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

Overview[ - collapse ][ - ]

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.
ConditionDiabetes Mellitus, Type 2
InterventionDrug: metformin placebo
Drug: linagliptin placebo
Drug: metformin
Drug: placebo metformin
Drug: metformin
Drug: linagliptin
PhasePhase 4
SponsorBoehringer Ingelheim
Responsible PartyBoehringer Ingelheim
ClinicalTrials.gov IdentifierNCT01438814
First ReceivedSeptember 21, 2011
Last UpdatedJuly 24, 2013
Last verifiedJuly 2013

Tracking Information[ + expand ][ + ]

First Received DateSeptember 21, 2011
Last Updated DateJuly 24, 2013
Start DateNovember 2011
Estimated Primary Completion DateMarch 2013
Current Primary Outcome MeasuresThe change from baseline in Glycosylated Hemoglobin A1c (HbA1c) after 14 weeks treatment [Time Frame: 14 weeks] [Designated as safety issue: No]
Current Secondary Outcome Measures
  • 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]
  • 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]
  • 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]
  • 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]
  • change from baseline in HbA1c by visit over time [Time Frame: 14 weeks] [Designated as safety issue: No]
  • change from baseline in body weight by visit over time [Time Frame: 14 weeks] [Designated as safety issue: No]
  • Composite endpoint of occurence of treat to target efficacy response, that is an HbA1c under treatment of <7.0% after 14 weeks of treatment, and no occurence of moderate or severe gastrointestinal (GI) side effects during 14 weeks of treatment [Time Frame: 14 weeks] [Designated as safety issue: No]
  • Change from baseline in fasting plasma glucose (FPG) after 14 weeks of treatment [Time Frame: 14 weeks] [Designated as safety issue: No]
  • Metformin pre-specified GI symptom intensity score assessed by investigators during 14 weeks of treatment [Time Frame: 14 weeks] [Designated as safety issue: No]
  • Metformin pre-specified GI symptom intensity score assessed by patients during 14 weeks of treatment [Time Frame: 14 weeks] [Designated as safety issue: No]
  • 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 on occurence of moderate or severe metformin pre-specified GI side effects assessed by investigators [Time Frame: 14 weeks] [Designated as safety issue: No]
  • 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]

Descriptive Information[ + expand ][ + ]

Brief TitleLinagliptin in Combination With Metformin in Treatment Naive Patients With Type 2 Diabetes Mellitus and Insufficient Glycaemic Control
Official TitleA 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
Brief Summary
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.
Detailed DescriptionNot Provided
Study TypeInterventional
Study PhasePhase 4
Study DesignAllocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double-Blind, Primary Purpose: Treatment
ConditionDiabetes Mellitus, Type 2
InterventionDrug: metformin placebo
metformin placebo tablets 500mg
Drug: linagliptin placebo
linagliptin placebo tablets 5mg
Drug: metformin
metformin tablets 500mg
Drug: placebo metformin
placebo metformin 500 mg
Drug: metformin
metformin tablets 500 mg
Drug: linagliptin
linaglitpin tablets 5mg
Study Arm (s)
  • Experimental: linagliptin + metformin
    patients to receive lingliptin +metformin QD
  • Active Comparator: metformin
    patients to receive metformin BID

Recruitment Information[ + expand ][ + ]

Recruitment StatusCompleted
Estimated Enrollment689
Estimated Completion DateMarch 2013
Estimated Primary Completion DateMarch 2013
Eligibility 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 mmol/mol)at visit 1 (screening);

4. Age>/=18 and
5. Body Mass Index(BMI)
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. Myocardial infarction,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,

5. Impaired renal function, defined as eGFR< 60ml/min (severe renal impairment,
modification of diet in renal disease (MDRD) formula) as determined 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
transdermal patch, intra-uterine devices/systems (IUDs/IUSs), oral, implantable
or injectable contraceptives, sexual abstinence and vasectomised 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 drgu 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
GenderBoth
Ages18 Years
Accepts Healthy VolunteersNo
ContactsNot Provided
Location CountriesBangladesh, Belgium, Canada, China, Germany, Guatemala, Hong Kong, India, Lebanon, Mexico, Peru, Philippines, Spain, Taiwan

Administrative Information[ + expand ][ + ]

NCT Number NCT01438814
Other Study ID Numbers1218.60
Has Data Monitoring CommitteeNot Provided
Information Provided ByBoehringer Ingelheim
Study SponsorBoehringer Ingelheim
CollaboratorsEli Lilly and Company
Investigators Study Chair: Boehringer Ingelheim Boehringer Ingelheim
Verification DateJuly 2013

Locations[ + expand ][ + ]

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
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
1218.60.20009 Boehringer Ingelheim Investigational Site
Calgary, Alberta, Canada
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
1218.60.20004 Boehringer Ingelheim Investigational Site
Halifax, Nova Scotia, Canada
1218.60.20012 Boehringer Ingelheim Investigational Site
Corunna, Ontario, Canada
1218.60.20015 Boehringer Ingelheim Investigational Site
Hamilton, Ontario, Canada
1218.60.20013 Boehringer Ingelheim Investigational Site
London, Ontario, Canada
1218.60.20006 Boehringer Ingelheim Investigational Site
London, Ontario, Canada
1218.60.20011 Boehringer Ingelheim Investigational Site
Sarnia, Ontario, Canada
1218.60.20002 Boehringer Ingelheim Investigational Site
Sarnia, Ontario, Canada
1218.60.20005 Boehringer Ingelheim Investigational Site
Strathroy, Ontario, Canada
1218.60.20016 Boehringer Ingelheim Investigational Site
Toronto, Ontario, Canada
1218.60.20007 Boehringer Ingelheim Investigational Site
Toronto, Ontario, Canada
1218.60.20001 Boehringer Ingelheim Investigational Site
St-Romuald, Quebec, Canada
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
1218.60.86014 Boehringer Ingelheim Investigational Site
Hubei, China
1218.60.86013 Boehringer Ingelheim Investigational Site
Hubei, China
1218.60.86007 Boehringer Ingelheim Investigational Site
Nanjing, China
1218.60.86006 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
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
1218.60.50002 Boehringer Ingelheim Investigational Site
Guatemala, Guatemala
1218.60.50001 Boehringer Ingelheim Investigational Site
Guatemala, Guatemala
1218.60.50003 Boehringer Ingelheim Investigational Site
Guatemala, Guatemala
1218.60.85001 Boehringer Ingelheim Investigational Site
Hong Kong, Hong Kong
1218.60.85002 Boehringer Ingelheim Investigational Site
Hong Kong, Hong Kong
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
1218.60.91006 Boehringer Ingelheim Investigational Site
Pune, India
1218.60.91003 Boehringer Ingelheim Investigational Site
Pune, India
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
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
1218.60.51002 Boehringer Ingelheim Investigational Site
Lima, Peru
1218.60.51001 Boehringer Ingelheim Investigational Site
Lima, Peru
1218.60.51004 Boehringer Ingelheim Investigational Site
Piura, Peru
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
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
1218.60.88006 Boehringer Ingelheim Investigational Site
Chiayi County, Taiwan
1218.60.88003 Boehringer Ingelheim Investigational Site
Kaohsiung,, Taiwan
1218.60.88007 Boehringer Ingelheim Investigational Site
Taichung, Taiwan
1218.60.88001 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