Clinical trial NCT02489968: Linagliptin as Add on Therapy to Empagliflozin 10 mg or 25 mg With Japanese Patients With Type 2 Diabetes Mellitus
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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Diabetes Mellitus, Type 2
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
Collaborators: name: Eli Lilly and Company
First posted: 2015-07-03
Enrollment: 880
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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)

Primary outcomes:
measure: Change in Glycated Haemoglobin A1c (HbA1c) (%) From Baseline After 24 Weeks of Treatment
timeFrame: Baseline and 24 week
Secondary outcomes:
Other outcomes:
Locations:
city: Aichi, Kasugai
country: Japan
facility: Tokai Memorial Hospital
city: Aichi, Nagoya
country: Japan
facility: Japan Organization of Occupational Health and Safety Chubu Rosai Hospital
city: Chiba, Chiba
country: Japan
facility: Tokuyama Clinic
city: Ehime, Matsuyama
country: Japan
facility: Matsuyama Shimin Hospital
city: Ehime, Niihama
country: Japan
facility: Tanaka Int. Clinic, Ehime, DIA Med.,CV Med.
city: Ehime, Saijo
country: Japan
facility: Murakami Memorial Hp., Ehime, I.M.
city: Fukuoka, Fukuoka
country: Japan
facility: Kunisaki Makoto Clinic, Fukuoka, I.M./CV Med.
city: Fukuoka, Onga
country: Japan
facility: Fukuoka Shin Mizumaki Hospital
city: Fukuoka, Yukuhashi
country: Japan
facility: Shin Yukuhashi Hospital
city: Gifu, Gifu
country: Japan
facility: Hashimoto I.M., Gifu, I.M.
city: Gunma, Maebashi
country: Japan
facility: Kikuchi Naika Clinic, Gunma, I.M.
city: Hokkaido, Chitose
country: Japan
facility: Hasegawa Internal Medicine Clinic
city: Hokkaido, Ebetsu
country: Japan
facility: Ebetsu Internal Medicine Clinic
city: Hokkaido, Hakodate
country: Japan
facility: Hakodate Koseiin Hakodate Central General Hospital
city: Hokkaido, Hakodate
country: Japan
facility: Iida Medical Clinic
city: Hokkaido, Sapporo
country: Japan
facility: Kurihara Clinic
city: Hokkaido, Sapporo
country: Japan
facility: Uehara Clinic
city: Hokkaido, Sapporo
country: Japan
facility: Manda Memorial Hospital
city: Hokkaido, Sapporo
country: Japan
facility: Sapporo Diabetes, Thyroid Clinic
city: Hokkaido, Sapporo
country: Japan
facility: Japan Community Health Care Organization Hokkaido Hospital
city: Hyogo, Ashiya
country: Japan
facility: Ashiya Municipal Hospital
city: Ibaraki, Koga
country: Japan
facility: Itabashi DIA Med. and DERM Clinic, Ibaraki, I.M.
city: Ibaraki, Namegata
country: Japan
facility: Namegata District General Hospital
city: Ishikawa, Kanazawa
country: Japan
facility: Hokuriku Hp., Ishikawa, I.M.
city: Iwate, Morioka
country: Japan
facility: Oikawa Clinic
city: Iwate, Morioka
country: Japan
facility: Hirano Medical Clinic
city: Kagawa, Zentsuji
country: Japan
facility: Iwamoto Clinic, Kagawa, DIAB I.M.
city: Kagoshima, Kagoshima
country: Japan
facility: Tenpozan Clinic of I.M., Kagoshima, I.M.
city: Kanagawa, Chigasaki
country: Japan
facility: Hayashi DIA Clinic, Kanagawa, DIA Tract Med.·I.M.
city: Kanagawa, Kamakura
country: Japan
facility: Takai Naika Clinic
city: Kanagawa, Yokohama
country: Japan
facility: Nagatsuta Family Clinic, Kanagawa, I.M.
city: Kanagawa, Yokohama
country: Japan
facility: Motomachi Takatsuka Naika Clinic, Kanagawa, I.M.
city: Kanagawa, Yokohama
country: Japan
facility: Yokohama Minoru Clinic
city: Kumamoto, Kumamoto
country: Japan
facility: Morinagaueno clinic, Kumamoto, Digestive Tract I.M.
city: Kumamoto, Kumamoto
country: Japan
facility: Kumamoto University Hospital
city: Kumamoto, Kumamoto
country: Japan
facility: Jinnouchi Clinic Diabetes Care Center
city: Kyoto, Kyoto
country: Japan
facility: Kajiyama Clinic, Kyoto, I.M.
