A Pharmacokinetics Study of Favipiravir in Patients With Severe Influenza

May 14, 2019 updated by: Bin Cao, Capital Medical University

An Adaptive Study of the Pharmacokinetics of Favipiravir in Patients With Severe

Title: An adaptive study of the pharmacokinetics of favipiravir in patients with severe influenza Study Design: An open label, single group assignment, adaptive study to evaluate the pharmacokinetics of favipiravir in adult patients with severe influenza.

In the first stage, participants will receive favipiravir 1600mg BID on day 1, followed by favipiravir 600mg BID for 9 days.

If the proportion of patients with a minimum observed plasma trough concentration above the MEC (20μg/ml) at all measured time points after the second dose is less than 80% then a second patient cohort will be recruited and will receive favipiravir 1800mg BID on day 1, followed by favipiravir 800mg BID for 9 days.

Intervention: The 1st stage: 1600mg BID on day 1, followed with 600mg BID for 9 days. Sample size: 15 The 2nd stage: 1800mg BID on day 1, followed with 800mg BID for 9 days. Sample size: 15 Population: Males and females aged 18 years or older admitted to hospital with a positive PCR test for influenza and a PaO2/FiO2≤300mmHg or/and on mechanical ventilation for severe lung infection on admission.

Sample size 15 or 30 severe influenza patients Research hypothesis The administration of oral favipiravir at either 1600mg/600mg BID or 1800/800mg BID will result in ≥ 80% patients achieving a minimum observed plasma trough concentration above the MEC (20μg/ml) at all measured time points after the second dose.

Phase: Phase 2a, PK, safety and feasibility study. Description of Study Agent: Favipiravir (T-705) a viral RNA-dependent RNA polymerase inhibitor.

Study Duration: 1 year Participant Duration: 38 days

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

34

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • China
      • Beijing, China, 100029
        • China-Japan Friendship Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Hospitalized males or females with a positive PCR test for influenza virus infection
  2. Adults aged ≥18years
  3. PaO2/FiO2≤300mmHg or on mechanical ventilation
  4. < 10 days since symptom onset
  5. Negative pregnancy testing for childbearing age females (under 60 years)
  6. Willingness to use contraception for 7 days after end of treatment
  7. Informed consent

  8. In addition, male subjects must:

    1. Agree not to donate sperm during the study and for 7 days following the last dose of study drug, and
    2. Agree to adhere strictly to one of the following contraceptive measures from the Screening Visit until 7 days after the last dose of study drug:

    i. abstain from sexual intercourse or ii. have a female partner using effective means of birth control as noted below or iii. use a condom with spermicide or a second barrier method by female partner.

Female subjects

a. Of child-bearing potential must agree to adhere strictly to one of the following approved contraceptive measures during the study and for 7 days after the last dose of study drug: i. abstain from sexual intercourse or ii. have a male partner incapable of fathering a child (eg, had a vasectomy at least 6 months with history of negative semen analysis prior Screening or iii. use of one of the following methods, in combination with condom and spermicide use by a male partner: nonhormonal intrauterine device (IUD); diaphragm; or hormonal contraceptives including oral contraceptives, injectable subdermal implants, hormonal IUD, or vaginal ring b. Be unable to bear children defined as one of the following: i. absence of a menstrual period for ≥12 consecutive months with FSH confirmation, ii. be 60 years of age or greater, iii. had surgical removal of uterus or removal of both ovaries, or iv. had undergone tubal ligation >6 weeks prior to Day 1 dosing

Exclusion Criteria:

  1. Any condition that does not allow for safely following the protocol
  2. Patient refusal to accept invasive organ support treatment if needed
  3. Pregnant or breastfeeding
  4. Any condition resulted to reception of renal replacement therapy
  5. AST > 5 times upper of limit or Child Pugh score ≥ C
  6. Serum uric acid level > 3 times upper level of normal (430 ummol/L) associated with symptoms of gout
  7. Has a history of gout or is under treatment for: gout or hyperuricemia; hereditary xanthinuria; hypouricemia or xanthine calculi of the urinary tract
  8. Has a history of hypersensitivity to an anti-viral nucleoside-analog drug targeting a viral RNA polymerase
  9. Physician makes a decision that trial involvement is not in patients' best interest.
  10. Currently or have been involved in another anti-influenza treatment trial in the last 28 days

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Favipiravir+oseltamivir
Favipiravir+oseltamivir will be given twice daily for a 10-day period.
Drug: Favipiravir

In first step: favipiravir tablet is orally administered. This drug will be given twice daily for a 10-day period. For the First day, the dosage is 1600 mg twice daily. Starting from the second day, the dosage is 600 mg twice daily.

