Pharmacokinetics and Pharmacodynamics of BI 1356 in Subjects With Different Degrees of Liver Impairment as Compared to Healthy Subjects

NCT02183376 | Completed Phase 1

• 1 other identifier: 1218.27
• Study Type: interventional
• Target: 33
• Locations: 0 countries
• Sites: N/A

Brief Summary

To investigate the influence of mild, moderate, and severe liver impairment on the pharmacokinetics and pharmacodynamics of linagliptin in comparison with a control group with normal hepatic function after single or multiple oral administration of 5 mg linagliptin tablets

Conditions

Hepatic Insufficiency

Outcome Measures

Primary Outcomes (4)

• AUCτ,ss (area under the concentration time curve of the analyte in plasma over the time interval from 0 to 24 h after the last dose at steady state) for healthy patients and patients with mild and moderate liver impairment

  up to day 12

• Cmax,ss (maximum concentration of the analyte in plasma at steady state) for healthy patients and patients with mild and moderate liver impairment

  up to day 12

• AUC0-24 (area under the concentration time curve of the analyte in plasma over the time interval from 0 to 24 h after the first dose) for patients with severe liver impairment

  up to 24 hours after drug administration

• Cmax (maximum concentration of the analyte in plasma) for patients with severe liver impairment

  up to day 6

Secondary Outcomes (22)

• Plasma protein binding

  up to day 12

• Model-derived AUCτ,ss for patients with severe liver impairment

  up to day 6

• Model-derived Cmax,ss for patients with severe liver impairment

  up to day 6

• Plasma dipeptidyl peptidase-4 (DPP-4) activity

  up to day 6

• Plasma DPP-4 concentration

  Day 1 (Baseline)

Study Arms (4)

BI 1356 - healthy subjects

EXPERIMENTAL

Drug: BI 1356

BI 1356 - mild liver impairment

EXPERIMENTAL

Drug: BI 1356

BI 1356 - moderate liver impairment

EXPERIMENTAL

Drug: BI 1356

BI 1356 - severe liver impairment

EXPERIMENTAL

Drug: BI 1356

Interventions

BI 1356 DRUG

BI 1356 - healthy subjects; BI 1356 - mild liver impairment; BI 1356 - moderate liver impairment; BI 1356 - severe liver impairment

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with hepatic impairment determined by results of screening classified as mild (Child-Pugh class A, score 6 points), moderate (Child-Pugh class B, score 7 to 9 points) or severe (Child-Pugh class C, score 10 to 15 points)
• Healthy males and females based on a complete medical history, including physical examination, vital signs (BP, PR), 12-lead ECG, and clinical laboratory tests
• Subjects in the respective groups were matched with regard to age (±10 years), weight (±20%) and gender
• Age 18 to 70 years, inclusive
• Body mass index 18.5 to 29.9 kg/m2, inclusive

You may not qualify if:

• Signed and dated written informed consent prior to admission to the study in accordance with good clinical practice and local legislation
• Surgery of the gastrointestinal tract (except appendectomy and oesophageal varices)
• Diseases of the central nervous system (such as epilepsy) or psychiatric disorders or neurological disorders (except hepatoportal encephalopathy)
• History of relevant orthostatic hypotension, fainting spells, or blackouts
• Chronic or relevant acute infections (except non-progressive chronic hepatitis not being in a progressive state)
• History of relevant allergy or hypersensitivity (including allergy to study drug or its excipients)
• Use of drugs which might reasonably influence the results of the trial or prolong the QT or QTc intervals (based on the knowledge at the time of preparing the Clinical Trial Protocol) within 10 days prior to study drug administration or during the trial
• Participation in another trial with an investigational drug within 2 months prior to study drug administration or during the trial
• Smoking (more than 10 cigarettes, 3 cigars, or 3 pipes per day)
• Inability to refrain from smoking on trial days
• Alcohol abuse (more than 60 g/day)
• Drug abuse
• Blood donation (\>100 mL within 4 weeks prior to study drug administration or during the trial)
• Excessive physical activities (within 1 week prior to study drug administration or during the trial)
• Inability to comply with dietary regimen of trial site

Sponsors & Collaborators

• Boehringer Ingelheim: lead

MeSH Terms

Conditions

Hepatic Insufficiency

Interventions

Linagliptin

Condition Hierarchy (Ancestors)

Liver Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Quinazolines

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 4, 2014
• First Posted: July 8, 2014
• Study Start: July 1, 2008
• Primary Completion: March 1, 2009
• Last Updated: July 8, 2014

Record last verified: 2014-07