A Study Assessing the Mass Balance, Pharmacokinetics, and Metabolite Profiles of a Single Oral Dose of [14C]INCB099280 in Healthy Male Participants

Phase 1

Completed

Conditions: Healthy Participants

Interventions: Drug: INCB099280

Registration Number: NCT06309394

Lead Sponsor: Incyte Corporation

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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: Male

Target Recruitment: 5

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/Exclusion Criteria may apply.

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
INCB099280	INCB099280	Participants will be administered INCB099280 tablet orally, followed approximately 10 minutes later by an oral dose solution of radiolabeled INCB099280.

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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."
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).
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).
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.