Type: DRUG

empagliflozin high dose once daily

Placebo

Intervention Type: DRUG

Interventions

empagliflozin 10 mg + linagliptin 5 mg

empagliflozin low dose + linagliptin once daily

Intervention Type: DRUG

empagliflozin 10 mg

empagliflozin low dose once daily

Intervention Type: DRUG

empagliflozin 25 mg + linagliptin 5 mg

empagliflozin high dose + linagliptin once daily

Intervention Type: DRUG

empagliflozin 25 mg

empagliflozin high dose once daily

Intervention Type: DRUG

Placebo

Intervention Type: DRUG

Eligibility Criteria

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)

• Minimum Eligible Age: 20 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Eli Lilly and Company

INDUSTRY

Sponsor Role: collaborator

Boehringer Ingelheim

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Boehringer Ingelheim

Role: STUDY_CHAIR

Boehringer Ingelheim

Locations

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

Kurihara Clinic

Hokkaido, Sapporo, , Japan

Uehara Clinic

Hokkaido, Sapporo, , Japan

Manda Memorial Hospital

Hokkaido, Sapporo, , Japan

Sapporo Diabetes, Thyroid Clinic

Hokkaido, Sapporo, , Japan

Japan Community Health Care Organization Hokkaido Hospital

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

Oikawa Clinic

Iwate, Morioka, , Japan

Hirano Medical 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

Nagatsuta Family Clinic, Kanagawa, I.M.

Kanagawa, Yokohama, , Japan

Motomachi Takatsuka Naika Clinic, Kanagawa, I.M.

Kanagawa, Yokohama, , Japan

Yokohama Minoru Clinic

Kanagawa, Yokohama, , Japan

Morinagaueno clinic, Kumamoto, Digestive Tract I.M.

Kumamoto, Kumamoto, , Japan

Kumamoto University Hospital

Kumamoto, Kumamoto, , Japan

Jinnouchi Clinic Diabetes Care Center

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

Umeda Oak Clinic, Osaka, I.M.

Osaka, Osaka, , Japan

Kinugawa CARDIOL Clinic, Osaka, I.M.

Osaka, Osaka, , Japan

Ikeoka Clinic, Osaka, I.M.

Osaka, Osaka, , Japan

Nanko 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

Nihonbashi Sakura Clinic

Tokyo, Chuo-ku, , Japan

Fukuwa Clinic

Tokyo, Chuo-ku, , Japan

Nihonbashi Enomoto Internal Medicine

Tokyo, Chuo-ku, , Japan

Tokyo-Eki Center-building Clinic

Tokyo, Chuo-ku, , Japan

Tokyo Center Clinic

Tokyo, Chuo-ku, , Japan

Hosono Clinic

Tokyo, Chuo-ku, , Japan

AGE Makita Medical Clinic

Tokyo, Chuo-ku, , Japan

Kasai Diabetes Clinic

Tokyo, Edogawa-ku, , Japan

New Medical Research System Clinic

Tokyo, Hachioji, , Japan

Medical Corporation Keikokai P1-Clinic

Tokyo, Hachioji, , Japan

Minamino Heart 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

Kenkoukan Suzuki Clinic

Tokyo, Ota-ku, , Japan

Honda Hidehiko Clinic

Tokyo, Ota-ku, , Japan

Sakayori Clinic

Tokyo, Shinagawa-ku, , Japan

Miho 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, , Japan

Countries

Japan

References

Kaku K, Haneda M, Tanaka Y, Lee G, Shiki K, Miyamoto Y, Solimando F, Lee J, Lee C, George J. Linagliptin as add-on to empagliflozin in a fixed-dose combination in Japanese patients with type 2 diabetes: Glycaemic efficacy and safety profile in a two-part, randomized, placebo-controlled trial. Diabetes Obes Metab. 2019 Jan;21(1):136-145. doi: 10.1111/dom.13496. Epub 2018 Sep 6.

Reference Type: DERIVED

PMID: 30091172 (View on PubMed)

Other Identifiers

1275.13

Identifier Type: -

Identifier Source: org_study_id