Safety and Efficacy of Linagliptin (BI 1356) as Monotherapy or in Combination in Type 2 DM - Full Text View

Sponsor:	Boehringer Ingelheim Pharmaceuticals
Information provided by (Responsible Party):	Boehringer Ingelheim Pharmaceuticals
ClinicalTrials.gov Identifier:	NCT00736099

Purpose

The objective of the current study is to investigate the safety and tolerability of BI 1356 (5 mg / once daily) given for 78 weeks in different modalities of treatment.

The treatment modalities are determined by the treatment in the blinded trial in which every patient was included previously as BI 1356 in monotherapy (patients in 1218.16 trial), BI 1356 in combination with pioglitazone (patients in 1218.15 trial), BI 1356 added to metformin background (patients in 1218.17 trial) or BI 1356 added to a background therapy of metformin in combination with a sulphonylurea (patients in 1218.18 study)

Condition	Intervention	Phase
Diabetes Mellitus, Type 2	Drug: linagliptine 5 mg Drug: linagliptine 5 mg and pioglitazone 30 mg	Phase 3

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Safety Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	A 78 Week Open Label Extension to Trials Assessing the Safety and Efficacy of BI 1356 (5 mg) as Monotherapy or in Combination With Other Antidiabetic Medications in Type 2 Diabetic Patients.

Resource links provided by NLM:

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

MedlinePlus related topics: Diabetes Diabetes Medicines Diabetes Type 2 Potassium

Drug Information available for: Pioglitazone Pioglitazone hydrochloride Linagliptin

U.S. FDA Resources

Further study details as provided by Boehringer Ingelheim Pharmaceuticals:

Primary Outcome Measures:

