Clinical trial NCT01512979: Linagliptin and Metformin Versus Linagliptin in Newly Diagnosed, Untreated Type 2 Diabetes
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Diabetes Mellitus, Type 2
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
Collaborators: name: Eli Lilly and Company
First posted: 2012-01-20
Enrollment: 316
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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.).

Primary outcomes:
measure: Change From Baseline in HbA1c After 24 Weeks
timeFrame: Baseline and 24 weeks
Secondary outcomes:
measure: Change From Baseline in Fasting Plasma Glucose (FPG) After 24 Weeks of Treatment
timeFrame: Baseline and 24 weeks
measure: Change From Baseline in HbA1c by Visit Over Time
timeFrame: Baseline, 6, 12, 18 and 24 weeks
measure: Occurrence of Relative Efficacy Response (HbA1c Lowering by at Least 0.5% After 24 Weeks of Treatment)
timeFrame: Baseline and 24 weeks
measure: Occurrence of Relative Efficacy Response (HbA1c Lowering by at Least 1.0% After 24 Weeks of Treatment)
timeFrame: Baseline and 24 weeks
measure: Occurrence of Treat to Target Efficacy Response (HbA1c <7.0%) After 24 Weeks of Treatment
timeFrame: Baseline and 24 weeks
measure: Change From Baseline in FPG by Visit Over Time
timeFrame: Baseline, 6, 12, 18 and 24 weeks
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: 1218.83.11002 Boehringer Ingelheim Investigational Site
state: Arizona
city: Little Rock
country: United States
facility: 1218.83.11036 Boehringer Ingelheim Investigational Site
state: Arkansas
city: Chino
country: United States
facility: 1218.83.11011 Boehringer Ingelheim Investigational Site
state: California
city: Huntington Beach
country: United States
facility: 1218.83.11001 Boehringer Ingelheim Investigational Site
state: California
city: Huntington Park
country: United States
facility: 1218.83.11019 Boehringer Ingelheim Investigational Site
state: California
city: Lomita
country: United States
facility: 1218.83.11015 Boehringer Ingelheim Investigational Site
state: California
city: Norwalk
country: United States
facility: 1218.83.11023 Boehringer Ingelheim Investigational Site
state: California
city: Roseville
country: United States
facility: 1218.83.11014 Boehringer Ingelheim Investigational Site
state: California
city: San Diego
country: United States
facility: 1218.83.11031 Boehringer Ingelheim Investigational Site
state: California
city: Fort Lauderdale
country: United States
facility: 1218.83.11022 Boehringer Ingelheim Investigational Site
state: Florida
city: Orlando
country: United States
facility: 1218.83.11025 Boehringer Ingelheim Investigational Site
state: Florida
city: Sanford
country: United States
facility: 1218.83.11033 Boehringer Ingelheim Investigational Site
state: Florida
city: Oakwood
country: United States
facility: 1218.83.11029 Boehringer Ingelheim Investigational Site
state: Georgia
city: Owensboro
country: United States
facility: 1218.83.11026 Boehringer Ingelheim Investigational Site
state: Kentucky
city: Elkton
country: United States
facility: 1218.83.11008 Boehringer Ingelheim Investigational Site
state: Maryland
city: Freemont
country: United States
facility: 1218.83.11027 Boehringer Ingelheim Investigational Site
state: Nebraska
city: Edison
country: United States
facility: 1218.83.11005 Boehringer Ingelheim Investigational Site
state: New Jersey
city: Jacksonville
country: United States
facility: 1218.83.11013 Boehringer Ingelheim Investigational Site
state: North Carolina
city: Salisbury
country: United States
facility: 1218.83.11028 Boehringer Ingelheim Investigational Site
