Clinical trial NCT00328172: Efficacy and Safety of 3 Doses of BI1356 (Linagliptin) in Type 2 Diabetes Patients
Official title: A 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Diabetes Mellitus, Type 2
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2006-05-19
Enrollment: 302
Sex: ALL
Minimum age (years): 21
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Change From Baseline in HbA1c (Glycosylated Haemoglobin) at Week 12
timeFrame: Baseline, week 12
Secondary outcomes:
measure: Change From Baseline in Fasting Plasma Glucose (FPG) at Week 12
timeFrame: Baseline, week 12
measure: Percentage of Patients With Absolute Efficacy Response (HbA1c <= 7.0%) at 12 Weeks
timeFrame: Baseline, week 12
Other outcomes:
Locations:
city: Chula Vista
country: United States
facility: 1218.5.10020 Boehringer Ingelheim Investigational Site
state: California
city: La Jolla
country: United States
facility: 1218.5.10001 Boehringer Ingelheim Investigational Site
state: California
city: Walnut Creek
country: United States
facility: 1218.5.10007 Boehringer Ingelheim Investigational Site
state: California
city: Denver
country: United States
facility: 1218.5.10041 Boehringer Ingelheim Investigational Site
state: Colorado
city: Hollywood
country: United States
facility: 1218.5.10018 Boehringer Ingelheim Investigational Site
state: Florida
city: Jacksonville
country: United States
facility: 1218.5.10016 Boehringer Ingelheim Investigational Site
state: Florida
city: Miami
country: United States
facility: 1218.5.10003 Boehringer Ingelheim Investigational Site
state: Florida
city: Miami
country: United States
facility: 1218.5.10011 Boehringer Ingelheim Investigational Site
state: Florida
city: Orlando
country: United States
facility: 1218.5.10012 Boehringer Ingelheim Investigational Site
state: Florida
city: Indianapolis
country: United States
facility: 1218.5.10017 Boehringer Ingelheim Investigational Site
state: Indiana
city: Topeka
country: United States
facility: 1218.5.10008 Boehringer Ingelheim Investigational Site
state: Kansas
city: Wichita
country: United States
facility: 1218.5.10024 Boehringer Ingelheim Investigational Site
state: Kansas
city: Baltimore
country: United States
facility: 1218.5.10039 Boehringer Ingelheim Investigational Site
state: Maryland
city: Springfield
country: United States
facility: 1218.5.10032 Boehringer Ingelheim Investigational Site
state: Massachusetts
city: Chesterfield
country: United States
facility: 1218.5.10025 Boehringer Ingelheim Investigational Site
state: Missouri
city: Butte
country: United States
facility: 1218.5.10034 Boehringer Ingelheim Investigational Site
state: Montana
city: Omaha
country: United States
facility: 1218.5.10009 Boehringer Ingelheim Investigational Site
state: Nebraska
city: Albany
country: United States
facility: 1218.5.10042 Boehringer Ingelheim Investigational Site
state: New York
city: Endwell
country: United States
facility: 1218.5.10029 Boehringer Ingelheim Investigational Site
state: New York
city: New Hyde Park
country: United States
facility: 1218.5.10004 Boehringer Ingelheim Investigational Site
state: New York
city: Columbus
country: United States
facility: 1218.5.10026 Boehringer Ingelheim Investigational Site
state: Ohio
city: Mentor
country: United States
facility: 1218.5.10035 Boehringer Ingelheim Investigational Site
state: Ohio
city: Medford
country: United States
facility: 1218.5.10023 Boehringer Ingelheim Investigational Site
state: Oregon
city: Philadelphia
country: United States
facility: 1218.5.10030 Boehringer Ingelheim Investigational Site
state: Pennsylvania
city: Columbia
country: United States
facility: 1218.5.10044 Boehringer Ingelheim Investigational Site
state: South Carolina
city: Greer
country: United States
facility: 1218.5.10033 Boehringer Ingelheim Investigational Site
state: South Carolina
city: Simpsonville
country: United States
facility: 1218.5.10038 Boehringer Ingelheim Investigational Site
state: South Carolina
city: Dallas
country: United States
facility: 1218.5.10006 Boehringer Ingelheim Investigational Site
state: Texas
city: Houston
country: United States
facility: 1218.5.10040 Boehringer Ingelheim Investigational Site
state: Texas
city: San Antonio
country: United States
facility: 1218.5.10036 Boehringer Ingelheim Investigational Site
state: Texas
city: Tyler
country: United States
facility: 1218.5.10021 Boehringer Ingelheim Investigational Site
state: Texas
city: Salem
country: United States
