Empagliflozin Add on to Linagliptin Study in Japanese Patient With Type 2 Diabetes Mellitus

NCT02453555 | Completed Phase 3 Results

• 1 other identifier: 1275.19
• Study Type: interventional
• Target: 275
• Locations: 1 country
• Sites: 40

Brief Summary

This trial will compare the use of fixed dose combination of empagliflozin and linagliptin to linagliptin alone in patient with type 2 diabetes mellitus

Conditions

Diabetes Mellitus, Type 2

Outcome Measures

Primary Outcomes (1)

• Change of Glycosylated Haemoglobin A1c (Glycosylated Haemoglobin A1c After 24 Weeks of Double-blind Treatment From Baseline)

  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

Secondary Outcomes (4)

• Change in HbA1c From Week 28 at Week 52 (Empagliflozin 25 mg/Linagliptin 5 mg Only)

  28 Week (pre up-titration) and 52 Week

• Change in HbA1c From Baseline at Week 52 (All Empagliflozin Versus All Placebo)

  Baseline and 52 week

• Change in HbA1c From Baseline at Week 52 (Empagliflozin 25 mg/Linagliptin 5 mg Versus Linagliptin 5 mg + Placebo 25 mg)

  Baseline and 52 week

• Change in HbA1c From Baseline at Week 52 (Empagliflozin 25 mg/Linagliptin 5 mg Versus All Placebo)

  Baseline and 52 week

Study Arms (6)

Linagliptin

ACTIVE COMPARATOR

patient to receive 5 mg linagliptin once daily

Drug: Linagliptin; Drug: Empagliflozin placebo + linagliptin placebo low dose; Drug: Empa + lina highdose placebo

Empagliflozin + linagliptin low dose

EXPERIMENTAL

patient to receive one tablet once daily

Drug: Empagliflozin + linagliptin low dose; Drug: Linagliptin placebo

Empagliflozin + linagliptin high dose

EXPERIMENTAL

patient to receive one tablet once daily

Drug: Linagliptin placebo; Drug: Empagliflozin + linagliptin high dose

Linagliptin placebo

PLACEBO COMPARATOR

Drug: Empagliflozin + linagliptin low dose; Drug: Linagliptin placebo; Drug: Empagliflozin + linagliptin high dose

Empagliflozin + linagliptin high dose placebo

PLACEBO COMPARATOR

Drug: Linagliptin; Drug: Empa + lina highdose placebo

Empagliflozin + linagliptin low dose placebo

PLACEBO COMPARATOR

Drug: Linagliptin; Drug: Empagliflozin placebo + linagliptin placebo low dose

Interventions

Linagliptin DRUG

Also known as: tablet

Empagliflozin + linagliptin high dose placebo; Empagliflozin + linagliptin low dose placebo; Linagliptin

Empagliflozin placebo + linagliptin placebo low dose DRUG

Matching placebo empagliflozin + linagliptin

Empagliflozin + linagliptin low dose placebo; Linagliptin

Empagliflozin + linagliptin low dose DRUG

tablet

Empagliflozin + linagliptin low dose; Linagliptin placebo

Linagliptin placebo DRUG

Matching placebo linagliptin

Empagliflozin + linagliptin high dose; Empagliflozin + linagliptin low dose; Linagliptin placebo

Empagliflozin + linagliptin high dose DRUG

tablet

Empagliflozin + linagliptin high dose; Linagliptin placebo

Empa + lina highdose placebo DRUG

Empagliflozin + linagliptin high dose placebo; Linagliptin

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 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:
• 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 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
• HbA1c =8.0% and =10.5% for patients who are drug-naïve, or
• HbA1c =7.5% and =10.5% for patients with one oral antidiabetic drug (except linagliptin), or
• 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

You may not qualify if:

• 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:
• are nursing or pregnant or
• 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

Sponsors & Collaborators

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

Study Sites (40)

Nagoya Kyoritsu Hospital

Aichi, Nagoya, 454-0933, Japan

Location

Kashiwa City Hospital

Chiba, Kashiwa, 277-0825, Japan

Location

Otabe internal medicine clinic

Fukuoka, Fukuoka, 811-1346, Japan

Location

Nakamura Cardiovascular Clinic

Fukuoka, Itoshima, 819-1104, Japan

Location

Tanaka I.M. Clinic, Fukuoka, I.M.

Fukuoka, Kurume, 830-0023, Japan

Location

Seino I.M. Clinic, Fukushima, I.M.

Fukushima, Koriyama, 963-8851, Japan

Location

Hiraoka Naika Clinic, Hiroshima, I.M.