Frequency of Patients With Adverse Events (AEs) [ Time Frame: 78 weeks ] [ Designated as safety issue: Yes ]
This includes any AEs detected during routine physical examination and electrocardiogram (ECG) procedures.
Frequency of Patients With Investigator-defined Hypoglycaemic Adverse Events [ Time Frame: 78 weeks ] [ Designated as safety issue: Yes ]
Frequency of Patients With Significant Adverse Events Based on Standardised MedDRA Query (SMQ) [ Time Frame: 78 weeks ] [ Designated as safety issue: Yes ]
As significant adverse events are considered: renal Aes (SMQ 'acute renal failure'), hypersensitivity reactions ('anaphylactic reactions' and 'angioedema'), hepatic Aes ('hepatitis, non-infectious', 'hepatic failure, fibrosis, cirrhosis and other liver damage-related conditions', 'liver-related investigations, signs and symptoms', 'cholestasis and jaundice of hepatic origin'), severe cutaneous adverse reactions ('severe cutaneous adverse reaction'), pancreatitis ('acute pancreatitis', 'chronic pancreatitis'').
Number of Patients With Abnormalities in Vital Signs [ Time Frame: 78 weeks ] [ Designated as safety issue: Yes ]
vital sign abnormalities (any abnormalities found during PE or ECG are reported with adverse events)
Number of Patients With Abnormalities in Haematology: Eosinophils [ Time Frame: 78 weeks ] [ Designated as safety issue: Yes ]
For this laboratory parameter, a possibly clinically significant abnormality is defined as a value greater than or equal to 10%.
Number of Patients With Abnormalities in Haematology: Haemoglobin [ Time Frame: 78 weeks ] [ Designated as safety issue: Yes ]
For this laboratory parameter, a possibly clinically significant abnormality is defined as a value less than or equal to 11.5 g/dL for male and as a value less than or equal to 9.5 g/dL for female patients.
Number of Patients With Abnormalities in Haematology: Haematocrit [ Time Frame: 78 weeks ] [ Designated as safety issue: Yes ]
For this laboratory parameter, a possibly clinically significant abnormality is defined as a value less than or equal to 32%.
Number of Patients With Abnormalities in Haematology: Red Blood Cell Count [ Time Frame: 78 weeks ] [ Designated as safety issue: Yes ]
For this laboratory parameter, a possibly clinically significant abnormality is defined as a value less than 3 * 10^12/L.
Number of Patients With Abnormalities in Haematology: White Blood Cell Count [ Time Frame: 78 weeks ] [ Designated as safety issue: Yes ]
For this laboratory parameter, a possibly clinically significant abnormality is defined as a value less than 3 * 10^9/L (decrease) or a value greater than 20.1 * 10^9/L (increase).
Number of Patients With Abnormalities in Haematology: Platelets [ Time Frame: 78 weeks ] [ Designated as safety issue: Yes ]
For this laboratory parameter, a possibly clinically significant abnormality is defined as value less than or equal to 75 * 10^9/L (decrease) or a value greater than or equal to 700 * 10^9/L (increase).
Number of Patients With Abnormalities in Clinical Chemistry: Potassium [ Time Frame: 78 weeks ] [ Designated as safety issue: Yes ]
For this laboratory parameter, a possibly clinically significant abnormality is defined as a value less than 3 mmol/L (decrease) or a value greater than 5.8 mmol/L (increase).
Number of Patients With Abnormalities in Clinical Chemistry: Uric Acid [ Time Frame: 78 weeks ] [ Designated as safety issue: Yes ]
For this laboratory parameter, a possibly clinically significant abnormality is defined as a value greater than 11 mg/dL for male and as a value greater than 10 mg/dL for female patients.
Number of Patients With Abnormalities in Clinical Chemistry: Triglycerides [ Time Frame: 78 weeks ] [ Designated as safety issue: Yes ]
For this laboratory parameter, a possibly clinically significant abnormality is defined as a value greater than 300 mg/dL.
Number of Patients With Abnormalities in Clinical Chemistry: Amylase [ Time Frame: 78 weeks ] [ Designated as safety issue: Yes ]
For this laboratory parameter, a possibly clinically significant abnormality is defined as a value greater than 1.5 times the upper limit of normal (ULN).
Number of Patients With Abnormalities in Clinical Chemistry: γ-Glutamyl-transferase (GGT) [ Time Frame: 78 weeks ] [ Designated as safety issue: Yes ]
For this laboratory parameter, a possibly clinically significant abnormality is defined as a value greater than or equal to 3 times the ULN.
Number of Patients With Abnormalities in Clinical Chemistry: Creatinine [ Time Frame: 78 weeks ] [ Designated as safety issue: Yes ]
For this laboratory parameter, a possibly clinically significant abnormality is defined as a value greater than or equal to 1.5 mg/dL.
Number of Patients With Abnormalities in Clinical Chemistry: Creatinine Kinase [ Time Frame: 78 weeks ] [ Designated as safety issue: Yes ]
For this laboratory parameter, a possibly clinically significant abnormality is defined as a value greater than or equal to 3 times the ULN.
Number of Patients With Abnormalities in Clinical Chemistry: Phosphate [ Time Frame: 78 weeks ] [ Designated as safety issue: Yes ]
For this laboratory parameter, a possibly clinically significant abnormality is defined as a value less than 0.7 mmol/L (decrease) or a value greater than 1.7 mmol/L (increase).
Number of Patients With Abnormalities in Clinical Chemistry: Calcium [ Time Frame: 78 weeks ] [ Designated as safety issue: Yes ]
For this laboratory parameter, a possibly clinically significant abnormality is defined as a value less than 1.8 mmol/L (decrease) or a value greater than 3 mmol/L (increase).
Number of Patients With Abnormalities in Clinical Chemistry: Sodium [ Time Frame: 78 weeks ] [ Designated as safety issue: Yes ]
For this laboratory parameter, a possibly clinically significant abnormality is defined as a value less than 130 mmol/L (decrease) or a value greater than 160 mmol/L (increase).
Number of Patients With Abnormalities in Clinical Chemistry: Alanine Transaminase (ALT) [ Time Frame: 78 weeks ] [ Designated as safety issue: Yes ]
For this laboratory parameter, a possibly clinically significant abnormality is defined as a value greater than or equal to 3 times the ULN.
Number of Patients With Abnormalities in Clinical Chemistry: Aspartate Transaminase (AST) [ Time Frame: 78 weeks ] [ Designated as safety issue: Yes ]
For this laboratory parameter, a possibly clinically significant abnormality is defined as a value greater than or equal to 3 times the ULN.
Number of Patients With Abnormalities in Clinical Chemistry: Glucose [ Time Frame: 78 weeks ] [ Designated as safety issue: Yes ]
For this laboratory parameter, a possibly clinically significant abnormality is defined as a value less than 54 mg/dL.
Number of Patients With Abnormalities in Clinical Chemistry: Bilirubin [ Time Frame: 78 weeks ] [ Designated as safety issue: Yes ]
For this laboratory parameter, a possibly clinically significant abnormality is defined as a value greater than or equal to 2 mg/dL.
Number of Patients With Abnormalities in Clinical Chemistry: Alkaline Phosphatase (AP) [ Time Frame: 78 weeks ] [ Designated as safety issue: Yes ]
For this laboratory parameter, a possibly clinically significant abnormality is defined as a value greater than or equal to 2 times the ULN.
Number of Patients With Abnormalities in Clinical Chemistry: Albumin [ Time Frame: 78 weeks ] [ Designated as safety issue: Yes ]
For this laboratory parameter, a possibly clinically significant abnormality is defined as a value less than 2.5 g/dL.
Number of Patients With Abnormalities in Clinical Chemistry: Lactate Dehydrogenase (LDH) [ Time Frame: 78 weeks ] [ Designated as safety issue: Yes ]
For this laboratory parameter, a possibly clinically significant abnormality is defined as a value greater than or equal to 3 times the ULN.
Number of Patients With Abnormalities in Clinical Chemistry: Cholesterol [ Time Frame: 78 weeks ] [ Designated as safety issue: Yes ]
For this laboratory parameter, a possibly clinically significant abnormality is defined as a value greater than 300 mg/dL.

