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Diabetes Mellitus, Type 2Phase 3NCT02453555

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

A Phase 3 study testing Linagliptin, Empagliflozin + linagliptin low dose and Empagliflozin + linagliptin high dose in people with Diabetes Mellitus, Type 2, run by Boehringer Ingelheim at 40 sites in Japan.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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 Read more about this study

Who is it for?
Ages 20 years and older
Conditions the study is for
Diabetes Mellitus, Type 2
What is being tested?
Linagliptin, Empagliflozin + linagliptin low dose and Empagliflozin + linagliptin high dose
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
275 participants
Where
40 sitesJapan
Study dates
14 May 2015to 27 Mar 2017
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 20 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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:
  • 1 drug-naïve, defined as no antidiabetic drugs for at least 12 weeks prior to informed consent, or
  • 2 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
  • 1 HbA1c =8.0% and =10.5% for patients who are drug-naïve, or
Show all 12Show fewer
  • 2 HbA1c =7.5% and =10.5% for patients with one oral antidiabetic drug (except linagliptin), or
  • 3 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

Who cannot join

  • 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
Show all 19Show fewer
  • 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:
  • 1 are nursing or pregnant or
  • 2 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
  • Known or suspected allergy or hypersensitivity to trial products or related products (e.g., Dipeptidyl-peptidase-4 inhibitors or Sodium-glucose co-transporter-2 inhibitors)
  • Alcohol or drug abuse within the 12 weeks prior to informed consent that would interfere with trial participation or any ongoing condition leading to a decreased compliance to trial procedures or trial drug intake, by the judgment of the investigator
  • Intake of an investigational drug in another trial within 30 days prior to Visit 1 or participation in the follow-up period of another trial (participation in observational studies is permitted)
  • Any other clinical condition that, in the opinion of the investigator, would jeopardize patient's safety while participating in this clinical trial

Trial locations and contacts

40 sites in 1 country.

40 sites in 1 country

Japan40 sites

  • Nagoya Kyoritsu Hospital

    Aichi, Nagoya, 454-0933

  • Kashiwa City Hospital

    Chiba, Kashiwa, 277-0825

  • Otabe internal medicine clinic

    Fukuoka, Fukuoka, 811-1346

  • Nakamura Cardiovascular Clinic

    Fukuoka, Itoshima, 819-1104

  • Tanaka I.M. Clinic, Fukuoka, I.M.

    Fukuoka, Kurume, 830-0023

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

    Fukushima, Koriyama, 963-8851

  • Hiraoka Naika Clinic, Hiroshima, I.M.

    Hiroshima, Hiroshima, 733-0011

  • Matsuda Cardiovascular Clinic

    Hokkaido, Sapporo, 003-0026

  • Teine Keijinkai Clinic

    Hokkaido, Sapporo, 006-0811

  • Mita Internal Medicine Cardiology Clinic

    Hokkaido, Sapporo, 006-0852

  • Miyanosawa Clinic of Internal Medicine and Cardiology

    Hokkaido, Sapporo, 063-0826

  • Itabashi Diabetic medicine and Dermatology Clinic

    Ibaraki, Koga, 306-0232

  • Nakakinen Clinic

    Ibaraki, Naka, 311-0113

  • Kubota Clinic

    Kanagawa, Kawasaki, 214-0014

  • Kitasato University Hospital

    Kanagawa, Sagamihara, 252-0375

  • H.E.C Science Clinic

    Kanagawa, Yokohama, 235-0045

  • Yoshimasa Diabetes & Endocrine Clinic

    Kyoto, Kyoto, 604-8151

  • Rakuwakai Otowa Hospital

    Kyoto, Kyoto, 607-8062

  • Medical Corporation Hayashi Katagihara Clinic

    Kyoto, Kyoto, 615-8125

  • Miyamoto Naika Clinic, Nagano, I.M.

    Nagano, Matsumoto, 390-0848

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

    Nagano, Matsumoto, 399-0036

  • Takekawa Clinic, Osaka, I.M.

