Clinical trial NCT04567316: A Study in Healthy Men to Test How BI 1358894 is Taken up and Handled by the Body
Official title: A Phase I, Open-label Trial to Investigate Metabolism and Pharmacokinetics of a Single Dose of [14C] BI 1358894 Administered as Oral Solution (Part 1) and Multiple Doses of BI 1358894 Administered as Film-coated Tablets (Part 2) in Healthy Male Volunteers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2020-09-28
Enrollment: 15
Sex: MALE
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: The main objective of this trial is to investigate the basic pharmacokinetics of BI 1358894 and its metabolites, total radioactivity, including mass balance, excretion pathways and metabolism following a single oral dose of \[14C\] BI 1358894 in Part 1 and to investigate the pharmacokinetics of BI 1358894 and its metabolite(s) following multiple-dose treatment over 21 days with non- radiolabelled compound of BI 1358894 in Part 2.


Eligibility criteria: Inclusion Criteria:

* Healthy male subjects according to the assessment of the investigator, as 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 65 years (inclusive)
* 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 GCP and local legislation
* Male subjects who meet any of the following criteria from screening until 90 days after trial completion:

  * Use of adequate contraception of the female partner, e.g. any of the following methods plus condom: implants, injectables, combined oral or vaginal contraceptives, intrauterine device that started at least two months prior to first study drug administration or barrier method (e.g. diaphragm with spermicide) or,
  * Sexually abstinent or,
  * A vasectomy performed at least 1 year prior to screening (with medical assessment of the surgical success) or,
  * Surgically sterilised female partner (including hysterectomy, bilateral tubal occlusion, or bilateral oophorectomy) or,
  * Postmenopausal female partner, defined as at least 1 year of spontaneous amenorrhea (in questionable cases a blood sample with levels of follicle-stimulating Hormone (FSH) above 40 U/L and estradiol below 30 ng/L is confirmatory)

Exclusion Criteria:

* Any finding in the medical examination (including BP, PR or 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 40 to 100 bpm
* Any laboratory value outside the reference range that the investigator considers to be of clinical relevance
* C-reactive protein (CRP) \> upper limit of normal (ULN), liver or kidney parameter above ULN
* 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
* For Part 1 only:

  * Participation in another absorption, distribution, metabolism, and excretion (ADME) pharmacokinetics study with a radiation burden of \>0.1 millisievert (mSv) in the period of 1 year prior to screening
  * Exposure to radiation for diagnostic reasons (except dental X-rays and plain X-rays of thorax and bony skeleton (excluding spinal column)) in the period of 1 year prior to screening
  * Irregular defecation pattern (less than a mean of one bowel movement every 1 or 2 days)

In addition, the following Severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) specific exclusion criterion apply:

* A positive test indicating an ongoing infection with SARS-CoV-2 and clinical symptoms suggestive of the disease
* Further exclusion criteria apply

Primary outcomes:
measure: Part 1: Mass Balance and Recoveries of [14C] BI 1358894 Total Radioactivity in Urine and Faeces After Single Oral Dose (Fe0-tz)
timeFrame: From within 2 hours predose up to 50 days after dosing. For detailed time frames please refer to the intervals given under "measure description" above.
Secondary outcomes:
measure: Part 1: Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz)
timeFrame: At 2 hours (h) before first drug administration and at 20 minutes (min), 40min, 1h, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 36h, 48h, 72h, 96h, 120h, 144h, 192h, 240h, 288h, 336h, 485h, 653h after first drug administration.
measure: Part 1: Maximum Measured Concentration of the Analyte in Plasma (Cmax)
timeFrame: At 2 hours (h) before first drug administration and at 20 minutes (min), 40min, 1h, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 36h, 48h, 72h, 96h, 120h, 144h, 192h, 240h, 288h, 336h, 485h, 653h after first drug administration.
measure: Part 2: Area Under the Concentration-time Curve of Non-radiolabeled BI 1358894 in Plasma Over the Time Interval From 0 to 24 (AUC0-24)
timeFrame: At 2 hours (h) before first drug administration and at 30 minutes (min), 1h, 2h, 4h, 5h, 6h, 7h, 8h, 10h, 12h, 14h and 24h after first drug administration.
measure: Part 2: Maximum Measured Concentration of Non-radiolabeled BI 1358894 in Plasma (Cmax)
timeFrame: At 2 hours (h) before first drug administration and at 30 minutes (min), 1h, 2h, 4h, 5h, 6h, 7h, 8h, 10h, 12h, 14h and 24h after first drug administration.
measure: Part 2: Area Under the Concentration-time Curve of Non-radiolabeled BI 1358894 in Plasma at Steady State Over a Uniform Dosing Interval τ (AUCτ,ss)
timeFrame: At 480h, 480.5h, 481h, 482h, 484h, 485h, 486h, 487h,488h, 490h, 492h, 494h and 504h after first drug administration.
measure: Part 2: Maximum Measured Concentration of Non-radiolabeled BI 1358894 in Plasma at Steady State Over a Uniform Dosing Interval τ (Cmax,ss)
timeFrame: At 480h, 480.5h, 481h, 482h, 484h, 485h, 486h, 487h,488h, 490h, 492h, 494h and 504h after first drug administration.
Other outcomes:
Locations:
city: Groningen
country: Netherlands
facility: ICON
Study officials:
References: