A Study to Investigate the Effects of Donepezil on the Pharmacokinetics of BI 425809 and Vice Versa in Healthy Male and Female Subjects (Open-label, Two-treatment, Two-period, One Fixed Sequence Cross-over Design)
Overview
- Phase
- Phase 1
- Intervention
- Donepezil
- Conditions
- Healthy
- Sponsor
- Boehringer Ingelheim
- Enrollment
- 32
- Locations
- 1
- Primary Endpoint
- Area Under the Concentration-time Curve of BI 425809 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞)
- Status
- Completed
- Last Updated
- 5 years ago
Overview
Brief Summary
The main objective of Part 1of this trial is to investigate the effect of co-administration of multiple doses of donepezil on the single-dose pharmacokinetics of BI 425809 in healthy subjects. In Part 2 the main objective is the investigation of the effect of co-administration of multiple doses of BI 425809 on the single-dose pharmacokinetics of donepezil in healthy subjects.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Healthy male or female subjects according to the assessment of the investigator, as based on a complete medical history including a physical examination, vital signs (Blood Pressure (BP), Pulse Rate (PR)), 12- lead Electrocardiogram (ECG), and clinical laboratory tests
- •Age of 18 to 50 years (inclusive)
- •Body Mass Index (BMI) of 18.5 to 29.9 kg/m2 (inclusive)
- •Signed and dated written informed consent prior to admission to the study, in accordance with Good Clinical Practice (GCP) and local legislation
- •Male subjects, or female subjects who meet any of the following criteria from the first administration of trial medication until 30 days after trial completion:
- •Use of adequate contraception that does not contain hormones, i.e. non-hormonal intrauterine device plus condom
- •Sexually abstinent
- •A vasectomised sexual partner (vasectomy at least 1 year prior to enrolment)
- •Surgically sterilised (including hysterectomy)
- •Postmenopausal, defined as at least 1 year of spontaneous amenorrhea (in questionable cases a blood sample with levels of FSH above 40 U/L and estradiol below 30 ng/L is confirmatory)
Exclusion Criteria
- •Any finding in the medical examination (including Blood Pressure (BP), Pulse Rate (PR) or Electrocardiogram (ECG)) deviating from normal and assessed 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 50 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 assessed as clinically relevant by the investigator
- •Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders
- •Cholecystectomy or other surgery of the gastrointestinal tract that could interfere with the pharmacokinetics of the trial medication (except appendectomy or 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)
Arms & Interventions
Part 2
Intervention: Donepezil
Part 1
Intervention: BI 425809
Part 1
Intervention: Donepezil
Part 2
Intervention: BI 425809
Outcomes
Primary Outcomes
Area Under the Concentration-time Curve of BI 425809 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞)
Time Frame: Detailed time frame is in the description section
Area under the concentration-time curve of BI 425809 in plasma over the time interval from 0 extrapolated to infinity (AUC0-∞). For BI 425809 alone (Part 1: Treatment A, Reference 1) and BI 425809 + donepezil (Part 1: Treatment B, Test 1) plasma concentrations of BI 425809 were measured within 2 hours (h) before and at 30 minutes (min), 1 h, 2h, 3h, 3h 30min, 4h, 4h 30min, 5h, 6h, 8h, 10h, 12h, 24h, 34h, 48h, 72h, 96h, 120h, 144h, 168h after administration of BI 425809 alone or in combination with donepezil.
Area Under the Concentration-time Curve of Donepezil in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞)
Time Frame: Detailed time frame is in the description section
Area under the concentration-time curve of donepezil in plasma over the time interval from 0 extrapolated to infinity (AUC0-∞). For donepezil alone (Part 2: Treatment C, Reference 2) and donepezil + BI 425809 (Part 2: Treatment D, Test 2) concentrations of donepezil were measured within 2 hours (h) before and at 1h, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 18h, 24h, 48h, 72h, 96h, 120h, 144h, 168h, 192h, 216h, 240h, 264h, 288h, 312h, 336h, after administration of donepezil alone or in combination with BI 425809.
Maximum Measured Concentration of BI 425809 in Plasma (Cmax)
Time Frame: Detailed time frame is in the description section
Maximum measured concentration of BI 425809 in plasma (Cmax). For BI 425809 alone (Part 1: Treatment A, Reference 1) and BI 425809 + donepezil (Part 1: Treatment B, Test 1) concentrations of BI 425809 were measured within 2 hours (h) before and at 30 minutes (min), 1 h, 2h, 3h, 3h 30min, 4h, 4h 30min, 5h, 6h, 8h, 10h, 12h, 24h, 34h, 48h, 72h, 96h, 120h, 144h, 168h after administration of BI 425809 alone or in combination with donepezil.
Maximum Measured Concentration of Donepezil in Plasma (Cmax)
Time Frame: Detailed time frame is in the description section
Maximum measured concentration of donepezil in plasma (Cmax). For donepezil alone (Part 2: Treatment C, Reference 2) and donepezil + BI 425809 (Part 2: Treatment D, Test 2) concentrations of donepezil were measured withing 2 hours (h) before and at 1h, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 18h, 24h, 48h, 72h, 96h, 120h, 144h, 168h, 192h, 216h, 240h, 264h, 288h, 312h, 336h, after administration of donepezil alone or in combination with BI 425809.
Secondary Outcomes
- Area Under the Concentration-time Curve of BI 425809 in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz)(Detailed time frame is in the description section)
- Area Under the Concentration-time Curve of Donepezil in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz)(Detailed time frame is in the description section)