Study of WPV01 in Healthy Subjects

Phase I Study on the Safety, Tolerability, Pharmacokinetics, and Food Effect Evaluation of WPV01 and WPV01 Co-administrated Ritonavir in Healthy Subjects

A Phase I Clinical Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of WPV01 and WPV01 Co-administrated With Ritonavir in Healthy Adult Subjects.

Study Overview

• Status: Completed
• Conditions: Healthy Participants
• Intervention / Treatment: Drug: WPV01 Dose 1-4; Drug: WPV01 Dose 5-8 and Ritonavir; Drug: WPV01 Dose 9-12; Drug: WPV01 Dose 13-15 and Ritonavir; Drug: WPV01 Dose 16

• Study Type: Interventional
• Enrollment (Actual): 108
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Hangzhou, China
    • Shulan（Hangzhou） Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Subjects signed an informed consent form with full understanding of the test content, procedure and possible adverse effects
• Chinese healthy male or female subjects between aged from 18 to 45 years
• Subjects must agree to comply with the contraceptive requirements during the trial and for 3 months after the last dose
• Body weight ≥ 50 kg for men and ≥ 45 kg for women and body mass index in the range of 18.0 ~ 28.0 kg/m2 (including 18.0 and 28.0)
• Subjects must be willing to understand and comply with study procedures and limitations, have the ability to complete the trial as planned, and be able to communicate effectively with the investigator

Exclusion Criteria:

• Participants who have special dietary requirements and cannot abide by the provided food
• Pregnant or lactating women; Women who have pregnancy plan 1 month before trail, during trail or within 3 months after last dose; Women with positive serum pregnancy tests at screening or baseline
• Participants who have evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic disease
• Participants who have history of any other acute or chronic illness
• Participants who have known allergy to any ingredient in the study treatment drug
• Participants who are judged by the investigator to be unsuitable to participate in this study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: WPV01 Dose 1-4; WPV01 Dose 1-4 or Placebo	Drug: WPV01 Dose 1-4; WPV01 Dose 1-4 or Placebo on day 1
Experimental: WPV01 Dose 5-8; WPV01 Dose 5-8 co-administrated with ritonavir or Placebo	Drug: WPV01 Dose 5-8 and Ritonavir; WPV01 Dose 5-8 and Ritonavir or Placebo on day 1
Experimental: WPV01 Dose 9-12; WPV01 Dose 9-12 or Placebo	Drug: WPV01 Dose 9-12; WPV01 Dose 9-12 or Placebo from day 1 to day 6
Experimental: WPV01 Dose 13-15; WPV01 Dose 13-15 or Placebo	Drug: WPV01 Dose 13-15 and Ritonavir; WPV01 Dose 13-15 and Ritonavir or Placebo from day 1 to day 6
Experimental: WPV01 Dose 16; WPV01 Dose 16(with high fat meal) or WPV01 Dose 16 (fed)	Drug: WPV01 Dose 16; Cohort 1:WPV01 Dose 16 or Placebo (with high fat meal) Cohort 2:WPV01 Dose 16 or Placebo (fasted)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To evaluate the safety and tolerability of single and multiple oral doses of WPV01 and WPV01 in combination with ritonavir in healthy subjects.	Adverse events, including type, incidence, grade (determined with reference to NCI-CTCAE V5.0)	Day 1 to Day 18

