InfluenzaPhase 3CAPSTONE 2NCT02949011
Study of S-033188 (Baloxavir Marboxil) Compared With Placebo or Oseltamivir in Patients With Influenza at High Risk of Influenza Complications
A Phase 3 study testing Baloxavir Marboxil and Oseltamivir in people with Influenza, run by Shionogi.
Trial 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 improvement of influenza symptoms in patients with influenza presenting within 48 hours of symptom onset. Read more about this study
- Who is it for?
- Ages 12 years and older
- Conditions the study is for
- Influenza
- What is being tested?
- Baloxavir Marboxil and Oseltamivir
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 2,184 participants
- Where
- No sites listed yet
- Study dates
- 11 Jan 2017to 20 Apr 2018
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 12 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Patients or their legal guardians who provide written informed consent to participate in the study on a voluntary basis. For adolescent patients, informed consent/assent of voluntary participation should be obtained in accordance with local requirements.
- Male or female patients ≥ 12 years at the time of signing the informed consent/assent form.
- Patients with a diagnosis of influenza confirmed by all of the following:
- Fever ≥ 38ºC (axillary) during the predose examinations or within the 4 hours prior if antipyretics were taken
- A positive rapid influenza diagnostic test (RIDT) result OR A patient with a negative RIDT may be enrolled if the patient reports contact with a known case of influenza within the prior 7 days and all other inclusion criteria are met.
- At least 1 each of the following general and respiratory symptoms associated with influenza is present with a severity of moderate or greater:
Show all 24Show fewer
- General symptoms (headache, feverishness or chills, muscle or joint pain, or fatigue) ii. Respiratory symptoms (cough, sore throat, or 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)
- Time when the patient experiences at least 1 new general or respiratory symptom
- If a women of childbearing potential, agrees to use a highly effective method of contraception for 3 months after the first dose of study drug
- Patients will be considered at high risk* of influenza complications due to the presence of at least 1 of the following inclusion criteria:
- Asthma or chronic lung disease (such as chronic obstructive pulmonary disease or cystic fibrosis)
- Endocrine disorders (including diabetes mellitus)
- Residents of long-term care facilities (eg, nursing homes)
- Compromised immune system (including patients receiving corticosteroids not exceeding 20 mg of prednisolone or equivalent, and patients being treated for human immunodeficiency virus [HIV] infection with a CD4 count > 350 cells/mm³ within the last 6 months)
- Neurological and neurodevelopmental disorders (including disorders of the brain, spinal cord, peripheral nerve, and muscle, eg, cerebral palsy, epilepsy [seizure disorders], stroke, 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
- Adults aged ≥ 65 years
- American Indians and Alaskan Natives
- Blood disorders (such as sickle cell disease)
- Metabolic disorders (such as inherited metabolic disorders and mitochondrial disorders)
- Morbid obesity (body mass index ≥ 40 kg/m²)
- Women who are within 2 weeks postpartum and are not breastfeeding
Who cannot join
- Patients with severe influenza virus infection requiring inpatient treatment.
- Patients with known allergy to oseltamivir (Tamiflu®).
- Patients unable to swallow tablets or capsules.
- Patients who have previously received baloxavir marboxil.
- Patients weighing ≤ 40 kg.
- Patients who have been exposed to an investigational drug within 30 days prior to the predose examinations.
Show all 19Show fewer
- Women who are pregnant, breastfeeding, or have a positive pregnancy test at the predose examinations. The following female patients who have documentation of either a or b below do not need to undergo a pregnancy test at the predose examinations:
- Postmenopausal women (defined as cessation of regular menstrual periods for 2 years or more and confirmed by a follicle-stimulating hormone test)
- Women who are surgically sterile by hysterectomy, bilateral oophorectomy, or tubal ligation
- Patients with concurrent infections at the predose examinations requiring systemic antimicrobial therapy.
- Patients with liver disease associated with hepatic impairment.
- Patients with cancer within the last 5 years (unless nonmelanoma skin cancer).
- Patients with untreated HIV infection or treated HIV infection with a CD4 count below 350 cells/mm3 in the last 6 months.
- Patients with immunosuppression following organ or bone marrow transplants.
- Patients exceeding 20 mg of prednisolone or equivalent dose of chronic systemic corticosteroids.
- Patients who have received peramivir, laninamivir, oseltamivir, zanamivir, rimantadine, umifenovir or amantadine within 30 days prior to the predose examinations.
- Patients who have received an investigational monoclonal antibody for a viral disease in the last year.
- Patients with known creatinine clearance ≤ 60 mL/min.
- Patients who, in the opinion of the investigator, would be unlikely to comply with required study visits, self-assessments, and interventions
About this study
Official title: A Phase 3, Multicenter, Randomized, Double-blind Study of a Single Dose of S-033188 Compared With Placebo or Oseltamivir 75 mg Twice Daily for 5 Days in Patients With Influenza at High Risk of Influenza Complications
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 improvement of influenza symptoms in patients with influenza presenting within 48 hours of symptom onset.
- Conditions
- Influenza
- Being tested
- Baloxavir Marboxil, Placebo to Baloxavir Marboxil, Oseltamivir, Placebo to Oseltamivir
- Keywords
- Tamiflu®, Influenza, Oseltamivir, Flu, S-033188
- Medical subject headings
- Influenza, Human
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Baloxavir MarboxilDrug
Also called S-033188, Xofluza®
Tablets taken orally
Placebo to Baloxavir MarboxilDrug
Matching tablets taken orally
OseltamivirDrug
Also called Tamiflu®
Capsules taken orally
Placebo to OseltamivirDrug
Matching placebo capsules taken orally
| Study group | Role | What they receive |
|---|---|---|
| Baloxavir Marboxil | Experimental | Participants received either 40 mg or 80 mg of baloxavir marboxil orally on Day 1 based on body weight of < 80 kg or ≥ 80 kg at Screening, respectively. Participants also received placebo to oseltamivir orally twice a day (BID) on Days 1 to 5. Receives: Drug: Baloxavir Marboxil; Drug: Placebo to Oseltamivir |
| Oseltamivir | Active comparator | Participants received 75 mg oseltamivir twice a day on Days 1 to 5 and placebo to baloxavir marboxil on Day 1. Receives: Drug: Placebo to Baloxavir Marboxil; Drug: Oseltamivir |
| Placebo | Placebo comparator | Participants received placebo to baloxavir marboxil on Day 1 and placebo to oseltamivir orally twice a day on Days 1 to 5. Receives: Drug: Placebo to Baloxavir Marboxil; Drug: Placebo to Oseltamivir |
What is being measured
The primary outcome is the main question the study is designed to answer.
Time to Improvement of Influenza Symptoms
Participants assessed the severity of 7 influenza-associated symptoms (cough, sore throat, headache, nasal congestion, feverishness/chills, muscle/joint pain, and fatigue) on a 4-point scale (0 = no symptoms, 1= mild, 2 = moderate, and 3 = severe). Time to improvement of symptoms was defined as the time from the start of treatment to the time when all influenza symptoms were alleviated, maintained, or improved, as defined below, for a duration of at least 21.5 hours:
- Preexisting symptoms (cough, fatigue, or muscle/joint pain that existed prior to influenza) that were worse at baseline must have improved at least 1 point from baseline
- Preexisting symptoms not worse at baseline must have maintained baseline severity
- New symptoms must have alleviated, defined as a symptom score of none (0) or mild (1).
Time to improvement of symptoms was analyzed using Kaplan-Meier (KM) methods; participants who did not experience improvement of symptom s were censored at the last observation.
Measured: From Day 1 pretreatment up to Day 14
Secondary outcomes (20)
Percentage of Participants With Positive Influenza Virus Titer at Each Time Point
Virus titer was quantified from nasopharyngeal swabs (or throat swabs if nasopharyngeal swabbing was not feasible) using tissue culture methods. Positive influenza virus titer was defined as virus titer not less than the lower limit of quantification (0.7 log₁₀ of the 50% tissue culture infective dose (TCID₅₀/mL) among those assessed for virus titer on Days 2, 3, 4, 5, 6, and 9.
Measured: Days 2, 3, 4 (optional), 5, 6 (optional), and 9
Percentage of Participants With Positive Influenza Virus by RT-PCR at Each Time Point
Influenza virus ribonucleic acid (RNA) was quantified from nasopharyngeal swabs (or throat swabs, if nasopharyngeal swabbing was not feasible). The percentage of participants with detectable virus RNA (2.05 for flu A and 2.83 for flu B log₁₀ virus particles/mL) measured by reverse transcription polymerase chain reaction (RT-PCR) among those assessed on Days 2, 3, 4, 5, 6 and 9.
Measured: Days 2, 3, 4 (optional), 5, 6 (optional), and 9.
