Linagliptin and Metformin Versus Linagliptin in Newly Diagnosed, Untreated Type 2 Diabetes

Diabetes Mellitus, Type 2 Clinical Trial

Official title:

A 24-week, Randomized, Double-blind, Active-controlled, Parallel Group Trial to Assess the Superiority of Oral Linagliptin and Metformin Compared to Linagliptin Monotherapy in Newly Diagnosed, Treatment-naïve, Uncontrolled Type 2 Diabetes Mellitus Patients

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01512979
• Other study ID #: 1218.83
• Secondary ID: 2011-004158-24
• Status: Completed
• Phase: Phase 4
• First received: January 16, 2012
• Last updated: May 12, 2014
• Start date: January 2012
• Est. completion date: April 2013

Study information

• Verified date: May 2014
• Source: Boehringer Ingelheim
• Contact: n/a
• Is FDA regulated: No
• Health authority: Canada: Health CanadaIndia: Drugs Controller General of IndiaIsrael: Israeli Health Ministry Pharmaceutical AdministrationMalaysia: Ministry of HealthMexico: Federal Commission for Sanitary Risks ProtectionPhilippines: Bureau of Food and DrugsRussia: Pharmacological Committee, Ministry of HealthSri Lanka: Ministry of Healthcare and NutritionThailand: Food and Drug AdministrationUkraine: State Pharmacological Center - Ministry of HealthUnited States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

The purpose of this trial is to determine whether a initial combination of linagliptin and metformin compared to linagliptin alone for 24 weeks is effective in newly diagnosed, treatment-naïve patients with Type 2 Diabetes.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 316
• Est. completion date: April 2013
• Est. primary completion date: April 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion criteria:

1. Patients must sign and date an Informed Consent consistent with International Conference on Harmonisation / Good Clinical Practice guidelines and local regulations prior to any evaluation and participation in the trial.

2. Male and female patients, 18 years of age or older at Visit 1 (Screen), with newly diagnosed (less than 12 months prior to Screen) Type 2 Diabetes Mellitus.

3. Patients who are treatment-naïve, defined as absence of any oral antidiabetic therapy, injectable glucagon-like peptide-1 agonist/analogue, or insulin, and uncontrolled for the 12 weeks prior to randomisation.

4. Patients must have an glycated (or glycosylated) haemoglobin (HbA1c) between 8.5% [69 millimoles per mole (mmol/mol)] and 12.0% (108 mmol/mol) at Visit 1 (Screen).

5. Patients must have a Body Mass Index (BMI) of 45 kg/m2 or less at Visit 1 (Screen).

6. In the investigators opinion, patients must be reliable, honest, compliant, and agree to cooperate with all planned future trial evaluations as explained in detail during the informed consent process and to be able to perform them.

Exclusion criteria:

Patients with, who are, who have, or who have had:

1. Acute coronary syndrome (non-ST Elevation Myocardial Infarction (STEMI), STEMI, and unstable angina pectoris), stroke or transient ischemic attack within 3 months prior to informed consent.

2. Indication of liver disease determined during Screen and/or Run-In Period, defined by a serum level above 3 times the upper limit of normal (ULN) in any of the following: alanine aminotransferase, aspartate aminotransferase, or alkaline phosphatase. Gilbert-Meulengracht syndrome (also known as conjugated hyperbilirubinemia, constitutional hepatic dysfunction, or familial nonhemolytic jaundice) will be permitted.

3. Impaired renal function, defined as calculated creatinine clearance of less than 60 milliliters per minute (< 60 mL/min), by the Cockcroft-Gault Equation, as determined during Screen and/or Run-In Period.

4. Bariatric, gastric bypass, and other gastrointestinal surgeries (including all types of gastric banding and/or LapBand) within the past two years.

5. Medical history of cancer (except for basal cell carcinoma) and/or treatment for cancer within the last 5 years.

6. Medical history of pancreatitis.

7. Blood dyscrasias or any disorders causing hemolysis or unstable red blood cells (e.g., malaria, babesiosis, haemolytic anaemia).

