Myelofibrosis and other blood disorders Not Specified
Conditions
Interventions
Each participant will receive a single dose of [14C]-pelabresib Oral Suspension, 0.5 mg/mL, 20 mL (not more than [NMT] 37.0 kBq) on one occasion
Sponsors
Constellation Pharmaceuticals (United States)
Eligibility
Sex/Gender
Male
Inclusion criteria
Inclusion criteria: 1. Must provide written informed consent 2. Must be willing and able to communicate and participate in the whole study 3. Aged 30 to 65 years inclusive at the time of signing informed consent 4. Must agree to adhere to the contraception requirements defined in the Clinical Protocol 5. Must not plan to father children or donate sperm in the 184 days (6 months + 5 half lives) after IMP administration 6. Healthy males 7. Body mass index (BMI) of 18.0 to 32.0 kg/m² as measured at screening 8. Weight of at least 60 kg as measured at screening 9. Must have regular bowel movements (i.e. average stool production of =1 and =3 stools per day)
Exclusion criteria
Exclusion criteria: 1. Serious adverse reaction or serious hypersensitivity to any drug or formulation excipients 2. Presence or history of clinically significant allergy requiring treatment, as judged by the investigator. Hay fever is allowed unless it is active 3. History of clinically significant cardiovascular, renal, hepatic, testicular, dermatological, chronic respiratory or GI disease, neurological or psychiatric disorder, as judged by the investigator 4. Subjects who do not have suitable veins for multiple venepunctures/cannulation as assessed by the investigator or delegate at screening 5. Evidence of current SARS-CoV-2 infection within 4 weeks of first IMP administration 6. Clinically significant abnormal clinical chemistry, haematology or urinalysis as judged by the investigator. Subjects with Gilbert’s Syndrome are not allowed 7. Any of the following: haemoglobin 21 units per week (1 unit = ½ pint beer, or a 25 mL shot of 40% spirit, 1.5 to 2 units = 125 mL glass of wine, depending on type) 20. A confirmed positive alcohol breath test at screening or admission 21. Current smokers and those who have smoked within the last 6 months. A confirmed breath carbon monoxide reading of greater than ppm at screening or admission 22. Current users of e-cigarettes and nicotine replacement products and
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1. Mass balance recovery of total radioactivity in all excreta (urine and faeces): CumAe and Cum%Ae at multiple timepoints up to 432 h post dose 2. Identification of the chemical structure of each metabolite accounting for more than 10% (in plasma) by AUC of circulating total radioactivity or accounting for 10% or more of the dose in excreta (urine and faeces) at multiple timepoints up to 432 h post dose | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Determination of routes and rates of elimination of 14C by Ae, %Ae, CumAe and Cum%Ae by time interval 2. Assessment of the PK of an oral [14C]-pelabresib formulation by calculation of PK parameters, as appropriate, for pelabresib, its metabolites M4, M5, M542 and M544 and total radioactivity in plasma: Tmax, Cmax, AUC(0-last), AUC(0-inf) and T1/2 (additional parameters may be determined) at multiple timepoints up to 432 h post dose 3. Evaluation of whole blood:plasma concentration ratios for total radioactivity at multiple timepoints up to 432 h post dose 4. To provide additional safety and tolerability information for pelabresib by assessing: incidence of adverse events (AEs), serious AEs (SAEs) and changes in physical examinations, vital signs, electrocardiograms (ECGs), and laboratory results, from the time of signing the informed consent form up until discharge from the study | — |
Countries
England, United Kingdom
Contacts
Public ContactFaith Stevison
Outcome results
None listed