A Phase 3, Multicenter, Randomized, Double-blind Study of a Single Dose of S-033188 (Baloxavir Marboxil) Compared With Placebo or Oseltamivir 75 mg Twice Daily for 5 Days in Otherwise Healthy Patients With Influenza
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 1,436
- 主要终点
- Time to Alleviation of Symptoms in Participants Randomized to Baloxavir or Placebo
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 12 Years 至 64 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
- •Feverishness or chills
- •Muscle or joint pain
- •At least one of the following respiratory symptoms associated with influenza are present with a severity of moderate or greater
- •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)
- •Time when the patient experiences at least one general or respiratory symptom
- •Women of childbearing potential who agree to use a highly effective method of contraception for 3 months after the first dose of study drug
排除标准
- •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)
- •Morbid obesity (body mass index [BMI] ≥ 40)
- •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.
- •Women who are breastfeeding or have a positive pregnancy test in the predose examinations. The following female patients who have documentation of either a or b below do not need to undergo a pregnancy test in the predose examinations:
- •Postmenopausal (defined as cessation of regular menstrual periods for 2 years or more and confirmed by a follicle-stimulating hormone test) women
- •Women who are surgically sterile by hysterectomy, bilateral oophorectomy, or tubal ligation
- •Patients with concurrent infections requiring systemic antimicrobial and/or antiviral therapy at the predose examinations.
- •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 severe underlying diseases.
- •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
研究组 & 干预措施
Adults: Baloxavir Marboxil
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.
干预措施: Baloxavir Marboxil (Drug)
Adults: Baloxavir Marboxil
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.
干预措施: Placebo to Oseltamivir (Drug)
Adults: Oseltamivir
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.
干预措施: Placebo to Baloxavir Marboxil (Drug)
Adults: Oseltamivir
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.
干预措施: Oseltamivir (Drug)
Adults: Placebo
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.
干预措施: Placebo to Baloxavir Marboxil (Drug)
Adults: Placebo
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.
干预措施: Placebo to Oseltamivir (Drug)
Adolescents: Baloxavir Marboxil
Participants aged 12 to 19 years will receive two or four baloxavir marboxil 20 mg tablets on Day 1.
干预措施: Baloxavir Marboxil (Drug)
Adolescents: Placebo
Participants aged 12 to 19 years will receive two or four baloxavir marboxil placebo tablets on Day 1.
干预措施: Placebo to Baloxavir Marboxil (Drug)
结局指标
主要结局
Time to Alleviation of Symptoms in Participants Randomized to Baloxavir or Placebo
时间窗: Initiation of study treatment up to Day 14
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.
Time to Alleviation of Symptoms in Adults Randomized to Baloxavir or Oseltamivir
时间窗: Initiation of study treatment up to Day 14
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.
次要结局
- Change From Baseline in Composite Symptom Score at Each Time Point in Participants Randomized to Baloxavir or Placebo(Day 1 pretreatment (Baseline) and 12, 24, 36, 48, 72, 96, 120, 144, 168, 192, and 216 hours after the initial dose of study treatment.)
- Change From Baseline in Composite Symptom Score at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir(Day 1 pretreatment (Baseline) and 12, 24, 36, 48, 72, 96, 120, 144, 168, 192, and 216 hours after the initial dose of study treatment.)
