Hepatic impairment Digestive System
Conditions
Interventions
Participants will be enrolled into one of three cohorts:
Cohort 1 (Participants with normal hepatic function)
Cohort 2 (Participants with moderate hepatic impairment),
Sponsors
Roche (United States)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Males or females of non-childbearing potential, between 18 and 74 years of age, inclusive 2. Normal hepatic function, moderate hepatic impairment, or severe hepatic impairment based on the Child-Pugh classification
Exclusion criteria
Exclusion criteria: 1. History of surgical or artificial shunts (i.e., transjugular intrahepatic portosystemic procedure) 2. QT interval corrected using Fridericia’s formula >480 ms demonstrated on at least two ECGs that are performed >30 minutes apart or history or presence of an abnormal ECG, which, in the investigator’s opinion, is clinically significant 3. History of alcoholism or drug addiction within 1 year prior to Check-in (Day -1) 4. Use of oral antibiotics to treat an active infection within 4 weeks or intravenous antibiotics to treat an active infection within 8 weeks prior to Screening 5. Prior exposure to pralsetinib or other RET kinase inhibitor within 30 days prior to Check-in
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Pharmacokinetic (PK) parameters of pralsetinib will be measured using blood samples on Day 1 at predose, 0.5, 1, 2, 3, 4, 6, 8, 12 h., Day 2 at 24 and 36 h., Day 3 at 48 h., Day 4 at 72 h., Day 5 at 96 h., Day 7 at 144 h. and Day 9 at 192 h. The following PK parameters will be calculated if data allows: 1. Maximum concentration (Cmax) 2. Time to maximum observed concentration (Tmax) 3. Area under the concentration-time curve (AUC) from Hour 0 to the time of the last measurable concentration (AUC0-t) 4. AUC from Hour 0 to “t” (AUC0-“t”) 5. AUC extrapolated to infinity (AUC0-8) 6. Percentage of AUC that is due to extrapolation from the last quantifiable concentration to infinity (%AUCextrap) 7. Apparent terminal elimination rate constant (?z) 8. Apparent terminal elimination half-life (t1/2) 9. Fraction of unbound drug (fu) 10. Cmax of free drug (Cmax,u) 11. AUC0-t of free drug (AUC0-t,u) 12. AUC0-“t” of free drug (AUC0-“t”,u) 13. AUC0-8 of free drug (AUC0-8,u) 14. Apparent total clearance (CL/F) 15. Apparent volume of distribution during the terminal elimination phase (Vz/F) | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Incidence, nature and severity of adverse events with severity determined according to National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 (NCI CTCAE v5.0), measured throughout the study. 2. Incidence of electrocardiogram (ECG) abnormalities as measured by 12-lead ECG at screening, days 1, 2 and 5 and at study completion. | — |
Countries
United States of America
Contacts
Public ContactClinical Trials
Outcome results
None listed