A Multicenter, Randomized, Double-blind, Positive Controlled Phase Ⅲ Clinical Trial of ZX-7101A Tablets to Evaluate the Safety and Efficacy in the Treatment of Uncomplicated Influenza in Children Aged 5-11 Years
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 发起方
- 入组人数
- 98
- 试验地点
- 3
- 主要终点
- Pharmacokinetic parameters of ZX-7101A and its metabolite ZX-7101 in plasma
研究概览
简要总结
A multicenter, randomized, double-blind, positive controlled, phase III trial to evaluate the safety and efficacy of ZX-7101A tablets versus oseltamivir phosphate suspension in children aged ≥5 years and < 12 years with uncomplicated influenza.
详细描述
Part 1:
A pilot study of pharmacokinetics, safety, and efficacy was conducted in children (5-11 years old, weight ≥20kg) with uncomplicated influenza. A total of 12 subjects were planned to be enrolled. (Pharmacokinetic and safety data from at least 8 children are required.) On the first day, ZX-7101A 20 mg tablets, 2 tablets (specification: 10 mg/ tablet) were taken orally. PK samples were collected before and after the first (D1) dose: 1 to 2 h, 4 h, 8 h, 24 h (D2), 96 h (D5), 192 h (D9) and 336 h (D15) after administration.
Part 2:
A randomized phase III study with safety as primary endpoint was conducted in children (5-11 years old, body weight ≥20kg) with uncomplicated influenza. Eligible subjects were randomly assigned in a 2:1 ratio to receive either ZX-7101A or oseltamivir phosphate.
Enrolled subjects were required to have typical systemic and/or respiratory influenza symptoms, with first influenza symptoms occurring within 48 hours of randomization. The study was divided into a screening/treatment period (D1) and an observation period (approximately 2 weeks).
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 5 Years 至 11 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •1.≥5 to<12 years of age at the time of randomization, males or females.
- •2.Patients in the screening period met the following criteria:
- •Rapid influenza diagnostic test (RIDT) or polymerase chain reaction (PCR) test positive;
- •Axillary temperature ≥ 37.5℃ at screening; If taking antipyretics, axillary temperature ≥ 37.5℃ after taking the drug (more than 4 hours).
- •At least one of influenza -related systemic symptoms is moderate or greater in severity: a. muscle or joint pain, b. fatigue, c. headache, d. fever.
- •At least one of the influenza-related respiratory symptoms is moderate or greater in severity: a. nasal congestion, b. sore throat, c. cough.
- •The first occurrence of influenza symptoms ≤ 48 hours from the time of patient randomization.
- •Body temperature ≥ 37.5 ℃ (axillary temperature) or 37.5 ℃ (oral temperature) or 38.0 ℃ (rectal or tympanic membrane temperature)for the first time;
- •Or at least one systemic or respiratory symptom may occur: a. nasal congestion, b. sore throat, c. cough, d. muscle or joint pain, e. fatigue, f. headache, g. fever.
- •Both the subject and his/her guardian are volunteer to participate in the study and sign the written informed consent form (ICF), the subject could comply with all the study procedures, complete the subject diary as required (the guardian is allowed to fill in if necessary).
排除标准
- •Patients with severe influenza virus infection requiring inpatient treatment. (Meet any one of the following criteria)
- •Severe cases with one of the following conditions：
- •Persistent high fever for more than 3 days, accompanied by severe cough, purulent sputum, bloody sputum, or chest pain;
- •Fast breathing rate, difficulty breathing, cyanosis of lips;
- •Delayed response, drowsiness, restlessness, and other mental changes or seizures;
- •Severe vomiting, diarrhea, and dehydration symptoms;
- •Concomitant pneumonia;
- •Significant exacerbation of existing underlying diseases;
- •Other clinical situations that require hospitalization.
- •Critical cases with one of the following conditions (Including but not limited to)：
- •Respiratory failure;
- •Acute necrotizing encephalopathy;
- •Multiple organ dysfunction;
- •Other serious clinical situations that require monitoring and treatment.
- •High risk population for severe cases. (Meet any one of the following criteria):
- •Accompanied by the following basic diseases and judged by the investigators to be clinically significant, such as lung diseases, liver diseases, kidney diseases, hematological system diseases, heart diseases, neurological and neuromuscular diseases that affect the ability to clear respiratory secretions, metabolic and endocrine system diseases, etc;
- •Subjects with low immune function, such as malignant tumors, organ or bone marrow transplants, HIV infections, or those who have been taking immunosuppressants for the past 3 months;
- •Clinical significance of correcting QT interval abnormalities in electrocardiogram display; (QTc>440ms in male or QTc>450ms in female);
- •Subjects who require long-term use of drugs containing aspirin or salicylates : It is necessary to take medication containing aspirin or salicylate regularly every day for more than 14 days;
- •BMI exceeds the standards.
