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

Phase 3

Completed

Conditions: Diabetes Mellitus, Type 2

Interventions: Drug: linagliptine 5 mg
Drug: linagliptine 5 mg and pioglitazone 30 mg

Registration Number: NCT00736099

Lead Sponsor: Boehringer Ingelheim

Brief Summary: 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)

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 2122

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
linagliptin 5 mg	linagliptine 5 mg	open label
linagliptin 5 mg and pioglitazone 30 mg	linagliptine 5 mg and pioglitazone 30 mg	open label

Primary Outcome Measures

Name	Time	Method
Frequency of Patients With Adverse Events (AEs)	78 weeks	This includes any AEs detected during routine physical examination and electrocardiogram (ECG) procedures.
Frequency of Patients With Investigator-defined Hypoglycaemic Adverse Events	78 weeks
Frequency of Patients With Significant Adverse Events Based on Standardised MedDRA Query (SMQ)	78 weeks	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'').
Frequency of Patients With Adjudication of Cardiac and Cerebrovascular Events	78 weeks	Patients reported with cardiac and cerebrovascular events qualified for adjudication by the Clinical Event Committee (CEC)
Number of Patients With Abnormalities in Vital Signs	78 weeks	Vital sign abnormalities (any abnormalities found during PE or ECG are reported with adverse events)
Number of Patients With Abnormalities in Haematology: Eosinophils	78 weeks	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	78 weeks	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	78 weeks	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	78 weeks	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	78 weeks	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	78 weeks	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	78 weeks	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: Triglycerides	78 weeks	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: Calcium	78 weeks	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: Alanine Transaminase (ALT)	78 weeks	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: Bilirubin	78 weeks	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: Albumin	78 weeks	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: Uric Acid	78 weeks	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: γ-Glutamyl-transferase (GGT)	78 weeks	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: Lactate Dehydrogenase (LDH)	78 weeks	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: Amylase	78 weeks	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: Creatinine	78 weeks	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: Sodium	78 weeks	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: Glucose	78 weeks	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: Cholesterol	78 weeks	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: Creatinine Kinase	78 weeks	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)	78 weeks	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	78 weeks	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: Alkaline Phosphatase (AP)	78 weeks	For this laboratory parameter, a possibly clinically significant abnormality is defined as a value greater than or equal to 2 times the ULN.

Secondary Outcome Measures

Name	Time	Method
Change in HbA1c From Baseline to Week 6	Baseline and week 6
Change in HbA1c From Baseline to Week 18	Baseline and week 18
Change in HbA1c From Baseline to Week 30	Baseline and week 30
Change in HbA1c From Baseline to Week 42	Baseline and week 42
Change in HbA1c From Baseline to Week 54	Baseline and week 54
Change in HbA1c From Baseline to Week 66	Baseline and week 66
Change in HbA1c From Baseline to Week 78	Baseline and week 78
Number of Patients With HbA1c<7.0% Over Time	78 weeks
Number of Patients With HbA1c<6.5% Over Time	78 weeks
Number of Patients With Lowered HbA1c by at Least 0.5% Over Time	78 weeks
Change in FPG From Baseline to Week 6	Baseline and week 6
Change in FPG From Baseline to Week 18	Baseline and week 18
Change in FPG From Baseline to Week 30	Baseline and week 30
Change in FPG From Baseline to Week 42	Baseline and week 42
Change in FPG From Baseline to Week 54	Baseline and week 54
Change in FPG From Baseline to Week 66	Baseline and week 66
Change in FPG From Baseline to Week 78	Baseline and week 78

Trial Locations

Locations (232): 1218.40.10003 Boehringer Ingelheim Investigational Site
🇺🇸
Chula Vista, California, United States
1218.40.10014 Boehringer Ingelheim Investigational Site
🇺🇸
Spring Valley, California, United States
1218.40.10001 Boehringer Ingelheim Investigational Site
🇺🇸
Walnut Creek, California, United States
1218.40.10021 Boehringer Ingelheim Investigational Site
🇺🇸
Northglenn, Colorado, United States
1218.40.10010 Boehringer Ingelheim Investigational Site
🇺🇸
Hollywood, Florida, United States
1218.40.10011 Boehringer Ingelheim Investigational Site
🇺🇸
Miami, Florida, United States
1218.40.10016 Boehringer Ingelheim Investigational Site
🇺🇸
Eugene, Oregon, United States
1218.40.10002 Boehringer Ingelheim Investigational Site
🇺🇸
Greer, South Carolina, United States
1218.40.10004 Boehringer Ingelheim Investigational Site
🇺🇸
Simpsonville, South Carolina, United States
1218.40.10005 Boehringer Ingelheim Investigational Site
🇺🇸
Dallas, Texas, United States
Scroll for more (222 remaining)
1218.40.10003 Boehringer Ingelheim Investigational Site
🇺🇸Chula Vista, California, United States