Bioequivalence Study (Preliminary Study) of Ritonavir Versus NORVIR in Healthy Chinese Subjects

An Open-label, Randomized Bioequivalence Study (Preliminary Study) of Ritonavir Versus NORVIR in Healthy Chinese Subjects

The purpose of this study is to evaluate the pharmacokinetics and bioequivalence of Ritonavir tablet 100 mg versus NORVIR 100 mg tablet in healthy Chinese adult participants under fasting condition.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteer
• Intervention / Treatment: Drug: Ritonavir Tablet 100mg; Drug: NORVIR tablet 100mg

Detailed Description

The study design is an Open-Label Randomized, Single-Dose, 2-way Crossover Bioequivalence Study with a washout period of 6 days. During each session, the subjects will be administered a single dose of 100mg Ritonavir (one Ritonavir Tablet 100mg or one NORVIR Tablet 100mg) under fasting condition.

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310003
      • First Affiliated Hospital of Zhejiang University
    • Hanzhou, Zhejiang, China, 310003
      • First Affiliated Hospital of Zhejiang University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

1. Healthy adult volunteers of 18-45 years old.
2. Male (weight ≥50kg)
3. Body mass index (BMI) between 19~28 kg/m2;
4. In good health as determined by a physician/investigator based on medical history, vital signs, electrocardiogram (ECG), laboratory tests and physical examination findings at screening;
5. Male participant agrees to use adequate contraception and have no plan to donate sperm from signing of informed consent form throughout the duration of the study and for 6 months after the last dose of study drug;
6. Subject who totally understand the aim and progress of this clinical trial, make decision by his/her free will, and signed a consent form to follow the progress;
7. In the opinion of the investigator, the participant is capable of understanding and complying with protocol requirements.

Exclusion Criteria:

1. Subject who cannot tolerate venipuncture.
2. Allergy/hypersensitivity (including drug allergy) which is deemed relevant to the trial as judged by the investigator;
3. Subject who has past or present history of any serious diseases, including (but not limited to) digestive, cardiovascular, respiratory, urinary, musculoskeletal, endocrine, psychiatric or neurological, hematologic, immunological or metabolic disorders;
4. Abnormal results of physical examination (hematology, urine test,blood biochemistry etc.), vital signs, laboratory profile, a 12-lead electrocardiogram (ECG) or x-ray with clinical significance.
5. A positive result in hepatitis B surface antigen (HBsAg), anti-hepatitis C virus (HCV) antibodies, a syphilis test, or an human immunodeficiency virus (HIV) test;
6. Subject who refuse to use adequate contraception from signing of informed consent form throughout the duration of the study and for 6 months after the last dose of study drug;
7. Has a history of drug abuse (defined as any illicit drug use) or a history of alcohol abuse (defined as alcohol consumption exceeding 14 units per week) within 6 months preceding this study or is unwilling to agree to abstain from alcohol and drugs throughout the study;
8. Heavy smokers (>5 cigarettes per day) within 6 months preceding this study or is unwilling to agree to abstain from smoking throughout the study;
9. Positive test results for alcohol or drug at Screening;
10. History of hospitalization or surgery within 3 months preceding this study.
11. Blood donation within the last 2 months (>= 400 ml), or have a plan to donate blood within 1 month after this study;
12. Intake of any other drug which might influence the results of the trial during two weeks previous to the start of the study.
13. Participation in another study with an investigational drug within the last 3 months preceding this study;
14. History of gastrointestinal surgery, vagotomy, enterotomy or other surgery that may influence gastrointestinal motility,PH or gastrointestinal absorption.
15. Intake of grapefruit or orange (or other food containing grapefruit or orange) 3 days previous to the start of the study. Intake of tea,coffee or other drink containing coffee more than 1L per day.
16. Consideration by the investigator, for any reason, that the subject is an unsuitable candidate to receive Ritonavir.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: group 1; During the study session, healthy subjects will be administered a single dose of Ritonavir or Tablet 100mg or NORVIR tablet 100mg under fasting condition. Intervention: cylcle 1 Drug: Ritonavir tablet 100mg cylcle 2 Drug: NORVIR tablet 100mg cylcle 3 Drug: Ritonavir tablet 100mg cylcle 4 Drug: NORVIR tablet 100mg	Drug: Ritonavir Tablet 100mg; Ritonavir Tablet 100mg is a generic product manufactured by Ascletis Pharmaceutical Co., Ltd.; Drug: NORVIR tablet 100mg; NORVIR Tablet is a generic product manufactured by AbbVie. NORVIR Tablet 100mg will be used as a comparator drug for the BE study.
Experimental: group 2; During the study session, healthy subjects will be administered a single dose of Ritonavir or Tablet 100mg or NORVIR tablet 100mg under fasting condition. Intervention: cylcle 1 Drug: NORVIR tablet 100mg cylcle 2 Drug: Ritonavir tablet 100mg cylcle 3 Drug: NORVIR tablet 100mg cylcle 4 Drug: Ritonavir tablet 100mg	Drug: Ritonavir Tablet 100mg; Ritonavir Tablet 100mg is a generic product manufactured by Ascletis Pharmaceutical Co., Ltd.; Drug: NORVIR tablet 100mg; NORVIR Tablet is a generic product manufactured by AbbVie. NORVIR Tablet 100mg will be used as a comparator drug for the BE study.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cmax: Maximum Observed Plasma Concentration for ritonavir	Maximum observed plasma concentration (Cmax) is the peak plasma concentration of a drug after administration, obtained directly from the plasma concentration-time curve.	36 hours post-dose on Day 1,7,13 and 19
Tmax	Time to Reach the Maximum Plasma Concentration	36 hours post-dose on Day 1,7,13 and 19
AUC(0-inf): Area Under the Plasma Concentration-time Curve from Time 0 to Infinity for ritonavir	AUC (0-inf) is a measure of total plasma exposure to the drug from time zero extrapolated to infinity	Time Frame: 36 hours post-dose on Day 1,7,13 and 19
AUC(0-36h): Area Under the Plasma Concentration-Time Curve From Time 0 to 36 hours Postdose for ritonavir	AUC(0-36h) is measure of area under the plasma concentration and time curve from Time 0 to 36 hours postdose.	36 hours post-dose on Day 1,7,13 and 19

Collaborators and Investigators

• Sponsor: First Affiliated Hospital of Zhejiang University
• Collaborators: Ascletis Pharmaceutical Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): July 11, 2017
• Primary Completion (Actual): August 31, 2017
• Study Completion (Actual): September 20, 2017

Study Registration Dates

• First Submitted: July 9, 2017
• First Submitted That Met QC Criteria: July 9, 2017
• First Posted (Actual): July 11, 2017

Study Record Updates

• Last Update Posted (Actual): October 3, 2017
• Last Update Submitted That Met QC Criteria: September 30, 2017
• Last Verified: July 1, 2017

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: ZYYY-LTNW-BE-2017-05

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: There is no plan to make individual participant data (IPD) available to other researchers

Drug and device information, study documents

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