Clinical trial NCT02597998: Metabolism and Pharmacokinetics of [14C]-BI 409306 After Administration as Oral Solution in Healthy Male Volunteers
Official title: Metabolism and Pharmacokinetics of [14C]-BI 409306 After Administration of 25 mg [14C]-BI 409306 as Oral Solution in Healthy Male Volunteers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2015-11-05
Enrollment: 6
Sex: MALE
Minimum age (years): 30
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The aim of this study is to assess the mass balance recovery from excreta of carbon 14 labelled BI409306 (\[14C\] BI 409306) in healthy, CYP2C19 genotyped subjects and to provide plasma, urine and faecal samples for metabolite profiling and structural identification.


Eligibility criteria: Inclusion criteria:

1. Healthy male genotyped as CY2C19 poor metabolizer (PM) or extensive metabolizer (EM) according to the investigator's assessment, based on a complete medical history including a physical examination, vital signs (BP - Blood Pressure, PR - Pulse Rate), 12-lead ECG (Electrogardiogramm), and clinical laboratory tests. PM is defined as carrier of two non-functional alleles \*2 and \*3 of the CYP2C19 gene (diplotypes \*2/\*2; \*2/\*3; \*3/\*3). EM is defined as carrier of two functional alleles of the CYP2C19 gene (absence of \*2, \*3, \*17; diplotype \*1/\*1).
2. Age of 30 to 65 years (incl.).
3. BMI (Body Mass Index) of 18.5 to 29.9 kg/m2 (incl.).
4. Signed and dated written informed consent prior to admission to the study in accordance with GCP and local legislation.
5. A history of regular bowel movements (averaging 1 or more bowel movements per day; subjects with regular bowel movements of \>3 per day will be excluded).
6. Subjects who are sexually active must use, with their partner, 2 approved methods of highly effective contraception from the time of IMP administration until 90 days after the last dose of IMP.

Exclusion criteria:

1. Any finding in the medical examination (including BP - Blood Pressure, PR - Pulse Rate or ECG - Electrocardiogramm) is deviating from normal and judged as clinically relevant by the investigator
2. 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
3. Any laboratory value outside the reference range that the investigator considers to be of clinical relevance
4. Any evidence of a concomitant disease judged as clinically relevant by the investigator
5. Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders. Any significant history of ocular or eye disease.
6. Surgery of the gastrointestinal tract that could interfere with kinetics of the trial medication (except appendectomy and simple hernia repair)
7. Diseases of the central nervous system (including but not limited to any kind of seizures or stroke), and other relevant neurological or psychiatric disorders

Primary outcomes:
measure: Mass Balance Recovery of Total Radioactivity in Urine and Faeces: Amount Excreted Within the Time Interval From 0 to the Time of the Last Quantifiable Data Point as a Percentage of the Administered Dose (fe0-tz) for Urine and Faeces
timeFrame: Urine and faeces sample collection: 17 hours before and up to 216 hours after drug administration. The details are mentioned in description section.
Secondary outcomes:
measure: Maximum Measured Concentration of BI 409306 in Plasma (Cmax)
timeFrame: PK plasma samples were taken at: 2:00 (hour: minute) before drug administration and 0:10, 0:20, 0:30, 0:45, 1, 1:30, 2, 2:30, 3, 4, 6, 8, 10, 12, 14, 24, 36, 48, 72, 96, 120, 144, 168 hours after drug administration.
measure: Maximum Measured Concentration of 14C-BI 409306 Related Radioactivity in Plasma (Cmax)
timeFrame: PK plasma samples were taken at: 2:00 (hour: minute) before drug administration and 0:10, 0:20, 0:30, 0:45, 1, 1:30, 2, 2:30, 3, 4, 6, 8, 10, 12, 14, 24, 36, 48, 72, 96, 120, 144, 168 hours after drug administration.
measure: Area Under the Concentration-time Curve Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz) for BI 409306 in Plasma
timeFrame: PK plasma samples were taken at: 2:00 (hour: minute) before drug administration and 0:10, 0:20, 0:30, 0:45, 1, 1:30, 2, 2:30, 3, 4, 6, 8, 10, 12, 14, 24, 36, 48, 72, 96, 120, 144, 168 hours after drug administration.
measure: Area Under the Concentration-time Curve Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz) for 14C-BI 409306 Related Radioactivity in Plasma
timeFrame: PK plasma samples were taken at: 2:00 (hour: minute) before drug administration and 0:10, 0:20, 0:30, 0:45, 1, 1:30, 2, 2:30, 3, 4, 6, 8, 10, 12, 14, 24, 36, 48, 72, 96, 120, 144, 168 hours after drug administration.
Other outcomes:
Locations:
city: Nottingham
country: United Kingdom
facility: Quotient Sciences
Study officials:
affiliation: Boehringer Ingelheim
name: Boehringer Ingelheim
role: STUDY_CHAIR
References: