Linagliptin in Combination With Metformin in Treatment Naive Patients With Type 2 Diabetes Mellitus and Insufficient Glycaemic Control

This study has been completed.
Sponsor:
Collaborator:
Eli Lilly and Company
Information provided by (Responsible Party):
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT01438814
First received: September 21, 2011
Last updated: May 2, 2014
Last verified: May 2014
  Purpose

This phase IV, randomized, double-blind, double-dummy, active-comparator controlled study is to compare the efficacy and safety of linagliptin (5mg) co-administered with metformin (QD, metformin daily dose 1000mg) at evening time with metformin BID (min daily dose 1000mg, max.daily dose 2000mg) over 14 weeks in treatment naive patients with type 2 diabetes mellitus and insufficient glycaemic control.


Condition Intervention Phase
Diabetes Mellitus, Type 2
Drug: metformin placebo
Drug: linagliptin placebo
Drug: metformin
Drug: linagliptin
Phase 4

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 Randomised, Double-blind, Double-dummy, Active-comparator Controlled Study Investigating the Efficacy and Safety of Linagliptin Co-administered With Metformin QD at Evening Time Versus Metformin BID Over 14 Weeks in Treatment Naive Patients With Type 2 Diabetes Mellitus and Insufficient Glycaemic Control

Resource links provided by NLM:


Further study details as provided by Boehringer Ingelheim:

Primary Outcome Measures:
  • Change From Baseline in Glycosylated Hemoglobin A1c (HbA1c) After 14 Weeks Treatment [ Time Frame: Baseline and 14 weeks ] [ Designated as safety issue: No ]
    Adjusted mean change in HbA1c from baseline at Week 14 was analysed using an ANCOVA model. The Model included treatment and continuous baseline HbA1c.


Secondary Outcome Measures:
  • Composite Endpoint of Occurrence of Treat to Target Efficacy Response, That is an HbA1c Under Treatment of <7.0% After 14 Weeks of Treatment, on no Occurrence of Moderate or Severe Gastrointestinal (GI) Side Effects During 14 Weeks of Treatment [ Time Frame: 14 weeks ] [ Designated as safety issue: No ]
    The proportion of patients who achieved all the targets in a composite endpoint (HbA1c below 7.0% after 14 weeks of treatment; no occurrence of pre-specified moderate or severe gastrointestinal (GI) side effects of metformin, as assessed by the investigators during 14 weeks of treatment)

  • Occurence of Metformin Pre-specified Moderate to Severe GI Side Effects Assessed by Investigators During 14 Weeks of Treatment [ Time Frame: 14 weeks ] [ Designated as safety issue: No ]
    Proportion of patients who experienced at least one metformin pre-specified moderate or severe GI side effect during 14 weeks

  • Change From Baseline in Fasting Plasma Glucose (FPG) After 14 Weeks of Treatment [ Time Frame: Baseline and 14 weeks ] [ Designated as safety issue: No ]
    Means are adjusted by treatment, continuous baseline HbA1c and continuous baseline fasting plasma glucose.

  • Metformin Pre-specified GI Symptom Intensity Score Assessed by Investigators During 14 Weeks of Treatment [ Time Frame: 14 weeks ] [ Designated as safety issue: No ]
    Patients could experience multiple events, therefore, multiple answers were possible for each patient.

  • Metformin Pre-specified GI Symptom Intensity Score Assessed by Patients During 14 Weeks of Treatment [ Time Frame: 14 weeks ] [ Designated as safety issue: No ]
    The intensity of the GI side effects was also assessed by the patients using VAS scaled from 0 to 10; higher scores indicate more severe events. Means are adjusted by treatment and continuous baseline HbA1c.

  • Composite Endpoint of Occurrence of Treat to Target Efficacy Response, That is an HbA1c Under Treatment of <6.5% After 14 Weeks of Treatment, and no Occurrence of Moderate or Severe Metformin Pre-specified GI Side Effects Assessed by Investigators [ Time Frame: 14 weeks ] [ Designated as safety issue: No ]
    The proportion of patients who achieved all the targets in a composite endpoint (HbA1c below 6.5% after 14 weeks of treatment; no occurrence of pre-specified moderate or severe GI side effects of metformin, as assessed by the investigators during 14 weeks of treatment).

  • Occurrence of Relative Efficacy Response (HbA1c Lowering by at Least 0.5% After 14 Weeks of Treatment) [ Time Frame: 14 weeks ] [ Designated as safety issue: No ]
    The proportion of patients who achieved a relative efficacy response (HbA1c lowering by at least 0.5% after 14 weeks of treatment).

  • Occurrence of Relative Efficacy Response (HbA1c Lowering by at Least 0.8% After 14 Weeks of Treatment) [ Time Frame: 14 weeks ] [ Designated as safety issue: No ]
    The proportion of patients who achieved a relative efficacy response (HbA1c lowering by at least 0.8% after 14 weeks of treatment).

  • Composite Endpoint of Occurence of Relative Efficacy Response (HbA1c Lowering by at Least 0.5% After 14 Weeks of Treatment) and no Occurence of Moderate and Severe Metformin Pre-specified GI Side Effects Assessed by the Investigators During 14 Weeks [ Time Frame: 14 weeks ] [ Designated as safety issue: No ]
    The proportion of patients who achieved all the targets in a composite endpoint (HbA1c lowered by at least 0.5% after 14 weeks of treatment; no occurrence of pre-specified moderate or severe GI side effects of metformin, as assessed by the investigators during 14 weeks of treatment).

