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

NCT02489968 | Completed Phase 3 Results

• 1 other identifier: 1275.13
• Study Type: interventional
• Target: 880
• Locations: 1 country
• Sites: 83

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

Outcome Measures

Primary Outcomes (1)

• 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

Study Arms (4)

empagliflozin 10 mg + linagliptin 5 mg

EXPERIMENTAL

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

Drug: empagliflozin 10 mg + linagliptin 5 mg

empagliflozin 10 mg

EXPERIMENTAL

patient to receive a tablet containing low dose empagliflozin once daily

Drug: empagliflozin 10 mg; Drug: Placebo

empagliflozin 25 mg + linagliptin 5 mg

EXPERIMENTAL

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

Drug: empagliflozin 25 mg + linagliptin 5 mg

empagliflozin 25 mg

EXPERIMENTAL

patients to receive a tablet containing high dose empagliflozin once daily

Drug: empagliflozin 25 mg; Drug: Placebo

Interventions

empagliflozin 10 mg + linagliptin 5 mg DRUG

empagliflozin low dose + linagliptin once daily

empagliflozin 10 mg + linagliptin 5 mg

empagliflozin 10 mg DRUG

empagliflozin low dose once daily

empagliflozin 10 mg

empagliflozin 25 mg + linagliptin 5 mg DRUG

empagliflozin high dose + linagliptin once daily

empagliflozin 25 mg + linagliptin 5 mg

empagliflozin 25 mg DRUG

empagliflozin high dose once daily

empagliflozin 25 mg

Placebo DRUG

empagliflozin 10 mg; empagliflozin 25 mg

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Boehringer Ingelheim: lead
• Eli Lilly and Company: collaborator

Study Sites (83)

Tokai Memorial Hospital

Aichi, Kasugai, 487-0031, Japan

Location

Japan Organization of Occupational Health and Safety Chubu Rosai Hospital

Aichi, Nagoya, 455-8530, Japan

Location

Tokuyama Clinic

Chiba, Chiba, 261-0004, Japan

Location

Matsuyama Shimin Hospital

Ehime, Matsuyama, 790-0067, Japan

Location

Tanaka Int. Clinic, Ehime, DIA Med.,CV Med.

Ehime, Niihama, 792-0045, Japan

Location

Murakami Memorial Hp., Ehime, I.M.

Ehime, Saijo, 793-0030, Japan

Location

Kunisaki Makoto Clinic, Fukuoka, I.M./CV Med.

Fukuoka, Fukuoka, 819-0168, Japan

Location

Fukuoka Shin Mizumaki Hospital

Fukuoka, Onga, 807-0051, Japan

Location

Shin Yukuhashi Hospital

Fukuoka, Yukuhashi, 824-0026, Japan

Location

Hashimoto I.M., Gifu, I.M.

Gifu, Gifu, 500-8225, Japan

Location

Kikuchi Naika Clinic, Gunma, I.M.

Gunma, Maebashi, 370-3573, Japan

Location

Hasegawa Internal Medicine Clinic

Hokkaido, Chitose, 066-0032, Japan

Location

Ebetsu Internal Medicine Clinic

Hokkaido, Ebetsu, 067-0041, Japan

Location

Hakodate Koseiin Hakodate Central General Hospital

Hokkaido, Hakodate, 040-8585, Japan

Location

Iida Medical Clinic

Hokkaido, Hakodate, 042-0942, Japan

Location

Kurihara Clinic

Hokkaido, Sapporo, 004-0053, Japan

Location

Uehara Clinic

Hokkaido, Sapporo, 006-0031, Japan

Location

Manda Memorial Hospital

Hokkaido, Sapporo, 060-0062, Japan

Location

Sapporo Diabetes, Thyroid Clinic

Hokkaido, Sapporo, 060-0807, Japan

Location

Japan Community Health Care Organization Hokkaido Hospital

Hokkaido, Sapporo, 062-8618, Japan

Location

Ashiya Municipal Hospital

Hyogo, Ashiya, 659-8502, Japan

Location

Itabashi DIA Med. and DERM Clinic, Ibaraki, I.M.

Ibaraki, Koga, 306-0232, Japan

Location

Namegata District General Hospital

Ibaraki, Namegata, 311-3516, Japan

Location

Hokuriku Hp., Ishikawa, I.M.

Ishikawa, Kanazawa, 921-8035, Japan

Location

Oikawa Clinic

Iwate, Morioka, 020-0066, Japan

Location

Hirano Medical Clinic

Iwate, Morioka, 020-0132, Japan

Location

Iwamoto Clinic, Kagawa, DIAB I.M.

Kagawa, Zentsuji, 765-0071, Japan

Location

Tenpozan Clinic of I.M., Kagoshima, I.M.

Kagoshima, Kagoshima, 890-0061, Japan

Location

Hayashi DIA Clinic, Kanagawa, DIA Tract Med.·I.M.

Kanagawa, Chigasaki, 253-0044, Japan

Location

Takai Naika Clinic

Kanagawa, Kamakura, 247-0056, Japan

Location

Nagatsuta Family Clinic, Kanagawa, I.M.

Kanagawa, Yokohama, 226-0027, Japan

Location

Motomachi Takatsuka Naika Clinic, Kanagawa, I.M.

Kanagawa, Yokohama, 231-0023, Japan

Location

Yokohama Minoru Clinic

Kanagawa, Yokohama, 232-0064, Japan

Location

Morinagaueno clinic, Kumamoto, Digestive Tract I.M.

Kumamoto, Kumamoto, 860-0863, Japan

Location

Kumamoto University Hospital

Kumamoto, Kumamoto, 860-8556, Japan

Location

Jinnouchi Clinic Diabetes Care Center

Kumamoto, Kumamoto, 862-0976, Japan

Location

Kajiyama Clinic, Kyoto, I.M.

