Investigation of Drug-drug Interaction of Nintedanib and Ketoconazole in Healthy Male Volunteers

Study Overview
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Brief Summary
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The objective of the current study is to investigate the relative bioavailability of a single dose of nintedanib low or high dose with and without coadministration of ketoconazole at steady state

Official Title
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Relative Bioavailability of Nintedanib Given Alone and in Combination With Ketoconazole at Steady State in Healthy Male Volunteers (an Open-label, Randomised, Two-way Cross-over Clinical Phase I Study)

Conditions
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Healthy

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


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: 1. healthy male subjects Exclusion criteria: 1. Any relevant deviation from healthy conditions

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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Male

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: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1 Nintedanib (Reference)<br>single dose, oral with 240 ml water | Drug: Nintedanib<br>* low dose oral administration<br>|
| Experimental: 2 Nintedanib + Ketoconazole (Test)<br>Nintedanib single dose, Ketoconazole steady state, oral with 240 ml water | Drug: Ketoconazole<br>* oral administration<br>Drug: Nintedanib<br>* low dose oral administration<br>|
| Experimental: 3 Nintedanib (Reference)<br>single dose, oral with 240 ml water | Drug: Nintedanib<br>* low or medium dose depending on pilot part<br>|
| Experimental: 4 Nintedanib + Ketoconazole (Test)<br>Nintedanib single dose, Ketoconazole steady state, oral with 240 ml water | Drug: Nintedanib<br>* low or medium dose depending on pilot part<br>Drug: Ketoconazole<br>* oral administration<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area Under the Curve From 0 Extrapolated to Infinity (AUC0-∞) | AUC0-∞ represents the Area under the concentration-time curve of nintedanib in plasma over the time interval from 0 extrapolated to infinity For this endpoint, the measured values show inter-individual variabilities, whereas the statistical analyses show intra-individual variabilities | 1 hour (h) before drug administration and 1h, 1.5h, 2h, 2.5h, 3h, 3.5h, 4h, 6h, 8h, 10h, 12h, 15h, 24h, 36h, 48h and 72h after the drug administration | 
| Maximum Measured Concentration (Cmax) | Cmax represents the maximum concentration of nintedanib in plasma For this endpoint, the measured values show inter-individual variabilities, whereas the statistical analyses show intra-individual variabilities | 1 hour (h) before drug administration and 1h, 1.5h, 2h, 2.5h, 3h, 3.5h, 4h, 6h, 8h, 10h, 12h, 15h, 24h, 36h, 48h and 72h after the drug administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area Under the Curve From 0 to the Last Quantifiable Concentration (AUC0-tz) | AUC0-tz represents the area under the plasma concentration-time curve of nintedanib from time 0 to the last quantifiable nintedanib plasma concentration. For this endpoint, the measured values show inter-individual variabilities, whereas the statistical analyses show intra-individual variabilities | 1 hour (h) before drug administration and 1h, 1.5h, 2h, 2.5h, 3h, 3.5h, 4h, 6h, 8h, 10h, 12h, 15h, 24h, 36h, 48h and 72h after the drug administration |