    Osaka, Higashi-Osaka, 577-0803

  • Medical Corporation Koseikai Fukuda Naika Clinic

    Osaka, Osaka, 532-0003

  • Kinugawa Cardiovascular Internal Medicine clinic

    Osaka, Osaka, 532-0026

  • Sato Hospital

    Osaka, Osaka, 536-0023

  • Nakaoka Clinic

    Osaka, Osaka, 555-0032

  • OCROM Clinic

    Osaka, Suita, 565-0853

  • Miyauchi Medical Center

    Osaka, Takatsuki, 569-1123

  • Medical Corporation Shinseikai Mashiba Clinic

    Saitama, Hanno, 357-0024

  • Asano Clinic

    Saitama, Kawagoe, 350-0851

  • Medical Corporation Fusa Shimizu Clinic Fusa

    Saitama, Saitama, 336-0963

  • Ogino Clinic

    Saitama, Tokorozawa, 359-1161

  • Kanda Clinic

    Tokyo, Chiyoda-ku, 101-0047

  • Fukuwa Clinic

    Tokyo, Chuo-ku, 103-0027

  • Tokyo-Eki Center-building Clinic

    Tokyo, Chuo-ku, 103-0027

  • Myojin Tou Clinic

    Tokyo, Hachioji, 192-0046

  • Sawai Medical Clinic

    Tokyo, Koto-ku, 136-0073

  • Mishuku Hospital

    Tokyo, Meguro-ku, 153-0051

  • Toshiba General Hospital

    Tokyo, Shinagawa-ku, 140-8522

  • ToCROM Clinic

    Tokyo, Shinjuku-ku, 160-0022

Other trials in Japan

About this study

Official title: A Phase III, Randomised, Double-blind, Parallel Group, 52 Week Study to Evaluate Efficacy and Safety of Once Daily Empagliflozin and Linagliptin Fixed Dose Combination Compared With Linagliptin Plus Placebo in Japanese Type 2 Diabetes Mellitus Patients With Insufficient Glycaemic Control After 16 Weeks Treatment With Once Daily Linagliptin 5 mg.

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

Being tested
Linagliptin, Empagliflozin placebo + linagliptin placebo low dose, Empagliflozin + linagliptin low dose, Linagliptin placebo, Empagliflozin + linagliptin high dose
Medical subject headings
Diabetes Mellitus, Type 2

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • LinagliptinDrug

    Also called tablet

  • Empagliflozin placebo + linagliptin placebo low doseDrug

    Matching placebo empagliflozin + linagliptin

  • Empagliflozin + linagliptin low doseDrug

    tablet

  • Linagliptin placeboDrug

    Matching placebo linagliptin

  • Empagliflozin + linagliptin high doseDrug

    tablet

  • Empa + lina highdose placeboDrug

Study groups in NCT02453555
Study groupRoleWhat they receive
LinagliptinActive comparatorpatient to receive 5 mg linagliptin once daily
Receives: Drug: Linagliptin; Drug: Empagliflozin placebo + linagliptin placebo low dose; Drug: Empa + lina highdose placebo
Empagliflozin + linagliptin low doseExperimentalpatient to receive one tablet once daily
Receives: Drug: Empagliflozin + linagliptin low dose; Drug: Linagliptin placebo
Empagliflozin + linagliptin high doseExperimentalpatient to receive one tablet once daily
Receives: Drug: Linagliptin placebo; Drug: Empagliflozin + linagliptin high dose
Linagliptin placeboPlacebo comparatorNot described
Receives: Drug: Empagliflozin + linagliptin low dose; Drug: Linagliptin placebo; Drug: Empagliflozin + linagliptin high dose
Empagliflozin + linagliptin high dose placeboPlacebo comparatorNot described
Receives: Drug: Linagliptin; Drug: Empa + lina highdose placebo
Empagliflozin + linagliptin low dose placeboPlacebo comparatorNot described
Receives: Drug: Linagliptin; Drug: Empagliflozin placebo + linagliptin placebo low dose

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: Baseline and 24 week

Secondary outcomes (4)

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

    Change from Week 28 in HbA1c at Week 52 was calculated as: HbA1c at Week 52 - HbA1c at Week 28. Week 28 (pre up-titration) is referred to the last observed measurement prior to the first administration of any double-blind randomized trial medication in the up-titration period. Adjusted mean (Least square mean) and its standard error (SE) is presented.

    This endpoint was based on 1 group of the Full analysis set with up-titration (FASUT-II) whose dose was up-titrated to Empagliflozin 25 mg/Linagliptin 5 mg fixed dose combination thus there is no comparison group. Hence, no comparison is made. A restricted maximum likelihood (REML)-based mixed model repeated measures (MMRM) approach was used with baseline HbA1c as linear covariate and baseline eGFR, prior use of antidiabetic drug, visit as fixed effect(s). The covariance used to fit the model was unstructured.

    Measured: 28 Week (pre up-titration) and 52 Week

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

    Change from baseline in HbA1c at Week 52 was calculated as: HbA1c at Week 52 - 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.

    Measured: Baseline and 52 week

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

    Change from baseline in HbA1c at Week 52 was calculated as: HbA1c at Week 52 - 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.

    Measured: Baseline and 52 week

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

    Change from baseline in HbA1c at Week 52 was calculated as: HbA1c at Week 52 - 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.

    Measured: Baseline and 52 week

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted25 May 2015 (estimated)
  2. Study start14 May 2015
  3. Primary completion26 Aug 2016
  4. Study completion27 Mar 2017

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
275 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02453555
Sponsor's protocol ID
1275.19
Status last verified
Sep 2018
First submitted
21 May 2015
Last updated
15 Feb 2019

Publications

  • 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.

    PubMed 29766636

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Linagliptin, Empagliflozin + linagliptin low dose and Empagliflozin + linagliptin high dose in people with Diabetes Mellitus, Type 2, run by Boehringer Ingelheim at 40 sites in Japan.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 12 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 15 Feb 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 40 sites in Japan. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 15 Feb 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change of Glycosylated Haemoglobin A1c (Glycosylated Haemoglobin A1c After 24 Weeks of Double-blind Treatment From Baseline) (time frame: Baseline and 24 week). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02453555, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Feb 2019.

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