BI 1356 (Linagliptin) in Combination With Metformin and a Sulphonylurea in Type 2 Diabetes - Full Text View

Sponsor:	Boehringer Ingelheim Pharmaceuticals
Information provided by:	Boehringer Ingelheim Pharmaceuticals
ClinicalTrials.gov Identifier:	NCT00602472

Purpose

The objective of the current study is to investigate the efficacy, safety and tolerability of BI 1356 (5 mg once daily) compared to placebo given for 24 weeks as add-on therapy to metformin in combination with a sulphonylurea in patients with type 2 diabetes mellitus with insufficient glycaemic control.

Condition	Intervention	Phase
Diabetes Mellitus, Type 2	Drug: linagliptin Drug: placebo	Phase III

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double-Blind Primary Purpose: Treatment
Official Title:	A Randomised, Double-blind, Placebo-controlled Parallel Group Efficacy and Safety Study of BI 1356 (5 mg) Administered Orally Once Daily Over 24 Weeks, With an Open-label Extension to One Year (Placebo Patients Switched to BI 1356), in Type 2 Diabetic Patients With Insufficient Glycaemic Control Despite a Therapy of Metformin in Combination With a Sulphonylurea

Resource links provided by NLM:

Genetics Home Reference related topics: 6q24-related transient neonatal diabetes mellitus

MedlinePlus related topics: Diabetes Diabetes Type 2

Drug Information available for: Metformin Metformin hydrochloride

U.S. FDA Resources

Further study details as provided by Boehringer Ingelheim Pharmaceuticals:

Primary Outcome Measures:

HbA1c Change From Baseline to Week 24 [ Time Frame: Baseline and week 24 ] [ Designated as safety issue: No ]
HbA1c is measured as a percentage. Thus, this change from baseline reflects the Week 24 HbA1c percent minus the baseline HbA1c percent. Means are treatment adjusted for baseline HbA1c and previous anti-diabetic medication.

Secondary Outcome Measures:

HbA1c Change From Baseline to Week 6 [ Time Frame: Baseline and week 6 ] [ Designated as safety issue: No ]
HbA1c is measured as a percentage. Thus, this change from baseline reflects the Week 6 HbA1c percent minus the baseline HbA1c percent. Means are treatment adjusted for baseline HbA1c and previous anti-diabetic medication.
HbA1c Change From Baseline to Week 12 [ Time Frame: Baseline and week 12 ] [ Designated as safety issue: No ]
HbA1c is measured as a percentage. Thus, this change from baseline reflects the Week 12 HbA1c percent minus the baseline HbA1c percent. Means are treatment adjusted for baseline HbA1c and previous anti-diabetic medication.
HbA1c Change From Baseline to Week 18 [ Time Frame: Baseline and week 18 ] [ Designated as safety issue: No ]
HbA1c is measured as a percentage. Thus, this change from baseline reflects the Week 18 HbA1c percent minus the baseline HbA1c percent. Means are treatment adjusted for baseline HbA1c and previous anti-diabetic medication.
FPG Change From Baseline to Week 24 [ Time Frame: Baseline and week 24 ] [ Designated as safety issue: No ]
This change from baseline reflects the Week 24 FPG minus the baseline FPG. Means are treatment-adjusted for baseline HbA1c, baseline FPG and previous anti-diabetic medication.
FPG Change From Baseline to Week 6 [ Time Frame: Baseline and week 6 ] [ Designated as safety issue: No ]
This change from baseline reflects the Week 6 FPG minus the baseline FPG. Means are treatment-adjusted for baseline HbA1c, baseline FPG and previous anti-diabetic medication.
FPG Change From Baseline to Week 12 [ Time Frame: Baseline and week 12 ] [ Designated as safety issue: No ]
This change from baseline reflects the Week 12 FPG minus the baseline FPG. Means are treatment adjusted for baseline HbA1c, baseline FPG and previous anti-diabetic medication.
FPG Change From Baseline to Week 18 [ Time Frame: Baseline and week 18 ] [ Designated as safety issue: No ]
This change from baseline reflects the Week 18 FPG minus the Week 0 FPG. Means are treatment-adjusted for baseline HbA1c, baseline FPG and previous anti-diabetic medication
Percentage of Patients With HbA1c <7.0% at Week 24 [ Time Frame: Baseline and week 24 ] [ Designated as safety issue: No ]
The percentage of patients with an HbA1c value below 7% at week 24 was calculated for each treatment arm. If a patient did not have an HbA1c value at week 24 they were considered a failure, so HbA1c above 7%. Only patients with baseline HbA1c >= 7%
Percentage of Patients With HbA1c < 7.0% at Week 24 [ Time Frame: Baseline and week 24 ] [ Designated as safety issue: No ]
The percentage of patients with an HbA1c value below 7% at week 24 was calculated for each treatment arm. If a patient did not have an HbA1c value at week 24 they were considered a failure, so HbA1c above 7%.
Percentage of Patients With HbA1c <6.5% at Week 24 [ Time Frame: Baseline and week 24 ] [ Designated as safety issue: No ]
The percentage of patients with an HbA1c value below 6.5% at week 24 was calculated for each treatment arm. If a patient did not have an HbA1c value at week 24 they were considered a failure, so HbA1c above 6.5%. Only patients with baseline HbA1c >= 6.5%
Percentage of Patients With HbA1c<6.5% at Week 24 [ Time Frame: Baseline and week 24 ] [ Designated as safety issue: No ]
The percentage of patients with an HbA1c value below 6.5% at week 24 was calculated for each treatment arm. If a patient did not have an HbA1c value at week 24 they were considered a failure, so HbA1c above 6.5%
Percentage of Patients Who Have a HbA1c Lowering by 0.5% at Week 24 [ Time Frame: Baseline and week 24 ] [ Designated as safety issue: No ]
The percentage of patients with an HbA1c reduction greater than 0.5% at week 24 from baseline was calculated for each treatment arm. If a patient did not have an HbA1c value at week 24 they were considered a failure, so HbA1c reduction less than 0.5%

