Influence of Bosentan on the Pharmacokinetics of Nintedanib

March 2, 2017 updated by: Boehringer Ingelheim

Influence of Bosentan on the Pharmacokinetics of Nintedanib in Healthy Male Subjects

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

13

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

      • Biberach, Germany
        • Boehringer Ingelheim Investigational Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 55 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Male

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Bosentan
Experimental: Nintedanib

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Up to 216 hours. The details are mentioned in description.
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.
Up to 216 hours. The details are mentioned in description.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Up to 216 hours. The details are mentioned in description.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

February 1, 2016

Primary Completion (Actual)

March 1, 2016

Study Completion (Actual)

March 1, 2016

Study Registration Dates

First Submitted

January 21, 2016

First Submitted That Met QC Criteria

January 28, 2016

First Posted (Estimate)

January 29, 2016

Study Record Updates

Last Update Posted (Actual)

April 13, 2017

Last Update Submitted That Met QC Criteria

March 2, 2017

Last Verified

March 1, 2017

More Information

Terms related to this study

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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