Nintedanib in Volunteers With Hepatic Impairment Compared With Healthy Volunteers

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)

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.

Study Overview

• Status: Completed
• Conditions: Hepatic Insufficiency
• Intervention / Treatment: Drug: Nintedanib

• Study Type: Interventional
• Enrollment (Actual): 33
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Kiel, Germany
    • 1199.200.49001 Boehringer Ingelheim Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 79 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: July 1, 2014
• Primary Completion (Actual): December 1, 2014
• Study Completion (Actual): January 1, 2015

Study Registration Dates

• First Submitted: July 14, 2014
• First Submitted That Met QC Criteria: July 14, 2014
• First Posted (Estimate): July 16, 2014

Study Record Updates

• Last Update Posted (Estimate): February 1, 2016
• Last Update Submitted That Met QC Criteria: December 21, 2015
• Last Verified: December 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Liver Failure; Hepatic Insufficiency; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Nintedanib
• Other Study ID Numbers: 1199.200; 2014-000690-39 (EudraCT Number: EudraCT)