A Randomized, Double-blind Phase III Clinical Study of ZSP1273 Tablets Compared With Placebo or Oseltamivir Patients With Acute Uncomplicated Influenza A
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 750
- 试验地点
- 76
- 主要终点
- Time to Alleviation of Symptoms in Participants Randomized to ZSP1273 or Placebo
研究概览
简要总结
This is a multi-center, randomized, double-blind, placebo-controlled, and active controlled clinical trial to assess the efficacy and safety of ZSP1273 tablets in the treatment of Acute Uncomplicated influenza A.
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
- 18 Years 至 64 Years（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.
- •Male or female patient s aged ≥ 18 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
- •Positive Rapid Antigen Test (RAT) with throat swabs;and
- •Fever ≥ 38ºC (axillary) in the predose examinations or > 4 hours after dosing of antipyretics if they were taken;and
- •At least one of the following general systemic symptoms associated with influenza are present with a severity of moderate or greater I. Headache II. Feverishness or chills III. Muscle or joint pain IV. Fatigue
- •At least one of the following respiratory symptoms associated with influenza are present with a severity of moderate or greater I. Cough II. Sore throat III. 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 (WOCBP) who agree to use a highly effective method of contraception for 3 months after the first dose of ZSP1273 or oseltamivir
排除标准
- •Patients with severe influenza virus infection requiring inpatient treatment
- •Patients aged ≥ 18 years with known allergy to oseltamivir (Tamiflu) or ZSP1273
- •Patients unable to swallow tablets or capsules or any medical history in gastrointestinal that interferes with the absorption of drugs
- •Patients who have received antiviral medication including peramivir, laninamivir, oseltamivir, zanamivir, rimantadine, umifenovir, or amantadine within 7 days prior to the predose examinations
- •Patients who have received Chinese patent medicine or herbal medicine with antiviral effect within 7 days prior to the predose examinations
- •Patients who have received Anti-influenzal prescription within 7 days prior to the predose examinations
- •Subject who produces purulent sputum or has suppurative tonsillitis.
- •White blood cells(WBC)>10.0×109/L at screening.
- •Chest X - ray examination confirmed bronchitis,pneumonia,pleural effusion or pulmonary interstitial lesions.
- •Patients who have experienced respiratory tract infection,Otitis media,nasosinusitis.
- •Patients with severe or uncontrollable underlying diseases:blood disorders,severe chronic obstructive pulmonary disease(COPD),liver disorders(ALT or AST≥3 ULN,total bilirubin≥1.5 ULN),kidney disorders(serum creatinine>177μmol/L or 2mg/dL),chronic congestive heart failure(NYHA III-IV),mental disorders
- •Immunodeficiency,including malignant tumor,organ or marrow transplant,human immunodeficiency virus [HIV] infection,or patients receiving immunosuppressant therapy 3 months prior to enrollment.
- •Concomitant therapy with aspirin or salicylic acid.
- •Patients weighing < 40 kg or morbid obesity(Body mass index [BMI]≥30kg/m2)
- •Known history of alcohol abuse or drug abuse
- •Pregnancy or breastfeeding at screening and during the study.All female subjects of childbearing potential must have a negative urine pregnancy test at screening and during the trial.
- •Have received any other investigational products within 3 months prior to dosing.
- •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
ZSP1273 600 mg + Oseltamivir Placebo BID
Subjects received 5 doses of ZSP1273 at 600 mg once a day along with matching placebo of oseltamivir placebo orally twice daily (BID) with approximately 12 hour (+/- 2) intervals, over 5 days
干预措施: ZSP1273 600 mg (Drug)
ZSP1273 600 mg + Oseltamivir Placebo BID
Subjects received 5 doses of ZSP1273 at 600 mg once a day along with matching placebo of oseltamivir placebo orally twice daily (BID) with approximately 12 hour (+/- 2) intervals, over 5 days
干预措施: Placebo to Oseltamivir (Drug)
Oseltamivir 75mg + ZSP1273 Placebo
Subjects received 10 doses of Oseltamivir at a dose of 75 mg twice daily (BID) with matching placebo of ZSP1273 orally once a day with approximately 12 hour (+/- 2) intervals, over 5 days
干预措施: Oseltamivir(oral) (Drug)
Oseltamivir 75mg + ZSP1273 Placebo
Subjects received 10 doses of Oseltamivir at a dose of 75 mg twice daily (BID) with matching placebo of ZSP1273 orally once a day with approximately 12 hour (+/- 2) intervals, over 5 days
干预措施: Placebo to ZSP1273 (Drug)
Placebo Comparator
Subjects received 5 doses of matching placebo of ZSP1273 and Oseltamivir twice daily (BID) with approximately 12 hour (+/- 2) intervals, over 5 days
干预措施: Placebo to Oseltamivir (Drug)
Placebo Comparator
Subjects received 5 doses of matching placebo of ZSP1273 and Oseltamivir twice daily (BID) with approximately 12 hour (+/- 2) intervals, over 5 days
