Healthy Participants
Conditions
Keywords
INCB099280
Brief summary
This study is being conducted to assess the Mass Balance, Pharmacokinetics, and Metabolite Profiles of a Single Oral Dose of \[14C\]INCB099280 in Healthy Male Participants.
Interventions
DRUGINCB099280
INCB099280 will be administered orally, followed approximately 10 minutes later by an oral dose solution of radiolabeled INCB099280.
Sponsors
Incyte Corporation
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
35 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* Ability to comprehend and willingness to sign a written ICF for the study. * Healthy males, as determined by the investigator based upon physical examinations, ECGs, vital signs, and safety laboratory assessments, aged 35 to 55 years, inclusive, at the time of signing the ICF. * Body mass index between 18.0 and 32.0 kg/m2, inclusive, at the time of screening. * No clinically significant findings in screening evaluations (eg, clinical, laboratory, vital signs, and ECG) at screening and Day -1. * Ability to swallow and retain oral medication.
Exclusion criteria
* History of clinically significant respiratory, renal, gastrointestinal, endocrine, hematopoietic, psychiatric, and/or neurological disease as judged by the investigator. * History of cardiovascular, cerebrovascular, peripheral vascular, or thrombotic disease or uncontrolled hypertension (systolic blood pressure \> 140 mm Hg or diastolic blood pressure \> 90 mmHg at screening, confirmed by repeat testing). * Presence of a malabsorption syndrome (eg, Crohn's disease or chronic pancreatitis) that could possibly affect drug absorption. * Current or recent (within 6 months before screening), clinically significant, gastrointestinal disease or surgery (including cholecystectomy, excluding appendectomy) that could affect the absorption of study drug. * Any major surgery within 6 months of screening. * Donation of blood to a blood bank or in a clinical study (except a screening visit) within 3 months before screening (within 2 weeks for plasma donation). * Positive test for HBV, HCV, or HIV at screening. Participants whose HBV results are compatible with prior immunization or immunity due to infection may be included at the discretion of the investigator. * Regular alcohol consumption \> 21 units per week (1 unit = 8 oz of beer or a 25-mL shot of a 40% spirit; 1.5 to 2 units = a 125-mL glass of wine, depending on type). * Positive breath test for alcohol or positive urine screen for drugs of abuse (confirmed by repeat) at screening or admission (Day -1). * Treatment with another investigational medication within 90 days or 5 half-lives (whichever is longer) before Day 1 or current enrollment in another investigational drug study. * Participation in any clinical study involving a 14C-radiolabeled investigational product within 12 months prior to admission (Day -1). * Radiation exposure, including that from the present study, excluding background radiation but including diagnostic x-rays and other medical exposures, exceeding 5 mSv in the last 12 months or 10 mSv in the last 5 years. No occupationally exposed worker, as defined in the Ionising Radiation Regulations 2017, shall participate in the study. * History of tobacco- or nicotine-containing product use within 1 month before screening. Consumption of tobacco- or nicotine-containing products 72 hours before admission (Day -1) until CRU discharge is not permitted. Breath test for carbon monoxide \> 10 ppm (confirmed by repeat) at screening or admission (Day -1). * Use of prescription drugs within 14 days before Day 1 or nonprescription medications/products (including vitamins, minerals, and phytotherapeutic, herbal, or plant-derived preparations) within 7 days before Day 1 until CRU discharge. However, paracetamol up to 4000 mg Q24H and ibuprofen up to 600 mg Q24H are permitted. Other protocol-defined Inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Total Recovery (Urine + Feces) of the Administered Radioactivity | 264 hours in urine; 408 hours in feces | Radioactivity in urine and feces was reported as the percentage of the administered radioactivity excreted. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Abundance of INCB099280 Metabolites Detected in Feces | 0 hours (predose) and up to 96 hours post-dose | Homogenized fecal samples from individual participants were pooled for each collection interval by taking a fixed percentage of the total amount excreted from each collection interval/participant. The reported values are single measurements of pooled plasma or fecal samples; therefore, no statistical analysis is possible, and data have been reported with a measure type of number. |
