Influence of Bosentan on the Pharmacokinetics of Nintedanib

• ClinicalTrials.gov Identifier: NCT02667704
• Recruitment Status: Completed
• First Posted: January 29, 2016
• Results First Posted: April 13, 2017
• Last Update Posted: April 13, 2017
• Sponsor: Boehringer Ingelheim
• Information provided by (Responsible Party): Boehringer Ingelheim

Study Description

Brief Summary:

The trial was designed to investigate whether, and to which extent, multiple doses of bosentan may influence the plasma levels of nintedanib administered as a single dose.

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

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 13 participants
• Allocation: Non-Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Influence of Bosentan on the Pharmacokinetics of Nintedanib in Healthy Male Subjects
• Study Start Date: February 2016
• Actual Primary Completion Date: March 2016
• Actual Study Completion Date: March 2016

Arms and Interventions

Arm	Intervention/treatment
Experimental: Nintedanib	Drug: Nintedanib
Experimental: Bosentan	Drug: Bosentan

Outcome Measures

Primary Outcome Measures :

1. Area Under the Concentration-time Curve of Nintedanib in Plasma Over the Time Interval From 0 to the Last Quantifiable Concentration (AUC0-tz) [ Time Frame: Up to 216 hours. The details are mentioned in description. ]
   Area under the concentration-time curve of Nintedanib in plasma over the time interval from 0 to the last quantifiable concentration (AUC0-tz). PK plasma samples were taken at: 1 hour (h) before drug administration (approximate time for predose sample) and 30 minutes, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 5h, 6h, 8h, 10h, 12h, 24h, 36h, 48h, 72h, 144h, 144.5h, 145h, 145.5h, 146h, 146.5h, 147h, 148h, 149h, 150h, 152h, 154h, 156h, 168h, 180h, 192h, 216h after drug administration. Two different visits; Visit 2 (R): -1 to 72 h, Visit 3 (T) 144 to 216 h. AUC0-tz was calculated for each visit separately.
2. Maximum Measured Concentration of Nintedanib in Plasma (Cmax) [ Time Frame: Up to 216 hours. The details are mentioned in description. ]
   Maximum measured concentration of Nintedanib in plasma (Cmax). PK plasma samples were taken at: 1 hour (h) before drug administration and 30 minutes, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 5h, 6h, 8h, 10h, 12h, 24h, 36h, 48h, 72h, 144h, 144.5h, 145h, 145.5h, 146h, 146.5h, 147h, 148h, 149h, 150h, 152h, 154h, 156h, 168h, 180h, 192h, 216h after drug administration. Two different visits; Visit 2 (R): -1 to 72 h, Visit 3 (T) 144 to 216 h. Cmax was determined for each visit separately.

Secondary Outcome Measures :

1. Area Under the Concentration-time Curve of Nintedanib in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-infinity) [ Time Frame: Up to 216 hours. The details are mentioned in description. ]
   Area under the concentration-time curve of Nintedanib in plasma over the time interval from 0 extrapolated to infinity (AUC0-infinity). PK plasma samples were taken at: 1 hour (h) before drug administration and 30 minutes, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 5h, 6h, 8h, 10h, 12h, 24h, 36h, 48h, 72h, 144h, 144.5h, 145h, 145.5h, 146h, 146.5h, 147h, 148h, 149h, 150h, 152h, 154h, 156h, 168h, 180h, 192h, 216h after drug administration. Two different visits; Visit 2 (R): -1 to 72 h, Visit 3 (T) 144 to 216 h. AUC0-infinity was calculated for each visit separately.

Eligibility Criteria

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

Criteria

Inclusion criteria:

• Healthy male subjects according to the investigators assessment, based on a complete medical history including a physical examination, vital signs (BP, PR), 12-lead ECG, and clinical laboratory tests
• Age of 18 to 55 years (incl.)
• BMI of 18.5 to 29.9 kg/m2 (incl.)
• Signed and dated written informed consent prior to admission to the study in accordance with GCP and local legislation
• Males who are willing to use a medically acceptable method of contraception during the study (from start of treatment until end of trial examination). Acceptable methods of contraception for use by male volunteers include sexual abstinence, a vasectomy performed at least 1 year prior to dosing, and barrier contraception (condom). Subjects, who are not vasectomised or sexually abstinent have to ensure that an additional acceptable method of contraception will be used by his female partner such as IUD (intrauterine device), surgical sterilisation (including hysterectomy), hormonal contraception (e.g. implants, injectables, combined oral or vaginal contraceptives) that started at least 2 months prior to first nintedanib administration, or barrier method (e.g. diaphragm with spermicide).

Exclusion criteria:

• Any finding in the medical examination (including BP, PR or ECG) is deviating from normal and judged as clinically relevant by the investigator
• Repeated measurement of systolic blood pressure outside the range of 90 to 140 mmHg, diastolic blood pressure outside the range of 50 to 90 mmHg, or pulse rate outside the range of 45 to 90 bpm
• Any laboratory value outside the reference range that the investigator considers to be of clinical relevance
• Any evidence of a concomitant disease judged as clinically relevant by the investigator
• Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders
• Cholecystectomy and/or surgery of the gastrointestinal tract that could interfere with the pharmacokinetics of the trial medication (except appendectomy and simple hernia repair)
• Diseases of the central nervous system (including but not limited to any kind of seizures or stroke), and other relevant neurological or psychiatric disorders
• History of relevant orthostatic hypotension, fainting spells, or blackouts
• Chronic or relevant acute infections
• History of relevant allergy or hypersensitivity (including allergy to the trial medication or its excipients)
• Intake of drugs with a long half-life (more than 24 h) within 30 days or less than 10 half-lives of the respective drug prior to administration of trial medication
• Within 10 days prior to administration of trial medication, use of drugs that might reasonably influence the results of the trial
• Participation in another trial where an investigational drug has been administered within 60 days prior to planned administration of trial medication
• Smoker (more than 10 cigarettes or 3 cigars or 3 pipes per day)
• Inability to refrain from smoking on specified trial days
• Alcohol abuse (consumption of more than 30 g per day for males)
• Drug abuse or positive drug screening
• Blood donation of more than 100 mL within 30 days prior to administration of trial medication or intended donation during the trial
• Intention to perform excessive physical activities within one week prior to administration of trial medication or during the trial
• Inability to comply with dietary regimen of trial site
• Subject is assessed as unsuitable for inclusion by the investigator, for instance, because considered not able to understand and comply with study requirements, or has a condition that would not allow safe participation in the study
• Laboratory parameters ALT, AST or GGT outside the reference range
• Intake of drugs that inhibit the efflux of bile salts (e.g. rifampicin, glibenclamide, cyclosporine) within 30 days prior to administration of trial medication

Contacts and Locations

Locations

Germany

Boehringer Ingelheim Investigational Site

Biberach, Germany

Sponsors and Collaborators

Boehringer Ingelheim

Investigators

• Study Chair: Boehringer Ingelheim; Boehringer Ingelheim

More Information

Additional Information:

Related Info 

• Responsible Party: Boehringer Ingelheim
• ClinicalTrials.gov Identifier: NCT02667704
• Other Study ID Numbers: 1199.239; 2015-003819-38 ( EudraCT Number: EudraCT )
• First Posted: January 29, 2016
• Results First Posted: April 13, 2017
• Last Update Posted: April 13, 2017
• Last Verified: March 2017

Additional relevant MeSH terms:

Nintedanib; Bosentan; Antineoplastic Agents; Protein Kinase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Endothelin Receptor Antagonists