Healthy
Conditions
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.
Interventions
DRUG14C-BI 409306
Sponsors
Boehringer Ingelheim
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
30 Years to 65 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 | Urine and faeces sample collection: 17 hours before and up to 216 hours after drug administration. The details are mentioned in description section. | 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. Urine collection intervals: -17:00-0:00 hours before drug administration and, 0-4, 4-8, 8-12, 12-24, 24-48, 48-72, 72-96, 96-120, 120-144, 144-168, 168-192 and 192-216 hours after drug administration. Faeces collection intervals: -17:00-0:00, 0-24, 24-48, 48-72, 72-96, 96- 20, 120-144, 144-168, 168-192 and 192-216 hours after drug administration. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Measured Concentration of BI 409306 in Plasma (Cmax) | 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. | Maximum measured concentration of BI 409306 in plasma (Cmax). |
| Maximum Measured Concentration of 14C-BI 409306 Related Radioactivity in Plasma (Cmax) | 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. | Maximum measured concentration of 14C-BI 409306 related radioactivity in plasma (Cmax). |
| 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 | 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. | 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. |
| 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 | 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. | 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. |
Countries
United Kingdom
Participant flow
Recruitment details
The study was an open-label, single-arm, single-dose Phase I trial with healthy male subjects.
Pre-assignment details
All subjects were screened for eligibility prior to participation in the trial. Subjects attended a specialist site which ensured that they (the subjects) strictly met all inclusion and none of the exclusion criteria. Subjects were not to be allocated to a treatment group if any of the entry criteria were violated.
Participants by arm
| Arm | Count |
|---|---|
| 14C-BI 409306 - 25 mg Healthy subjects received one single dose of oral solution containing 25 milligram (mg) of \[14C\]-BI 409306 containing a radioactive dose of approximately 2.00 Megabecquerel (MBq), reconstituted in 50 milliliter (mL) solvent (5 mg/mL tartaric acid solution) | 6 |
| Total | 6 |
Baseline characteristics
| Characteristic | 14C-BI 409306 - 25 mg |
|---|---|
| Age, Continuous | 46.0 Years STANDARD_DEVIATION 6.1 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 5 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 6 Participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 2 / 6 |
| serious Total, serious adverse events | 0 / 6 |
Outcome results
Primary
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
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. Urine collection intervals: -17:00-0:00 hours before drug administration and, 0-4, 4-8, 8-12, 12-24, 24-48, 48-72, 72-96, 96-120, 120-144, 144-168, 168-192 and 192-216 hours after drug administration. Faeces collection intervals: -17:00-0:00, 0-24, 24-48, 48-72, 72-96, 96- 20, 120-144, 144-168, 168-192 and 192-216 hours after drug administration.
Time frame: Urine and faeces sample collection: 17 hours before and up to 216 hours after drug administration. The details are mentioned in description section.
Population: The pharmacokinetic parameter analysis set (PKS) included all subjects in the treated set (TS) who provided at least one primary or secondary pharmacokinetic endpoint value, which was not flagged for exclusion.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| 14C-BI 409306 - 25 mg | 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 | Urine | 84.0 Percentage (%) of dose administered | Geometric Coefficient of Variation 4.42 |
| 14C-BI 409306 - 25 mg | 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 | Faeces | 10.4 Percentage (%) of dose administered | Geometric Coefficient of Variation 10.5 |
| 14C-BI 409306 - 25 mg | 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 | Urine and Faeces | 94.4 Percentage (%) of dose administered | Geometric Coefficient of Variation 4.45 |
Secondary
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
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.
Time frame: 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.
Population: The pharmacokinetic parameter analysis set (PKS) included all subjects in the treated set (TS) who provided at least one primary or secondary pharmacokinetic endpoint value, which was not flagged for exclusion.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 14C-BI 409306 - 25 mg | 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 | 3560 nanomole (nmol) * hour(h) / Litre (L) | Geometric Coefficient of Variation 9.6 |
Secondary
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
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.
Time frame: 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.
Population: The pharmacokinetic parameter analysis set (PKS) included all subjects in the treated set (TS) who provided at least one primary or secondary pharmacokinetic endpoint value, which was not flagged for exclusion.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 14C-BI 409306 - 25 mg | 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 | 357 nanomole (nmol) * hour(h) / Litre (L) | Geometric Coefficient of Variation 36.8 |
Secondary
Maximum Measured Concentration of 14C-BI 409306 Related Radioactivity in Plasma (Cmax)
Maximum measured concentration of 14C-BI 409306 related radioactivity in plasma (Cmax).
Time frame: 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.
Population: The pharmacokinetic parameter analysis set (PKS) included all subjects in the treated set (TS) who provided at least one primary or secondary pharmacokinetic endpoint value, which was not flagged for exclusion.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 14C-BI 409306 - 25 mg | Maximum Measured Concentration of 14C-BI 409306 Related Radioactivity in Plasma (Cmax) | 1600 nanomole (nmol) / Litre (L) | Geometric Coefficient of Variation 15.6 |
Secondary
Maximum Measured Concentration of BI 409306 in Plasma (Cmax)
Maximum measured concentration of BI 409306 in plasma (Cmax).
Time frame: 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.
Population: The pharmacokinetic parameter analysis set (PKS) included all subjects in the treated set (TS) who provided at least one primary or secondary pharmacokinetic endpoint value, which was not flagged for exclusion.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 14C-BI 409306 - 25 mg | Maximum Measured Concentration of BI 409306 in Plasma (Cmax) | 275 nanomole (nmol) / Litre (L) | Geometric Coefficient of Variation 24.3 |