Linagliptin Add-on to Insulin Background Therapy

March 24, 2020 updated by: Boehringer Ingelheim

A Phase III, Randomised, Double-blind, Placebo-controlled, Parallel Group, Efficacy and Safety Study of Linagliptin, Administered Orally Once Daily, in Combination With Insulin Therapy for 24 Weeks in Chinese Type 2 Diabetes Mellitus Patients With Insufficient Glycaemic Control

To evaluate the efficacy and safety of linagliptin compared to placebo when added on to insulin therapy alone or in combination with metformin in Chinese patients with type 2 diabetes mellitus with insufficient glycaemic control

Study Overview

Study Type

Interventional

Enrollment (Actual)

206

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

      • Beijing, China, 100029
        • China-Japan Friendship Hospital
      • Beijing, China, 100730
        • Beijing Tongren Hospital
      • Beijing, China, 100854
        • the General Hospital of Chinese People's Armed Police Forces
      • Changchun, China, 130021
        • First Hospital of Jilin University
      • Fuzhou, China, 350025
        • No.900 Hospital of PLA Joint Logistics Support Force
      • Guangzhou, China, 510150
        • Third Affiliated Hospital of Guangzhou Medical University
      • Guiyang, China, 550004
        • The Affiliated Hospital of Guizhou Medical University
      • Hangzhou, China, 310015
        • The Affiliated Hospital of Hangzhou Normal University
      • Jinan, China, 250000
        • General Hospital of Jinan Military Area
      • Nanjing, China, 210006
        • Nanjing First Hospital
      • Qingdao, China, 266005
        • The affiliated hospital of medicalcollege qingdao university
      • Shanghai, China, 200072
        • Shanghai Tenth People's Hospital
      • Shanghai, China, 200062
        • Centre Hospital of Putuo District, Shanghai
      • Shanghai, China, 200090
        • Yangpu Hospital, Tongji University
      • Shantou, China, 515041
        • Second Hospital Affiliated to Shantou Medical University
      • Shengyang, China, 110072
        • Shengjing Hospital of China Medical University
      • Siping, China, 136000
        • Siping Central People's Hospital
      • Suzhou, China, 215006
        • The First Affiliated Hospital of Soochow University
      • Tianjin, China, 300000
        • NanKai University Affiliated Hospital
      • Tianjin, China, 300000
        • The 2nd Hospital of Tianjin Medical University
      • Tianjin, China, 30052
        • Tianjin Medical University General Hospital
      • Wuhan, China, 430060
        • Renmin Hospital of Wuhan University
      • Xiamen, China, 361003
        • First Affiliated Hospital of Xiamen University
      • Yueyang, China, 414000
        • the first people hospital of Yue Yang
      • Zhenjiang, China, 212013
        • Affiliated Hospital of Jiangsu University

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion criteria:

  • Diagnosis of type 2 diabetes mellitus prior to informed consent.
  • Chinese male or female patients who are pre-treated with insulin alone or in combination with metformin:

    • With maximum insulin dose of <= 1 unit/kg/day. Acceptable basal insulins could be insulin glargin, insulin detemir or NPH (neutral protamin hagedorn) insulin with duration of action up to 24 h; acceptable pre-mixed insulins could be preparations with 25/75 or 30/70 ratio, with once or twice daily posology only. The total insulin dose should not be changed by more than 10% of the baseline value within the 12 weeks prior to randomisation (Visit 3). Both human insulin & insulin analogue are accepted.
    • If the patient is taking metformin, stable dose (at least 1500 mg daily) must be maintained for at least 12 weeks without dose adjustments prior to randomisation (Visit 3).
  • HbA1c fulfills the following criteria: >= 7.5 % to <= 10.0 % at Visit 1.
  • Age >= 18 years at Visit 1.
  • BMI <= 45 kg/m2 (Body Mass Index) at Visit 1.
  • Women of childbearing potential must be ready and able to use highly effective methods of birth control per ICH (International Conference on Harmonisation) M3 (R2) that result in a low failure rate of less than 1% per year when used consistently and correctly. A list of contraception methods meeting these criteria is provided in the patient information.

    • A woman is considered of childbearing potential (WOCBP), i.e. fertile, following menarche and until becoming post-menopausal unless permanently sterile.
    • Permanent sterilisation methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy.
  • Signed and dated written informed consent by date of Visit 1 in accordance with ICH-GCP (Good Clinical Practice) and local legislation

Exclusion criteria:

