Clinical trial NCT01215097: Efficacy and Safety Study of Linagliptin (5 mg Administered Orally Once Daily) Over 24 Weeks in Type 2 Diabetic Patients With Insufficient Glycaemic Control Despite Metformin Therapy
Official title: A Randomized, Double-blind, Placebo-controlled Parallel Group Efficacy and Safety Study of BI 1356 Over 24 Weeks in T2D Patients With Insufficient Glycaemic Control Despite Metformin Therapy
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: 2010-10-06
Enrollment: 306
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: In this randomised, double-blind, parallel group trial, the safety and efficacy of 5 mg of Linagliptin administered orally once daily will be compared with a placebo after 24 weeks of treatment as add-on therapy to metformin in patients with type 2 diabetes and insufficient glycaemic control.


Eligibility criteria: Inclusion criteria:

1. Male and female patients with a diagnosis of type 2 diabetes mellitus and previously treated with metformin alone, or with metformin and not more than one other oral antidiabetic drug (antidiabetic therapy has to be unchanged for 6 weeks prior to informed consent and patients should receive standard diet and exercise counseling) A dose of \>/=1500 mg/day metformin is required for inclusion into the trial. The dosage needs to be stable for at least 8 weeks before randomisation. Patients with a total daily dose of less than 1500 mg metformin will only be included; if the investigator has documented them to be on their maximum tolerated dose (also in this case the 8 week time interval will apply for a stable dose).
2. Diagnosis of type 2 diabetes prior to informed consent
3. Glycosylated haemoglobin A1 (HbA1c) at Visit 1a (Screening):

   For patients undergoing wash out of previous medication: HbA1c =7.0 to =9.5% For patients not undergoing wash-out of previous medication: HbA1c =7.0 to =10.0%
4. Glycosylated haemoglobin A1 (HbA1c) =7.0 to =10.0% at Visit 2 (Start of Run-in)
5. Age = 18 and \< 80 years at Visit 1a (Screening)
6. BMI (Body Mass Index) = 45 kg/m2 at Visit 1a (Screening)
7. Signed and dated written informed consent by date of Visit 1a in accordance with GCP and local legislation

Exclusion criteria:

1. Myocardial infarction, stroke or TIA within 6 months prior to informed consent
2. Impaired hepatic function, defined by serum levels of either Alanine transaminase,Aspartate transaminase, or alkaline phosphatase above 3 x upper limit of normal (ULN) as determined at Visit 1a
3. Uncontrolled hyperglycaemia with a glucose level \>240 mg/dl (\>13.3 mmol/L) after an overnight fast during wash-out / placebo run-in and confirmed by a second measurement (not on the same day).
4. Known hypersensitivity or allergy to the investigational product or its excipients or metformin or placebo
5. Treatment with rosiglitazone or pioglitazone within 3 months prior to informed consent
6. Treatment with an injectable Glucagon-like peptide- 1 (GLP-1) analogue (e.g. exenatide) , Dipeptidyl-Peptidase 4 (DPP-IV) inhibitor within 3 months prior to informed consent
7. Treatment with insulin within 3 months prior to informed consent
8. Treatment with anti-obesity drugs (e.g. sibutramine, orlistat, rimonabant) within 3 months prior to informed consent.
9. Alcohol abuse within the 3 months prior to informed consent that would interfere with trial participation or drug abuse
10. Participation in another trial with an investigational drug within 2 months prior to informed consent
11. 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 study and do not agree to submit to periodic pregnancy testing during participation in the trial. Acceptable methods of birth control include transdermal patch, intra-uterine devices/systems (IUDs/IUSs), oral, implantable or injectable contraceptives, sexual abstinence and vasectomised partner. No exception will be made.
12. Current treatment with systemic steroids at time of informed consent or change in dosage of thyroid hormones within 6 weeks prior to informed consent.
13. Renal failure or renal impairment (serum creatinine =1.5 mg/dl as determined at Visit 1a)
14. Dehydration by clinical judgement of the investigator
15. Unstable or acute congestive heart failure
16. Acute or chronic metabolic acidosis (present in patient history)
17. Hereditary galactose intolerance

