Clinical trial NCT02897349: Linagliptin Add-on to Insulin Background Therapy
Official title: 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
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: 2016-09-13
Enrollment: 206
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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


Eligibility criteria: 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.

Primary outcomes:
measure: Percentage Change From Baseline in Glycosylated Haemoglobin A1c (HbA1c) After 24 Weeks of Treatment
timeFrame: Baseline and week 24
Secondary outcomes:
measure: Change From Baseline in Fasting Plasma Glucose (FPG) After 24 Weeks of Treatment
timeFrame: Baseline and week 24
measure: Change From Baseline in 2-hour (2-h) Postprandial Plasma Glucose (PPG) After 24 Weeks of Treatment
timeFrame: Baseline and week 24
measure: Percentage of Participants With HbA1c on Treatment <7.0 Percentage (%) After 24 Weeks of Treatment
timeFrame: 24 weeks
measure: Percentage of Participants With HbA1c on Treatment < 6.5% After 24 Weeks of Treatment
timeFrame: 24 weeks
measure: Percentage of Participants With HbA1c Lowering by at Least 0.5% After 24 Weeks of Treatment
timeFrame: 24 weeks
measure: Percentage of Participants With Any Investigator-defined Hypoglycaemic Adverse Event (AE) With Plasma Glucose (PG) ≤70 mg/dL
timeFrame: 24 weeks
measure: Percentage of Participants With Any Severe Hypoglycaemic AE
timeFrame: 24 weeks
Other outcomes:
Locations:
city: Beijing
country: China
facility: China-Japan Friendship Hospital
city: Beijing
country: China
facility: Beijing Tongren Hospital
city: Beijing
country: China
facility: The General Hospital of Chinese People's Armed Police Forces
city: Changchun
country: China
facility: First Hospital of Jilin University
city: Fuzhou
country: China
facility: No.900 Hospital of PLA Joint Logistics Support Force
city: Guangzhou
country: China
facility: Third Affiliated Hospital of Guangzhou Medical University
city: Guiyang
country: China
facility: The Affiliated Hospital of Guizhou Medical University
city: Hangzhou
country: China
facility: The Affiliated Hospital of Hangzhou Normal University
city: Jinan
country: China
facility: General Hospital of Jinan Military Area
city: Nanjing
country: China
facility: Nanjing First Hospital
city: Qingdao
country: China
facility: The affiliated hospital of medicalcollege qingdao university
city: Shanghai
country: China
facility: Centre Hospital of Putuo District, Shanghai
city: Shanghai
country: China
facility: Shanghai Tenth People's Hospital
city: Shanghai
country: China
facility: Yangpu Hospital, Tongji University
city: Shantou
country: China
facility: Second Hospital Affiliated to Shantou Medical University
city: Shengyang
country: China
facility: Shengjing Hospital of China Medical University
city: Siping
country: China
facility: Siping Central People's Hospital
city: Suzhou
country: China
facility: The First Affiliated Hospital of Soochow University
city: Tianjin
country: China
facility: Nankai University Affiliated Hospital
city: Tianjin
country: China
facility: The 2nd Hospital of Tianjin Medical University
city: Tianjin
country: China
facility: Tianjin Medical University General Hospital
city: Wuhan
country: China
facility: Renmin Hospital of Wuhan University
city: Xiamen
country: China
facility: First Affiliated Hospital of Xiamen University
city: Yueyang
country: China
facility: the first people hospital of Yue Yang
city: Zhenjiang
country: China
facility: Affiliated Hospital of Jiangsu University
Study officials:
affiliation: Boehringer Ingelheim
name: Boehringer Ingelheim
role: STUDY_CHAIR
References: