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

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

This is a drug-drug interaction study in volunteers to evaluate the effect of ritonavir or cobicistat on the pharmacokinetics (PK) of PBI-200.

Study Overview

• Status: Completed
• Conditions: Drug-drug Interaction
• Intervention / Treatment: Drug: PBI-200 Tablet; Drug: Ritonavir Oral Tablet; Drug: Cobicistat Oral Tablet

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.

• Study Type: Interventional
• Enrollment (Actual): 21
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Tempe, Arizona, United States, 85283
      • Celerion, Inc.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Single-sequence, 3-period; 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; PBI-200 is a TRK inhibitor; Drug: Ritonavir Oral Tablet; Ritonavir is a potent CYP3A inhibitor; Other Names: Norvir; Drug: Cobicistat Oral Tablet; Cobicistat is a potent CYP3A inhibitor; Other Names: Tybost

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Pyramid Biosciences

Study record dates

Study Major Dates

• Study Start (Actual): September 9, 2022
• Primary Completion (Actual): November 12, 2022
• Study Completion (Actual): November 12, 2022

Study Registration Dates

• First Submitted: January 11, 2023
• First Submitted That Met QC Criteria: January 11, 2023
• First Posted (Actual): January 20, 2023

Study Record Updates

• Last Update Posted (Actual): January 20, 2023
• Last Update Submitted That Met QC Criteria: January 11, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Protease Inhibitors; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; HIV Protease Inhibitors; Viral Protease Inhibitors; Cobicistat; Ritonavir
• Other Study ID Numbers: PBI-200-106

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No