Enrollment:	1058
Study Start Date:	February 2008
Primary Completion Date:	May 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: linagliptin 5 mg linagliptin 5 mg once daily	Drug: linagliptin active
Placebo Comparator: placebo placebo matching linagliptin 5 mg tablets	Drug: placebo placebo to linagliptin 5 mg

Eligibility

Ages Eligible for Study:	18 Years to 80 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion criteria:

Male and female patients with a diagnosis of type 2 diabetes mellitus, currently treated only with a stable total daily dose of preferably* >/= 1500 mg metformin and a dose of a sulphonylurea drug that has been documented, by the Investigator, to be the individual maximum tolerated dose of that sulphonylurea drug. Both the dose and dosing regimen of metformin and the sulphonylurea must be stable (i.e. unchanged) for 10 weeks prior to informed consent, and must not be changed for the duration of the trial
Glycosylated haemoglobin A1 (HbA1c) >/= 7.0 and </= 10.0% at the screening Visit 1a and at Visit 2 (start of placebo run-in phase)
Age >/= 18 and </= 80 years at Visit 1a (screening)
BMI (Body Mass Index) </= 40 kg/m2 at Visit 1a (screening)
Signed and dated written informed consent, at the latest by the date of Visit 1a, in accordance with GCP and local legislation *Patients currently treated with a total daily dose of less than 1500 mg metformin can be included in the trial if the Investigator has documented that the dose is the maximum tolerated dose of metformin for that patient.

Exclusion criteria:

Myocardial infarction, stroke or TIA (transient ischaemic attack) within 6 months prior to the date of informed consent
Impaired hepatic function, defined by serum levels of either alanine transaminase (ALT/SGPT), aspartase transaminase (AST/SGOT), or alkaline phosphatase (ALP) above 3 times the upper limit of normal (ULN), as determined at Visit 1a
Renal failure or renal impairment (serum creatinine >/= 1.5 mg/dl) as determined at Visit 1a
Treatment with rosiglitazone or pioglitazone within 3 months prior to the date of informed consent
Treatment with GLP-1 analogues (e.g. exenatide) within 3 months prior to the date of informed consent
Treatment with insulin within 3 months prior to the date of informed consent
Treatment with anti-obesity drugs (e.g. sibutramine, rimonabant, orlistat) within 3 months prior to the date of informed consent
Current treatment with systemic steroids (i.e. at the time of informed consent) or a change in the dosage of thyroid hormones within 6 weeks prior to the date of informed consent
Pre-menopausal women (last menstruation </= 1 year prior to the date of informed consent) who:
- are nursing or pregnant
- 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 periodic pregnancy testing during their participation in the trial. Acceptable methods of birth control include transdermal patch, intra uterine devices/systems (IUDs/IUSs), oral, implantable or injectable contraceptives, sexual abstinence and vasectomised partner. No exception will be made.
Known hypersensitivity or allergy to the investigational product or its excipients or to the trial background therapy (i.e. metformin in combination with a sulphonylurea) or sulphonamides
Dehydration (as confirmed by the Investigators clinical opinion)
Current acute or chronic metabolic acidosis

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00602472

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Sponsors and Collaborators

Boehringer Ingelheim Pharmaceuticals

Investigators

Study Chair:

Boehringer Ingelheim

Boehringer Ingelheim Pharmaceuticals

More Information

Additional Information:

Related Info This link exits the ClinicalTrials.gov site

No publications provided by Boehringer Ingelheim Pharmaceuticals

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Owens DR, Swallow R, Dugi KA, Woerle HJ. Efficacy and safety of linagliptin in persons with Type 2 diabetes inadequately controlled by a combination of metformin and sulphonylurea: a 24-week randomized study. Diabet Med. 2011 Nov;28(11):1352-61.

Responsible Party:	Boehringer Ingelheim, Study Chair, Boehringer Ingelheim
ClinicalTrials.gov Identifier:	NCT00602472 History of Changes
Other Study ID Numbers:	1218.18, 2007-002450-28
Study First Received:	January 15, 2008
Results First Received:	May 13, 2011
Last Updated:	July 4, 2011
Health Authority:	Argentina: Ministry of Health; Belgium: Federal Agency for Medicines and Health Products; Canada: Therapeutic Products Directorate; China: State Food and Drug Administration; Germany: Federal Institute for Drugs and Medical Devices; Great Britain: MHRA; Korea, Republic of: Korea Food and Drug Administration; Philippines: Department of Health; Russia: Ministry of Healthcare and Social Development of Russian Federation, Moscow; Taiwan: Dept of Health Taiwan; Turkey: Ministery of Health; United States: Food and Drug Administration

Additional relevant MeSH terms:

Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
BI 1356
Metformin

Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions
Dipeptidyl-Peptidase IV Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on February 21, 2012