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

• ClinicalTrials.gov Identifier: NCT01679613
• Recruitment Status: Completed
• First Posted: September 6, 2012
• Results First Posted: November 27, 2014
• Last Update Posted: November 27, 2014
• Sponsor: Boehringer Ingelheim
• Information provided by (Responsible Party): Boehringer Ingelheim

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
Healthy	Drug: Nintedanib; Drug: Ketoconazole	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 34 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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)
• Study Start Date: September 2012
• Actual Primary Completion Date: November 2012
• Actual Study Completion Date: November 2012

Arms and Interventions

Arm	Intervention/treatment
Experimental: 1 Nintedanib (Reference); single dose, oral with 240 ml water	Drug: Nintedanib; low dose oral administration
Experimental: 2 Nintedanib + Ketoconazole (Test); Nintedanib single dose, Ketoconazole steady state, oral with 240 ml water	Drug: Ketoconazole; oral administration; Drug: Nintedanib; low dose oral administration
Experimental: 3 Nintedanib (Reference); single dose, oral with 240 ml water	Drug: Nintedanib; low or medium dose depending on pilot part
Experimental: 4 Nintedanib + Ketoconazole (Test); Nintedanib single dose, Ketoconazole steady state, oral with 240 ml water	Drug: Nintedanib; low or medium dose depending on pilot part; Drug: Ketoconazole; oral administration

Outcome Measures

Primary Outcome Measures :

1. Area Under the Curve From 0 Extrapolated to Infinity (AUC0-∞) [ Time Frame: 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 ]

   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

2. Maximum Measured Concentration (Cmax) [ Time Frame: 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 ]

   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

Secondary Outcome Measures :

1. Area Under the Curve From 0 to the Last Quantifiable Concentration (AUC0-tz) [ Time Frame: 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 ]

   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

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 55 Years (Adult)
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion criteria:

1. healthy male subjects

Exclusion criteria:

1. Any relevant deviation from healthy conditions

Contacts and Locations

Locations

Germany

1199.161.1 Boehringer Ingelheim Investigational Site

Biberach, Germany

Sponsors and Collaborators

Boehringer Ingelheim

Investigators

• Study Chair: Boehringer Ingelheim; Boehringer Ingelheim

More Information

Additional Information:

Related Info 

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Luedtke D, Marzin K, Jungnik A, von Wangenheim U, Dallinger C. Effects of Ketoconazole and Rifampicin on the Pharmacokinetics of Nintedanib in Healthy Subjects. Eur J Drug Metab Pharmacokinet. 2018 Oct;43(5):533-541. doi: 10.1007/s13318-018-0467-9.

• Responsible Party: Boehringer Ingelheim
• ClinicalTrials.gov Identifier: NCT01679613
• Other Study ID Numbers: 1199.161; 2012-001009-26 ( EudraCT Number: EudraCT )
• First Posted: September 6, 2012
• Results First Posted: November 27, 2014
• Last Update Posted: November 27, 2014
• Last Verified: November 2014

Additional relevant MeSH terms:

Ketoconazole; Nintedanib; Antifungal Agents; Anti-Infective Agents; 14-alpha Demethylase Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Steroid Synthesis Inhibitors; Hormone Antagonists; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Cytochrome P-450 CYP3A Inhibitors; Antineoplastic Agents