In second step: favipiravir tablet is orally administered. This drug will be given twice daily for a 10-day period. For the First day, the dosage is 1800 mg twice daily. Starting from the second day, the dosage is 800 mg twice daily.

Other Names:
  • T-705
Drug: Oseltamivir 75Mg Capsule
oseltamivir will be administered at 75mg twice daily orally for 10 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Proportion of patients with minimum plasma of Favipiravir trough concentration above the MEC (20μg/ml) at all measured time points after the second dose.
Time Frame: 10 days during the intervention period
10 days during the intervention period

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Maximum plasma concentration observed over the treatment period (Cmax )
Time Frame: 10 days during the intervention period
10 days during the intervention period
Minimum plasma concentration observed over the treatment period (Cmin)
Time Frame: 10 days during the intervention period
10 days during the intervention period
Average pre-dose plasma concentration (Trough)
Time Frame: 10 days during the intervention period
10 days during the intervention period
Proportion of patients whose favipiravir plasma concentration at least one time exceeds MEC in study days
Time Frame: 10 days during the intervention period
10 days during the intervention period
The proportion of patients falling into each category of a five-point ordinal scale on day 10 and day 28 after starting favipiravir
Time Frame: 28 days from starting intervention
The category of a five-point ordinal scale: death; hospitalised on ECMO and/or mechanical ventilation; hospitalised on supplemental oxygenation; hospitalised not on supplemental oxygenation; discharged.
28 days from starting intervention
Duration (days) of mechanical ventilation
Time Frame: from reception of mechanical ventilation to ventilator weening, an average of 10 days
from reception of mechanical ventilation to ventilator weening, an average of 10 days
Duration (days) of extracorporeal membrane oxygenation
Time Frame: from starting ECMO to weening, an average of 9 days
from starting ECMO to weening, an average of 9 days
Duration (days) of supplemental oxygenation
Time Frame: Duration (days) of hospitalization with oxygen therapy，an average of 13 days
Duration (days) of hospitalization with oxygen therapy，an average of 13 days
Duration (days) of hospitalization
Time Frame: Days from admission to discharge，an average of 19 days
Days from admission to discharge，an average of 19 days
The proportion of patients with a negative RT-PCR for influenza from upper and/or lower respiratory tract samples on day 10 after starting treatment
Time Frame: Duration of viral shedding,an average of 15 days
Duration of viral shedding,an average of 15 days
The time (days) to negative RT-PCR for influenza from upper and/or lower respiratory tract samples (capped at day 10)
Time Frame: Duration of viral shedding,an average of 15 days
Duration of viral shedding,an average of 15 days
The proportion of patients with drug related adverse events
Time Frame: 38 days from starting intervention
38 days from starting intervention
The proportion of patients with genetic and phenotypic markers of resistance to favipiravir and/or oseltamivir
Time Frame: Days from admission to discharge，an average of 19 days
Days from admission to discharge，an average of 19 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Capital Medical University

Collaborators

University of Oxford
Centers for Disease Control and Prevention, China
Beijing Institute of Pharmacology and Toxicology

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 6, 2018

Primary Completion (Actual)

February 20, 2019

Study Completion (Actual)

March 27, 2019

Study Registration Dates

First Submitted

December 25, 2017

First Submitted That Met QC Criteria

January 6, 2018

First Posted (Actual)

January 9, 2018

Study Record Updates

Last Update Posted (Actual)

May 15, 2019

Last Update Submitted That Met QC Criteria

May 14, 2019

Last Verified

May 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • FAVI-PK-2017001

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Undecided

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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