8. Any contraindication to metformin and/or linagliptin therapies, according to local labels.

9. Treatment with anti-obesity drugs, including over-the-counter drugs such as Alli (orlistat), 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.

10. 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 Type 2 Diabetes Mellitus.

11. Pre-menopausal women (last menstruation of 1 year or less prior to informed consent) who are nursing or pregnant, 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 trial and do not agree to submit to periodic pregnancy testing during participation in the trial.

Note: Acceptable methods of birth control include tubal ligation, transdermal patch, intra uterine devices/systems, oral, implantable, intra-vaginal, or injectable contraceptives, Essure micro-inserts placed more than six months prior to Screen Visit, complete sexual abstinence (if acceptable by local authorities), double barrier method (e.g., diaphragm or condom and spermicide), and vasectomised partner.

12. Alcohol or drug abuse within the 3 months prior to informed consent that would interfere with trial participation or any ongoing condition leading to decreased compliance to trial procedures or study medication intake in the opinion of the investigator.

13. Participation in another trial with an investigational drug within 2 months prior to informed consent.

14. Any other clinical condition that would jeopardize patient safety while participating in this clinical trial in the opinion of the Investigator.

15. Inability to commit to regular overnight fasting of at least 10 hours duration and attendance to study site visits between 07:00 and 11:00 ante meridiem (a.m.).

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double-Blind, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2

Intervention

Drug:
• metformin
1000 mg to 2000 mg per day
• linagliptin
5 mg daily
• metformin placebo
0 to 2 tablets daily
• metformin placebo
4 tablets daily

