A Phase 1 Bioequivalence Study of a Test Tablet Formulation of Ravidasvir With the Reference Tablet Formulation of Ravidasvir Study

NCT03602300 | Completed Phase 1

• 1 other identifier: DNDi-RDV-02-HCV
• Study Type: interventional
• Target: 37
• Locations: 1 country
• Sites: 1

Brief Summary

In a phase 1, open-label, crossover study to evaluate the relative bioavailability of a tablet formulation of ravidasvir (test) versus the capsule formulation of ravidasvir (reference) in 24 healthy adult volunteers (PPI-668-104 study), relatively high intra-subject coefficients of variation were observed for both Cmax and AUC0-t. A two-sequence, four-period replicate design will be used to allow the possibility to scale the acceptance range for Cmax if the observed intra-subject coefficient of variation for the reference formulation is greater than 30%

Conditions

Bioequivalence Study

Outcome Measures

Primary Outcomes (3)

• RDV Plasma CMax when administered as a single 200 mg oral dose of the test versus reference product

  Plasma RDV Cmax will be calculated based on plasma RDV concentrations at pre-dose (time 0 hours) and at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 10, 12, 24, 36, and 48 hours post-dose

  Measurement within 48 hours post-dose

• RDV area under the plasma concentration-time curve from time of intake until infinity (AUC0-∞) when administered as a single 200 mg oral dose of the test versus reference product

  Area under the plasma concentration-time curve from time of intake until infinity (AUC0-∞) will be calculated based on plasma RDV concentrations at pre-dose (time 0 hours) and at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 10, 12, 24, 36, and 48 hours post-dose.

  Measurement within 48 hours post-dose

• RDV area under the plasma concentration-time curve from time of intake until the last quantifiable concentration (AUC0-t) when administered as a single 200 mg oral dose of the test versus reference product

  Area under the plasma concentration-time curve from time of intake until the last quantifiable concentration (AUC0-t) will be calculated based on plasma RDV concentrations at pre-dose (time 0 hours) and at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 10, 12, 24, 36, and 48 hours post-dose.

  Measurement within 48 hours post-dose

Secondary Outcomes (9)

• RDV maximum plasma concentration (tmax) when administered as a single 200 mg oral dose of the test versus reference product

  Measurement within 48 hours post-dose

• RDV mean residence time (MRT) when administered as a single 200 mg oral dose of the test versus reference product

  Measurement within 48 hours post-dose

• RDV elimination rate constant (λz) when administered as a single 200 mg oral dose of the test versus reference product

  Measurement within 48 hours post-dose

• RDV elimination half-life (t1/2, estimated based on λz), when administered as a single 200 mg oral dose of the test versus reference product

  Measurement within 48 hours post-dose

• RDV apparent volume of distribution when administered as a single 200 mg oral dose of the test versus reference product

  Measurement within 48 hours post-dose

Study Arms (2)

Ravidasvir reference formulation

ACTIVE COMPARATOR

Ravidasvir 200 mg oral single dose manufactured by EEPI

Drug: Ravidasvir reference formulation produced by EEPI

Ravidasvir test formulation

EXPERIMENTAL

Ravidasvir 200 mg oral single dose manufactured by Doppel

Drug: Ravidasvir test formulation produced by Doppel

Interventions

Ravidasvir test formulation produced by Doppel DRUG

To compare the rate and extent of absorption for RDV when administered as a single 200 mg oral dose of the proposed commercial product ("test") produced by Doppel Farmaceutici with the clinical trial product ("reference") manufactured by EEPI in healthy volunteers, under fasted conditions.

Ravidasvir test formulation

Ravidasvir reference formulation produced by EEPI DRUG

To compare the rate and extent of absorption for RDV when administered as a single 200 mg oral dose of the proposed commercial product ("test") produced by Doppel Farmaceutici with the clinical trial product ("reference") manufactured by EEPI in healthy volunteers, under fasted conditions.

