Nintedanib in Volunteers With Hepatic Impairment Compared With Healthy Volunteers

Hepatic Insufficiency Clinical Trial

Official title:

Pharmacokinetics, Safety and Tolerability of Nintedanib Single Oral Dose in Male and Female Patients With Different Degrees of Hepatic Impairment (Child-Pugh Classification A and B) as Compared With Nintedanib Administration to Male and Female Healthy Subjects (a Non-blinded, Parallel Group Study of Phase I)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02191865
• Other study ID #: 1199.200
• Secondary ID: 2014-000690-39
• Status: Completed
• Phase: Phase 1
• First received: July 14, 2014
• Last updated: December 21, 2015
• Start date: July 2014
• Est. completion date: January 2015

Study information

• Verified date: December 2015
• Source: Boehringer Ingelheim
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Federal Institute for Drugs and Medical Devices
• Study type: Interventional

Clinical Trial Summary

The primary objective of this study is to investigate the effect of mild (Child-Pugh A, score 5-6) and moderate (Child-Pugh B, score 7-9) hepatic impairment on the pharmacokinetics, safety and tolerability of nintedanib, in comparison with a control group with normal hepatic function following oral administration of nintedanib as single dose.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 33
• Est. completion date: January 2015
• Est. primary completion date: December 2014
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 79 Years

Eligibility

Inclusion criteria:

Healthy subjects:

• Male or female subject, healthy according to the investigator's judgement based on a complete medical history, including a physical examination, vital signs (BP, PR), 12-lead ECG, and clinical laboratory

• Age of 18 to 79 years at screening visit

Hepatically impaired patients as determined by a hepatologist/ gastroenterologist:

• A documented diagnosis of the impaired hepatic function, determined by hepatologist/gastroenterologist/specialist for internal medicine, must be available in the patient´s source data.

• Male or female chronic hepatically impaired patient as determined by screening results and classified as Child-Pugh A (Child-Pugh score of 5-6 points) or as Child-Pugh B (Child-Pugh score of 7-9 points). Hepatic insufficiency must be diagnosed at least 3 months before screening.

• Age of 18 to 79 years at screening visit

Exclusion criteria:

Healthy subjects:

• Any finding in the medical examination (including BP, PR or ECG) deviating from normal and judged as clinically relevant by the investigator

• Any laboratory value outside the reference range at screening visit that the investigator considers to be of clinical relevance

• Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders judged as clinically relevant by the investigator

• Surgery of the gastrointestinal tract that could interfere with kinetics of the trial medication based on the investigator´s judgment

• Women who are breast feeding or of child-bearing potential not using a highly effective method of birth control for at least one month prior to inclusion and at least 3 month after administration of trial medication.

Hepatically impaired patients as determined by a hepatologist/gastroenterologist:

• Medical disorder, condition or history of such that would impair the patient's ability to participate or complete this study in the opinion of the investigator or the sponsor

• Patients with significant diseases other than underlying diagnose of hepatic impairment and concomitant diseases related to it. A significant disease is defined as a disease which in the opinion of the investigator:

• put the patient at risk because of participation in the study

• may influence the results of the study

• is not in a stable condition

• Surgery of the gastrointestinal tract that could interfere with the kinetics of the trial medication based on the investigator´s judgment

• Women who are breast feeding or of child-bearing potential not using a highly effective method of birth control for at least one month prior to inclusion and at least 3 month after administration of trial medication

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hepatic Insufficiency

Intervention

Drug:
• Nintedanib
Soft gelatine capsule
• Nintedanib
Soft gelatine capsule
• Nintedanib
Soft gelatine capsule

Locations

Country	Name	City	State
Germany	1199.200.49001 Boehringer Ingelheim Investigational Site	Kiel

Sponsors (1)

Lead Sponsor	Collaborator
Boehringer Ingelheim

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	AUC (0-inf) of Nintedanib	AUC (0-inf) (Area under the concentration-time curve of the Nintedanib in plasma over the time interval from 0 extrapolated to infinity)	Pre-dose and 1 hour (h), 1.5h, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 36h, 48h, 72h, 96h, 120h, 144h and 168h after drug administration	No
Primary	Cmax of Nintedanib	Cmax (Maximum measured concentration of the Nintedanib in plasma)	Pre-dose and 1 hour (h), 1.5h, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 36h, 48h, 72h, 96h, 120h, 144h and 168h after drug administration	No
Secondary	AUC (0-tz) of Nintedanib	AUC (0-tz) (Area under the concentration-time curve of the Nintedanib in plasma over the time interval from 0 to the last quantifiable drug plasma concentration)	Pre-dose and 1 hour (h), 1.5h, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 36h, 48h, 72h, 96h, 120h, 144h and 168h after drug administration	No
Secondary	Number (%) of Subjects With Drug-related Adverse Events (AEs)	Number (%) of subjects with drug-related Adverse events (AEs)	(AEs) during the 'on-treatment' period (from administration of trial medication until the end of the 28-day residual effect period); Up to 29 days	No

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