Locations

Country	Name	City	State
Canada	1218.83.12011 Boehringer Ingelheim Investigational Site	Calgary	Alberta
Canada	1218.83.12007 Boehringer Ingelheim Investigational Site	Edmonton	Alberta
Canada	1218.83.12005 Boehringer Ingelheim Investigational Site	Kitchener	Ontario
Canada	1218.83.12006 Boehringer Ingelheim Investigational Site	London	Ontario
Canada	1218.83.12002 Boehringer Ingelheim Investigational Site	Paradise	Newfoundland and Labrador
Canada	1218.83.12001 Boehringer Ingelheim Investigational Site	Red Deer	Alberta
Canada	1218.83.12003 Boehringer Ingelheim Investigational Site	Smiths Falls	Ontario
Canada	1218.83.12009 Boehringer Ingelheim Investigational Site	St. John's	Newfoundland and Labrador
Canada	1218.83.12010 Boehringer Ingelheim Investigational Site	Sudbury	Ontario
Canada	1218.83.12012 Boehringer Ingelheim Investigational Site	Winnipeg	Ontario
India	1218.83.91003 Boehringer Ingelheim Investigational Site	Bangalore
India	1218.83.91005 Boehringer Ingelheim Investigational Site	Chennai
India	1218.83.91001 Boehringer Ingelheim Investigational Site	Mumbai
Israel	1218.83.97004 Boehringer Ingelheim Investigational Site	Haifa
Israel	1218.83.97005 Boehringer Ingelheim Investigational Site	Haifa
Israel	1218.83.97007 Boehringer Ingelheim Investigational Site	Holon
Malaysia	1218.83.60001 Boehringer Ingelheim Investigational Site	Kelantan
Malaysia	1218.83.60002 Boehringer Ingelheim Investigational Site	Perak
Malaysia	1218.83.60003 Boehringer Ingelheim Investigational Site	Selangor, Malaysia
Mexico	1218.83.52004 Boehringer Ingelheim Investigational Site	Cuautla
Mexico	1218.83.52001 Boehringer Ingelheim Investigational Site	Guadalajara
Mexico	1218.83.52002 Boehringer Ingelheim Investigational Site	Guadalajara
Mexico	1218.83.52005 Boehringer Ingelheim Investigational Site	Merida
Mexico	1218.83.52003 Boehringer Ingelheim Investigational Site	Tampico
Philippines	1218.83.63001 Boehringer Ingelheim Investigational Site	Cebu
Philippines	1218.83.63007 Boehringer Ingelheim Investigational Site	Cebu City
Philippines	1218.83.63003 Boehringer Ingelheim Investigational Site	Iloilo
Philippines	1218.83.63008 Boehringer Ingelheim Investigational Site	Iloilo City
Philippines	1218.83.63002 Boehringer Ingelheim Investigational Site	Marikina City
Philippines	1218.83.63006 Boehringer Ingelheim Investigational Site	Marikina City
Philippines	1218.83.63004 Boehringer Ingelheim Investigational Site	Quezon
Puerto Rico	1218.83.11037 Boehringer Ingelheim Investigational Site	San Juan
Russian Federation	1218.83.07001 Boehringer Ingelheim Investigational Site	Kazan
Russian Federation	1218.83.07002 Boehringer Ingelheim Investigational Site	Petrozavodsk
Russian Federation	1218.83.07004 Boehringer Ingelheim Investigational Site	Samara
Russian Federation	1218.83.07006 Boehringer Ingelheim Investigational Site	Smolensk
Russian Federation	1218.83.07003 Boehringer Ingelheim Investigational Site	St. Petersburg
Russian Federation	1218.83.07007 Boehringer Ingelheim Investigational Site	St. Petersburg
Russian Federation	1218.83.07005 Boehringer Ingelheim Investigational Site	Yaroslavl
Sri Lanka	1218.83.94004 Boehringer Ingelheim Investigational Site	Dehiwela
Sri Lanka	1218.83.94002 Boehringer Ingelheim Investigational Site	Galle, Sri Lanka
Sri Lanka	1218.83.94003 Boehringer Ingelheim Investigational Site	Kandy
Sri Lanka	1218.83.94001 Boehringer Ingelheim Investigational Site	Ragama
Thailand	1218.83.66002 Boehringer Ingelheim Investigational Site	Bangkok
Thailand	1218.83.66003 Boehringer Ingelheim Investigational Site	Bangkok
Thailand	1218.83.66001 Boehringer Ingelheim Investigational Site	Muang, Khonkaen
Ukraine	1218.83.38007 Boehringer Ingelheim Investigational Site	Dnepropetrovsk
Ukraine	1218.83.38001 Boehringer Ingelheim Investigational Site	Ivano-Frankivsk
Ukraine	1218.83.38006 Boehringer Ingelheim Investigational Site	Kharkiv
Ukraine	1218.83.38004 Boehringer Ingelheim Investigational Site	Odessa
Ukraine	1218.83.38008 Boehringer Ingelheim Investigational Site	Vinnitsa
Ukraine	1218.83.38003 Boehringer Ingelheim Investigational Site	Vinnytsya
Ukraine	1218.83.38005 Boehringer Ingelheim Investigational Site	Vinnytsya
United States	1218.83.11004 Boehringer Ingelheim Investigational Site	Bristol	Tennessee
United States	1218.83.11017 Boehringer Ingelheim Investigational Site	Chattanooga	Tennessee
United States	1218.83.11011 Boehringer Ingelheim Investigational Site	Chino	California
United States	1218.83.11018 Boehringer Ingelheim Investigational Site	Columbia	South Carolina
United States	1218.83.11005 Boehringer Ingelheim Investigational Site	Edison	New Jersey
United States	1218.83.11008 Boehringer Ingelheim Investigational Site	Elkton	Maryland
United States	1218.83.11022 Boehringer Ingelheim Investigational Site	Fort Lauderdale	Florida
United States	1218.83.11003 Boehringer Ingelheim Investigational Site	Franklin	Ohio
United States	1218.83.11027 Boehringer Ingelheim Investigational Site	Freemont	Nebraska
United States	1218.83.11024 Boehringer Ingelheim Investigational Site	Gallipolis	Ohio
United States	1218.83.11032 Boehringer Ingelheim Investigational Site	Grand Prairie	Texas
United States	1218.83.11030 Boehringer Ingelheim Investigational Site	Houston	Texas
United States	1218.83.11001 Boehringer Ingelheim Investigational Site	Huntington Beach	California
United States	1218.83.11019 Boehringer Ingelheim Investigational Site	Huntington Park	California
United States	1218.83.11013 Boehringer Ingelheim Investigational Site	Jacksonville	North Carolina
United States	1218.83.11036 Boehringer Ingelheim Investigational Site	Little Rock	Arkansas
United States	1218.83.11015 Boehringer Ingelheim Investigational Site	Lomita	California
United States	1218.83.11023 Boehringer Ingelheim Investigational Site	Norwalk	California
United States	1218.83.11029 Boehringer Ingelheim Investigational Site	Oakwood	Georgia
United States	1218.83.11025 Boehringer Ingelheim Investigational Site	Orlando	Florida
United States	1218.83.11026 Boehringer Ingelheim Investigational Site	Owensboro	Kentucky
United States	1218.83.11002 Boehringer Ingelheim Investigational Site	Phoenix	Arizona
United States	1218.83.11014 Boehringer Ingelheim Investigational Site	Roseville	California
United States	1218.83.11028 Boehringer Ingelheim Investigational Site	Salisbury	North Carolina
United States	1218.83.11034 Boehringer Ingelheim Investigational Site	San Antonio	Texas
United States	1218.83.11031 Boehringer Ingelheim Investigational Site	San Diego	California
United States	1218.83.11033 Boehringer Ingelheim Investigational Site	Sanford	Florida
United States	1218.83.11009 Boehringer Ingelheim Investigational Site	Shelby	North Carolina
United States	1218.83.11021 Boehringer Ingelheim Investigational Site	Tomball	Texas