Change From Baseline in Virus Titer at Each Time Point
Virus titer was quantified from nasopharyngeal swabs (or throat swabs if nasopharyngeal swabbing was not feasible) by tissue culture methods.
If virus titer was less than the lower limit of quantification, the virus titer was imputed 0.7 (TCID₅₀/mL).
Measured: Day 1 pretreatment (Baseline) and Days 2, 3, 4 (optional), 5, 6 (optional), and 9
Change From Baseline in Virus RNA (RT-PCR) at Each Time Point
Nasopharyngeal swabs (or throat swabs, if nasopharyngeal swabbing was not feasible) were obtained for viral quantitation. Virus RNA was measured by reverse transcription polymerase chain reaction (RT-PCR).
Measured: Day 1 pretreatment (Baseline) and Days 2, 3, 4 (optional), 5, 6 (optional), and 9
Area Under the Curve (AUC) Adjusted by Baseline in Influenza Virus Titer
This endpoint was defined as AUC of change from Baseline in virus titer from Day 1 to Day 9. AUC was calculated using the trapezoidal method.
Measured: Day 1 to Day 9
Area Under the Curve (AUC) Adjusted by Baseline in Viral RNA
This endpoint was defined as AUC of change from baseline in the amount of virus RNA (RT-PCR) from Day 1 to Day 9. The AUC was calculated using the trapezoidal method.
Measured: Day 1 to Day 9
Time to Cessation of Viral Shedding Determined by Virus Titer
Time to cessation of viral shedding by virus titer was defined as the time between the initiation of the study treatment and first time when the virus titer was below the limit of detection (0.7 log₁₀[TCID₅₀/mL]). The median and 95% confidence interval (CI) for time to cessation of viral shedding determined by virus titer was analyzed using the Kaplan-Meier (KM) method; participants whose virus titer had not reached cessation by the last observation time point were treated as censored at that time point.
Measured: Day 1 to Day 9
Time to Cessation of Viral Shedding Determined by Virus RNA
Time to cessation of viral shedding by RT-PCR was defined as the time between the initiation of the study treatment and first time when the virus RNA was below the limit of detection measured by RT-PCR.
Time to cessation of viral shedding by RT-PCR was analyzed using the KM method; participants whose virus RNA had not reached cessation by the last observation time point were treated as censored at that time point.
Measured: Day 1 to Day 9
Percentage of Participants Whose Symptoms Were Improved at Each Time Point
Participants assessed the severity of 7 influenza-associated symptoms (cough, sore throat, headache, nasal congestion, feverishness or chills, muscle or joint pain, and fatigue) on a 4-point scale (0 = no symptoms, 1= mild, 2 = moderate, and 3 = severe).
Improvement of symptoms was defined as all influenza symptoms alleviated, maintained, or improved, as defined below, for a duration of at least 21.5 hours:
- Preexisting symptoms (cough, fatigue, or muscle/joint pain that existed prior to influenza) judged to be worse at baseline must have improved at least 1 point from baseline severity
- Preexisting symptoms judged not to be worse at baseline must have maintained baseline severity
- New symptoms at baseline must have alleviated, defined as a symptom score of none (0) or mild (1).
Measured: 12, 24, 36, 48, 72, 96, 120, 144, 168, 192, and 216 hours after the initial dose of study treatment
Time to Alleviation of Symptoms
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 Kaplan-Meier (KM) methods; participants who did not experience alleviation of symptoms were censored at the last observation time point.
Measured: Initiation of study treatment up to Day 14
Time to Improvement of the Four Systemic Symptoms
Participants assessed the severity of 7 influenza-associated symptoms on a 4-point scale (from 0 = no symptoms to 3 = severe symptoms). Time to improvement of the 4 systemic symptoms was defined as the time between the initiation of study treatment to the time when all 4 systemic symptoms (headache, feverishness or chills, muscle or joint pain, and fatigue) were alleviated, maintained, or improved, as defined below, for a duration of at least 21.5 hours:
- Preexisting symptoms (cough, fatigue, or muscle/joint pain that existed prior to influenza) that were worse at baseline must have improved at least 1 point from baseline
- Preexisting symptoms not worse at baseline must have maintained baseline severity
- New symptoms at baseline must have alleviated, defined as a symptom score of none (0) or mild (1).
Time to improvement of the 4 systemic symptoms was analyzed using KM methods; participants who did not experience improvement of symptoms were censored at the last observation.
