Efficacy and Safety of 3 Doses of BI1356 (Linagliptin) in Type 2 Diabetes Patients

Overview[ - collapse ][ - ]

Purpose The objective of the current study is to investigate the efficacy, safety and tolerability of several doses of BI 1356 BS (0.5, 2.5 and 5 mg daily) compared to placebo over 12 weeks of treatment in patients with Type 2 diabetes and insufficient glycemic control. In addition, there will be an open-label treatment arm with metformin for sensitivity measurement with this patient population. Population pharmacokinetics of BI 1356 BS will also be assessed in this study.
ConditionDiabetes Mellitus, Type 2
InterventionDrug: Placebo
Drug: BI 1356 dose 3 once daily
Drug: BI 1356 dose 2 once daily
Drug: BI 1356 dose 1 once daily
Drug: Metformin
PhasePhase 2
SponsorBoehringer Ingelheim
Responsible PartyBoehringer Ingelheim
ClinicalTrials.gov IdentifierNCT00328172
First ReceivedMay 18, 2006
Last UpdatedFebruary 15, 2014
Last verifiedFebruary 2014

Tracking Information[ + expand ][ + ]

First Received DateMay 18, 2006
Last Updated DateFebruary 15, 2014
Start DateMay 2006
Estimated Primary Completion DateNot Provided
Current Primary Outcome MeasuresChange From Baseline in HbA1c (Glycosylated Haemoglobin) at Week 12 [Time Frame: Baseline, week 12] [Designated as safety issue: No]The change from baseline reflects the Week 12 HbA1c minus the Week 0 HbA1c. Means are adjusted for baseline HbA1c.
Current Secondary Outcome Measures
  • Change From Baseline in Fasting Plasma Glucose (FPG) at Week 12 [Time Frame: Baseline, week 12] [Designated as safety issue: No]Change from baseline reflects the Week 12 FPG minus the Week 0 FPG. Means are adjusted for baseline FPG.
  • Percentage of Patients With Absolute Efficacy Response (HbA1c <= 7.0%) at 12 Weeks [Time Frame: Baseline, week 12] [Designated as safety issue: No]An absolute efficacy response is defined as HbA1c <= 7.0% at 12 weeks. A non-response is defined as HbA1c > 7.0% at 12 weeks.

Descriptive Information[ + expand ][ + ]

Brief TitleEfficacy and Safety of 3 Doses of BI1356 (Linagliptin) in Type 2 Diabetes Patients
Official TitleA Randomized, Double-blind, Placebo-controlled, Five Parallel Group Study Investigating the Efficacy and Safety of BI 1356 BS (0.5 mg, 2.5 mg and 5.0 mg Administered Orally Once Daily) Over 12 Weeks in Drug Naive and Treated Patients With Type 2 Diabetes With Insufficient Glycemic Control (Study Includes an Open-label Metformin Treatment Arm)
Brief Summary
The objective of the current study is to investigate the efficacy, safety and tolerability
of several doses of BI 1356 BS (0.5, 2.5 and 5 mg daily) compared to placebo over 12 weeks
of treatment in patients with Type 2 diabetes and insufficient glycemic control. In
addition, there will be an open-label treatment arm with metformin for sensitivity
measurement with this patient population. Population pharmacokinetics of BI 1356 BS will
also be assessed in this study.
Detailed DescriptionNot Provided
Study TypeInterventional
Study PhasePhase 2
Study DesignAllocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double-Blind, Primary Purpose: Treatment
ConditionDiabetes Mellitus, Type 2
InterventionDrug: Placebo
Placebo matching BI 1356
Drug: BI 1356 dose 3 once daily
BI 1356 dose 3 once daily
Drug: BI 1356 dose 2 once daily
BI 1356 dose 2 once daily
Drug: BI 1356 dose 1 once daily
BI 1356 dose 1 once daily
Drug: Metformin
Metformin
Study Arm (s)
  • Placebo Comparator: Placebo
    Placebo tablets matching BI 1356
  • Experimental: BI 1356 0.5 mg
    BI 1356 dose 1 once daily
  • Experimental: BI 1356 2.5 mg
    BI 1356 dose 2 once daily
  • Experimental: BI 1356 5.0 mg
    BI 1356 dose 3 once daily
  • Active Comparator: Metformin
    Metformin

Recruitment Information[ + expand ][ + ]

Recruitment StatusCompleted
Estimated Enrollment302
Estimated Completion DateNot Provided
Estimated Primary Completion DateAugust 2007
Eligibility Criteria
Inclusion criteria:

1. Male and female patients with a diagnosis of Type 2 diabetes treated only with diet
and exercise (drug naïve) or with one or two oral hypoglycemic agents (as single
treatment or in combination) other than rosiglitazone or pioglitazone -treatment.
Antidiabetic therapy has to be stable for at least 10 weeks prior to screening.

2. Diagnosis of Type 2 diabetes with duration of at least 3 months

3. Glycosylated haemoglobin A1 (HbA1c) of:

7.5-10.0% at screening for drug naïve patients (no wash-out needed) 7.0-9.0% at
screening for patients treated with only one oral antidiabetic agent (wash-out
required) 6.5-8.0% at screening for patients treated with two oral antidiabetic
agents (wash-out required)

4. HbA1c of 7.5%-10.0% at Visit 3 (beginning of the 2-week placebo run-in period).

5. Age >=21 and <=75 years.

6. BMI (Body Mass Index) >=25.0 and <=40 kg/m2.

7. Signed and dated written informed consent prior to admission to the study in
accordance with Good Clinical Practice (GCP) and local legislation

Exclusion criteria:

1. Clinically relevant cardiovascular disease (e.g., myocardial infarction, stroke or
transient ischemic attack within six months before enrollment)

2. Impaired hepatic function defined by serum levels of either alanine aminotransferase,
aspartate aminotransferase or alkaline phosphatase above 3-fold upper limit of normal

3. Renal insufficiency or impaired renal function defined by serum creatinine above
upper limit of normal at screening

4. Diseases of the central nervous system (such as epilepsy) or psychiatric disorders or
clinically relevant neurologic disorders (including cerebrovascular but with the
exception of polyneuropathy) that would interfere with participation in the trial

5. Chronic or clinically relevant acute infections (e.g., Human immunodeficiency virus,
Hepatitis)

6. History of relevant allergy/hypersensitivity that would interfere with trial
participation (including allergy to investigational product or its excipients)

7. Treatment with rosiglitazone or pioglitazone within 6 months prior to screening

8. Treatment with insulin within 3 months prior to screening

9. Alcohol or drug abuse within the last 3 months that would interfere with trial
participation)

10. Participation in another trial with an investigational drug within two months prior
to administration or during the trial

11. Fasting plasma glucose >240 mg/dl (= 13.3 mmol/L) at Visit 2, 3 or 4 any visit and
confirmed by a second measurement (not on the same day)

12. Pre-menopausal women (last menstruation <=1 year prior to signing informed consent)
who:

1. are not surgically sterile,

2. or are nursing or pregnant;

3. 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, oral, implantable or injectable
contraceptives and vasectomised partner. No exception will be made.

13. Intolerance of metformin
GenderBoth
Ages21 Years
Accepts Healthy VolunteersNo
ContactsNot Provided
Location CountriesUnited States, Australia, Canada, Czech Republic, Russian Federation, Ukraine

Administrative Information[ + expand ][ + ]

NCT Number NCT00328172
Other Study ID Numbers1218.5
Has Data Monitoring CommitteeNot Provided
Information Provided ByBoehringer Ingelheim
Study SponsorBoehringer Ingelheim
CollaboratorsNot Provided
Investigators Study Chair: Boehringer Ingelheim Boehringer Ingelheim
Verification DateFebruary 2014

Locations[ + expand ][ + ]