Ravidasvir reference formulation

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Have the ability to understand and sign a written informed consent form, which must be obtained prior to initiation of study procedures.
• Must be between 18 and 55 years of age, inclusive.
• Must be a non-smoker. The use of nicotine or nicotine-containing products must be discontinued 90 days prior to the first dose of study drug. Users of electronic cigarette are not allowed to participate in this study. A smokerlyzer test will be performed to estimate the amount of carbon monoxide in the breath.
• Must have a calculated body mass index (BMI) of 18.0 to 29.9 kg/m2.
• Must be HIV-1 antibody negative.
• Must be hepatitis B (HBV) surface antigen negative.
• Must be hepatitis C (HCV) antibody negative.
• Females of childbearing potential must have a negative serum pregnancy test at Screening and on Day 0.
• Females of childbearing potential must agree to utilize highly effective contraception methods (with the exception of hormonal contraceptive) from 3 weeks prior to baseline (Day 0) throughout the duration of study treatment and for 30 days following the last dose of study drug. Female healthy volunteers who utilize hormonal contraceptive as one of their birth control methods are not allowed to participate in this study.
• Men who participate in this study must not father a child and must agree to use contraceptive protection in the form of a double barrier method (condom or diaphragm) from the moment they sign the ICF until the Post-Study Safety Assessment.
• Healthy volunteers must, in the opinion of the Investigator, be in good health based upon medical history, physical examination (including vital signs), and screening laboratory evaluations (haematology, chemistry, and urinalysis) must fall within the normal range of the local laboratory's reference ranges unless the results have been determined by the Investigator to have no clinical significance.
• Have either a normal 12-lead electrocardiogram (ECG) or one with abnormalities that are considered clinically insignificant by the Investigator.
• Must have negative urine screen for drugs of abuse (including ketamine, amphetamines, tetrahydrocannabinol, morphine, methamphetamine, and benzodiazepines)
• Must be willing and able to comply with all study requirements

You may not qualify if:

• Healthy volunteers with any hematologic or urinary analyte that is outside the normal limits of the study laboratory and have been determined by the Investigator to have clinical significance at Screening will be excluded
• Pregnant or lactating female healthy volunteers.
• Have any serious or active medical or psychiatric illness which, in the opinion of the Investigator, would interfere with subject treatment, assessment, or compliance with the protocol. This would include renal, cardiac, hematologic, hepatic, pulmonary (including chronic asthma), endocrine (e.g., diabetes), central or peripheral nervous, gastrointestinal (including an ulcer), vascular, metabolic (thyroid disorders, adrenal disease), or immunodeficiency disorders, active infection, or malignancy that is clinically significant or requiring treatment.
• Have participated in an investigational trial involving administration of any investigational compound within 90 days prior to the study dosing or 5-times the half-life of the drug tested in the previous clinical trial, whichever is longer (time calculated relative to the last dose in the previous clinical trial).
• Current alcohol or substance abuse judged by the Investigator to potentially interfere with subject compliance.
• Have poor venous access and unable to donate blood.
• Have donated or lost blood (≥500ml) within two months of study dosing.
• Have donated plasma within 7 days of study dosing.
• Have difficulty in swallowing solids like tablets.
• Have taken any prescription medications or over-the-counter medications including herbal products within 1 week of commencing study drug dosing with the exception of vitamins and/or acetaminophen and/or ibuprofen.
• Female healthy volunteers who utilize hormonal contraceptive as one of their birth control methods.
• Have a history of significant drug allergy.
• Smokers and users of electronic cigarette.
• Unable to comply with study requirements.
• Believed by the study Investigator to be inappropriate for study participation for any reason

Sponsors & Collaborators

• Drugs for Neglected Diseases: lead

Study Sites (1)

Ampang hospital

Ampang, Selangor, 68000, Malaysia

Location

Study Officials

• Damenthi Nair, MD

  KPJ Ampang Puteri Specialist Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: A Phase 1, Open-Label, Four-Period, Two-Sequence, Two-Treatment, Single Dose, Randomized, Crossover Bioequivalence Study

Study Record Dates

• First Submitted: June 21, 2018
• First Posted: July 26, 2018
• Study Start: June 5, 2018
• Primary Completion: August 17, 2018
• Study Completion: August 17, 2018
• Last Updated: January 31, 2020

Record last verified: 2020-01

Locations

MY (1)