Measured: Initiation of study treatment up to Day 14
Time to Improvement of the Three Respiratory Symptoms
Participants assessed the severity of 7 influenza-associated symptoms on a 4-point scale (from 0 = no symptoms to 3 = severe symptoms). Time to improvement of the 3 respiratory symptoms was defined as the time from the start of study treatment to the time when all 3 respiratory symptoms (cough, sore throat, and nasal congestion) were alleviated, maintained, or improved, as defined below, for a duration of at least 21.5 hours:
- Preexisting symptoms (cough, fatigue, or muscle/joint pain that existed prior to influenza) that were worse at baseline must have improved at least 1 point from baseline
- Preexisting symptoms not worse at baseline must have maintained baseline severity
- New symptoms at baseline must have alleviated, defined as a symptom score of none (0) or mild (1).
Time to improvement of the 3 respiratory symptoms was analyzed using KM methods; participants who did not experience improvement of symptoms were censored at the last observation time point.
Measured: Initiation of study treatment up to Day 14
Time to Resolution of Fever
Time to resolution of fever was defined as the time between the initiation of the study treatment and the resolution of fever. The resolution of fever was defined as the time when the participant's self-measured axillary temperature became less than 37ºC and was maintained at less than 37ºC for at least 12 hours. Time to resolution of fever was analyzed using KM methods; participants who did not experience resolution of fever by the last observation time point were censored at that time point.
Measured: Initiation of study treatment up to Day 14
Percentage of Participants Reporting Normal Temperature at Each Time Point
Defined as the percentage of patrticipants whose axillary body temperature dropped to less than 37ºC after the initiation of the study treatment.
Measured: 12, 24, 36, 48, 72, 96, 120, 144, 168, 192, and 216 hours after the initial dose of study treatment
Body Temperature at Each Time Point
Participant's self-measured axillary temperature using an electronic thermometer.
Measured: 12, 24, 36, 48, 72, 96 and 120 hours after the initial dose of study treatment
Time to Improvement of Individual Symptoms
Participants assessed the severity of 7 influenza-associated symptoms on a 4-point scale (0 = no symptoms to 3 = severe). Time to improvement of cough, fatigue, and muscle/joint pain was defined as the time from the start of treatment to the time when each symptom was alleviated, maintained, or improved, as defined below, for at least 21.5 hours:
- Preexisting symptoms that were worse at baseline must have improved at least 1 point from baseline
- Preexisting symptoms not worse at baseline must have maintained baseline severity
- New symptoms must have alleviated, defined as a score of 0 (None) or 1 (Mild). Time to improvement of sore throat, headache, nasal congestion, and feverish/chills was defined as the time from the start of treatment to the time when the symptom was assessed as 0 (None) or 1 (Mild) for at least 21.5 hours.
Time to improvement of symptoms was analyzed using KM methods; participants with no improvement of symptoms were censored at the last observation.
Measured: Initiation of study treatment up to Day 14
Time to Return to Preinfluenza Health Status
Participants were asked to record their preinfluenza health status on a scale from 0 (worst possible health) to 10 (normal health [for someone your age and condition]), and their health status at baseline and every day after initiation of study treatment on the same scale. Return to preinfluenza health status was defined as time from the initiation of the study treatment to the first time when the health status score was equal to or higher than the preinfluenza health status score.
Time to return to preinfluenza health status was analyzed using KM methods; participants with a smaller number on the scale for health status by the last observation time point were censored at that time point.
Measured: Baseline to Day 14
Percentage of Participants Requiring Systemic Antibiotics for Infections Secondary to Influenza Infection
The percentage of participants who received systemic antibiotics for any of the predefined complications (sinusitis, otitis media, bronchitis and pneumonia).
Measured: Day 2 to Day 22
Percentage of Participants With Influenza-related Complications
Defined as the percentage of patients who experience each influenza-related complication (hospitalization, death, sinusitis, otitis media, bronchitis, and radiologically-confirmed pneumonia) as an adverse event after the initiation of study treatment.
Measured: Day 1 to Day 22
Percentage of Participants With Adverse Events (AEs)
Measured: From first dose of study drug to Day 22
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Oct 2016 (estimated)
- Study start11 Jan 2017
- Primary completion12 Apr 2018
- Study completion20 Apr 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for InfluenzaStudies of the same condition, open and under way.