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Plasma Concentration (Cmax) in Single Ascending Dose (SAD)	The maximum observed plasma concentration (Cmax) is estimated based on the plasma concentrations	SAD part: Day 1 to Day 18
Time for Cmax (Tmax) in SAD	Tmax was summarized by dosing regimen. It was observed directly from data as time of first occurrence.	SAD part: Day 1 to Day 18
Area Under the Concentration-Time Profile From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) in SAD	AUClast is summarized by dosing regimen and determined by linear/log trapezoidal method.	SAD part: Day 1 to Day 18
Area Under the Plasma Concentration-Time Profile From Time 0 Extrapolated to Infinite Time (AUCinf) in SAD	AUCinf = Area under the plasma concentration versus time curve (AUC) from time 0 (pre-dose) to extrapolated infinite time (0-inf). It is obtained from AUC (0-t) plus AUC (t-inf).	SAD part: Day 1 to Day 18
Terminal Elimination Half-Life (t½) in SAD	t1/2 is summarized by dosing regimen . It is determined by loge(2)/kel, where kel is the terminal phase rate constant calculated by a linear regression of the log linear concentration time curve. Only those data points judged to describe the terminal log linear decline is used in the regression.	SAD part: Day 1 to Day 18
Apparent Clearance (CL/F) in SAD	CL/F is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Calculated as Dose/AUCinf. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.	SAD part: Day 1 to Day 18
Apparent Volume of Distribution (Vz/F) in SAD	Vz/F is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Vz/F is influenced by the fraction absorbed.	SAD part: Day 1 to Day 18
Cmax in Multiple Ascending Dose (MAD)-Day 1	Observed Cmax is estimated based on the plasma concentrations	MAD part: Day 1 to Day 22
Cmax in MAD-Day 6	Observed Cmax is estimated based on the plasma concentrations	MAD part: Day 1 to Day 22
Time for Cmax (Tmax) in MAD-Day 1	Tmax was summarized by dosing regimen. It was observed directly from data as time of first occurrence.	MAD part: Day 1 to Day 22
Time for Cmax (Tmax) in MAD-Day 6	Tmax was summarized by dosing regimen. It was observed directly from data as time of first occurrence.	MAD part: Day 1 to Day 22
Area Under the Plasma Concentration-Time Profile From Time Zero To End of Dosing Interval (AUCtau) in MAD-Day 1	AUCtau is summarized by dosing regimen and period. Dosing interval is the interval tau between administration of doses of drug. In this study, the dosing interval is 8 hours for three times daily (TID) dosing and 12 hours for twice daily (BID) dosing. It is determined by linear/log trapezoidal method.	MAD part: Day 1 to Day 22
AUCtau in MAD-Day 6	AUCtau is summarized by dosing regimen and period. Dosing interval is the interval tau between administration of doses of drug. In this study, the dosing interval is 8 hours for three times daily (TID) dosing and 12 hours for twice daily (BID) dosing. It is determined by linear/log trapezoidal method.	MAD part: Day 1 to Day 22
Observed Accumulation Ratio Based on AUC (RAauc) in MAD-Day 6	In this study, Rac = AUCtau(Day 6) / AUCtau(Day 1). Rac is summarized by dosing regimen.	MAD part: Day 1 to Day 22
Observed Accumulation Ratio Based on Cmax (RAcmax) in MAD-Day 6	In this study, Rac = Cmax(Day 6) / Cmax(Day 1). Rac is summarized by dosing regimen.	MAD part: Day 1 to Day 22
To evaluate the metabolites of single oral doses of WPV01 and WPV01 in combination with ritonavir in healthy subjects	Urine and stool samples will be collected for metabolite analysis. The major metabolites will be identified and, if necessary, quantitatively identified.	MAD part: Day 1 to Day 22
Cmax in Food Effect (FE)	The maximum observed plasma concentration (Cmax) is estimated based on the plasma concentrations of cohort 1 and cohort 2 in FE part.	Day 1 to Day 22
Tmax in FE	It was observed directly from data as time of first occurrence in cohort 1 and cohort 2 of FE part.	Day 1 to Day 22
Area Under the Concentration-Time Profile From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) in FE	AUClast was summarized using the data in cohort 1 and cohort 2 of FE part.	Day 1to Day 22

Collaborators and Investigators

• Sponsor: Westlake Pharmaceuticals (Hangzhou) Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): October 3, 2022
• Primary Completion (Actual): March 11, 2023
• Study Completion (Actual): July 26, 2023

Study Registration Dates

• First Submitted: March 28, 2023
• First Submitted That Met QC Criteria: January 9, 2024
• First Posted (Actual): January 16, 2024

Study Record Updates

• Last Update Posted (Actual): January 16, 2024
• Last Update Submitted That Met QC Criteria: January 9, 2024
• Last Verified: March 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; Ritonavir
• Other Study ID Numbers: WPV01-CP-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: 6 months after summary data has been published, sponsor will share the IPD and additional supporting information after internal approval process.

Drug and device information, study documents

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