| Cmax of INCB099280 | 0 hours (predose) and 0.5, 1, 2, 4, 6, 8, 12, and 16 hours post-dose (Day 1); 24 and 36 hours post-dose (Day 2); 48 hours post-dose (Day 3), 72 hours post-dose (Day 4), 96 hours post-dose (Day 5), 120 hours post-dose (Day 6) | Cmax was defined as the maximum observed plasma or serum concentration of INCB099280. |
| Tmax of INCB099280 | 0 hours (predose) and 0.5, 1, 2, 4, 6, 8, 12, and 16 hours post-dose (Day 1); 24 and 36 hours post-dose (Day 2); 48 hours post-dose (Day 3), 72 hours post-dose (Day 4), 96 hours post-dose (Day 5), 120 hours post-dose (Day 6) | tmax was defined as the time to the maximum concentration of INCB099280. |
| AUC0-t of INCB099280 | 0 hours (predose) and 0.5, 1, 2, 4, 6, 8, 12, and 16 hours post-dose (Day 1); 24 and 36 hours post-dose (Day 2); 48 hours post-dose (Day 3), 72 hours post-dose (Day 4), 96 hours post-dose (Day 5), 120 hours post-dose (Day 6) | AUC0-t was defined as the area under the steady-state plasma or serum concentration-time curve up to the last measurable concentration of INCB099280. |
| AUC0-∞ of INCB099280 | 0 hours (predose) and 0.5, 1, 2, 4, 6, 8, 12, and 16 hours post-dose (Day 1); 24 and 36 hours post-dose (Day 2); 48 hours post-dose (Day 3), 72 hours post-dose (Day 4), 96 hours post-dose (Day 5), 120 hours post-dose (Day 6) | AUC0-∞ was defined as the area under the single-dose plasma or serum concentration-time curve extrapolated to time of infinity. |
| t½ of INCB099280 | 0 hours (predose) and 0.5, 1, 2, 4, 6, 8, 12, and 16 hours post-dose (Day 1); 24 and 36 hours post-dose (Day 2); 48 hours post-dose (Day 3), 72 hours post-dose (Day 4), 96 hours post-dose (Day 5), 120 hours post-dose (Day 6) | t½ was defined as the apparent terminal-phase disposition half-life of INCB099280. |
| CL/F of INCB099280 | 0 hours (predose) and 0.5, 1, 2, 4, 6, 8, 12, and 16 hours post-dose (Day 1); 24 and 36 hours post-dose (Day 2); 48 hours post-dose (Day 3), 72 hours post-dose (Day 4), 96 hours post-dose (Day 5), 120 hours post-dose (Day 6) | CL/F was defined as the apparent oral dose clearance of INCB099280. |
| Vz/F of INCB099280 | 0 hours (predose) and 0.5, 1, 2, 4, 6, 8, 12, and 16 hours post-dose (Day 1); 24 and 36 hours post-dose (Day 2); 48 hours post-dose (Day 3), 72 hours post-dose (Day 4), 96 hours post-dose (Day 5), 120 hours post-dose (Day 6) | Vz/F was defined as the maximum observed plasma or serum concentration of INCB099280. |
| Cmax of Total Radioactivity in Blood | 0 hours (predose) and 0.5, 1, 2, 4, 6, 8, 12, and 16 hours post-dose (Day 1); 24 and 36 hours post-dose (Day 2); 48 hours post-dose (Day 3), 72 hours post-dose (Day 4), 96 hours post-dose (Day 5), 120 hours post-dose (Day 6) | Cmax was defined as the maximum observed concentration of total radioactivity in blood. Additional samples were collected every 24 hours until discharge (up to 264 hours). |
| Tmax of Total Radioactivity in Blood | 0 hours (predose) and 0.5, 1, 2, 4, 6, 8, 12, and 16 hours post-dose (Day 1); 24 and 36 hours post-dose (Day 2); 48 hours post-dose (Day 3), 72 hours post-dose (Day 4), 96 hours post-dose (Day 5), 120 hours post-dose (Day 6) | tmax was defined as the time to the maximum concentration of total radioactivity in blood. Additional samples were collected every 24 hours until discharge (up to 264 hours). |
| AUC0-t of Total Radioactivity in Blood | 0 hours (predose) and 0.5, 1, 2, 4, 6, 8, 12, and 16 hours post-dose (Day 1); 24 and 36 hours post-dose (Day 2); 48 hours post-dose (Day 3), 72 hours post-dose (Day 4), 96 hours post-dose (Day 5), 120 hours post-dose (Day 6) | AUC0-t was defined as the area under the steady-state plasma or serum concentration-time curve up to the last measurable concentration of total radioactivity in blood. Additional samples were collected every 24 hours until discharge (up to 264 hours). |
| Abundance of INCB099280 Detected in Plasma | 0 hours (predose) and up to 24 hours post-dose | Plasma samples for metabolism investigations were obtained at 0, 1, 2, 4, 8, 12, 16, and 24 hours post-dose and were pooled across participants at each timepoint. TRPA=total radioactive peak area. The reported values are single measurements of pooled plasma or fecal samples; therefore, no statistical analysis is possible, and data have been reported with a measure type of number. |
| t½ of Total Radioactivity in Blood | 0 hours (predose) and 0.5, 1, 2, 4, 6, 8, 12, and 16 hours post-dose (Day 1); 24 and 36 hours post-dose (Day 2); 48 hours post-dose (Day 3), 72 hours post-dose (Day 4), 96 hours post-dose (Day 5), 120 hours post-dose (Day 6) | t½ was defined as the apparent terminal-phase disposition half-life of total radioactivity in blood. Additional samples were collected every 24 hours until discharge (up to 264 hours). |
| CL/F of Total Radioactivity in Blood | 0 hours (predose) and 0.5, 1, 2, 4, 6, 8, 12, and 16 hours post-dose (Day 1); 24 and 36 hours post-dose (Day 2); 48 hours post-dose (Day 3), 72 hours post-dose (Day 4), 96 hours post-dose (Day 5), 120 hours post-dose (Day 6) | CL/F was defined as the apparent oral dose clearance of total radioactivity in blood. Additional samples were collected every 24 hours until discharge (up to 264 hours). |
| Vz/F of Total Radioactivity in Blood | 0 hours (predose) and 0.5, 1, 2, 4, 6, 8, 12, and 16 hours post-dose (Day 1); 24 and 36 hours post-dose (Day 2); 48 hours post-dose (Day 3), 72 hours post-dose (Day 4), 96 hours post-dose (Day 5), 120 hours post-dose (Day 6) | Vz/F was defined as the maximum observed plasma or serum concentration of total radioactivity in blood. Additional samples were collected every 24 hours until discharge (up to 264 hours). |
| Cmax of Total Radioactivity in Plasma | 0 hours (predose) and 0.5, 1, 2, 4, 6, 8, 12, and 16 hours post-dose (Day 1); 24 and 36 hours post-dose (Day 2); 48 hours post-dose (Day 3), 72 hours post-dose (Day 4), 96 hours post-dose (Day 5), 120 hours post-dose (Day 6) | Cmax was defined as the maximum observed concentration of total radioactivity in plasma. Additional samples were collected every 24 hours until discharge (up to 264 hours). |
| Tmax of Total Radioactivity in Plasma | 0 hours (predose) and 0.5, 1, 2, 4, 6, 8, 12, and 16 hours post-dose (Day 1); 24 and 36 hours post-dose (Day 2); 48 hours post-dose (Day 3), 72 hours post-dose (Day 4), 96 hours post-dose (Day 5), 120 hours post-dose (Day 6) | tmax was defined as the time to the maximum concentration of total radioactivity in plasma. Additional samples were collected every 24 hours until discharge (up to 264 hours). |
| AUC0-t of Total Radioactivity in Plasma | 0 hours (predose) and 0.5, 1, 2, 4, 6, 8, 12, and 16 hours post-dose (Day 1); 24 and 36 hours post-dose (Day 2); 48 hours post-dose (Day 3), 72 hours post-dose (Day 4), 96 hours post-dose (Day 5), 120 hours post-dose (Day 6) | AUC0-t was defined as the area under the steady-state plasma or serum concentration-time curve up to the last measurable concentration of total radioactivity in plasma. Additional samples were collected every 24 hours until discharge (up to 264 hours). |
| AUC0-∞ of Total Radioactivity in Plasma | 0 hours (predose) and 0.5, 1, 2, 4, 6, 8, 12, and 16 hours post-dose (Day 1); 24 and 36 hours post-dose (Day 2); 48 hours post-dose (Day 3), 72 hours post-dose (Day 4), 96 hours post-dose (Day 5), 120 hours post-dose (Day 6) | AUC0-∞ was defined as the area under the single-dose plasma or serum concentration-time curve extrapolated to time of infinity. Additional samples were collected every 24 hours until discharge (up to 264 hours). |
| t½ of Total Radioactivity in Plasma | 0 hours (predose) and 0.5, 1, 2, 4, 6, 8, 12, and 16 hours post-dose (Day 1); 24 and 36 hours post-dose (Day 2); 48 hours post-dose (Day 3), 72 hours post-dose (Day 4), 96 hours post-dose (Day 5), 120 hours post-dose (Day 6) | t½ was defined as the apparent terminal-phase disposition half-life of total radioactivity in plasma. Additional samples were collected every 24 hours until discharge (up to 264 hours). |
| CL/F of Total Radioactivity in Plasma | 0 hours (predose) and 0.5, 1, 2, 4, 6, 8, 12, and 16 hours post-dose (Day 1); 24 and 36 hours post-dose (Day 2); 48 hours post-dose (Day 3), 72 hours post-dose (Day 4), 96 hours post-dose (Day 5), 120 hours post-dose (Day 6) | CL/F was defined as the apparent oral dose clearance of total radioactivity in plasma. Additional samples were collected every 24 hours until discharge (up to 264 hours). |
| Vz/F of Total Radioactivity in Plasma | 0 hours (predose) and 0.5, 1, 2, 4, 6, 8, 12, and 16 hours post-dose (Day 1); 24 and 36 hours post-dose (Day 2); 48 hours post-dose (Day 3), 72 hours post-dose (Day 4), 96 hours post-dose (Day 5), 120 hours post-dose (Day 6) | Vz/F was defined as the maximum observed plasma or serum concentration of total radioactivity in plasma. Additional samples were collected every 24 hours until discharge (up to 264 hours). |