Primary outcomes:
measure: HbA1c Change From Baseline at Week 24
timeFrame: Baseline and at week 24
Secondary outcomes:
measure: HbA1c Change From Baseline at Week 6
timeFrame: Baseline and at week 6
measure: HbA1c Change From Baseline at Week 12
timeFrame: Baseline and at week 12
measure: HbA1c Change From Baseline at Week 18
timeFrame: Baseline and at week 18
measure: HbA1c Change From Baseline at Week 24(Chinese Only)
timeFrame: Baseline and at 24 weeks
measure: FPG Change From Baseline at Week 24
timeFrame: Baseline and at week 24
measure: FPG Change From Baseline at Week 6
timeFrame: Baseline and at week 6
measure: FPG Change From Baseline at Week 12
timeFrame: Baseline and at week 12
measure: FPG Change From Baseline at Week 18
timeFrame: Baseline and at week 18
measure: Number of Patients With HbA1c < 7.0%
timeFrame: baseline and at week 24
measure: Number of Patients With HbA1c < 7.0% at Week 24 With Baseline HbA1c >= 7.0%.
timeFrame: baseline and at week 24
measure: Number of Patients With HbA1c < 6.5%
timeFrame: baseline and at week 24
measure: Number of Patients With HbA1c < 6.5% at Week 24 With Baseline HbA1c >= 6.5%.
timeFrame: baseline and at week 24
measure: Number With HbA1c at Least Lowering 0.5%
timeFrame: baseline and at week 24
Other outcomes:
Locations:
city: Beijing
country: China
facility: 1218.65.86007 Boehringer Ingelheim Investigational Site
city: Chongqing
country: China
facility: 1218.65.86011 Boehringer Ingelheim Investigational Site
city: Dalian
country: China
facility: 1218.65.86008 Boehringer Ingelheim Investigational Site
city: Fuzhou
country: China
facility: 1218.65.86010 Boehringer Ingelheim Investigational Site
city: Hangzhou
country: China
facility: 1218.65.86014 Boehringer Ingelheim Investigational Site
city: Hefei
country: China
facility: 1218.65.86005 Boehringer Ingelheim Investigational Site
city: Hefei
country: China
facility: 1218.65.86006 Boehringer Ingelheim Investigational Site
city: Nanjing
country: China
facility: 1218.65.86012 Boehringer Ingelheim Investigational Site
city: Shanghai
country: China
facility: 1218.65.86001 Boehringer Ingelheim Investigational Site
city: Shanghai
country: China
facility: 1218.65.86002 Boehringer Ingelheim Investigational Site
city: Shanghai
country: China
facility: 1218.65.86003 Boehringer Ingelheim Investigational Site
city: Suzhou
country: China
facility: 1218.65.86004 Boehringer Ingelheim Investigational Site
city: Wenzhou
country: China
facility: 1218.65.86015 Boehringer Ingelheim Investigational Site
city: Wuhan
country: China
facility: 1218.65.86009 Boehringer Ingelheim Investigational Site
city: Yangzhou
country: China
facility: 1218.65.86013 Boehringer Ingelheim Investigational Site
city: Johor Bahru,
country: Malaysia
facility: 1218.65.60002 Boehringer Ingelheim Investigational Site
city: Kelantan
country: Malaysia
facility: 1218.65.60001 Boehringer Ingelheim Investigational Site
city: Marikina
country: Philippines
facility: 1218.65.63001 Boehringer Ingelheim Investigational Site
city: San Juan
country: Philippines
facility: 1218.65.63002 Boehringer Ingelheim Investigational Site
Study officials:
affiliation: Boehringer Ingelheim
name: Boehringer Ingelheim
role: STUDY_CHAIR
References: