Nintedanib in Volunteers With Hepatic Impairment Compared With Healthy Volunteers

Study Overview
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Brief Summary
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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.

Official Title
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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)

Conditions
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Hepatic Insufficiency

Intervention / Treatment
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* Drug: Nintedanib
* Drug: Nintedanib
* Drug: Nintedanib


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 79 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Mild liver impairment<br>Patients with mild hepatic impaired function (Child-Pugh A) | Drug: Nintedanib<br>* Soft gelatine capsule<br>|
| Experimental: Moderate liver impairment<br>Patients with moderate hepatic impaired function (Child-Pugh B) | Drug: Nintedanib<br>* Soft gelatine capsule<br>|
| Experimental: Healthy volunteers<br>Healthy control subjects | Drug: Nintedanib<br>* Soft gelatine capsule<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| 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 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| 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 |