| Number of Participants With Any Treatment-emergent Adverse Event (TEAE) | up to Day 22 | An adverse event (AE) was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not it was considered drug-related. An AE could be any unfavorable or unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of study treatment. A TEAE was defined as any AE either reported for the first time or the worsening of a pre-existing event after the first dose of study drug. |
| AUC0-∞ of Total Radioactivity in Blood | 0 hours (predose) and 0.5, 1, 2, 4, 6, 8, 12, and 16 hours post-dose (Day 1); 24 and 36 hours post-dose (Day 2); 48 hours post-dose (Day 3), 72 hours post-dose (Day 4), 96 hours post-dose (Day 5), 120 hours post-dose (Day 6) | AUC0-∞ was defined as the area under the single-dose plasma or serum concentration-time curve extrapolated to time of infinity. Additional samples were collected every 24 hours until discharge (up to 264 hours). |
Countries
United Kingdom
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| INCB099280 400 mg + [14C]INCB099280 78.3 μCi Participants received a single dose of INCB099280 400 milligrams (mg) administered in tablet form (4 × 100-mg tablets) followed approximately 10 minutes later by an oral dose solution containing 78.3 microcuries (μCi) (2.9 megabecquerel \[MBq\]) of \[14C\]INCB099280 (not more than 97.2 μCi \[3.6 MBq\]). | 5 |
| Total | 5 |
Baseline characteristics
| Characteristic | INCB099280 400 mg + [14C]INCB099280 78.3 μCi |
|---|---|
| Age, Continuous | 44.2 years STANDARD_DEVIATION 5.81 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 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 | 5 Participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 5 |
| other Total, other adverse events | 1 / 5 |
| serious Total, serious adverse events | 0 / 5 |
Outcome results
Primary
Total Recovery (Urine + Feces) of the Administered Radioactivity
Radioactivity in urine and feces was reported as the percentage of the administered radioactivity excreted.
Time frame: 264 hours in urine; 408 hours in feces
Population: Pharmacokinetic (PK)-Evaluable Population: all participants who received the study treatment and provided at least 1 postdose PK sample.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| INCB099280 400 mg + [14C]INCB099280 78.3 μCi | Total Recovery (Urine + Feces) of the Administered Radioactivity | 83.2 percentage of radioactivity |
Secondary
Abundance of INCB099280 Detected in Plasma
Plasma samples for metabolism investigations were obtained at 0, 1, 2, 4, 8, 12, 16, and 24 hours post-dose and were pooled across participants at each timepoint. TRPA=total radioactive peak area. The reported values are single measurements of pooled plasma or fecal samples; therefore, no statistical analysis is possible, and data have been reported with a measure type of number.
Time frame: 0 hours (predose) and up to 24 hours post-dose
Population: PK-Evaluable Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| INCB099280 400 mg + [14C]INCB099280 78.3 μCi | Abundance of INCB099280 Detected in Plasma | 1 hour post-dose | 33.4 percentage of TRPA |
| INCB099280 400 mg + [14C]INCB099280 78.3 μCi | Abundance of INCB099280 Detected in Plasma | 2 hours post-dose | 70.3 percentage of TRPA |
| INCB099280 400 mg + [14C]INCB099280 78.3 μCi | Abundance of INCB099280 Detected in Plasma | 4 hours post-dose | 57.2 percentage of TRPA |
| INCB099280 400 mg + [14C]INCB099280 78.3 μCi | Abundance of INCB099280 Detected in Plasma | 8 hours post-dose | 35.3 percentage of TRPA |
| INCB099280 400 mg + [14C]INCB099280 78.3 μCi | Abundance of INCB099280 Detected in Plasma | 12 hours post-dose | 38.3 percentage of TRPA |
| INCB099280 400 mg + [14C]INCB099280 78.3 μCi | Abundance of INCB099280 Detected in Plasma | 16 hours post-dose | 44.9 percentage of TRPA |
| INCB099280 400 mg + [14C]INCB099280 78.3 μCi | Abundance of INCB099280 Detected in Plasma | 24 hours post-dose | 23.2 percentage of TRPA |
Secondary
Abundance of INCB099280 Metabolites Detected in Feces
Homogenized fecal samples from individual participants were pooled for each collection interval by taking a fixed percentage of the total amount excreted from each collection interval/participant. The reported values are single measurements of pooled plasma or fecal samples; therefore, no statistical analysis is possible, and data have been reported with a measure type of number.
Time frame: 0 hours (predose) and up to 96 hours post-dose
Population: PK-Evaluable Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| INCB099280 400 mg + [14C]INCB099280 78.3 μCi | Abundance of INCB099280 Metabolites Detected in Feces | INCB099280, 0 to 24 hours post-dose | 1.98 percentage of total dosed radioactivity |
| INCB099280 400 mg + [14C]INCB099280 78.3 μCi | Abundance of INCB099280 Metabolites Detected in Feces | INCB099280, 24 to 48 hours post-dose | 13.3 percentage of total dosed radioactivity |
| INCB099280 400 mg + [14C]INCB099280 78.3 μCi | Abundance of INCB099280 Metabolites Detected in Feces | INCB099280, 48 to 72 hours post-dose | 36.6 percentage of total dosed radioactivity |
| INCB099280 400 mg + [14C]INCB099280 78.3 μCi | Abundance of INCB099280 Metabolites Detected in Feces | INCB099280, 72 to 96 hours post-dose | 5.37 percentage of total dosed radioactivity |
| INCB099280 400 mg + [14C]INCB099280 78.3 μCi | Abundance of INCB099280 Metabolites Detected in Feces | M12, 0 to 24 hours post-dose | 0 percentage of total dosed radioactivity |
| INCB099280 400 mg + [14C]INCB099280 78.3 μCi | Abundance of INCB099280 Metabolites Detected in Feces | M12, 24 to 48 hours post-dose | 2.30 percentage of total dosed radioactivity |
| INCB099280 400 mg + [14C]INCB099280 78.3 μCi | Abundance of INCB099280 Metabolites Detected in Feces | M12, 48 to 72 hours post-dose | 4.06 percentage of total dosed radioactivity |
| INCB099280 400 mg + [14C]INCB099280 78.3 μCi | Abundance of INCB099280 Metabolites Detected in Feces | M12, 72 to 96 hours post-dose | 1.63 percentage of total dosed radioactivity |
Secondary
AUC0-∞ of INCB099280
AUC0-∞ was defined as the area under the single-dose plasma or serum concentration-time curve extrapolated to time of infinity.
Time frame: 0 hours (predose) and 0.5, 1, 2, 4, 6, 8, 12, and 16 hours post-dose (Day 1); 24 and 36 hours post-dose (Day 2); 48 hours post-dose (Day 3), 72 hours post-dose (Day 4), 96 hours post-dose (Day 5), 120 hours post-dose (Day 6)
Population: PK-Evaluable Population
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| INCB099280 400 mg + [14C]INCB099280 78.3 μCi | AUC0-∞ of INCB099280 | 11200 hours * nanomolar | Geometric Coefficient of Variation 117 |
Secondary
AUC0-∞ of Total Radioactivity in Blood
AUC0-∞ was defined as the area under the single-dose plasma or serum concentration-time curve extrapolated to time of infinity. Additional samples were collected every 24 hours until discharge (up to 264 hours).
Time frame: 0 hours (predose) and 0.5, 1, 2, 4, 6, 8, 12, and 16 hours post-dose (Day 1); 24 and 36 hours post-dose (Day 2); 48 hours post-dose (Day 3), 72 hours post-dose (Day 4), 96 hours post-dose (Day 5), 120 hours post-dose (Day 6)
Population: PK-Evaluable Population. Analysis was not conducted as %AUCextrapolation ≥ 20%.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| INCB099280 400 mg + [14C]INCB099280 78.3 μCi | AUC0-∞ of Total Radioactivity in Blood | 37200 hours * nanomolar | Geometric Coefficient of Variation 151 |
Secondary
AUC0-∞ of Total Radioactivity in Plasma
AUC0-∞ was defined as the area under the single-dose plasma or serum concentration-time curve extrapolated to time of infinity. Additional samples were collected every 24 hours until discharge (up to 264 hours).
Time frame: 0 hours (predose) and 0.5, 1, 2, 4, 6, 8, 12, and 16 hours post-dose (Day 1); 24 and 36 hours post-dose (Day 2); 48 hours post-dose (Day 3), 72 hours post-dose (Day 4), 96 hours post-dose (Day 5), 120 hours post-dose (Day 6)
Population: PK-Evaluable Population. Only participants with available data were analyzed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| INCB099280 400 mg + [14C]INCB099280 78.3 μCi | AUC0-∞ of Total Radioactivity in Plasma | 18500 hours * nanomolar | Geometric Coefficient of Variation 105 |
Secondary
AUC0-t of INCB099280
AUC0-t was defined as the area under the steady-state plasma or serum concentration-time curve up to the last measurable concentration of INCB099280.
Time frame: 0 hours (predose) and 0.5, 1, 2, 4, 6, 8, 12, and 16 hours post-dose (Day 1); 24 and 36 hours post-dose (Day 2); 48 hours post-dose (Day 3), 72 hours post-dose (Day 4), 96 hours post-dose (Day 5), 120 hours post-dose (Day 6)
Population: PK-Evaluable Population
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| INCB099280 400 mg + [14C]INCB099280 78.3 μCi | AUC0-t of INCB099280 | 11100 hours * nanomolar | Geometric Coefficient of Variation 118 |
Secondary
AUC0-t of Total Radioactivity in Blood
AUC0-t was defined as the area under the steady-state plasma or serum concentration-time curve up to the last measurable concentration of total radioactivity in blood. Additional samples were collected every 24 hours until discharge (up to 264 hours).
Time frame: 0 hours (predose) and 0.5, 1, 2, 4, 6, 8, 12, and 16 hours post-dose (Day 1); 24 and 36 hours post-dose (Day 2); 48 hours post-dose (Day 3), 72 hours post-dose (Day 4), 96 hours post-dose (Day 5), 120 hours post-dose (Day 6)
Population: PK-Evaluable Population
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| INCB099280 400 mg + [14C]INCB099280 78.3 μCi | AUC0-t of Total Radioactivity in Blood | 14100 hours * nanomolar | Geometric Coefficient of Variation 79.5 |
Secondary
AUC0-t of Total Radioactivity in Plasma
AUC0-t was defined as the area under the steady-state plasma or serum concentration-time curve up to the last measurable concentration of total radioactivity in plasma. Additional samples were collected every 24 hours until discharge (up to 264 hours).
Time frame: 0 hours (predose) and 0.5, 1, 2, 4, 6, 8, 12, and 16 hours post-dose (Day 1); 24 and 36 hours post-dose (Day 2); 48 hours post-dose (Day 3), 72 hours post-dose (Day 4), 96 hours post-dose (Day 5), 120 hours post-dose (Day 6)
Population: PK-Evaluable Population
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| INCB099280 400 mg + [14C]INCB099280 78.3 μCi | AUC0-t of Total Radioactivity in Plasma | 14100 hours * nanomolar | Geometric Coefficient of Variation 126 |
Secondary
CL/F of INCB099280
CL/F was defined as the apparent oral dose clearance of INCB099280.
Time frame: 0 hours (predose) and 0.5, 1, 2, 4, 6, 8, 12, and 16 hours post-dose (Day 1); 24 and 36 hours post-dose (Day 2); 48 hours post-dose (Day 3), 72 hours post-dose (Day 4), 96 hours post-dose (Day 5), 120 hours post-dose (Day 6)
Population: PK-Evaluable Population
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| INCB099280 400 mg + [14C]INCB099280 78.3 μCi | CL/F of INCB099280 | 46.9 liters per hour | Geometric Coefficient of Variation 117 |
Secondary
CL/F of Total Radioactivity in Blood
CL/F was defined as the apparent oral dose clearance of total radioactivity in blood. Additional samples were collected every 24 hours until discharge (up to 264 hours).
Time frame: 0 hours (predose) and 0.5, 1, 2, 4, 6, 8, 12, and 16 hours post-dose (Day 1); 24 and 36 hours post-dose (Day 2); 48 hours post-dose (Day 3), 72 hours post-dose (Day 4), 96 hours post-dose (Day 5), 120 hours post-dose (Day 6)
Population: PK-Evaluable Population. Analysis was not conducted as %AUCextrapolation ≥ 20%.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| INCB099280 400 mg + [14C]INCB099280 78.3 μCi | CL/F of Total Radioactivity in Blood | 14.2 liters per hour | Geometric Coefficient of Variation 151 |
Secondary
CL/F of Total Radioactivity in Plasma
CL/F was defined as the apparent oral dose clearance of total radioactivity in plasma. Additional samples were collected every 24 hours until discharge (up to 264 hours).
Time frame: 0 hours (predose) and 0.5, 1, 2, 4, 6, 8, 12, and 16 hours post-dose (Day 1); 24 and 36 hours post-dose (Day 2); 48 hours post-dose (Day 3), 72 hours post-dose (Day 4), 96 hours post-dose (Day 5), 120 hours post-dose (Day 6)
Population: PK-Evaluable Population. Only participants with available data were analyzed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| INCB099280 400 mg + [14C]INCB099280 78.3 μCi | CL/F of Total Radioactivity in Plasma | 28.5 liters per hour | Geometric Coefficient of Variation 105 |
Secondary
Cmax of INCB099280
Cmax was defined as the maximum observed plasma or serum concentration of INCB099280.
Time frame: 0 hours (predose) and 0.5, 1, 2, 4, 6, 8, 12, and 16 hours post-dose (Day 1); 24 and 36 hours post-dose (Day 2); 48 hours post-dose (Day 3), 72 hours post-dose (Day 4), 96 hours post-dose (Day 5), 120 hours post-dose (Day 6)
Population: PK-Evaluable Population
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| INCB099280 400 mg + [14C]INCB099280 78.3 μCi | Cmax of INCB099280 | 994 nanomolar | Geometric Coefficient of Variation 90.8 |
Secondary
Cmax of Total Radioactivity in Blood
Cmax was defined as the maximum observed concentration of total radioactivity in blood. Additional samples were collected every 24 hours until discharge (up to 264 hours).
Time frame: 0 hours (predose) and 0.5, 1, 2, 4, 6, 8, 12, and 16 hours post-dose (Day 1); 24 and 36 hours post-dose (Day 2); 48 hours post-dose (Day 3), 72 hours post-dose (Day 4), 96 hours post-dose (Day 5), 120 hours post-dose (Day 6)
Population: PK-Evaluable Population
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| INCB099280 400 mg + [14C]INCB099280 78.3 μCi | Cmax of Total Radioactivity in Blood | 1010 nanomolar | Geometric Coefficient of Variation 61.1 |
Secondary
Cmax of Total Radioactivity in Plasma
Cmax was defined as the maximum observed concentration of total radioactivity in plasma. Additional samples were collected every 24 hours until discharge (up to 264 hours).
Time frame: 0 hours (predose) and 0.5, 1, 2, 4, 6, 8, 12, and 16 hours post-dose (Day 1); 24 and 36 hours post-dose (Day 2); 48 hours post-dose (Day 3), 72 hours post-dose (Day 4), 96 hours post-dose (Day 5), 120 hours post-dose (Day 6)
Population: PK-Evaluable Population
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| INCB099280 400 mg + [14C]INCB099280 78.3 μCi | Cmax of Total Radioactivity in Plasma | 1450 nanomolar | Geometric Coefficient of Variation 69.3 |
Secondary
Number of Participants With Any Treatment-emergent Adverse Event (TEAE)
An adverse event (AE) was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not it was considered drug-related. An AE could be any unfavorable or unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of study treatment. A TEAE was defined as any AE either reported for the first time or the worsening of a pre-existing event after the first dose of study drug.
Time frame: up to Day 22
Population: Safety Population: all participants who received the study treatment
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| INCB099280 400 mg + [14C]INCB099280 78.3 μCi | Number of Participants With Any Treatment-emergent Adverse Event (TEAE) | 1 Participants |
Secondary
t½ of INCB099280
t½ was defined as the apparent terminal-phase disposition half-life of INCB099280.
Time frame: 0 hours (predose) and 0.5, 1, 2, 4, 6, 8, 12, and 16 hours post-dose (Day 1); 24 and 36 hours post-dose (Day 2); 48 hours post-dose (Day 3), 72 hours post-dose (Day 4), 96 hours post-dose (Day 5), 120 hours post-dose (Day 6)
Population: PK-Evaluable Population
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| INCB099280 400 mg + [14C]INCB099280 78.3 μCi | t½ of INCB099280 | 14.8 hours | Geometric Coefficient of Variation 17.9 |
Secondary
t½ of Total Radioactivity in Blood
t½ was defined as the apparent terminal-phase disposition half-life of total radioactivity in blood. Additional samples were collected every 24 hours until discharge (up to 264 hours).
Time frame: 0 hours (predose) and 0.5, 1, 2, 4, 6, 8, 12, and 16 hours post-dose (Day 1); 24 and 36 hours post-dose (Day 2); 48 hours post-dose (Day 3), 72 hours post-dose (Day 4), 96 hours post-dose (Day 5), 120 hours post-dose (Day 6)
Population: PK-Evaluable Population. Analysis was not conducted as Rsq\_adjusted ≤ 0.7 and/or %AUCextrapolation ≥ 20%.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| INCB099280 400 mg + [14C]INCB099280 78.3 μCi | t½ of Total Radioactivity in Blood | 36.1 hours | Geometric Coefficient of Variation 321 |
Secondary
t½ of Total Radioactivity in Plasma
t½ was defined as the apparent terminal-phase disposition half-life of total radioactivity in plasma. Additional samples were collected every 24 hours until discharge (up to 264 hours).