facility: 1218.5.10027 Boehringer Ingelheim Investigational Site
state: Virginia
city: Federal Way
country: United States
facility: 1218.5.10022 Boehringer Ingelheim Investigational Site
state: Washington
city: Renton
country: United States
facility: 1218.5.10014 Boehringer Ingelheim Investigational Site
state: Washington
city: Miranda
country: Australia
facility: 1218.5.61001 Boehringer Ingelheim Investigational Site
state: New South Wales
city: Box Hill
country: Australia
facility: 1218.5.61005 Boehringer Ingelheim Investigational Site
state: Victoria
city: Dandenong
country: Australia
facility: 1218.5.61006 Boehringer Ingelheim Investigational Site
state: Victoria
city: East Ringwood
country: Australia
facility: 1218.5.61007 Boehringer Ingelheim Investigational Site
state: Victoria
city: Fremantle
country: Australia
facility: 1218.5.61004 Boehringer Ingelheim Investigational Site
state: Western Australia
city: Nedlands
country: Australia
facility: 1218.5.61002 Boehringer Ingelheim Investigational Site
state: Western Australia
city: Calgary
country: Canada
facility: 1218.5.11011 Boehringer Ingelheim Investigational Site
state: Alberta
city: Calgary
country: Canada
facility: 1218.5.11016 Boehringer Ingelheim Investigational Site
state: Alberta
city: Red Deer
country: Canada
facility: 1218.5.11003 Boehringer Ingelheim Investigational Site
state: Alberta
city: Vancouver
country: Canada
facility: 1218.5.11004 Boehringer Ingelheim Investigational Site
state: British Columbia
city: Vancouver
country: Canada
facility: 1218.5.11013 Boehringer Ingelheim Investigational Site
state: British Columbia
city: Winnipeg
country: Canada
facility: 1218.5.11015 Boehringer Ingelheim Investigational Site
state: Manitoba
city: Hamilton
country: Canada
facility: 1218.5.11005 Boehringer Ingelheim Investigational Site
state: Ontario
city: Oakville
country: Canada
facility: 1218.5.11014 Boehringer Ingelheim Investigational Site
state: Ontario
city: Ottawa
country: Canada
facility: 1218.5.11010 Boehringer Ingelheim Investigational Site
state: Ontario
city: Sarnia
country: Canada
facility: 1218.5.11009 Boehringer Ingelheim Investigational Site
state: Ontario
city: Thornhill
country: Canada
facility: 1218.5.11012 Boehringer Ingelheim Investigational Site
state: Ontario
city: Toronto
country: Canada
facility: 1218.5.11002 Boehringer Ingelheim Investigational Site
state: Ontario
city: Montague
country: Canada
facility: 1218.5.11006 Boehringer Ingelheim Investigational Site
state: Prince Edward Island
city: Sainte-Foy
country: Canada
facility: 1218.5.11017 Boehringer Ingelheim Investigational Site
state: Quebec
city: Saskatoon
country: Canada
facility: 1218.5.11018 Boehringer Ingelheim Investigational Site
state: Saskatchewan
city: Olomouc 9
country: Czech Republic
facility: 1218.5.42002 Boehringer Ingelheim Investigational Site
city: Praha 4
country: Czech Republic
facility: 1218.5.42003 Boehringer Ingelheim Investigational Site
city: Praha 4
country: Czech Republic
facility: 1218.5.42005 Boehringer Ingelheim Investigational Site
city: Praha 9
country: Czech Republic
facility: 1218.5.42004 Boehringer Ingelheim Investigational Site
city: Sternberk
country: Czech Republic
facility: 1218.5.42001 Boehringer Ingelheim Investigational Site
city: Moscow
country: Russian Federation
facility: 1218.5.70001 Boehringer Ingelheim Investigational Site
city: Moscow
country: Russian Federation
facility: 1218.5.70002 Boehringer Ingelheim Investigational Site
city: Moscow
country: Russian Federation
facility: 1218.5.70003 Boehringer Ingelheim Investigational Site
city: St. Petersburg
country: Russian Federation
facility: 1218.5.70004 Boehringer Ingelheim Investigational Site
city: St. Petersburg
country: Russian Federation
facility: 1218.5.70005 Boehringer Ingelheim Investigational Site
city: Kharkov
country: Ukraine
facility: 1218.5.38005 Boehringer Ingelheim Investigational Site
city: Kiev
country: Ukraine
facility: 1218.5.38001 Boehringer Ingelheim Investigational Site
city: Kiev
country: Ukraine
facility: 1218.5.38002 Boehringer Ingelheim Investigational Site
city: Kiev
country: Ukraine
facility: 1218.5.38003 Boehringer Ingelheim Investigational Site
city: Lvov
country: Ukraine
facility: 1218.5.38004 Boehringer Ingelheim Investigational Site
city: Vinnitsa
country: Ukraine
facility: 1218.5.38006 Boehringer Ingelheim Investigational Site
Study officials:
affiliation: Boehringer Ingelheim
name: Boehringer Ingelheim
role: STUDY_CHAIR
References: