Linagliptin in Combination With Metformin in Treatment Naive Patients With Type 2 Diabetes Mellitus and Insufficient Glycaemic Control
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| ClinicalTrials.gov Identifier: NCT01438814 |
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Recruitment Status :
Completed
First Posted : September 22, 2011
Results First Posted : June 3, 2014
Last Update Posted : November 25, 2014
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Sponsor:
Boehringer Ingelheim
Collaborator:
Eli Lilly and Company
Information provided by (Responsible Party):
Boehringer Ingelheim
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Brief Summary:
The aim of this study is to investigate the impact of the combination therapy of linagliptin and metformin at submaximal doses in reduction of Glycosylated haemoglobin (HbA1c) and metformin pre-specified gastro-intestinal (GI) side effects in treatment naive patients of with type 2 diabetes mellitus.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Diabetes Mellitus, Type 2 | Drug: metformin placebo Drug: linagliptin placebo Drug: metformin Drug: linagliptin | Phase 4 |
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 689 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | Double |
| 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 |
| Study Start Date : | November 2011 |
| Actual Primary Completion Date : | March 2013 |
| Actual Study Completion Date : | March 2013 |
Resource links provided by the National Library of Medicine
Genetics Home Reference related topics:
Type 2 diabetes
| Arm | Intervention/treatment |
|---|---|
|
Experimental: linagliptin + metformin
patients to receive linagliptin +metformin QD
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Drug: metformin
metformin tablets 500 mg Drug: linagliptin linagliptin tablets 5mg |
|
Active Comparator: metformin
patients to receive metformin BID
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Drug: metformin placebo
metformin placebo tablets 500mg Drug: linagliptin placebo linagliptin placebo tablets 5mg Drug: metformin metformin tablets 500mg |
Primary Outcome Measures :
- Change From Baseline in Glycosylated Hemoglobin A1c (HbA1c) After 14 Weeks Treatment [ Time Frame: Baseline and 14 weeks ]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 ]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 ]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 ]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 ]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 ]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 ]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 ]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 ]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 ]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 ]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 ]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 ]Means are adjusted by treatment and continuous baseline HbA1c
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| Ages Eligible for Study: | 18 Years to 80 Years (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion criteria:
- Diagnosis of Type 2 diabetes mellitus (T2DM) prior to informed consent;
- 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
- Glycosylated haemoglobin A1c (HbA1c) >/= 7.0% (53 mmol/mol) to </= 10.0% (86 mmol/mol) at visit 1 (screening);
- Age>/=18 and </=80 years at visit 1(screening);
- Body Mass Index (BMI)</= 45kg/m2 at visit 1 (screening);
- Signed and dated written informed consent by date of visit 1 in accordance with Good Clinical Practice (GCP) and local legislation
Exclusion criteria:
- 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);
- Treatment with any oral antidiabetic drug or insulin within 12 weeks prior to randomization
- Acute coronary syndrome (non-STEMI, STEMI and unstable angina pectoris),stroke or Transient ischemia attack (TIA) within 3 months prior to informed consent;
- 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,
- 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
- Bariatric surgery within the past two years and other gastrointestinal surgeries that induced chronic malabsorption
- Medical history of Cancer (except for basal cell carcinoma) and/or treatment for cancer within the last 5 years
- Blood dyscrasia or any other disorders causing haemolysis or unstable Red Blood Cell (eg. malaria, babesiosis, haemolytic anemia)
- Known history of pancreatitis and chronic pancreatitis
- Contraindications to metformin according to the local label
- 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
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Pre-menopausal women (last menstruation less than 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 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.