Secondary Outcome Measures:

Change in HbA1c From Baseline to Week 6 [ Time Frame: Baseline and week 6 ] [ Designated as safety issue: No ]
Change in HbA1c From Baseline to Week 18 [ Time Frame: Baseline and week 18 ] [ Designated as safety issue: No ]
Change in HbA1c From Baseline to Week 30 [ Time Frame: Baseline and week 30 ] [ Designated as safety issue: No ]
Change in HbA1c From Baseline to Week 42 [ Time Frame: Baseline and week 42 ] [ Designated as safety issue: No ]
Change in HbA1c From Baseline to Week 54 [ Time Frame: Baseline and week 54 ] [ Designated as safety issue: No ]
Change in HbA1c From Baseline to Week 66 [ Time Frame: Baseline and week 66 ] [ Designated as safety issue: No ]
Change in HbA1c From Baseline to Week 78 [ Time Frame: Baseline and week 78 ] [ Designated as safety issue: No ]
Number of Patients With HbA1c<7.0% Over Time [ Time Frame: 78 weeks ] [ Designated as safety issue: No ]
Number of Patients With HbA1c<6.5% Over Time [ Time Frame: 78 weeks ] [ Designated as safety issue: No ]
Number of Patients With Lowered HbA1c by at Least 0.5% Over Time [ Time Frame: 78 weeks ] [ Designated as safety issue: No ]
Change in FPG From Baseline to Week 6 [ Time Frame: Baseline and week 6 ] [ Designated as safety issue: No ]
Change in FPG From Baseline to Week 18 [ Time Frame: Baseline and week 18 ] [ Designated as safety issue: No ]
Change in FPG From Baseline to Week 30 [ Time Frame: Baseline and week 30 ] [ Designated as safety issue: No ]
Change in FPG From Baseline to Week 42 [ Time Frame: Baseline and week 42 ] [ Designated as safety issue: No ]
Change in FPG From Baseline to Week 54 [ Time Frame: Baseline and week 54 ] [ Designated as safety issue: No ]
Change in FPG From Baseline to Week 66 [ Time Frame: Baseline and week 66 ] [ Designated as safety issue: No ]
Change in FPG From Baseline to Week 78 [ Time Frame: Baseline and week 78 ] [ Designated as safety issue: No ]

Enrollment:	2122
Study Start Date:	August 2008
Primary Completion Date:	December 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: linagliptin 5 mg open label	Drug: linagliptine 5 mg safety and efficacy of linagliptine 5 mg open label
Experimental: linagliptin 5 mg and pioglitazone 30 mg open label	Drug: linagliptine 5 mg and pioglitazone 30 mg efficacy and safety of the combination linagliptine and pioglitazone

More Information

Additional Information:

Related Info This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Boehringer Ingelheim Pharmaceuticals
ClinicalTrials.gov Identifier:	NCT00736099 History of Changes
Other Study ID Numbers:	1218.40, 2008-000750-13
Study First Received:	August 14, 2008
Results First Received:	December 21, 2011
Last Updated:	May 18, 2012
Health Authority:	Argentina: A.N.M.A.T. (Administración Nacional de Medicamentos, Alimentos y Tecnología Médica) Austria: Bundesamt für Sicherheit im Gesundheitswesen, A-1030 Vienna Belgium: Federal Agency for Medicines and Health Products Canada: Health Canada, Therapeutic Products Directorate China: State Food and Drug Administration Croatia: Croatian Institute for Medicines Control, HR-10000 Zagreb Czech Republic: State Institute for Drug Control (SUKL), CZ-100 41 Prague 10 Finland: Finnish Medicines Agency Germany: Bundesinstitut fuer Arzneimittel und Medizinprodukte (BfArM), Kurt-Georg-Kiesinger-Allee 3, D-53175 Bonn Great Britain: Medicines and Healthcare products Regulatory Agency (MHRA) Greece: National Organization of Medicines (EOF) National Ethics Committee Hungary: National Institute of Pharmacy, H-1051 Budapest India: Drugs Controller General of India Israel: Ministry of Health Italy: Comitato di Bioetica Azienda Ospedaliero - Universitaria Pisana - PISA Japan: Ministry of Health, Labor and Welfare Korea, Republic of: Korea Food and Drug Administration Malaysia: Drug Control Authority Mexico: Comision Federal para la Proteccion contra Riesgos Sanitarios (COFEPRIS) Netherlands: Centrale Commissie Mensgebonden Onderzoek New Zealand: Multi-Regional Ethics Committee / Medsafe Philippines: Bureau of Food and Drugs Poland: Registration Medicinal Product Medical Device Biocidal Product Romania: National Medicines Agency, Bucharest Russia: Ministry of Healthcare and Social Development of Russian Federation, Moscow Slovakia: SUKL (state institute for drug control), SK-825 08 Bratislava 26 Spain: Agencia Espanola del Medicamento y Productos Sanitarios Sweden: Sweden; Läkemedelsverket (Medical Product Agency) Region Etics Committee of Lund Taiwan: Department of Health, Executive Yuan, Taiwan Thailand: Food and Drug Administration Ukraine: Ministry of Health Care of Ukraine (MoH of Ukraine) United States: Food and Drug Administration

Additional relevant MeSH terms:

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

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 May 24, 2012

Ages Eligible for Study:	18 Years to 82 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No