A Study of PBI-200 With Ritonavir or Cobicistat in Healthy Volunteers

Study Overview
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Brief Summary
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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
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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.

Official Title
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A Phase 1, Open-label Drug Interaction Study of PBI-200 With Ritonavir or Cobicistat in Healthy Volunteers

Conditions
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Drug-drug Interaction

Intervention / Treatment
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* Drug: PBI-200 Tablet
* Drug: Ritonavir Oral Tablet
* Drug: Cobicistat Oral Tablet


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: Single-sequence, three-periods
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Single-sequence, 3-period<br>Period 1: single dose of PBI-200; Period 2: daily dosing of ritonavir with a single dose of PBI-200 co-administered once ritonavir steady state reached; Period 3: daily dosing of cobicistat with a single dose of PBI-200 co-administered once cobicistat steady state reached. | Drug: PBI-200 Tablet<br>* PBI-200 is a TRK inhibitor<br>Drug: Ritonavir Oral Tablet<br>* Ritonavir is a potent CYP3A inhibitor<br>* Other names: Norvir;Drug: Cobicistat Oral Tablet<br>* Cobicistat is a potent CYP3A inhibitor<br>* Other names: Tybost;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Plasma Concentration [C(max)] of PBI-200 | Maximum (peak) plasma drug concentration | 11 days | 
| Area Under the Concentration-Time Curve (AUC) from time zero to the time of the last measurable concentration [AUC(0-t)] | 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. | 11 days | 
| AUC from time zero to infinity [AUC(0-inf)] | 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. | 11 days | 
| Terminal elimination half-life [T(1/2)] | Apparent terminal elimination half-life, calculated as ln(2)/kel. | 11 days | 
| Incidence, frequency and severity of adverse events (AEs) |  | 45 days |