Study to Compare the Efficacy and Safety of Administration of the Fix Dose Combination of Linagliptin Plus Metformin in Drug naïve Type 2 Patients

Boehringer Ingelheim

Status and phase: Completed; Phase 3

Conditions: Diabetes Mellitus, Type 2

Treatments: Drug: Metformin 1000mg; Drug: linagliptin 5mg; Drug: linagliptin2.5mg/metformin500mg; Drug: linagliptin2.5mg/metformin1000mg; Drug: Metformin 500mg

Study type: Interventional

Funder types: Industry

Identifiers

NCT01708902

1288.18

Details and patient eligibility

About

Reduced factorial design study with 24 week randomized treatment of initial combination therapy with linagliptin and metformin in T2DM patients

Enrollment: 876 patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Diagnosis of Type 2 diabetes mellitus(T2DM) prior to informed consent
2. Male and female patients on diet and exercise regimen who are drug-naïve
3. Glycosylated haemoglobin A1c (HbA1c) at V1a >/=7.5 %<11% for main group and HbA1c >/= 11.0 % for the additional parallel group
4. Age >/= 18 and </= 80 years at Visit 1a (Screening)
5. Body Mass Index(BMI)</ = 40 kg/m2 at Visit 1a (Screening)
6. Signed and dated written informed consent by date of Visit 1a in accordance with good clinical practice(GCP) and local legislation

Exclusion criteria

1. Uncontrolled hyperglycaemia required for rescue medication during placebo run-in phase
2. In main group, the patients with investigational medicinal product(IMP) compliance < 80 % or >120 % during 2 weeks placebo run in period
3. Acute coronary syndrome stroke or Transient ischaemic attack (TIA) within 3 months prior to randomisation
4. Impaired hepatic function, defined by serum levels of either Alanine aminotransferase(ALT) ,Aspartate aminotransferase(AST), or alkaline phosphatase (AP) above 3 x upper limit of normal (ULN) ,or total bilirubin above 1.5 x ULN as determined at Visit 1a
5. Known hypersensitivity or allergy to linagliptin or its excipients or metformin or placebo
6. Treatment with anti-obesity drugs 3 months prior to informed consent or any other treatment at the time of screening
7. 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.
8. Concurrent participation in another clinical trial or any investigational therapy within thirty days prior to signing the consent form or during the trial.
9. 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
10. Current treatment with systemic steroids at time of informed consent or change in dosage of thyroid hormones within 6 weeks prior to informed consent.
11. Renal failure or renal impairment at Visit 1a (screening) with an Estimated Glomerular Filtration Rate(eGFR) < 60 ml/min
12. Bariatric surgery within the past two years and other gastrointestinal surgeries that induce chronic malabsorption
13. Dehydration by clinical judgement of the investigator
14. Clinical detected unstable or acute congestive heart failure
15. Acute or chronic metabolic acidosis (present in patient history)
16. Hereditary galactose intolerance
17. Known history of pancreatitis and chronic pancreatitis
18. Medical history of cancer (except for basal cell carcinoma) and/or treatment for cancer within last 5 years.
19. Any other clinical condition that would jeopardize patients safety while participating in this clinical trial at the discretion of investigator

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Factorial Assignment

Masking: Double Blind

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876 participants in 5 patient groups

linagliptin2.5mg / metformin500mg BID

Experimental group

Description:

patient to receive a tablet containing linagliptin 2.5mg and metformin 500mg BID

Treatment:

Drug: linagliptin 5mg

Drug: linagliptin 5mg

Drug: Metformin 500mg

linagliptin2.5mg / metformin1000mg BID

Experimental group

Description:

patient to receive a tablet containing linagliptin 2.5mg and metformin 1000mg BID

Treatment:

Drug: linagliptin 5mg

Drug: Metformin 1000mg

Drug: linagliptin 5mg

metformin 500mg BID

Active Comparator group

Description:

patient to receive a tablet containing metformin 500mg BID

Treatment:

Drug: linagliptin2.5mg/metformin500mg

Drug: linagliptin2.5mg/metformin500mg

metformin 1000mg BID

Active Comparator group

Description:

patient to receive a tablet containing metformin 1000mg BID

Treatment:

Drug: linagliptin2.5mg/metformin1000mg

Drug: linagliptin2.5mg/metformin1000mg

linagliptin 5 mg QD

Active Comparator group

Description:

patient to receive a tablet containing linagliptin 5mg once daily

Treatment:

Drug: linagliptin2.5mg/metformin1000mg

Drug: linagliptin2.5mg/metformin500mg

Drug: linagliptin2.5mg/metformin500mg

Drug: linagliptin2.5mg/metformin1000mg