Sponsors (2)

Lead Sponsor	Collaborator
Boehringer Ingelheim	Eli Lilly and Company

Countries where clinical trial is conducted

United States,  Canada,  India,  Israel,  Malaysia,  Mexico,  Philippines,  Puerto Rico,  Russian Federation,  Sri Lanka,  Thailand,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline in HbA1c After 24 Weeks	HbA1c is measured as a percentage. The change from baseline is the Week 24 HbA1c minus the baseline HbA1c. Means are adjusted for treatment and continuous baseline HbA1c	Baseline and 24 weeks	No
Secondary	Change From Baseline in Fasting Plasma Glucose (FPG) After 24 Weeks of Treatment	The change from baseline is the FPG after 24 weeks minus the baseline FPG. Means are adjusted for treatment, continuous baseline HbA1c and continuous baseline fasting plasma glucose.	Baseline and 24 weeks	No
Secondary	Change From Baseline in HbA1c by Visit Over Time	HbA1c is measured as a percentage. The change from baseline is the HbA1c over time minus the baseline HbA1c. The model includes treatment, continuous baseline HbA1c in addition to week repeated within patient, week by baseline HbA1c interaction and week by treatment interaction.	Baseline, 6, 12, 18 and 24 weeks	No
Secondary	Occurrence of Relative Efficacy Response (HbA1c Lowering by at Least 0.5% After 24 Weeks of Treatment)	The proportion of patients who achieved HbA1c lowering by at least 0.5% after 24 weeks of treatment.The model includes treatment, and continuous baseline HbA1c.	Baseline and 24 weeks	No
Secondary	Occurrence of Relative Efficacy Response (HbA1c Lowering by at Least 1.0% After 24 Weeks of Treatment)	The proportion of patients who achieved HbA1c lowering by at least 1.0% after 24 weeks of treatment. The model includes treatment, and continuous baseline HbA1c.	Baseline and 24 weeks	No
Secondary	Occurrence of Treat to Target Efficacy Response (HbA1c <7.0%) After 24 Weeks of Treatment	The proportion of patients who achieved HbA1c below 7.0% after 24 weeks of treatment. The model includes treatment, and continuous baseline HbA1c.	Baseline and 24 weeks	No
Secondary	Change From Baseline in FPG by Visit Over Time	The change from baseline is the FPG over time minus the baseline FPG. Means are adjusted for treatment, continuous baseline HbA1c, continuous baseline FPG in addition to week repeated within patient, week by baseline FPG interaction and week by treatment interaction.	Baseline, 6, 12, 18 and 24 weeks	No