  • Uncontrolled hyperglycaemic with a glucose level >240 mg/dl (>13.3 mmol/L) after an overnight fast during placebo run-in and confirmed by a second measurement (not on the same day).
  • Any other antidiabetic drug within 3 months prior to informed consent except those defined as background treatment via inclusion criterion 2.
  • Acute coronary syndrome (non-STEMI (ST Segment Elevation Myocardial Infarction), STEMI and unstable angina pectoris), stroke or TIA (Transient ischemic attack) within 3 months prior to informed consent.
  • Indication of liver disease, defined by serum levels of either ALT (Alanine aminotransferase) (SGPT (serum glutamic pyruvate transaminase )), AST (Aspartate aminotransferase) (SGOT (serum glutamic-oxaloacetic transaminase)), or alkaline phosphatase above 3 × upper limit of normal (ULN (upper limit of normal)) as determined during screening and/or run-in phase.
  • Any contraindications to metformin according to the local label for those patients that enter the study with metformin therapy as provided in ISF (Investigator Site File).
  • Bariatric surgery within the past two years and other gastrointestinal surgeries that induce chronic malabsorption.
  • Medical history of cancer (except for basal cell carcinoma) and/or treatment for cancer within the last 5 years.
  • Blood dyscrasias or any disorders causing hemolysis or unstable Red Blood Cell (e.g. malaria, babesiosis, haemolytic anemia).
  • Known hypersensitivity or allergy to the investigational product or its recipients.
  • Treatment with anti-obesity drugs 3 months 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 at time of informed consent or change in dosage of thyroid hormones within 6 weeks prior to informed consent or any other uncontrolled endocrine disorder except T2DM (Type 2 diabetes mellitus).
  • Women who are pregnant, nursing, or who plan to become pregnant while in the trial.
  • Alcohol or drug abuse within the 3 months prior to informed consent that would interfere with trial participation or any ongoing condition leading to a decreased compliance to study procedures or study drug intake in the opinion of the investigator.
  • Participation in another trial with an investigational drug within 2 months prior to informed consent or previous enrolment in this trial.
  • Any other clinical condition that would jeopardize patient's safety while participating in this clinical trial in the opinion of the investigator.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: Placebo
insulin with or without metformin
Experimental: linagliptin
insulin with or without metformin

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percentage Change From Baseline in Glycosylated Haemoglobin A1c (HbA1c) After 24 Weeks of Treatment
Time Frame: Baseline and week 24
Percentage change from baseline, that is, [[(HbA1c after 24 weeks of treatment) - (HbA1c at baseline)] / (HbA1c at baseline)] *100%, where baseline refers to the last observation prior to the start of randomised study drug, including the observation prior to the placebo run-in.
Baseline and week 24

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change From Baseline in Fasting Plasma Glucose (FPG) After 24 Weeks of Treatment
Time Frame: Baseline and week 24
Change from baseline in Fasting plasma glucose (FPG) after 24 weeks of treatment.
Baseline and week 24
Change From Baseline in 2-hour (2-h) Postprandial Plasma Glucose (PPG) After 24 Weeks of Treatment
Time Frame: Baseline and week 24
Change from baseline in 2-hour (2-h) postprandial plasma glucose (PPG) after 24 weeks of treatment.
Baseline and week 24
Percentage of Participants With HbA1c on Treatment <7.0 Percentage (%) After 24 Weeks of Treatment
Time Frame: 24 weeks
Percentage of participants with HbA1c on treatment <7.0 percentage (%) after 24 weeks of treatment. Participants with baseline HbA1c <7.0% were excluded from the analysis.
24 weeks
Percentage of Participants With HbA1c on Treatment < 6.5% After 24 Weeks of Treatment
Time Frame: 24 weeks
Percentage of participants with HbA1c on treatment < 6.5% after 24 weeks of treatment. Participants with baseline HbA1c <6.5% were excluded from the analysis.
24 weeks
Percentage of Participants With HbA1c Lowering by at Least 0.5% After 24 Weeks of Treatment
Time Frame: 24 weeks
Percentage of participants with HbA1c lowering by at least 0.5% after 24 weeks of treatment.
24 weeks
Percentage of Participants With Any Investigator-defined Hypoglycaemic Adverse Event (AE) With Plasma Glucose (PG) ≤70 mg/dL
Time Frame: 24 weeks
Incidence of investigator-reported hypoglycaemic events confirmed by a measured blood glucose ≤70 mg/dL (≤3.9 Millimoles Per Litre (mmol/L)). Severe hypoglycaemic AE = hypoglycaemic event requiring the assistance of another person to actively administer carbohydrate, glucagon or other resuscitative actions.
24 weeks
Percentage of Participants With Any Severe Hypoglycaemic AE
Time Frame: 24 weeks
Incidence of severe hypoglycaemic events (requiring active assistance by another person, or fatal). Severe hypoglycaemic AE = hypoglycaemic event requiring the assistance of another person to actively administer carbohydrate, glucagon or other resuscitative actions.
24 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 30, 2016

Primary Completion (Actual)

January 11, 2019

Study Completion (Actual)

January 18, 2019

Study Registration Dates

First Submitted

August 30, 2016

First Submitted That Met QC Criteria

September 7, 2016

First Posted (Estimate)

September 13, 2016

Study Record Updates

Last Update Posted (Actual)

March 25, 2020

Last Update Submitted That Met QC Criteria

March 24, 2020

Last Verified

March 1, 2020

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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