city: Nagano, Matsumoto
country: Japan
facility: Matsumoto Nakagawa Hospital
city: Nagano, Nagano
country: Japan
facility: Ota DIA I.M. Clinic, Nagano, I.M.
city: Niigata, Niigata
country: Japan
facility: Saiseikai Niigata Daini Hp., Niigata, METAB ENDO
city: Okayama, Tsuyama
country: Japan
facility: Tsuyama Chuo Hospital
city: Okinawa, Naha
country: Japan
facility: Yaesu Clinic, Okinawa, I.M.
city: Okinawa, Tomigusuku
country: Japan
facility: Tanaka Clinic, Okinawa, I.M.
city: Osaka, Osaka
country: Japan
facility: Umeda Oak Clinic, Osaka, I.M.
city: Osaka, Osaka
country: Japan
facility: Kinugawa CARDIOL Clinic, Osaka, I.M.
city: Osaka, Osaka
country: Japan
facility: Ikeoka Clinic, Osaka, I.M.
city: Osaka, Osaka
country: Japan
facility: Nanko Clinic, Osaka, I.M.
city: Osaka, Suita
country: Japan
facility: OCROM Clinic
city: Osaka
country: Japan
facility: AMC Nishi-umeda Clinic
city: Osaka
country: Japan
facility: Shiraiwa Medical Clinic, Osaka, I.M.
city: Saga, Saga
country: Japan
facility: Saga Memorial Hospital
city: Saitama, Koshigaya
country: Japan
facility: Odayaka Life Naika Clinic, Saitama, I.M.
city: Saitama, Okegawa
country: Japan
facility: Medical corporation Chisei-kai Watanabe clinic
city: Saitama, Sakado
country: Japan
facility: Medical Corporation Toujinkai Sakado Central Hospital
city: Saitama, Tokorozawa
country: Japan
facility: SAINO Clinic,
city: Shizuoka, Hamamatsu
country: Japan
facility: Hamamatsu Rosai Hospital
city: Shizuoka, Shizuoka
country: Japan
facility: Plumeria Clinic, Shizuoka, I.M.
city: Tochigi, Shimotsuke
country: Japan
facility: Wakakusa Clinic, Tochigi, I.M.
city: Tokyo, Chuo-ku
country: Japan
facility: Nihonbashi Sakura Clinic
city: Tokyo, Chuo-ku
country: Japan
facility: Fukuwa Clinic
city: Tokyo, Chuo-ku
country: Japan
facility: Nihonbashi Enomoto Internal Medicine
city: Tokyo, Chuo-ku
country: Japan
facility: Tokyo-Eki Center-building Clinic
city: Tokyo, Chuo-ku
country: Japan
facility: Tokyo Center Clinic
city: Tokyo, Chuo-ku
country: Japan
facility: Hosono Clinic
city: Tokyo, Chuo-ku
country: Japan
facility: AGE Makita Medical Clinic
city: Tokyo, Edogawa-ku
country: Japan
facility: Kasai Diabetes Clinic
city: Tokyo, Hachioji
country: Japan
facility: New Medical Research System Clinic
city: Tokyo, Hachioji
country: Japan
facility: Medical Corporation Keikokai P1-Clinic
city: Tokyo, Hachioji
country: Japan
facility: Minamino Heart Clinic
city: Tokyo, Katushika-ku
country: Japan
facility: Shinkoiwa Ekimae Sougou Clinic
city: Tokyo, Kiyose
country: Japan
facility: Musashino Polyclinic
city: Tokyo, Minato-ku
country: Japan
facility: Pedi Shiodome Clinic
city: Tokyo, Minato-ku
country: Japan
facility: Shinagawa East one Medical Clinic
city: Tokyo, Nerima-ku
country: Japan
facility: Shimamura Kinen Hospital
city: Tokyo, Ota-ku
country: Japan
facility: Kenkoukan Suzuki Clinic
city: Tokyo, Ota-ku
country: Japan
facility: Honda Hidehiko Clinic
city: Tokyo, Shinagawa-ku
country: Japan
facility: Sakayori Clinic
city: Tokyo, Shinagawa-ku
country: Japan
facility: Miho Clinic
city: Tokyo, Shinjuku-ku
country: Japan
facility: ToCROM Clinic
city: Tokyo, Toshima-ku
country: Japan
facility: Ikebukuro Metropolitan Clinic
city: Tokyo
country: Japan
facility: Kanda Clinic, Tokyo, I.M.
city: Toyama, Toyama
country: Japan
facility: Fujikoshi Hp., Toyama, I.M.
city: Yamagata, Yamagata
country: Japan
facility: Clinic Sugiyama, Yamagata, I.M.
Study officials:
affiliation: Boehringer Ingelheim
name: Boehringer Ingelheim
role: STUDY_CHAIR
References:
citation: 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.