Drug-drug Interaction
Conditions
Brief summary
This is a drug-drug interaction study in volunteers to evaluate the effect of ritonavir or cobicistat on the pharmacokinetics (PK) of PBI-200.
Detailed description
This is an open-label, single-sequence, three-period drug-drug interaction study in healthy male and female volunteers to evaluate the effect of a potent CYP3A inhibitor, ritonavir or cobicistat, on the single dose PK of orally administered PBI-200. It is expected that co-administration of ritonavir or cobicistat with PBI-200 will increase the exposure of PBI 200.
Interventions
DRUGPBI-200 Tablet
PBI-200 is a TRK inhibitor
DRUGRitonavir Oral Tablet
Ritonavir is a potent CYP3A inhibitor
Cobicistat is a potent CYP3A inhibitor
Sponsors
Pyramid Biosciences
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Single-sequence, three-periods
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* Male or female between 18 and 55 years of age (inclusive). * Body Mass Index (BMI) between 18.0 and 32.0 kg/m² (inclusive). * Non-smoking/non-vaping, healthy, with no history of clinically relevant medical illness.
Exclusion criteria
* History or presence of clinically significant cardiovascular, pulmonary, respiratory, hepatic, renal, hematological, gastrointestinal, endocrine, immunologic, dermatologic, neurological, or psychiatric disease which, in the opinion of the Investigator, would jeopardize the safety of the volunteer or impact the validity of the study results. * History of gastrointestinal/hepatobiliary or other surgery that may affect PK profiles (i.e., hepatectomy, gastric, bypass, or digestive organ resection). * Intolerance to repeated venipuncture. * Smoking or use of tobacco products (including vaping) within 3 months prior to the first study drug administration. * Have a positive drug/alcohol screen, or history or presence of alcoholism or drug abuse within 6 months of first study drug administration. * Volunteers with a corrected QT using Fridericia's formula (QTcF) prolongation over 450 milliseconds at Screening.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Plasma Concentration [C(max)] of PBI-200 | 11 days | Maximum (peak) plasma drug concentration |
| Area Under the Concentration-Time Curve (AUC) from time zero to the time of the last measurable concentration [AUC(0-t)] | 11 days | AUC, calculated using linear up / log down trapezoidal method from time zero to time t, where t is the time of the last measurable concentration. |
| AUC from time zero to infinity [AUC(0-inf)] | 11 days | AUC from time zero to infinity, AUC(0-inf) = AUC(0-t) + Ct/kel, where kel is the terminal rate constant and Ct is the last measurable concentration. |
| Terminal elimination half-life [T(1/2)] | 11 days | Apparent terminal elimination half-life, calculated as ln(2)/kel. |
| Incidence, frequency and severity of adverse events (AEs) | 45 days | — |
Countries
United States
Outcome results
None listed