- •Bronchitis, pneumonia, pleural effusion or interstitial disease confirmed by chest imaging [X-ray (anteroposterior or anteroposterior) /CT] and judged clinically significant by the investigator at screening.
- •Subjects who have developed acute respiratory tract infection, otitis media, and sinusitis within 2 weeks before screening.
- •Subjects with other respiratory infections requiring systemic anti-infective treatment, or blood routine examination at screening: white blood cell count (WBC) > (venous blood)
- •Subjects with purulent sputum or suppurative tonsillitis.
- •Have difficulty in swallowing drugs or have a history of gastrointestinal diseases that seriously affect drug absorption (including but not limited to reflux esophagitis, chronic diarrhea, inflammatory bowel disease, intestinal tuberculosis, gastrinoma, short bowel syndrome, subtotal gastrectomy, etc.).
- •Suspected allergic to active ingredients or excipients of the investigational product.
- •Body weight < 20 kg.
- •Medications against influenza virus within 7 days before screening (including but not limited to: neuraminidase inhibitors, hemagglutinin inhibitors, M2 ion channel blockers, and cap structure inhibitors. Lysine endonuclease (CEN) inhibitors, such as oseltamivir, zanamivir, peramivir, favipiravir, rimantadine, amantadine, abidol, baloxavir, etc.).
- •Have received live vaccines or attenuated live vaccines within 14 days before randomization, influenza vaccines within 6 months before randomization.
- •Suspected or confirmed a history of alcohol or drug abuse.
- •Ppregnancy test was positive
- •Participants who participated in another clinical trial and used any other investigational drug or device within 30 days before screening.
- •Subjects judged by the investigator to be ineligible for participation in the study.
研究组 & 干预措施
Single Arm
Part 1:
A pilot study of pharmacokinetics, safety, and efficacy was conducted in children (5-11 years old, weight ≥20kg) with uncomplicated influenza. A total of 12 subjects were planned to be enrolled.
干预措施: ZX-7101A (Drug)
Oseltamivir phosphate dry suspension:
Part 2:
A randomized phase III study with safety as primary endpoint was conducted in children (5-11 years old, body weight ≥20kg) with uncomplicated influenza. Eligible subjects were randomly assigned in a 2:1 ratio to receive either ZX-7101A (2 tablets，specification：10mg, single dose) or oseltamivir phosphate dry suspension（specification：0.36g）.
干预措施: Placebo for ZX-7101A tablet (Other)
Oseltamivir phosphate dry suspension:
Part 2:
A randomized phase III study with safety as primary endpoint was conducted in children (5-11 years old, body weight ≥20kg) with uncomplicated influenza. Eligible subjects were randomly assigned in a 2:1 ratio to receive either ZX-7101A (2 tablets，specification：10mg, single dose) or oseltamivir phosphate dry suspension（specification：0.36g）.
干预措施: Oseltamivir phosphate dry suspension (Drug)
ZX-7101A
Part 2:
A randomized phase III study with safety as primary endpoint was conducted in children (5-11 years old, body weight ≥20kg) with uncomplicated influenza. Eligible subjects were randomly assigned in a 2:1 ratio to receive either ZX-7101A (2 tablets，specification：10mg, single dose) or oseltamivir phosphate dry suspension（specification：0.36g）.
干预措施: ZX-7101A (Drug)
结局指标
主要结局
Pharmacokinetic parameters of ZX-7101A and its metabolite ZX-7101 in plasma
时间窗: Part 1: 1~2, 4, 8, 24, 96 ,192, 336 hours post-dose
Part 1: The terminal elimination half-life (t1/2)
Number of Participants with Treatment-Related Adverse Events as Assessed by CTCAE v5.0
时间窗: Part 2: From day1 up to day15
Part 2: The Number of Participants with Treatment-Related Adverse Event will be evalated as the change of vital signs, electrocardiogram, physical examination, and Laboratory test compared with the baseline.
次要结局
- Number of Participants with Treatment-Related Adverse Events as Assessed by CTCAE v5.0(Part 1: From day1 up to day15)
- Time (in hours) for relief of 7 all influenza symptoms(Part 2: Baseline, Day 1 up to Day 15)
- Proportion of all subjects with remission of influenza symptoms(Part 2: Baseline, Day 1 up to Day 15)
- Influenza virus RNA clearance time (in hours)(Part 2: Baseline, Day1, Day2, Day3, Day5, Day9, Day15)
- Time for influenza virus titer to become negative(Part 2: Baseline, Day1, Day2, Day3, Day5, Day9, Day15)
- Changes in influenza RNA and virus titers(Part 2: Baseline, Day1, Day2, Day3, Day5, Day9, Day15)
- Influenza virus RNA(Part 2: Baseline, Day1, Day2, Day3, Day5, Day9, Day15)