Bioequivalence Study of Ribavirin in Healthy Adult Subjects Under Fed Condition

A Randomized, Single Oral Dose, Two-way Crossover, Open-label, Laboratory Blind, Bioequivalence Study Comparing Ribavirin From Two Different Drug Products After Oral Administration to Healthy Adult Subjects Under Fed Conditions

To evaluate and compare the relative plasma bioavailability and therefore the bioequivalence of two different immediate release products each containing Ribavirin 400 mg, after administering a single oral dose, to healthy adult subjects under fed conditions.

Study Overview

• Status: Completed
• Conditions: Healthy Subjects
• Intervention / Treatment: Drug: Ribavirin 400 mg film coated tablet (1*400mg); Drug: Copegus® 200 mg film coated tablet (2*200mg)

Detailed Description

Enrolled subjects were randomized in a two-phase, two-sequence, cross-over design to receive a single dose of the test product (T) or the reference product (R) each phase, under fed conditions, with a wash-out period of 42 days.

Ribavirin plasma concentration was determined using a validated LC-MS-MS method, followed by Pharmacokinetics, and statistical analysis using Phoenix WinNonlin® software to determine the average bioequivalence.

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Phase 1

Contacts and Locations

Study Locations

• Egypt
  • New Cairo
    • Cairo, New Cairo, Egypt, 11835
      • Future Research Center (FRC)

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Written informed consent is obtained for the study
• Age 18 - 55 years
• Body mass index between 18.5 and 30 kg/m2
• Have no clinically significant diseases captured in the medical history or evidence of clinically significant findings on physical examination.
• Vital signs without significant deviations.
• All laboratory screening results are within the normal range or clinically non-significant

Exclusion Criteria:

• History or presence of any disorder or condition that would render the subject unsuitable for the study, place the subject at undue risk or interfere with the ability of the subject to complete the study in the opinion of the investigator.
• History of any significant cardiovascular, hepatic, renal, respiratory, gastrointestinal, endocrine, immunologic, allergic, dermatologic, hematologic, neurologic, or psychiatric disease, or cancer.
• Any confirmed significant allergic reactions against any drug or multiple allergies.
• Clinically significant illness 28 days before study phase I.
• Alcohol or any solvent intake.
• Regular use of medication.
• Positive urine screening of drugs of abuse.
• Use of any systemic medications (prescription medications, OTC products, supplements, or herbal preparations) for 14 days prior to dosing and during the study.
• History or presence of significant smoking (more than one pack per day of cigarettes) or refusal to abstain from smoking for 48 hours before dosing until checkout.
• Blood donation within the past 60 days.
• Participation in another bioequivalence study within 60 days prior to the start of phase I of the study.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Test product (T); Subjects were served a standardized high caloric meal 30 minutes before the administration of a single film-coated tablet containing 400 mg Ribavirin (1*400mg) with approximately 240 ml of water	Drug: Ribavirin 400 mg film coated tablet (1*400mg); an immediate release film-coated tablet containing 400 mg Ribavirin; Other Names: Test product (T)
Active Comparator: Reference product (R); Subjects were served a standardized high caloric meal 30 minutes before the administration of two film-coated tablets each containing 200 mg Ribavirin (2*200mg) with approximately 240 ml of water	Drug: Copegus® 200 mg film coated tablet (2*200mg); an immediate release film-coated tablet containing 200 mg Ribavirin; Other Names: Reference product (R)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum plasma concentration (Cmax)	Cmax is observed as the maximum of Ribavirin peak concentration	Pre-dose (0) and at 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 2.75, 3, 3.5, 4, 6, 8, 10, 12, 24, 48, 72 hours post dose
Truncated area under the plasma concentration curve from administration to last observed (AUC 0-72h)	The AUC (0-72h) is the area under the plasma concentration with time curve from the time of dosing to the 72-hour sample	Pre-dose (0) and at 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 2.75, 3, 3.5, 4, 6, 8, 10, 12, 24, 48, 72 hours post dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum time (Tmax)	Time until Cmax is reached	Pre-dose (0) and at 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 2.75, 3, 3.5, 4, 6, 8, 10, 12, 24, 48, 72 hours post dose

Collaborators and Investigators

• Sponsor: Future University in Egypt

Study record dates

Study Major Dates

• Study Start (Actual): October 11, 2020
• Primary Completion (Actual): November 23, 2020
• Study Completion (Actual): November 23, 2020

Study Registration Dates

• First Submitted: September 4, 2022
• First Submitted That Met QC Criteria: September 7, 2022
• First Posted (Actual): September 8, 2022

Study Record Updates

• Last Update Posted (Actual): September 8, 2022
• Last Update Submitted That Met QC Criteria: September 7, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Keywords: Bioequivalence; Crossover; Randomized; Ribavirin
• Additional Relevant MeSH Terms: Nutrition Disorders; Malnutrition; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Antimetabolites; Ribavirin
• Other Study ID Numbers: RIB-B-20-028

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Individual participant data that underlie the results reported in this study, after deidentification (text, tables, figures, and appendices).
• IPD Sharing Time Frame: Beginning 9 months following article publication and no end date
• IPD Sharing Access Criteria: Researchers who provide a methodologically sound proposal. Proposals should be directed to To gain access.
• IPD Sharing Supporting Information Type: Study Protocol

Drug and device information, study documents

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