A Study of S-033188 (Baloxavir Marboxil) Compared With Placebo or Oseltamivir in Otherwise Healthy Patients With Influenza

NCT02954354 | Completed Phase 3 Results

• 1 other identifier: 1601T0831
• Study Type: interventional
• Target: 1,436
• Locations: 0 countries
• Sites: N/A

Brief Summary

The primary objective of this study is to evaluate the efficacy of a single, oral dose of baloxavir marboxil compared with placebo by measuring the time to alleviation of symptoms in patients with uncomplicated influenza virus infection.

Conditions

Influenza

Keywords

Flu; Baloxavir Marboxil; Oseltamivir; Tamiflu®

Outcome Measures

Primary Outcomes (2)

• Time to Alleviation of Symptoms in Participants Randomized to Baloxavir or Placebo

  Participants assessed the severity of seven influenza-associated symptoms (cough, sore throat, headache, nasal congestion, feverishness or chills, muscle or joint pain, and fatigue) on a 4-point scale (with 0 indicating no symptoms, 1 mild symptoms, 2 moderate symptoms, and 3 severe symptoms). Time to alleviation of symptoms was defined as the time from the start of the study treatment to the time when all seven influenza-related symptoms were assessed by the participant as absent (0) or mild (1) for at least 21.5 hours. Time to alleviation of symptoms was analyzed using the Kaplan-Meier (KM) method; participants who did not experience alleviation of symptoms were censored at the last observation time point.

  Initiation of study treatment up to Day 14

• Time to Alleviation of Symptoms in Adults Randomized to Baloxavir or Oseltamivir

  Participants assessed the severity of seven influenza-associated symptoms (cough, sore throat, headache, nasal congestion, feverishness or chills, muscle or joint pain, and fatigue) on a 4-point scale (with 0 indicating no symptoms, 1 mild symptoms, 2 moderate symptoms, and 3 severe symptoms). Time to alleviation of symptoms was defined as the time from the start of the study treatment to the time when all seven influenza-related symptoms were assessed by the participant as absent (0) or mild (1) for at least 21.5 hours. Time to alleviation of symptoms was analyzed using the Kaplan-Meier(KM) method; participants who did not experience alleviation of symptoms were censored at the last observation time point.

  Initiation of study treatment up to Day 14

Secondary Outcomes (37)

• Percentage of Participants With Positive Influenza Virus Titer at Each Time Point in Participants Randomized to Baloxavir or Placebo

  Days 2, 3, 4 (optional), 5, 6 (optional), and 9

• Percentage of Participants With Positive Influenza Virus Titer at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir

  Days 2, 3, 4 (optional), 5, 6 (optional), and 9

• Percentage of Participants With Positive Influenza Virus by RT-PCR at Each Time Point in Participants Randomized to Baloxavir or Placebo

  Days 2, 3, 4 (optional), 5, 6 (optional), and 9

• Percentage of Participants With Positive Influenza Virus by RT-PCR at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir

  Days 2, 3, 4 (optional), 5, 6 (optional), and 9

• Change From Baseline in Virus Titer at Each Time Point in Participants Randomized to Baloxavir or Placebo

  Day 1 pretreatment (Baseline) and Days 2, 3, 4 (optional), 5, 6 (optional), and 9

Study Arms (5)

Adults: Baloxavir Marboxil

EXPERIMENTAL

Participants aged 20 to 64 years will receive two or four 20 mg baloxavir marboxil tablets orally on Day 1 and one oseltamivir placebo capsule orally twice a day (BID) on Days 1 to 5.

Drug: Baloxavir Marboxil; Drug: Placebo to Oseltamivir

Adults: Oseltamivir

ACTIVE COMPARATOR

Participants aged 20 to 64 years will receive 75 mg oseltamivir twice a day on Days 1 to 5 and two or four baloxavir marboxil placebo tablets on Day 1.

Drug: Placebo to Baloxavir Marboxil; Drug: Oseltamivir

Adults: Placebo

PLACEBO COMPARATOR

Participants aged 20 to 64 years will receive two or four baloxavir marboxil placebo tablets on Day 1 and one oseltamivir placebo capsule orally twice a day on Days 1 to 5.

Drug: Placebo to Baloxavir Marboxil; Drug: Placebo to Oseltamivir

Adolescents: Baloxavir Marboxil

EXPERIMENTAL

Participants aged 12 to 19 years will receive two or four baloxavir marboxil 20 mg tablets on Day 1.

Drug: Baloxavir Marboxil

Adolescents: Placebo

PLACEBO COMPARATOR

Participants aged 12 to 19 years will receive two or four baloxavir marboxil placebo tablets on Day 1.