- More trials run by ShionogiThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 2,184 participants (actual)
Sponsor and investigators
- Lead sponsor
- Shionogi
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Shionogi Clinical Trials Administrator Clinical Support Help Line, Study director, Shionogi
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02949011
- Sponsor's protocol ID
- 1602T0832
- Other IDs
- 2016-002688-32, 2016
- Acronym
- CAPSTONE 2
- Status last verified
- Nov 2019
- First submitted
- 27 Oct 2016
- Last updated
- 19 Nov 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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.
PubMed 35585696Ison MG, Portsmouth S, Yoshida Y, Shishido T, Mitchener M, Tsuchiya K, Uehara T, Hayden FG. Early treatment with baloxavir marboxil in high-risk adolescent and adult outpatients with uncomplicated influenza (CAPSTONE-2): a randomised, placebo-controlled, phase 3 trial. Lancet Infect Dis. 2020 Oct;20(10):1204-1214. doi: 10.1016/S1473-3099(20)30004-9. Epub 2020 Jun 8.
PubMed 32526195
Study at a glance
From the registry record, last updated by the sponsor on 19 Nov 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 3, Multicenter, Randomized, Double-blind Study of a Single Dose of S-033188 Compared With Placebo or Oseltamivir 75 mg Twice Daily for 5 Days in Patients With Influenza at High Risk of Influenza Complications
- ClinicalTrials.gov ID
- NCT02949011
- Acronym / sponsor ID
- CAPSTONE 2 / 1602T0832
- Conditions
- Influenza
- Keywords
- Tamiflu®, Influenza, Oseltamivir, Flu, S-033188
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 2,184 participants (actual)
- Lead sponsor
- ShionogiIndustry (pharma, biotech, devices)
- Study start
- 11 Jan 2017 (actual)
- Primary completion
- 12 Apr 2018 (actual)
- Study completion
- 20 Apr 2018 (actual)
- First posted
- 31 Oct 2016 (estimated)
- Results
- Posted 6 Nov 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 improvement of influenza symptoms in patients with influenza presenting within 48 hours of symptom onset.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Baloxavir Marboxil | Experimental | Drug: Baloxavir Marboxil, Drug: Placebo to OseltamivirParticipants received either 40 mg or 80 mg of baloxavir marboxil orally on Day 1 based on body weight of < 80 kg or ≥ 80 kg at Screening, respectively. Participants also received placebo to oseltamivir orally twice a day (BID) on Days 1 to 5. |
| Oseltamivir | Active comparator | Drug: Placebo to Baloxavir Marboxil, Drug: OseltamivirParticipants received 75 mg oseltamivir twice a day on Days 1 to 5 and placebo to baloxavir marboxil on Day 1. |
| Placebo | Placebo comparator | Drug: Placebo to Baloxavir Marboxil, Drug: Placebo to OseltamivirParticipants received placebo to baloxavir marboxil on Day 1 and placebo to oseltamivir orally twice a day on Days 1 to 5. |
Who may qualify
- Ages
- 12 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (24 listed)
- Patients or their legal guardians who provide written informed consent to participate in the study on a voluntary basis. For adolescent patients, informed consent/assent of voluntary participation should be obtained in accordance with local requirements.
- Male or female patients ≥ 12 years at the time of signing the informed consent/assent form.
- Patients with a diagnosis of influenza confirmed by all of the following:
- 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:
- If a women of childbearing potential, agrees to use a highly effective method of contraception for 3 months after the first dose of study drug
Key exclusion criteria (19 listed)
- Patients with severe influenza virus infection requiring inpatient treatment.
- Patients with known allergy to oseltamivir (Tamiflu®).
- Patients unable to swallow tablets or capsules.
- Patients who have previously received baloxavir marboxil.