Time frame: 0 hours (predose) and 0.5, 1, 2, 4, 6, 8, 12, and 16 hours post-dose (Day 1); 24 and 36 hours post-dose (Day 2); 48 hours post-dose (Day 3), 72 hours post-dose (Day 4), 96 hours post-dose (Day 5), 120 hours post-dose (Day 6)
Population: PK-Evaluable Population. Only participants with available data were analyzed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| INCB099280 400 mg + [14C]INCB099280 78.3 μCi | t½ of Total Radioactivity in Plasma | 8.88 hours | Geometric Coefficient of Variation 57.6 |
Secondary
Tmax of INCB099280
tmax was defined as the time to the maximum concentration of INCB099280.
Time frame: 0 hours (predose) and 0.5, 1, 2, 4, 6, 8, 12, and 16 hours post-dose (Day 1); 24 and 36 hours post-dose (Day 2); 48 hours post-dose (Day 3), 72 hours post-dose (Day 4), 96 hours post-dose (Day 5), 120 hours post-dose (Day 6)
Population: PK-Evaluable Population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| INCB099280 400 mg + [14C]INCB099280 78.3 μCi | Tmax of INCB099280 | 4.0 hours |
Secondary
Tmax of Total Radioactivity in Blood
tmax was defined as the time to the maximum concentration of total radioactivity in blood. Additional samples were collected every 24 hours until discharge (up to 264 hours).
Time frame: 0 hours (predose) and 0.5, 1, 2, 4, 6, 8, 12, and 16 hours post-dose (Day 1); 24 and 36 hours post-dose (Day 2); 48 hours post-dose (Day 3), 72 hours post-dose (Day 4), 96 hours post-dose (Day 5), 120 hours post-dose (Day 6)
Population: PK-Evaluable Population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| INCB099280 400 mg + [14C]INCB099280 78.3 μCi | Tmax of Total Radioactivity in Blood | 4.0 hours |
Secondary
Tmax of Total Radioactivity in Plasma
tmax was defined as the time to the maximum concentration of total radioactivity in plasma. Additional samples were collected every 24 hours until discharge (up to 264 hours).
Time frame: 0 hours (predose) and 0.5, 1, 2, 4, 6, 8, 12, and 16 hours post-dose (Day 1); 24 and 36 hours post-dose (Day 2); 48 hours post-dose (Day 3), 72 hours post-dose (Day 4), 96 hours post-dose (Day 5), 120 hours post-dose (Day 6)
Population: PK-Evaluable Population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| INCB099280 400 mg + [14C]INCB099280 78.3 μCi | Tmax of Total Radioactivity in Plasma | 4.0 hours |
Secondary
Vz/F of INCB099280
Vz/F was defined as the maximum observed plasma or serum concentration of INCB099280.
Time frame: 0 hours (predose) and 0.5, 1, 2, 4, 6, 8, 12, and 16 hours post-dose (Day 1); 24 and 36 hours post-dose (Day 2); 48 hours post-dose (Day 3), 72 hours post-dose (Day 4), 96 hours post-dose (Day 5), 120 hours post-dose (Day 6)
Population: PK-Evaluable Population
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| INCB099280 400 mg + [14C]INCB099280 78.3 μCi | Vz/F of INCB099280 | 1000 liters | Geometric Coefficient of Variation 91.3 |
Secondary
Vz/F of Total Radioactivity in Blood
Vz/F was defined as the maximum observed plasma or serum concentration of total radioactivity in blood. Additional samples were collected every 24 hours until discharge (up to 264 hours).
Time frame: 0 hours (predose) and 0.5, 1, 2, 4, 6, 8, 12, and 16 hours post-dose (Day 1); 24 and 36 hours post-dose (Day 2); 48 hours post-dose (Day 3), 72 hours post-dose (Day 4), 96 hours post-dose (Day 5), 120 hours post-dose (Day 6)
Population: PK-Evaluable Population. Analysis was not conducted as %AUCextrapolation ≥ 20%.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| INCB099280 400 mg + [14C]INCB099280 78.3 μCi | Vz/F of Total Radioactivity in Blood | 738 liters | Geometric Coefficient of Variation 69.7 |
Secondary
Vz/F of Total Radioactivity in Plasma
Vz/F was defined as the maximum observed plasma or serum concentration of total radioactivity in plasma. Additional samples were collected every 24 hours until discharge (up to 264 hours).
Time frame: 0 hours (predose) and 0.5, 1, 2, 4, 6, 8, 12, and 16 hours post-dose (Day 1); 24 and 36 hours post-dose (Day 2); 48 hours post-dose (Day 3), 72 hours post-dose (Day 4), 96 hours post-dose (Day 5), 120 hours post-dose (Day 6)
Population: PK-Evaluable Population. Only participants with available data were analyzed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| INCB099280 400 mg + [14C]INCB099280 78.3 μCi | Vz/F of Total Radioactivity in Plasma | 365 liters | Geometric Coefficient of Variation 40.4 |