state: North Carolina
city: Shelby
country: United States
facility: 1218.83.11009 Boehringer Ingelheim Investigational Site
state: North Carolina
city: Franklin
country: United States
facility: 1218.83.11003 Boehringer Ingelheim Investigational Site
state: Ohio
city: Gallipolis
country: United States
facility: 1218.83.11024 Boehringer Ingelheim Investigational Site
state: Ohio
city: Columbia
country: United States
facility: 1218.83.11018 Boehringer Ingelheim Investigational Site
state: South Carolina
city: Bristol
country: United States
facility: 1218.83.11004 Boehringer Ingelheim Investigational Site
state: Tennessee
city: Chattanooga
country: United States
facility: 1218.83.11017 Boehringer Ingelheim Investigational Site
state: Tennessee
city: Grand Prairie
country: United States
facility: 1218.83.11032 Boehringer Ingelheim Investigational Site
state: Texas
city: Houston
country: United States
facility: 1218.83.11030 Boehringer Ingelheim Investigational Site
state: Texas
city: San Antonio
country: United States
facility: 1218.83.11034 Boehringer Ingelheim Investigational Site
state: Texas
city: Tomball
country: United States
facility: 1218.83.11021 Boehringer Ingelheim Investigational Site
state: Texas
city: Calgary
country: Canada
facility: 1218.83.12011 Boehringer Ingelheim Investigational Site
state: Alberta
city: Edmonton
country: Canada
facility: 1218.83.12007 Boehringer Ingelheim Investigational Site
state: Alberta
city: Red Deer
country: Canada
facility: 1218.83.12001 Boehringer Ingelheim Investigational Site
state: Alberta
city: Paradise
country: Canada
facility: 1218.83.12002 Boehringer Ingelheim Investigational Site
state: Newfoundland and Labrador
city: St. John's
country: Canada
facility: 1218.83.12009 Boehringer Ingelheim Investigational Site
state: Newfoundland and Labrador
city: Kitchener
country: Canada
facility: 1218.83.12005 Boehringer Ingelheim Investigational Site
state: Ontario
city: London
country: Canada
facility: 1218.83.12006 Boehringer Ingelheim Investigational Site
state: Ontario
city: Smiths Falls
country: Canada
facility: 1218.83.12003 Boehringer Ingelheim Investigational Site
state: Ontario
city: Sudbury
country: Canada
facility: 1218.83.12010 Boehringer Ingelheim Investigational Site
state: Ontario
city: Winnipeg
country: Canada
facility: 1218.83.12012 Boehringer Ingelheim Investigational Site
state: Ontario
city: Bangalore
country: India
facility: 1218.83.91003 Boehringer Ingelheim Investigational Site
city: Chennai
country: India
facility: 1218.83.91005 Boehringer Ingelheim Investigational Site
city: Mumbai
country: India
facility: 1218.83.91001 Boehringer Ingelheim Investigational Site
city: Haifa
country: Israel
facility: 1218.83.97004 Boehringer Ingelheim Investigational Site
city: Haifa
country: Israel
facility: 1218.83.97005 Boehringer Ingelheim Investigational Site
city: Holon
country: Israel
facility: 1218.83.97007 Boehringer Ingelheim Investigational Site
city: Kelantan
country: Malaysia
facility: 1218.83.60001 Boehringer Ingelheim Investigational Site
city: Perak
country: Malaysia
facility: 1218.83.60002 Boehringer Ingelheim Investigational Site
city: Selangor, Malaysia
country: Malaysia
facility: 1218.83.60003 Boehringer Ingelheim Investigational Site
city: Cuautla
country: Mexico
facility: 1218.83.52004 Boehringer Ingelheim Investigational Site
city: Guadalajara
country: Mexico
facility: 1218.83.52001 Boehringer Ingelheim Investigational Site
city: Guadalajara
country: Mexico
facility: 1218.83.52002 Boehringer Ingelheim Investigational Site
city: Merida
country: Mexico
