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

This study has been completed.
Sponsor:
Collaborator:
Eli Lilly and Company
Information provided by (Responsible Party):
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT01215097
First received: September 28, 2010
Last updated: December 5, 2013
Last verified: June 2013
  Purpose

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.


Condition Intervention Phase
Diabetes Mellitus, Type 2
Drug: Linagliptin
Drug: placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double-Blind
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Boehringer Ingelheim:

Primary Outcome Measures:
  • HbA1c Change From Baseline at Week 24 [ Time Frame: Baseline and at week 24 ] [ Designated as safety issue: No ]
    Means are treatment adjusted for baseline HbA1c and previous anti-diabetic medication.


Secondary Outcome Measures:
  • HbA1c Change From Baseline at Week 6 [ Time Frame: Baseline and at week 6 ] [ Designated as safety issue: No ]
    Means are treatment adjusted for baseline HbA1c and previous anti-diabetic medication.

  • HbA1c Change From Baseline at Week 12 [ Time Frame: Baseline and at week 12 ] [ Designated as safety issue: No ]
    Means are treatment adjusted for baseline HbA1c and previous anti-diabetic medication.

  • HbA1c Change From Baseline at Week 18 [ Time Frame: Baseline and at week 18 ] [ Designated as safety issue: No ]
    Means are treatment adjusted for baseline HbA1c and previous anti-diabetic medication.

  • HbA1c Change From Baseline at Week 24(Chinese Only) [ Time Frame: Baseline and at 24 weeks ] [ Designated as safety issue: No ]
    Means are treatment adjusted for baseline HbA1c and previous anti-diabetic medication.

  • FPG Change From Baseline at Week 24 [ Time Frame: Baseline and at week 24 ] [ Designated as safety issue: No ]
    Means are treatment adjusted for baseline FPG and previous anti-diabetic medication.

  • FPG Change From Baseline at Week 6 [ Time Frame: Baseline and at week 6 ] [ Designated as safety issue: No ]
    Means are treatment adjusted for baseline FPG and previous anti-diabetic medication.

  • FPG Change From Baseline at Week 12 [ Time Frame: Baseline and at week 12 ] [ Designated as safety issue: No ]
    Means are treatment adjusted for baseline FPG and previous anti-diabetic medication.

  • FPG Change From Baseline at Week 18 [ Time Frame: Baseline and at week 18 ] [ Designated as safety issue: No ]
    Means are treatment adjusted for baseline FPG and previous anti-diabetic medication.

  • Number of Patients With HbA1c < 7.0% [ Time Frame: baseline and at week 24 ] [ Designated as safety issue: No ]
    Number of patients with HbA1c < 7.0% at week 24

  • Number of Patients With HbA1c < 7.0% at Week 24 With Baseline HbA1c >= 7.0%. [ Time Frame: baseline and at week 24 ] [ Designated as safety issue: No ]
    Number of patients with HbA1c < 7.0% at week 24 with baseline HbA1c >= 7.0%.

  • Number of Patients With HbA1c < 6.5% [ Time Frame: baseline and at week 24 ] [ Designated as safety issue: No ]
    Number of patients with HbA1c < 6.5% at week 24

  • Number of Patients With HbA1c < 6.5% at Week 24 With Baseline HbA1c >= 6.5%. [ Time Frame: baseline and at week 24 ] [ Designated as safety issue: No ]
    Number of patients with HbA1c < 6.5% at week 24 with baseline HbA1c >= 6.5%.

  • Number With HbA1c at Least Lowering 0.5% [ Time Frame: baseline and at week 24 ] [ Designated as safety issue: No ]
    Number with HbA1c at least 0.5% lowering from baseline at week 24


Enrollment: 306
Study Start Date: October 2010
Study Completion Date: April 2012
Primary Completion Date: April 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Linagliptin
once a day
Drug: Linagliptin
once a day
Placebo Comparator: placebo
once a day
Drug: placebo
once a day

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01215097

Locations
China
1218.65.86007 Boehringer Ingelheim Investigational Site
Beijing, China
1218.65.86011 Boehringer Ingelheim Investigational Site
Chongqing, China
1218.65.86008 Boehringer Ingelheim Investigational Site
Dalian, China
1218.65.86010 Boehringer Ingelheim Investigational Site
Fuzhou, China
1218.65.86014 Boehringer Ingelheim Investigational Site
Hangzhou, China
1218.65.86005 Boehringer Ingelheim Investigational Site
Hefei, China
1218.65.86006 Boehringer Ingelheim Investigational Site
Hefei, China
1218.65.86012 Boehringer Ingelheim Investigational Site
Nanjing, China
1218.65.86002 Boehringer Ingelheim Investigational Site
Shanghai, China
1218.65.86001 Boehringer Ingelheim Investigational Site
Shanghai, China
1218.65.86003 Boehringer Ingelheim Investigational Site
Shanghai, China
1218.65.86004 Boehringer Ingelheim Investigational Site
Suzhou, China
1218.65.86015 Boehringer Ingelheim Investigational Site
Wenzhou, China
1218.65.86009 Boehringer Ingelheim Investigational Site
Wuhan, China
1218.65.86013 Boehringer Ingelheim Investigational Site
Yangzhou, China
Malaysia
1218.65.60002 Boehringer Ingelheim Investigational Site
Johor Bahru,, Malaysia
1218.65.60001 Boehringer Ingelheim Investigational Site
Kelantan, Malaysia
Philippines
1218.65.63001 Boehringer Ingelheim Investigational Site
Marikina, Philippines
1218.65.63002 Boehringer Ingelheim Investigational Site
San Juan, Philippines
Sponsors and Collaborators
Boehringer Ingelheim
Eli Lilly and Company
Investigators
Study Chair: Boehringer Ingelheim Boehringer Ingelheim
  More Information

Additional Information:
No publications provided

Responsible Party: Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT01215097     History of Changes
Other Study ID Numbers: 1218.65
Study First Received: September 28, 2010
Results First Received: April 16, 2013
Last Updated: December 5, 2013
Health Authority: China: Food and Drug Administration
Malaysia: Ministry of Health
Philippines: Bureau of Food and Drugs

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Linagliptin
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions
Incretins
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Dipeptidyl-Peptidase IV Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on October 01, 2014