- Patients weighing ≤ 40 kg.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Baloxavir MarboxilAlso: S-033188, Xofluza®Tablets taken orally | Drug | Baloxavir Marboxil |
| Placebo to Baloxavir MarboxilMatching tablets taken orally | Drug | Oseltamivir, Placebo |
| OseltamivirAlso: Tamiflu®Capsules taken orally | Drug | Oseltamivir |
| Placebo to OseltamivirMatching placebo capsules taken orally | Drug | Baloxavir Marboxil, Placebo |
Primary outcome
Time to Improvement of Influenza Symptoms
Time frame: From Day 1 pretreatment up to Day 14
Participants assessed the severity of 7 influenza-associated symptoms (cough, sore throat, headache, nasal congestion, feverishness/chills, muscle/joint pain, and fatigue) on a 4-point scale (0 = no symptoms, 1= mild, 2 = moderate, and 3 = severe). Time to improvement of symptoms was defined as the time from the start of treatment to the time when all influenza symptoms were alleviated, maintained, or improved, as defined below, for a duration of at least 21.5 hours: * Preexisting symptoms (cough, fatigue, or muscle/joint pain that existed prior to influenza) that were worse at baseline must have improved at least 1 point from baseline * Preexisting symptoms not worse at baseline must have maintained baseline severity * New symptoms must have alleviated, defined as a symptom score of none (0) or mild (1). Time to improvement of symptoms was analyzed using Kaplan-Meier (KM) methods; participants who did not experience improvement of symptom s were censored at the last observation.
20 secondary outcomes
Percentage of Participants With Positive Influenza Virus Titer at Each Time Point
Time frame: Days 2, 3, 4 (optional), 5, 6 (optional), and 9
Percentage of Participants With Positive Influenza Virus by RT-PCR at Each Time Point
Time frame: Days 2, 3, 4 (optional), 5, 6 (optional), and 9.
Change From Baseline in Virus Titer at Each Time Point
Time frame: Day 1 pretreatment (Baseline) and Days 2, 3, 4 (optional), 5, 6 (optional), and 9
Change From Baseline in Virus RNA (RT-PCR) at Each Time Point
Time frame: Day 1 pretreatment (Baseline) and Days 2, 3, 4 (optional), 5, 6 (optional), and 9
Area Under the Curve (AUC) Adjusted by Baseline in Influenza Virus Titer
Time frame: Day 1 to Day 9
Area Under the Curve (AUC) Adjusted by Baseline in Viral RNA
Time frame: Day 1 to Day 9
Time to Cessation of Viral Shedding Determined by Virus Titer
Time frame: Day 1 to Day 9
Time to Cessation of Viral Shedding Determined by Virus RNA
Time frame: Day 1 to Day 9
Percentage of Participants Whose Symptoms Were Improved at Each Time Point
Time frame: 12, 24, 36, 48, 72, 96, 120, 144, 168, 192, and 216 hours after the initial dose of study treatment
Time to Alleviation of Symptoms
Time frame: Initiation of study treatment up to Day 14
Time to Improvement of the Four Systemic Symptoms
Time frame: Initiation of study treatment up to Day 14
Time to Improvement of the Three Respiratory Symptoms
Time frame: Initiation of study treatment up to Day 14
Time to Resolution of Fever
Time frame: Initiation of study treatment up to Day 14
Percentage of Participants Reporting Normal Temperature at Each Time Point
Time frame: 12, 24, 36, 48, 72, 96, 120, 144, 168, 192, and 216 hours after the initial dose of study treatment
Body Temperature at Each Time Point
Time frame: 12, 24, 36, 48, 72, 96 and 120 hours after the initial dose of study treatment
Time to Improvement of Individual Symptoms
Time frame: Initiation of study treatment up to Day 14
Time to Return to Preinfluenza Health Status
Time frame: Baseline to Day 14
Percentage of Participants Requiring Systemic Antibiotics for Infections Secondary to Influenza Infection
Time frame: Day 2 to Day 22
Percentage of Participants With Influenza-related Complications
Time frame: Day 1 to Day 22
Percentage of Participants With Adverse Events (AEs)
Time frame: From first dose of study drug to Day 22
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Nov 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 35585696Retout 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.
- Derived from this study: PubMed 32526195Ison MG, Portsmouth S, Yoshida Y, Shishido T, Mitchener M, Tsuchiya K, Uehara T, Hayden FG. Early treatment with baloxavir marboxil in high-risk adolescent and adult outpatients with uncomplicated influenza (CAPSTONE-2): a randomised, placebo-controlled, phase 3 trial. Lancet Infect Dis. 2020 Oct;20(10):1204-1214. doi: 10.1016/S1473-3099(20)30004-9. Epub 2020 Jun 8.
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Influenza
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Shionogi Clinical Trials Administrator Clinical Support Help Line study director
Shionogi
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Baloxavir Marboxil and Oseltamivir in people with Influenza, run by Shionogi.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 24 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 19 Nov 2019. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 6 Nov 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Time to Improvement of Influenza Symptoms (time frame: From Day 1 pretreatment up to Day 14). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02949011, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Nov 2019.