facility: 1218.83.52005 Boehringer Ingelheim Investigational Site
city: Tampico
country: Mexico
facility: 1218.83.52003 Boehringer Ingelheim Investigational Site
city: Cebu City
country: Philippines
facility: 1218.83.63007 Boehringer Ingelheim Investigational Site
city: Cebu
country: Philippines
facility: 1218.83.63001 Boehringer Ingelheim Investigational Site
city: Iloilo City
country: Philippines
facility: 1218.83.63008 Boehringer Ingelheim Investigational Site
city: Iloilo
country: Philippines
facility: 1218.83.63003 Boehringer Ingelheim Investigational Site
city: Marikina City
country: Philippines
facility: 1218.83.63002 Boehringer Ingelheim Investigational Site
city: Marikina City
country: Philippines
facility: 1218.83.63006 Boehringer Ingelheim Investigational Site
city: Quezon
country: Philippines
facility: 1218.83.63004 Boehringer Ingelheim Investigational Site
city: San Juan
country: Puerto Rico
facility: 1218.83.11037 Boehringer Ingelheim Investigational Site
city: Kazan
country: Russian Federation
facility: 1218.83.07001 Boehringer Ingelheim Investigational Site
city: Petrozavodsk
country: Russian Federation
facility: 1218.83.07002 Boehringer Ingelheim Investigational Site
city: Samara
country: Russian Federation
facility: 1218.83.07004 Boehringer Ingelheim Investigational Site
city: Smolensk
country: Russian Federation
facility: 1218.83.07006 Boehringer Ingelheim Investigational Site
city: St. Petersburg
country: Russian Federation
facility: 1218.83.07003 Boehringer Ingelheim Investigational Site
city: St. Petersburg
country: Russian Federation
facility: 1218.83.07007 Boehringer Ingelheim Investigational Site
city: Yaroslavl
country: Russian Federation
facility: 1218.83.07005 Boehringer Ingelheim Investigational Site
city: Dehiwela
country: Sri Lanka
facility: 1218.83.94004 Boehringer Ingelheim Investigational Site
city: Galle, Sri Lanka
country: Sri Lanka
facility: 1218.83.94002 Boehringer Ingelheim Investigational Site
city: Kandy
country: Sri Lanka
facility: 1218.83.94003 Boehringer Ingelheim Investigational Site
city: Ragama
country: Sri Lanka
facility: 1218.83.94001 Boehringer Ingelheim Investigational Site
city: Bangkok
country: Thailand
facility: 1218.83.66002 Boehringer Ingelheim Investigational Site
city: Bangkok
country: Thailand
facility: 1218.83.66003 Boehringer Ingelheim Investigational Site
city: Muang, Khonkaen
country: Thailand
facility: 1218.83.66001 Boehringer Ingelheim Investigational Site
city: Dnepropetrovsk
country: Ukraine
facility: 1218.83.38007 Boehringer Ingelheim Investigational Site
city: Ivano-Frankivsk
country: Ukraine
facility: 1218.83.38001 Boehringer Ingelheim Investigational Site
city: Kharkiv
country: Ukraine
facility: 1218.83.38006 Boehringer Ingelheim Investigational Site
city: Odessa
country: Ukraine
facility: 1218.83.38004 Boehringer Ingelheim Investigational Site
city: Vinnitsa
country: Ukraine
facility: 1218.83.38008 Boehringer Ingelheim Investigational Site
city: Vinnytsya
country: Ukraine
facility: 1218.83.38003 Boehringer Ingelheim Investigational Site
city: Vinnytsya
country: Ukraine
facility: 1218.83.38005 Boehringer Ingelheim Investigational Site
Study officials:
affiliation: Boehringer Ingelheim
name: Boehringer Ingelheim
role: STUDY_CHAIR
References:
citation: Ross SA, Caballero AE, Del Prato S, Gallwitz B, Lewis-D'Agostino D, Bailes Z, Thiemann S, Patel S, Woerle HJ, von Eynatten M. Linagliptin plus metformin in patients with newly diagnosed type 2 diabetes and marked hyperglycemia. Postgrad Med. 2016 Nov;128(8):747-754. doi: 10.1080/00325481.2016.1238280. Epub 2016 Sep 29.