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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT00736099
First received: August 14, 2008
Last updated: June 18, 2014
Last verified: December 2013
  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:


Further study details as provided by Boehringer Ingelheim:

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'').

  • Frequency of Patients With Adjudication of Cardiac and Cerebrovascular Events [ Time Frame: 78 weeks ] [ Designated as safety issue: Yes ]
    Patients reported with cardiac and cerebrovascular events qualified for adjudication by the Clinical Event Committee (CEC)

  • 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

  Eligibility

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

Inclusion criteria:

  1. Signed and dated written informed consent in accordance with the GCP and local legislation.
  2. Patients completing the entire treatment period as a double blind trial whether or not they have been treated with rescue medication.

Exclusion criteria:

  1. Patients who meet one or more of the withdrawal criteria of the treatment period of the previous trial.
  2. Pre-menopausal women (last menstruation =< 1 year prior to signing 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 submit to periodic pregnancy testing during participation in the trial. Acceptable methods of birth control include transdermal patch, intra uterine devices/systems (IUDs/IUSs), oral, implantable or injectable contraceptives, true sexual abstinence (when this is in line with the preferred and usual lifestyle of the patient; periodic abstinence [e.g. calendar, ovulation, symptothermal, post-ovulation methods] and withdrawal are not acceptable methods of birth control) and vasectomised partners. No exception will be made.
  3. Alcohol abuse within the 3 months prior to informed consent that would interfere with trial participation.
  4. Drug abuse which, in the opinion of the investigator, would interfere with trial participation.
  5. Any other clinical condition which, in the opinion of the investigator, would not allow safe completion of the protocol and safe administration of the trial medication.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00736099

  Show 232 Study Locations
Sponsors and Collaborators
Boehringer Ingelheim
Investigators
Study Chair: Boehringer Ingelheim Boehringer Ingelheim
  More Information

Additional Information:
No publications provided

Responsible Party: Boehringer Ingelheim
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: June 18, 2014
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, FAMHP
Canada: Health Canada, Therapeutic Products Directorate
China: 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 July 22, 2014