  • Change From Baseline in Body Weight by Visit at Week 14 [ Time Frame: Baseline and 14 weeks ] [ Designated as safety issue: No ]
    Means are adjusted by treatment, continuous baseline HbA1c and continuous baseline weight

  • Composite Endpoint of Occurrence of Relative Efficacy Response (HbA1c Lowering by at Least 0.8% After 14 Weeks of Treatment) and no Occurrence of Moderate and Severe Metformin Pre-specified GI Side Effects Assessed by Investigators During 14 Weeks [ Time Frame: 14 weeks ] [ Designated as safety issue: No ]
    The proportion of patients who achieved all the targets in a composite endpoint (HbA1c lowered by at least 0.8% after 14 weeks of treatment; no occurrence of pre-specified moderate or severe GI side effects of metformin, as assessed by the investigators during 14 weeks of treatment).

  • Change From Baseline in HbA1c Over Time [ Time Frame: Baseline, 2 weeks and 8 weeks ] [ Designated as safety issue: No ]
    Means are adjusted by treatment and continuous baseline HbA1c


Enrollment: 689
Study Start Date: November 2011
Study Completion Date: March 2013
Primary Completion Date: March 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: linagliptin + metformin
patients to receive linagliptin +metformin QD
Drug: metformin
metformin tablets 500 mg
Drug: linagliptin
linagliptin tablets 5mg
Active Comparator: metformin
patients to receive metformin BID
Drug: metformin placebo
metformin placebo tablets 500mg
Drug: linagliptin placebo
linagliptin placebo tablets 5mg
Drug: metformin
metformin tablets 500mg

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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 naive, defined as absence of any oral antidiabetic therapy or insulin for 12 weeks prior to randomization
  3. Glycosylated haemoglobin A1c (HbA1c) >/= 7.0% (53 mmol/mol) to </= 10.0% (86 mmol/mol) at visit 1 (screening);
  4. Age>/=18 and </=80 years at visit 1(screening);
  5. Body Mass Index (BMI)</= 45kg/m2 at visit 1 (screening);
  6. Signed and dated written informed consent by date of visit 1 in accordance with Good Clinical Practice (GCP) and local legislation

Exclusion criteria:

  1. Uncontrolled hyperglycaemia with a glucose level >240 mg/dl (13.3mmol/L) after an overnight fast during screening/placebo run-in and confirmed by a second measurement (Not on the same day);
  2. Treatment with any oral antidiabetic drug or insulin within 12 weeks prior to randomization
  3. Acute coronary syndrome (non-STEMI, STEMI and unstable angina pectoris),stroke or Transient ischemia attack (TIA) within 3 months prior to informed consent;
  4. Indication of liver disease/Impaired hepatic function, defined by serum levels of either Aspartate aminotransferase (ALT or SGPT), alanine aminotransferase (AST or SGOT), or alkaline phosphatase above 3 x upper limit of normal (ULN) as determined at visit 1 and/or run-in phase,
  5. Impaired renal function, defined as eGFR< 60ml/min (moderate or severe renal impairment, modification of diet in renal disease (MDRD) formula) as determined during screening or at run-in phase
  6. Bariatric surgery within the past two years and other gastrointestinal surgeries that induced chronic malabsorption
  7. Medical history of Cancer (except for basal cell carcinoma) and/or treatment for cancer within the last 5 years
  8. Blood dyscrasia or any other disorders causing haemolysis or unstable Red Blood Cell (eg. malaria, babesiosis, haemolytic anemia)
  9. Known history of pancreatitis and chronic pancreatitis
  10. Contraindications to metformin according to the local label
  11. 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
  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 or any other uncontrolled endocrine disorder except T2DM
  13. Pre-menopausal women (last menstruation less than 1 year prior to informed consent) who:

    1. are nursing or pregnant or
    2. 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 or who do not agree to continue contraception for at least 30 days after the last dose of study drug. Acceptable methods of birth control include tubal ligation, transdermal patch, intra-uterine devices/systems(IUDs/IUSs), oral, implantable, or injectable contraceptives, complete sexual abstinence (if acceptable by local authorities), double barrier method and vasectomized partner.
  14. Alcohol or drug abuse within 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
  15. Participation in another trial with application of any investigational drug within 30 days prior to informed consent
  16. Any other clinical condition that would jeopardize patients safety while participating in this trial
  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: NCT01438814

  Show 90 Study Locations
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: NCT01438814     History of Changes
Other Study ID Numbers: 1218.60, 2011-002276-16
Study First Received: September 21, 2011
Results First Received: February 28, 2014
Last Updated: May 2, 2014
Health Authority: Bangladesh: Directorate of Drug Administration
Belgium: Federal Agency for Medicinal and Health Products
Canada: Health Canada
China: Food and Drug Administration
Germany: Federal Institute for Drugs and Medical Devices
Guatemala: Ministry of Public Health and Social Assistance
Hong Kong: Department of Health
India: Drugs Controller General of India
Lebanon: Ministry of Public Health
Mexico: Federal Commission for Protection Against Health Risks
Peru: General Directorate of Pharmaceuticals, Devices, and Drugs
Philippines: Bureau of Food and Drugs
Spain: Spanish Agency of Medicines
Taiwan : Food and Drug Administration

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Linagliptin
Metformin
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 August 20, 2014