干预措施: Placebo to ZSP1273 (Drug)
结局指标
主要结局
Time to Alleviation of Symptoms in Participants Randomized to ZSP1273 or Placebo
时间窗: Up to 14 days after first dose
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 Participants Randomized to ZSP1273 or Oseltamivir
时间窗: Up to 14 days after first dose
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 Virus RNA (RT-PCR) at Each Time Point in Participants Randomized to ZSP1273 or Oseltamivir(Days 2, 4, 6)
- Percentage of Participants Reporting Normal Temperature at Each Time Point in Participants Randomized to ZSP1273 or Placebo(Up to 14 days after first dose)
- Percentage of Participants Reporting Normal Temperature at Each Time Point in Participants Randomized to ZSP1273 or Oseltamivir(Up to 14 days after first dose)
- Percentage of Participants With Positive Influenza Virus by RT-PCR at Each Time Point in Participants Randomized to ZSP1273 or Oseltamivir(Days 2, 4, 6)
- Change From Baseline in Virus Titer at Each Time Point in Participants Randomized to ZSP1273 or Oseltamivir(Days 2, 4, 6)
- Change From Baseline in Virus RNA (RT-PCR) at Each Time Point in Participants Randomized to ZSP1273 or Placebo(Days 2, 4, 6)
- Time to Cessation of Viral Shedding Determined by Virus Titer in Participants Randomized to ZSP1273 or Oseltamivir(Up to 6 days after first dose)
- Time to Cessation of Viral Shedding Determined by Virus RNA in Participants Randomized to ZSP1273 or Oseltamivir(Up to 6 days after first dose)
- Percentage of Participants With Positive Influenza Virus Titer at Each Time Point in Participants Randomized to ZSP1273 or Placebo(Days 2, 4, 6)
- Time to Resolution of Fever in Participants Randomized to ZSP1273 or Oseltamivir(Up to 14 days after first dose)
- Time to Alleviation of Individual Symptoms in Participants Randomized to ZSP1273 or Placebo(Up to 14 days after first dose)
- Percentage of Participants With Positive Influenza Virus Titer at Each Time Point in Participants Randomized to ZSP1273 or Oseltamivir(Days 2, 4, 6)
- Change From Baseline in Virus Titer at Each Time Point in Participants Randomized to ZSP1273 or Placebo(Days 2, 4, 6)
- Area Under the Curve (AUC) Adjusted by Baseline in Influenza Virus Titer in Participants Randomized to ZSP1273 or Placebo(Up to 6 days after first dose)
- Area Under the Curve (AUC) Adjusted by Baseline in Influenza Virus Titer in Participants Randomized to ZSP1273 or Oseltamivir(Up to 6 days after first dose)
- Time to Cessation of Viral Shedding Determined by Virus Titer in Participants Randomized to ZSP-1273 or Placebo(Up to 6 days after first dose)
- Time to Alleviation of the Four Systemic Symptoms in Participants Randomized to ZSP1273 or Oseltamivir(Up to 14 days after first dose)
- Time to Alleviation of the Three Respiratory Symptoms in Participants Randomized to ZSP1273 or Placebo(Up to 14 days after first dose)
- Change From Baseline in Composite Symptom Score at Each Time Point in Participants Randomized to ZSP1273 or Placebo(Up to 14 days after first dose)
- Percentage of Participants With Positive Influenza Virus by RT-PCR at Each Time Point in Participants Randomized to ZSP1273 or Placebo(Days 2, 4, 6)
- Time to Cessation of Viral Shedding Determined by Virus RNA in Participants Randomized to ZSP1273 or Placebo(Up to 6 days after first dose)
- Percentage of Participants Whose Symptoms Were Alleviated at Each Time Point in Participants Randomized to ZSP1273 or Placebo(Up to 14 days after first dose)
- Percentage of Participants With Influenza-related Complications in Participants Randomized to ZSP1273 or Oseltamivir(Up to 14 days after first dose)
- Change in EQ-5D-5L(Up to 14 days after first dose)
- Percentage of Participants Whose Symptoms Were Alleviated at Each Time Point in Participants Randomized to ZSP1273 or Oseltamivir(Up to 14 days after first dose)
- Time to Alleviation of the Four Systemic Symptoms in Participants Randomized to ZSP1273 or Placebo(Up to 14 days after first dose)
- Time to Alleviation of the Three Respiratory Symptoms in Participants Randomized to ZSP1273 or Oseltamivir(Up to 14 days after first dose)
- Change From Baseline in Composite Symptom Score at Each Time Point in Participants Randomized to ZSP1273 or Oseltamivir(Up to 14 days after first dose)
- Time to Resolution of Fever in Participants Randomized to ZSP1273 or Placebo(Up to 14 days after first dose)
- Time to Return to Preinfluenza Health Status in Participants Randomized to ZSP1273 or Placebo(Up to 14 days after first dose)
- Time to Return to Preinfluenza Health Status in Adults Randomized to ZSP1273 or Oseltamivir(Up to 14 days after first dose)
- Percentage of Participants With Influenza-related Complications in Participants Randomized to ZSP1273 or Placebo(Up to 14 days after first dose)
- Time to Alleviation of Individual Symptoms in Participants Randomized to ZSP1273 or Oseltamivir(Up to 14 days after first dose)