Kyoto, Kyoto, 615-0035, Japan

Location

Matsumoto Nakagawa Hospital

Nagano, Matsumoto, 399-0006, Japan

Location

Ota DIA I.M. Clinic, Nagano, I.M.

Nagano, Nagano, 380-0802, Japan

Location

Saiseikai Niigata Daini Hp., Niigata, METAB ENDO

Niigata, Niigata, 950-1104, Japan

Location

Tsuyama Chuo Hospital

Okayama, Tsuyama, 708-0841, Japan

Location

Yaesu Clinic, Okinawa, I.M.

Okinawa, Naha, 900-0032, Japan

Location

Tanaka Clinic, Okinawa, I.M.

Okinawa, Tomigusuku, 901-0244, Japan

Location

AMC Nishi-umeda Clinic

Osaka, 530-0001, Japan

Location

Shiraiwa Medical Clinic, Osaka, I.M.

Osaka, 582-0005, Japan

Location

Umeda Oak Clinic, Osaka, I.M.

Osaka, Osaka, 530-0057, Japan

Location

Kinugawa CARDIOL Clinic, Osaka, I.M.

Osaka, Osaka, 532-0026, Japan

Location

Ikeoka Clinic, Osaka, I.M.

Osaka, Osaka, 536-0008, Japan

Location

Nanko Clinic, Osaka, I.M.

Osaka, Osaka, 559-0011, Japan

Location

OCROM Clinic

Osaka, Suita, 565-0853, Japan

Location

Saga Memorial Hospital

Saga, Saga, 849-0917, Japan

Location

Odayaka Life Naika Clinic, Saitama, I.M.

Saitama, Koshigaya, 343-0828, Japan

Location

Medical corporation Chisei-kai Watanabe clinic

Saitama, Okegawa, 363-0022, Japan

Location

Medical Corporation Toujinkai Sakado Central Hospital

Saitama, Sakado, 350-0233, Japan

Location

SAINO Clinic,

Saitama, Tokorozawa, 359-1141, Japan

Location

Hamamatsu Rosai Hospital

Shizuoka, Hamamatsu, 430-8525, Japan

Location

Plumeria Clinic, Shizuoka, I.M.

Shizuoka, Shizuoka, 422-8006, Japan

Location

Wakakusa Clinic, Tochigi, I.M.

Tochigi, Shimotsuke, 329-0433, Japan

Location

Kanda Clinic, Tokyo, I.M.

Tokyo, 101-0047, Japan

Location

Nihonbashi Sakura Clinic

Tokyo, Chuo-ku, 103-0025, Japan

Location

Fukuwa Clinic

Tokyo, Chuo-ku, 103-0027, Japan

Location

Nihonbashi Enomoto Internal Medicine

Tokyo, Chuo-ku, 103-0027, Japan

Location

Tokyo-Eki Center-building Clinic

Tokyo, Chuo-ku, 103-0027, Japan

Location

Tokyo Center Clinic

Tokyo, Chuo-ku, 103-0028, Japan

Location

Hosono Clinic

Tokyo, Chuo-ku, 104-0031, Japan

Location

AGE Makita Medical Clinic

Tokyo, Chuo-ku, 104-0061, Japan

Location

Kasai Diabetes Clinic

Tokyo, Edogawa-ku, 134-0084, Japan

Location

New Medical Research System Clinic

Tokyo, Hachioji, 192-0046, Japan

Location

Medical Corporation Keikokai P1-Clinic

Tokyo, Hachioji, 192-0071, Japan

Location

Minamino Heart Clinic

Tokyo, Hachioji, 192-0918, Japan

Location

Shinkoiwa Ekimae Sougou Clinic

Tokyo, Katushika-ku, 124-0024, Japan

Location

Musashino Polyclinic

Tokyo, Kiyose, 204-0021, Japan

Location

Pedi Shiodome Clinic

Tokyo, Minato-ku, 105-7390, Japan

Location

Shinagawa East one Medical Clinic

Tokyo, Minato-ku, 108-0075, Japan

Location

Shimamura Kinen Hospital

Tokyo, Nerima-ku, 177-0051, Japan

Location

Kenkoukan Suzuki Clinic

Tokyo, Ota-ku, 143-0015, Japan

Location

Honda Hidehiko Clinic

Tokyo, Ota-ku, 143-0023, Japan

Location

Sakayori Clinic

Tokyo, Shinagawa-ku, 140-0011, Japan

Location

Miho Clinic

Tokyo, Shinagawa-ku, 141-0032, Japan

Location

ToCROM Clinic

Tokyo, Shinjuku-ku, 160-0022, Japan

Location

Ikebukuro Metropolitan Clinic

Tokyo, Toshima-ku, 171-0021, Japan

Location

Fujikoshi Hp., Toyama, I.M.

Toyama, Toyama, 930-0964, Japan

Location

Clinic Sugiyama, Yamagata, I.M.

Yamagata, Yamagata, 990-0885, Japan

Location

Related Publications (1)

• 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.

  PMID: 30091172 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

empagliflozin; Linagliptin

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Quinazolines

Results Point of Contact

• Title: Boehringer Ingelheim Call Center
• Organization: Boehringer Ingelheim

clintriage.rdg@boehringer-ingelheim.com

1-800-243-0127

Study Officials

• Boehringer Ingelheim

  Boehringer Ingelheim

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 27, 2015
• First Posted: July 3, 2015
• Study Start: May 12, 2015
• Primary Completion: November 18, 2016
• Study Completion: June 16, 2017
• Last Updated: September 6, 2018
• Results First Posted: September 6, 2018

Record last verified: 2018-09

Locations

JP (83)