Drug: Placebo to Baloxavir Marboxil

Interventions

Baloxavir Marboxil DRUG

2 to4 X 20-mg tablets taken orally

Also known as: S-033188

Adolescents: Baloxavir Marboxil; Adults: Baloxavir Marboxil

Placebo to Baloxavir Marboxil DRUG

2 to4 X 20-mg tablets taken orally

Adolescents: Placebo; Adults: Oseltamivir; Adults: Placebo

Oseltamivir DRUG

75 mg capsules taken orally

Also known as: Tamiflu®

Adults: Oseltamivir

Placebo to Oseltamivir DRUG

Placebo capsules matching oseltamivir 75 mg capsules

Adults: Baloxavir Marboxil; Adults: Placebo

Eligibility Criteria

• Age: 12 Years - 64 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Patients who are able to understand the study and comply with all study procedures, and willing to provide written informed consent/assent prior to the predose examinations appropriately. As for adolescent patients, informed consent/assent of voluntary participation should be obtained in accordance with local requirements
• Male or female patients aged ≥ 12 to ≤ 64 years at the time of signing the informed consent/assent form.
• Patients with a diagnosis of influenza virus infection confirmed by all of the following:
• Fever ≥ 38ºC (axillary) in the predose examinations or \> 4 hours after dosing of antipyretics if they were taken
• At least one of the following general systemic symptoms associated with influenza are present with a severity of moderate or greater
• Headache
• Feverishness or chills
• Muscle or joint pain
• Fatigue
• At least one of the following respiratory symptoms associated with influenza are present with a severity of moderate or greater
• Cough
• Sore throat
• Nasal congestion
• The time interval between the onset of symptoms and the predose examinations is 48 hours or less. The onset of symptoms is defined as either:
• Time of the first increase in body temperature (an increase of at least 1ºC from normal body temperature)

You may not qualify if:

• Patients with severe influenza virus infection requiring inpatient treatment.
• Patients aged ≥ 20 years with known allergy to oseltamivir (Tamiflu®).
• Patients with any of the following risk factors
• Women who are pregnant or within 2 weeks post-partum
• Residents of long-term care facilities (eg, welfare facilities for the elderly, nursing homes)
• Chronic respiratory diseases including bronchial asthma
• Neurological and neurodevelopmental disorders including disorders of the brain, spinal cord, peripheral nerve, and muscle (eg, cerebral palsy, epilepsy \[seizure disorders\], stroke, intellectual disability, moderate to severe developmental delay, muscular dystrophy, or spinal cord injury)
• Heart disease (such as congenital heart disease, congestive heart failure, or coronary artery disease), excluding hypertension without any other heart-related symptoms)
• American Indians and Alaskan natives
• Blood disorders (such as sickle cell disease)
• Endocrine disorders (including diabetes mellitus)
• Kidney disorders
• Liver disorders
• Metabolic disorders
• Compromised immune system (including patients receiving immunosuppressant therapy, or those with cancer or human immunodeficiency virus \[HIV\] infection)

Sponsors & Collaborators

• Shionogi: lead

Related Publications (3)

• Hayden FG, Sugaya N, Hirotsu N, Lee N, de Jong MD, Hurt AC, Ishida T, Sekino H, Yamada K, Portsmouth S, Kawaguchi K, Shishido T, Arai M, Tsuchiya K, Uehara T, Watanabe A; Baloxavir Marboxil Investigators Group. Baloxavir Marboxil for Uncomplicated Influenza in Adults and Adolescents. N Engl J Med. 2018 Sep 6;379(10):913-923. doi: 10.1056/NEJMoa1716197.

  PMID: 30184455 RESULT

• Retout S, De Buck S, Jolivet S, Duval V, Cosson V. A Pharmacokinetics-Time to Alleviation of Symptoms Model to Support Extrapolation of Baloxavir Marboxil Clinical Efficacy in Different Ethnic Groups with Influenza A or B. Clin Pharmacol Ther. 2022 Aug;112(2):372-381. doi: 10.1002/cpt.2648. Epub 2022 Jun 10.

  PMID: 35585696 DERIVED

• Uehara T, Hayden FG, Kawaguchi K, Omoto S, Hurt AC, De Jong MD, Hirotsu N, Sugaya N, Lee N, Baba K, Shishido T, Tsuchiya K, Portsmouth S, Kida H. Treatment-Emergent Influenza Variant Viruses With Reduced Baloxavir Susceptibility: Impact on Clinical and Virologic Outcomes in Uncomplicated Influenza. J Infect Dis. 2020 Jan 14;221(3):346-355. doi: 10.1093/infdis/jiz244.

  PMID: 31309975 DERIVED

MeSH Terms

Conditions

Influenza, Human

Interventions

baloxavir; Oseltamivir

Condition Hierarchy (Ancestors)

Respiratory Tract Infections; Infections; Orthomyxoviridae Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Acetamides; Amides; Organic Chemicals; Cyclohexenes; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons

Results Point of Contact

• Title: Shionogi Clinical Trials Administrator
• Organization: Shionogi Inc.

Shionogiclintrials-admin@shionogi.co.jp

800-849-9707

Study Officials

• Clinical Support Help Line Shionogi Clinical Trials Administrator

  Shionogi

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 27, 2016
• First Posted: November 3, 2016
• Study Start: December 8, 2016
• Primary Completion: April 4, 2017
• Study Completion: April 24, 2017
• Last Updated: May 8, 2019
• Results First Posted: December 14, 2018

Record last verified: 2019-04