1218.5.10020 Boehringer Ingelheim Investigational Site
Chula Vista, California, United States
1218.5.10001 Boehringer Ingelheim Investigational Site
La Jolla, California, United States
1218.5.10007 Boehringer Ingelheim Investigational Site
Walnut Creek, California, United States
1218.5.10041 Boehringer Ingelheim Investigational Site
Denver, Colorado, United States
1218.5.10018 Boehringer Ingelheim Investigational Site
Hollywood, Florida, United States
1218.5.10016 Boehringer Ingelheim Investigational Site
Jacksonville, Florida, United States
1218.5.10011 Boehringer Ingelheim Investigational Site
Miami, Florida, United States
1218.5.10003 Boehringer Ingelheim Investigational Site
Miami, Florida, United States
1218.5.10012 Boehringer Ingelheim Investigational Site
Orlando, Florida, United States
1218.5.10017 Boehringer Ingelheim Investigational Site
Indianapolis, Indiana, United States
1218.5.10008 Boehringer Ingelheim Investigational Site
Topeka, Kansas, United States
1218.5.10024 Boehringer Ingelheim Investigational Site
Wichita, Kansas, United States
1218.5.10039 Boehringer Ingelheim Investigational Site
Baltimore, Maryland, United States
1218.5.10032 Boehringer Ingelheim Investigational Site
Springfield, Massachusetts, United States
1218.5.10025 Boehringer Ingelheim Investigational Site
Chesterfield, Missouri, United States
1218.5.10034 Boehringer Ingelheim Investigational Site
Butte, Montana, United States
1218.5.10009 Boehringer Ingelheim Investigational Site
Omaha, Nebraska, United States
1218.5.10042 Boehringer Ingelheim Investigational Site
Albany, New York, United States
1218.5.10029 Boehringer Ingelheim Investigational Site
Endwell, New York, United States
1218.5.10004 Boehringer Ingelheim Investigational Site
New Hyde Park, New York, United States
1218.5.10026 Boehringer Ingelheim Investigational Site
Columbus, Ohio, United States
1218.5.10035 Boehringer Ingelheim Investigational Site
Mentor, Ohio, United States
1218.5.10023 Boehringer Ingelheim Investigational Site
Medford, Oregon, United States
1218.5.10030 Boehringer Ingelheim Investigational Site
Philadelphia, Pennsylvania, United States
1218.5.10044 Boehringer Ingelheim Investigational Site
Columbia, South Carolina, United States
1218.5.10033 Boehringer Ingelheim Investigational Site
Greer, South Carolina, United States
1218.5.10038 Boehringer Ingelheim Investigational Site
Simpsonville, South Carolina, United States
1218.5.10006 Boehringer Ingelheim Investigational Site
Dallas, Texas, United States
1218.5.10040 Boehringer Ingelheim Investigational Site
Houston, Texas, United States
1218.5.10036 Boehringer Ingelheim Investigational Site
San Antonio, Texas, United States
1218.5.10021 Boehringer Ingelheim Investigational Site
Tyler, Texas, United States
1218.5.10027 Boehringer Ingelheim Investigational Site
Salem, Virginia, United States
1218.5.10022 Boehringer Ingelheim Investigational Site
Federal Way, Washington, United States
1218.5.10014 Boehringer Ingelheim Investigational Site
Renton, Washington, United States
1218.5.61001 Boehringer Ingelheim Investigational Site
Miranda, New South Wales, Australia
1218.5.61005 Boehringer Ingelheim Investigational Site
Box Hill, Victoria, Australia
1218.5.61006 Boehringer Ingelheim Investigational Site
Dandenong, Victoria, Australia
1218.5.61007 Boehringer Ingelheim Investigational Site
East Ringwood, Victoria, Australia
1218.5.61004 Boehringer Ingelheim Investigational Site
Fremantle, Western Australia, Australia
1218.5.61002 Boehringer Ingelheim Investigational Site
Nedlands, Western Australia, Australia
1218.5.11016 Boehringer Ingelheim Investigational Site
Calgary, Alberta, Canada
1218.5.11011 Boehringer Ingelheim Investigational Site
Calgary, Alberta, Canada
1218.5.11003 Boehringer Ingelheim Investigational Site
Red Deer, Alberta, Canada
1218.5.11013 Boehringer Ingelheim Investigational Site
Vancouver, British Columbia, Canada
1218.5.11004 Boehringer Ingelheim Investigational Site
Vancouver, British Columbia, Canada
1218.5.11015 Boehringer Ingelheim Investigational Site
Winnipeg, Manitoba, Canada
1218.5.11005 Boehringer Ingelheim Investigational Site
Hamilton, Ontario, Canada
1218.5.11014 Boehringer Ingelheim Investigational Site
Oakville, Ontario, Canada
1218.5.11010 Boehringer Ingelheim Investigational Site
Ottawa, Ontario, Canada
1218.5.11009 Boehringer Ingelheim Investigational Site
Sarnia, Ontario, Canada
1218.5.11012 Boehringer Ingelheim Investigational Site
Thornhill, Ontario, Canada
1218.5.11002 Boehringer Ingelheim Investigational Site
Toronto, Ontario, Canada
1218.5.11006 Boehringer Ingelheim Investigational Site
Montague, Prince Edward Island, Canada
1218.5.11017 Boehringer Ingelheim Investigational Site
Sainte-Foy, Quebec, Canada
1218.5.11018 Boehringer Ingelheim Investigational Site
Saskatoon, Saskatchewan, Canada
1218.5.42002 Boehringer Ingelheim Investigational Site
Olomouc 9, Czech Republic
1218.5.42005 Boehringer Ingelheim Investigational Site
Praha 4, Czech Republic
1218.5.42003 Boehringer Ingelheim Investigational Site
Praha 4, Czech Republic
1218.5.42004 Boehringer Ingelheim Investigational Site
Praha 9, Czech Republic
1218.5.42001 Boehringer Ingelheim Investigational Site
Sternberk, Czech Republic
1218.5.70002 Boehringer Ingelheim Investigational Site
Moscow, Russian Federation
1218.5.70003 Boehringer Ingelheim Investigational Site
Moscow, Russian Federation
1218.5.70001 Boehringer Ingelheim Investigational Site
Moscow, Russian Federation
1218.5.70004 Boehringer Ingelheim Investigational Site
St. Petersburg, Russian Federation
1218.5.70005 Boehringer Ingelheim Investigational Site
St. Petersburg, Russian Federation
1218.5.38005 Boehringer Ingelheim Investigational Site
Kharkov, Ukraine
1218.5.38001 Boehringer Ingelheim Investigational Site
Kiev, Ukraine
1218.5.38003 Boehringer Ingelheim Investigational Site
Kiev, Ukraine
1218.5.38002 Boehringer Ingelheim Investigational Site
Kiev, Ukraine
1218.5.38004 Boehringer Ingelheim Investigational Site
Lvov, Ukraine
1218.5.38006 Boehringer Ingelheim Investigational Site
Vinnitsa, Ukraine