- 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
- Participation in another trial with application of any investigational drug within 30 days prior to informed consent
- Any other clinical condition that would jeopardize patients safety while participating in this trial
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01438814
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Locations
| Bangladesh | |
| 1218.60.90001 Boehringer Ingelheim Investigational Site | |
| Dhaka, Bangladesh | |
| 1218.60.90002 Boehringer Ingelheim Investigational Site | |
| Dhaka, Bangladesh | |
| 1218.60.90003 Boehringer Ingelheim Investigational Site | |
| Dhaka, Bangladesh | |
| Belgium | |
| 1218.60.32001 Boehringer Ingelheim Investigational Site | |
| Genk, Belgium | |
| 1218.60.32005 Boehringer Ingelheim Investigational Site | |
| Ham, Belgium | |
| 1218.60.32002 Boehringer Ingelheim Investigational Site | |
| Hasselt, Belgium | |
| 1218.60.32004 Boehringer Ingelheim Investigational Site | |
| Natoye, Belgium | |
| 1218.60.32003 Boehringer Ingelheim Investigational Site | |
| Tremelo, Belgium | |
| Canada, Alberta | |
| 1218.60.20009 Boehringer Ingelheim Investigational Site | |
| Calgary, Alberta, Canada | |
| Canada, British Columbia | |
| 1218.60.20003 Boehringer Ingelheim Investigational Site | |
| Burnaby, British Columbia, Canada | |
| 1218.60.20014 Boehringer Ingelheim Investigational Site | |
| Coquitlam, British Columbia, Canada | |
| 1218.60.20010 Boehringer Ingelheim Investigational Site | |
| Surrey, British Columbia, Canada | |
| Canada, Nova Scotia | |
| 1218.60.20004 Boehringer Ingelheim Investigational Site | |
| Halifax, Nova Scotia, Canada | |
| Canada, Ontario | |
| 1218.60.20012 Boehringer Ingelheim Investigational Site | |
| Corunna, Ontario, Canada | |
| 1218.60.20015 Boehringer Ingelheim Investigational Site | |
| Hamilton, Ontario, Canada | |
| 1218.60.20006 Boehringer Ingelheim Investigational Site | |
| London, Ontario, Canada | |
| 1218.60.20013 Boehringer Ingelheim Investigational Site | |
| London, Ontario, Canada | |
| 1218.60.20002 Boehringer Ingelheim Investigational Site | |
| Sarnia, Ontario, Canada | |
| 1218.60.20011 Boehringer Ingelheim Investigational Site | |
| Sarnia, Ontario, Canada | |
| 1218.60.20005 Boehringer Ingelheim Investigational Site | |
| Strathroy, Ontario, Canada | |
| 1218.60.20007 Boehringer Ingelheim Investigational Site | |
| Toronto, Ontario, Canada | |
| 1218.60.20016 Boehringer Ingelheim Investigational Site | |
| Toronto, Ontario, Canada | |
| Canada, Quebec | |
| 1218.60.20001 Boehringer Ingelheim Investigational Site | |
| St-Romuald, Quebec, Canada | |
| China | |
| 1218.60.86001 Boehringer Ingelheim Investigational Site | |
| Beijing, China | |
| 1218.60.86003 Boehringer Ingelheim Investigational Site | |
| Beijing, China | |
| 1218.60.86011 Boehringer Ingelheim Investigational Site | |
| Changsha, China | |
| 1218.60.86012 Boehringer Ingelheim Investigational Site | |
| Chengdu, China | |
| 1218.60.86010 Boehringer Ingelheim Investigational Site | |
| Chongqing, China | |
| 1218.60.86013 Boehringer Ingelheim Investigational Site | |
| Hubei, China | |
| 1218.60.86014 Boehringer Ingelheim Investigational Site | |
| Hubei, China | |
| 1218.60.86006 Boehringer Ingelheim Investigational Site | |
| Nanjing, China | |
| 1218.60.86007 Boehringer Ingelheim Investigational Site | |
| Nanjing, China | |
| 1218.60.86005 Boehringer Ingelheim Investigational Site | |
| Shanghai, China | |
| 1218.60.86009 Boehringer Ingelheim Investigational Site | |
| Shenyang, China | |
| 1218.60.86008 Boehringer Ingelheim Investigational Site | |
| Wuxi, China | |
| Germany | |
| 1218.60.49007 Boehringer Ingelheim Investigational Site | |
| Berlin, Germany | |
| 1218.60.49008 Boehringer Ingelheim Investigational Site | |
| Berlin, Germany | |
| 1218.60.49005 Boehringer Ingelheim Investigational Site | |
| Dresden, Germany | |
| 1218.60.49004 Boehringer Ingelheim Investigational Site | |
| Erfurt, Germany | |
| 1218.60.49006 Boehringer Ingelheim Investigational Site | |
| Frankfurt, Germany | |
| 1218.60.49003 Boehringer Ingelheim Investigational Site | |
| Hamburg, Germany | |
| 1218.60.49002 Boehringer Ingelheim Investigational Site | |
| Neuwied, Germany | |
| 1218.60.49001 Boehringer Ingelheim Investigational Site | |
| Unterschneidheim, Germany | |
| Guatemala | |
| 1218.60.50001 Boehringer Ingelheim Investigational Site | |
| Guatemala, Guatemala | |
| 1218.60.50002 Boehringer Ingelheim Investigational Site | |
| Guatemala, Guatemala | |
| 1218.60.50003 Boehringer Ingelheim Investigational Site | |
| Guatemala, Guatemala | |
| Hong Kong | |
| 1218.60.85001 Boehringer Ingelheim Investigational Site | |
| Hong Kong, Hong Kong | |
