Clinical trial NCT02191865: Nintedanib in Volunteers With Hepatic Impairment Compared With Healthy Volunteers
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Hepatic Insufficiency
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2014-07-16
Enrollment: 33
Sex: ALL
Minimum age (years): 18
Maximum age (years): 79
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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

Primary outcomes:
measure: AUC (0-inf) of Nintedanib
timeFrame: 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
measure: Cmax of Nintedanib
timeFrame: 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
Secondary outcomes:
measure: AUC (0-tz) of Nintedanib
timeFrame: 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
measure: Number (%) of Subjects With Drug-related Adverse Events (AEs)
timeFrame: (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
Other outcomes:
Locations:
city: Kiel
country: Germany
facility: 1199.200.49001 Boehringer Ingelheim Investigational Site
Study officials:
affiliation: Boehringer Ingelheim
name: Boehringer Ingelheim
role: STUDY_CHAIR
References: