Healthy
Conditions
Brief summary
Phase 1 study to assess the pharmacokinetics and routes of elimination of a single oral dose of \[14C\]-BI 207127 and to characterize the metabolic profile following single dose administration.
Interventions
DRUGBI 207127 NA
Single oral solution dose of BI 207127 NA combined with \[14C\]-BI 207127 NA
Sponsors
Boehringer Ingelheim
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* Body mass index =18.5 and BMI = 29.9 kg/m2 * Subject is willing to avoid sun exposure from the first administration of the trial drug until the end of the study * Male subjects must agree to minimise the risk of female partners becoming pregnant from the dosing day until three months after the completion of the study. Acceptable methods of contraception for male volunteers include a vasectomy no less than three months prior to dosing or barrier contraception. For female partners of male volunteers, acceptable methods of contraception include intra-uterine device, tubal ligation, or hormonal contraceptive for at least three months, or diaphragm with spermicide. * Signed and dated written informed consent prior to admission to the study in accordance with GCP and the local legislation.
Exclusion criteria
* Participation in more than one other radiolabelled investigational study drug trial within 12 months prior to check-in. The previous radiolabelled study drug must have been received more than 6 months prior to check-in for this study and the total exposure from this study and the previous study will be within the recommended levels considered safe, per 21 CFR 361.1 (eg. less than 5,000 mrem whole body annual exposure) * Exposure to significant radiation (eg. serial x-ray or computed tomography scans, barium meal, current employment in a job requiring radiation exposure monitoring) within 12 months prior to check-in * Participation in another trial with an investigational drug within two months prior to administration of the trial drug or during the trial * Use of drugs which might reasonably influence the results of the trial, including use of a broad spectrum antibiotic, within 10 days prior to administration of investigational medication in this trial or during the trial * Intake of a drug with a half-life of \>24 hours within the month prior to administration of trial medication, or if administration of trial medication would occur in the time period in which fewer than 10 half-lives had elapsed * Surgery of the gastrointestinal tract (except appendectomy or cholecystectomy) * Current smoker or smoker in last six months; alcohol abuse (more than 40 g/day); history of illicit drug abuse within the past 2 years * Blood donation (more than 100 mL within four weeks prior to first administration of the trial drug or during the trial) * A marked baseline prolongation of QT/QTc interval (e.g., repeated demonstration of a QTc interval \>450 ms); a history of additional risk factors for torsades de pointes (TdP) (e.g., heart failure, hypokalemia, family history of Long QT Syndrome) * History of photosensitivity or recurrent rash * Irregular defecation pattern (less than one bowel movement a day)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| AUC0-infinity of Plasma Deleobuvir | 15 minutes (min) before drug administration and 30min, 1 hour (h), 1h 30min, 2h, 2h 30min, 3h, 3h 30min, 4h, 5h, 6h, 8h, 10h, 12h, 15h, 24h, 36h, 48h, 72h and 96h after drug administration | Area under the plasma deleobuvir concentration-time curve over the time interval from 0 h extrapolated to infinity (AUC0-infinity) |
| Cmax of Plasma Deleobuvir | 15 minutes (min) before drug administration and 30min, 1 hour (h), 1h 30min, 2h, 2h 30min, 3h, 3h 30min, 4h, 5h, 6h, 8h, 10h, 12h, 15h, 24h, 36h, 48h, 72h and 96h after drug administration | Maximum measured concentration (Cmax) of plasma deleobuvir |
| t1/2 of [14C]-Radioactivity in Plasma | 15 minutes (min) before drug administration and 30min, 1 hour (h), 1h 30min, 2h, 2h 30min, 3h, 3h 30min, 4h, 5h, 6h, 8h, 10h, 12h, 15h, 24h, 36h, 48h, 72h and 96h after drug administration | Terminal half life (T1/2) of \[14C\]-radioactivity in plasma |
| Excretion Balance of Total [14C]-Radioactivity | Before drug administration (24hours (h) to 15 minutes pre-dose) and 0h-24h, 24h-48h, 48h-72h, 72h-96h, 96h-120h, 120h-144h, 144h-168h, 168h-192h and 192h-216h after drug administration | Excretion balance of total \[14C\]-radioactivity (urine and faeces) |
| Excretion of Total [14C]-Radioactivity in Urine | Before drug administration (24hours (h) to 15 minutes pre-dose) and 0h-24h, 24h-48h, 48h-72h, 72h-96h, 96h-120h, 120h-144h, 144h-168h, 168h-192h and 192h-216h after drug administration | Excretion of total \[14C\]-radioactivity in urine |
| Excretion of Total [14C]-Radioactivity in Faeces | Before drug administration (24hours (h) to 15 minutes pre-dose) and 0h-24h, 24h-48h, 48h-72h, 72h-96h, 96h-120h, 120h-144h, 144h-168h, 168h-192h and 192h-216h after drug administration | Excretion of total \[14C\]-radioactivity in faeces |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| All Participants Participants received a single oral dose of 800 mg deleobuvir (BI 207127) sodium salt (NA) powder dissolved in a 20 mL solution of compendial grade sodium lauryl sulfate, tromethamine, polyethylene glycol 400, and water. | 12 |
| Total | 12 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Lost to Follow-up | 3 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | All Participants |
|---|---|
| Age, Continuous | 29.1 Years STANDARD_DEVIATION 11.3 |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 6 / 12 |
| serious Total, serious adverse events | 0 / 12 |
Outcome results
Primary
AUC0-infinity of Plasma Deleobuvir
Area under the plasma deleobuvir concentration-time curve over the time interval from 0 h extrapolated to infinity (AUC0-infinity)
Time frame: 15 minutes (min) before drug administration and 30min, 1 hour (h), 1h 30min, 2h, 2h 30min, 3h, 3h 30min, 4h, 5h, 6h, 8h, 10h, 12h, 15h, 24h, 36h, 48h, 72h and 96h after drug administration
Population: Pharmacokinetic analysis set (PK set) which included all subjects in the treated set who provided at least 1 observation for at least 1 primary PK endpoint without important protocol violations relevant to the evaluation of PK.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| All Participants | AUC0-infinity of Plasma Deleobuvir | 19300 nmol*h/L | Geometric Coefficient of Variation 56.5 |
Primary
Cmax of Plasma Deleobuvir
Maximum measured concentration (Cmax) of plasma deleobuvir
Time frame: 15 minutes (min) before drug administration and 30min, 1 hour (h), 1h 30min, 2h, 2h 30min, 3h, 3h 30min, 4h, 5h, 6h, 8h, 10h, 12h, 15h, 24h, 36h, 48h, 72h and 96h after drug administration
Population: PK set
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| All Participants | Cmax of Plasma Deleobuvir | 3620 nmol/L | Geometric Coefficient of Variation 54.2 |
Primary
Excretion Balance of Total [14C]-Radioactivity
Excretion balance of total \[14C\]-radioactivity (urine and faeces)
Time frame: Before drug administration (24hours (h) to 15 minutes pre-dose) and 0h-24h, 24h-48h, 48h-72h, 72h-96h, 96h-120h, 120h-144h, 144h-168h, 168h-192h and 192h-216h after drug administration
Population: PK set
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| All Participants | Excretion Balance of Total [14C]-Radioactivity | 95.2 Percentage of radioactive dose recovered | Geometric Coefficient of Variation 1.29 |
Primary
Excretion of Total [14C]-Radioactivity in Faeces
Excretion of total \[14C\]-radioactivity in faeces
Time frame: Before drug administration (24hours (h) to 15 minutes pre-dose) and 0h-24h, 24h-48h, 48h-72h, 72h-96h, 96h-120h, 120h-144h, 144h-168h, 168h-192h and 192h-216h after drug administration
Population: PK set
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| All Participants | Excretion of Total [14C]-Radioactivity in Faeces | 95.1 Percentage of radioactive dose recovered | Geometric Coefficient of Variation 1.29 |
Primary
Excretion of Total [14C]-Radioactivity in Urine
Excretion of total \[14C\]-radioactivity in urine
Time frame: Before drug administration (24hours (h) to 15 minutes pre-dose) and 0h-24h, 24h-48h, 48h-72h, 72h-96h, 96h-120h, 120h-144h, 144h-168h, 168h-192h and 192h-216h after drug administration
Population: PK set
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| All Participants | Excretion of Total [14C]-Radioactivity in Urine | 0.137 Percentage of radioactive dose recovered | Geometric Coefficient of Variation 37.8 |
Primary
t1/2 of [14C]-Radioactivity in Plasma
Terminal half life (T1/2) of \[14C\]-radioactivity in plasma
Time frame: 15 minutes (min) before drug administration and 30min, 1 hour (h), 1h 30min, 2h, 2h 30min, 3h, 3h 30min, 4h, 5h, 6h, 8h, 10h, 12h, 15h, 24h, 36h, 48h, 72h and 96h after drug administration
Population: PK set
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| All Participants | t1/2 of [14C]-Radioactivity in Plasma | 2.89 hours | Geometric Coefficient of Variation 36.4 |