Hiroshima, Hiroshima, 733-0011, Japan

Location

Matsuda Cardiovascular Clinic

Hokkaido, Sapporo, 003-0026, Japan

Location

Teine Keijinkai Clinic

Hokkaido, Sapporo, 006-0811, Japan

Location

Mita Internal Medicine Cardiology Clinic

Hokkaido, Sapporo, 006-0852, Japan

Location

Miyanosawa Clinic of Internal Medicine and Cardiology

Hokkaido, Sapporo, 063-0826, Japan

Location

Itabashi Diabetic medicine and Dermatology Clinic

Ibaraki, Koga, 306-0232, Japan

Location

Nakakinen Clinic

Ibaraki, Naka, 311-0113, Japan

Location

Kubota Clinic

Kanagawa, Kawasaki, 214-0014, Japan

Location

Kitasato University Hospital

Kanagawa, Sagamihara, 252-0375, Japan

Location

H.E.C Science Clinic

Kanagawa, Yokohama, 235-0045, Japan

Location

Yoshimasa Diabetes & Endocrine Clinic

Kyoto, Kyoto, 604-8151, Japan

Location

Rakuwakai Otowa Hospital

Kyoto, Kyoto, 607-8062, Japan

Location

Medical Corporation Hayashi Katagihara Clinic

Kyoto, Kyoto, 615-8125, Japan

Location

Miyamoto Naika Clinic, Nagano, I.M.

Nagano, Matsumoto, 390-0848, Japan

Location

Gibo Hepatology Clinic, Nagano, Digestive Tract I.M.

Nagano, Matsumoto, 399-0036, Japan

Location

Takekawa Clinic, Osaka, I.M.

Osaka, Higashi-Osaka, 577-0803, Japan

Location

Medical Corporation Koseikai Fukuda Naika Clinic

Osaka, Osaka, 532-0003, Japan

Location

Kinugawa Cardiovascular Internal Medicine clinic

Osaka, Osaka, 532-0026, Japan

Location

Sato Hospital

Osaka, Osaka, 536-0023, Japan

Location

Nakaoka Clinic

Osaka, Osaka, 555-0032, Japan

Location

OCROM Clinic

Osaka, Suita, 565-0853, Japan

Location

Miyauchi Medical Center

Osaka, Takatsuki, 569-1123, Japan

Location

Medical Corporation Shinseikai Mashiba Clinic

Saitama, Hanno, 357-0024, Japan

Location

Asano Clinic

Saitama, Kawagoe, 350-0851, Japan

Location

Medical Corporation Fusa Shimizu Clinic Fusa

Saitama, Saitama, 336-0963, Japan

Location

Ogino Clinic

Saitama, Tokorozawa, 359-1161, Japan

Location

Kanda Clinic

Tokyo, Chiyoda-ku, 101-0047, Japan

Location

Fukuwa Clinic

Tokyo, Chuo-ku, 103-0027, Japan

Location

Tokyo-Eki Center-building Clinic

Tokyo, Chuo-ku, 103-0027, Japan

Location

Myojin Tou Clinic

Tokyo, Hachioji, 192-0046, Japan

Location

Sawai Medical Clinic

Tokyo, Koto-ku, 136-0073, Japan

Location

Mishuku Hospital

Tokyo, Meguro-ku, 153-0051, Japan

Location

Toshiba General Hospital

Tokyo, Shinagawa-ku, 140-8522, Japan

Location

ToCROM Clinic

Tokyo, Shinjuku-ku, 160-0022, Japan

Location

Related Publications (1)

• Kawamori R, Haneda M, Suzaki K, Cheng G, Shiki K, Miyamoto Y, Solimando F, Lee C, Lee J, George J. Empagliflozin as add-on to linagliptin in a fixed-dose combination in Japanese patients with type 2 diabetes: Glycaemic efficacy and safety profile in a 52-week, randomized, placebo-controlled trial. Diabetes Obes Metab. 2018 Sep;20(9):2200-2209. doi: 10.1111/dom.13352. Epub 2018 Jun 1.

  PMID: 29766636 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

Linagliptin; Tablets; empagliflozin

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; Dosage Forms; Pharmaceutical Preparations

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 21, 2015
• First Posted: May 25, 2015
• Study Start: May 14, 2015
• Primary Completion: August 26, 2016
• Study Completion: March 27, 2017
• Last Updated: February 15, 2019
• Results First Posted: February 15, 2019

Record last verified: 2018-09

Locations

JP (40)