| 1218.60.85002 Boehringer Ingelheim Investigational Site | |
| Hong Kong, Hong Kong | |
| India | |
| 1218.60.91004 Boehringer Ingelheim Investigational Site | |
| Aurangabad, India | |
| 1218.60.91010 Boehringer Ingelheim Investigational Site | |
| Bangalore, India | |
| 1218.60.91005 Boehringer Ingelheim Investigational Site | |
| Coimbatore, India | |
| 1218.60.91008 Boehringer Ingelheim Investigational Site | |
| Kolkata, India | |
| 1218.60.91001 Boehringer Ingelheim Investigational Site | |
| Nagpur, India | |
| 1218.60.91007 Boehringer Ingelheim Investigational Site | |
| Nagpur, India | |
| 1218.60.91003 Boehringer Ingelheim Investigational Site | |
| Pune, India | |
| 1218.60.91006 Boehringer Ingelheim Investigational Site | |
| Pune, India | |
| Lebanon | |
| 1218.60.96001 Boehringer Ingelheim Investigational Site | |
| Beirut, Lebanon | |
| 1218.60.96002 Boehringer Ingelheim Investigational Site | |
| Beirut, Lebanon | |
| 1218.60.96004 Boehringer Ingelheim Investigational Site | |
| Byblos, Lebanon | |
| 1218.60.96003 Boehringer Ingelheim Investigational Site | |
| Hazmieh, Lebanon | |
| 1218.60.96005 Boehringer Ingelheim Investigational Site | |
| Saida, Lebanon | |
| Mexico | |
| 1218.60.52005 Boehringer Ingelheim Investigational Site | |
| Aguascalientes, Mexico | |
| 1218.60.52003 Boehringer Ingelheim Investigational Site | |
| Cuernavaca, Mexico | |
| 1218.60.52001 Boehringer Ingelheim Investigational Site | |
| Durango, Mexico | |
| 1218.60.52002 Boehringer Ingelheim Investigational Site | |
| Durango, Mexico | |
| 1218.60.52004 Boehringer Ingelheim Investigational Site | |
| Monterrey, Mexico | |
| Peru | |
| 1218.60.51001 Boehringer Ingelheim Investigational Site | |
| Lima, Peru | |
| 1218.60.51002 Boehringer Ingelheim Investigational Site | |
| Lima, Peru | |
| 1218.60.51004 Boehringer Ingelheim Investigational Site | |
| Piura, Peru | |
| Philippines | |
| 1218.60.63001 Boehringer Ingelheim Investigational Site | |
| Cebu City, Philippines, Philippines | |
| 1218.60.63004 Boehringer Ingelheim Investigational Site | |
| Iloilo City, Philippines, Philippines | |
| 1218.60.63003 Boehringer Ingelheim Investigational Site | |
| Manila, Philippines | |
| 1218.60.63002 Boehringer Ingelheim Investigational Site | |
| Marikina City, Philippines, Philippines | |
| 1218.60.63005 Boehringer Ingelheim Investigational Site | |
| Quezon City, Philippines | |
| Spain | |
| 1218.60.34001 Boehringer Ingelheim Investigational Site | |
| Barcelona, Spain | |
| 1218.60.34002 Boehringer Ingelheim Investigational Site | |
| Barcelona, Spain | |
| 1218.60.34003 Boehringer Ingelheim Investigational Site | |
| Barcelona, Spain | |
| 1218.60.34004 Boehringer Ingelheim Investigational Site | |
| Barcelona, Spain | |
| 1218.60.34006 Boehringer Ingelheim Investigational Site | |
| Borges del Camp- Tarragona, Spain | |
| 1218.60.34005 Boehringer Ingelheim Investigational Site | |
| Centelles, Spain | |
| 1218.60.34009 Boehringer Ingelheim Investigational Site | |
| Granada, Spain | |
| 1218.60.34008 Boehringer Ingelheim Investigational Site | |
| L'Hospitalet de Llobregat, Spain | |
| 1218.60.34007 Boehringer Ingelheim Investigational Site | |
| Mataró, Spain | |
| 1218.60.34010 Boehringer Ingelheim Investigational Site | |
| Valencia, Spain | |
| Taiwan | |
| 1218.60.88006 Boehringer Ingelheim Investigational Site | |
| Chiayi County, Taiwan | |
| 1218.60.88003 Boehringer Ingelheim Investigational Site | |
| Kaohsiung,, Taiwan | |
| 1218.60.88001 Boehringer Ingelheim Investigational Site | |
| Taichung, Taiwan | |
| 1218.60.88007 Boehringer Ingelheim Investigational Site | |
| Taichung, Taiwan | |
| 1218.60.88002 Boehringer Ingelheim Investigational Site | |
| Tainan,, Taiwan | |
| 1218.60.88004 Boehringer Ingelheim Investigational Site | |
| Taipei County, Taiwan | |
Sponsors and Collaborators
Boehringer Ingelheim
Eli Lilly and Company
Investigators
| Study Chair: | Boehringer Ingelheim | Boehringer Ingelheim |
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | Boehringer Ingelheim |
| ClinicalTrials.gov Identifier: | NCT01438814 History of Changes |
| Other Study ID Numbers: |
1218.60 2011-002276-16 ( EudraCT Number: EudraCT ) |
| First Posted: | September 22, 2011 Key Record Dates |
| Results First Posted: | June 3, 2014 |
| Last Update Posted: | November 25, 2014 |
| Last Verified: | November 2014 |
Additional relevant MeSH terms:
|
Diabetes Mellitus Diabetes Mellitus, Type 2 Glucose Metabolism Disorders Metabolic Diseases Endocrine System Diseases Metformin Linagliptin Hypoglycemic Agents |
Physiological Effects of Drugs Incretins Hormones Hormones, Hormone Substitutes, and Hormone Antagonists Dipeptidyl-Peptidase IV Inhibitors Protease Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action |