- Time to Resolution of Fever in Participants Randomized to Baloxavir or Placebo(Initiation of study treatment up to Day 14)
- Time to Resolution of Fever in Adults Randomized to Baloxavir or Oseltamivir(Initiation of study treatment up to Day 14)
- Percentage of Participants Reporting Normal Temperature at Each Time Point in Participants Randomized to Baloxavir or Placebo(12, 24, 36, 48, 72, 96, 120, 144, 168, 192 and 216 hours after the initial dose of study treatment)
- Percentage of Participants Reporting Normal Temperature at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir(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 in Participants Randomized to Baloxavir or Placebo(12, 24, 36, 48, 72, 96 and 120 hours after the initial dose of study treatment)
- Body Temperature at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir(12, 24, 36, 48, 72, 96 and 120 hours after the initial dose of study treatment)
- Time to Alleviation of Individual Symptoms in Participants Randomized to Baloxavir or Placebo(Initiation of study treatment up to Day 14)
- Time to Alleviation of Individual Symptoms in Adults Randomized to Baloxavir or Oseltamivir(Initiation of study treatment up to Day 14)
- Time to Return to Preinfluenza Health Status in Participants Randomized to Baloxavir or Placebo(Initiation of study treatment up to Day 14)
- Time to Return to Preinfluenza Health Status in Adults Randomized to Baloxavir or Oseltamivir(Initiation of study treatment up to Day 14)
- Percentage of Participants With Influenza-related Complications in Participants Randomized to Baloxavir or Placebo(Initiation of study treatment up to Day 14)
- Percentage of Participants With Influenza-related Complications in Adults Randomized to Baloxavir or Oseltamivir(Initiation of study treatment up to Day 14)
- Percentage of Participants With Adverse Events (AEs)(From first dose of study drug to Day 22)
- 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)
- 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)
- Change From Baseline in Virus Titer at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir(Day 1 pretreatment (Baseline) and Days 2, 3, 4 (optional), 5, 6 (optional), and 9)
- Time to Alleviation of the Three Respiratory Symptoms in Adults Randomized to Baloxavir or Oseltamivir(Initiation of study treatment up to Day 14)
- 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)
- Area Under the Curve (AUC) Adjusted by Baseline of Influenza Virus RNA in Participants Randomized to Baloxavir or Placebo(Day 1 to Day 9)
- Time to Cessation of Viral Shedding Determined by Virus RNA in Adults Randomized to Baloxavir or Oseltamivir(Day 1 to Day 9)
- Percentage of Participants Whose Symptoms Were Alleviated at Each Time Point in Participants Randomized to Baloxavir or Placebo(12, 24, 36, 48, 72, 96, 120, 144, 168, 192 and 216 hours after the initial dose of study treatment)
- Percentage of Participants Whose Symptoms Were Alleviated at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir(12, 24, 36, 48, 72, 96, 120, 144, 168, 192 and 216 hours after the initial dose of study treatment)
- 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)
- Area Under the Curve (AUC) Adjusted by Baseline in Influenza Virus Titer in Participants Randomized to Baloxavir or Placebo(Day 1 to Day 9)
- Area Under the Curve (AUC) Adjusted by Baseline in Influenza Virus Titer in Adults Randomized to Baloxavir or Oseltamivir(Day 1 to Day 9)
- Area Under the Curve (AUC) Adjusted by Baseline of Influenza Virus RNA in Adults Randomized to Baloxavir or Oseltamivir(Day 1 to Day 9)
- Time to Cessation of Viral Shedding Determined by Virus Titer in Participants Randomized to Baloxavir or Placebo(Day 1 to Day 9)
- Time to Cessation of Viral Shedding Determined by Virus Titer in Adults Randomized to Baloxavir or Oseltamivir(Day 1 to Day 9)
- Time to Cessation of Viral Shedding Determined by Virus RNA in Participants Randomized to Baloxavir or Placebo(Day 1 to Day 9)
- Change From Baseline in Virus RNA (RT-PCR) 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)
- Change From Baseline in Virus RNA (RT-PCR) at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir(Day 1 pretreatment (Baseline) and Days 2, 3, 4 (optional), 5, 6 (optional), and 9)
- Time to Alleviation of the Four Systemic Symptoms in Participants Randomized to Baloxavir or Placebo(Initiation of study treatment up to Day 14)
- Time to Alleviation of the Four Systemic Symptoms in Adults Randomized to Baloxavir or Oseltamivir(Initiation of study treatment up to Day 14)
- Time to Alleviation of the Three Respiratory Symptoms in Participants Randomized to Baloxavir or Placebo(Initiation of study treatment up to Day 14)