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.
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).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
98
On day1: Take two tablets of ZX-7101A orally once (specification: 10mg/ tablet) with appropriate amount of warm water
Placebo for ZX-7101A tablet: The appearance and properties of placebo tablets were identical to those of the trial drug ZX-7101A tablets. On Day 1, two placebo for ZX-7101A tablets were taken orally with appropriate warm water.
Drug: Oseltamivir phosphate dry suspension: From Day1 to Day 5 : Oseltamivir phosphate suspension was orally administered twice a day, dose according to the label.
Baoding Hospital of Beijing Children's Hospital, Capital Medical University
Baoding, Hebei, China
West China Second University Hospital, Sichuan University
Chengdu, Sichuan, China
Children's Hospital Zhejiang University School of Medicine
Hangzhou, Zhejiang, China
Pharmacokinetic parameters of ZX-7101A and its metabolite ZX-7101 in plasma
Part 1: Time to peak drug concentration (Tmax)
Time frame: Part 1: 1~2, 4, 8, 24, 96 ,192, 336 hours post-dose
Pharmacokinetic parameters of ZX-7101A and its metabolite ZX-7101 in plasma
Part 1: Peak plasma concentration (Cmax)
Time frame: Part 1: 1~2, 4, 8, 24, 96 ,192, 336 hours post-dose
Pharmacokinetic parameters of ZX-7101A and its metabolite ZX-7101 in plasma
Part 1: Area under the plasma concentration versus time curve (AUC)
Time frame: Part 1: 1~2, 4, 8, 24, 96 ,192, 336 hours post-dose
Pharmacokinetic parameters of ZX-7101A and its metabolite ZX-7101 in plasma
Part 1: The terminal elimination half-life (t1/2)
Time frame: Part 1: 1~2, 4, 8, 24, 96 ,192, 336 hours post-dose
Number of Participants with Treatment-Related Adverse Events as Assessed by CTCAE v5.0
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.
Time frame: Part 2: From day1 up to day15
Number of Participants with Treatment-Related Adverse Events as Assessed by CTCAE v5.0
Part 1: 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.
Time frame: Part 1: From day1 up to day15
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Drug: Placebo for Oseltamivir phosphate dry suspension: From Day1 to Day 5 : Placebo for Oseltamivir phosphate suspension was orally administered twice a day, dose according to the label.
Time (in hours) for relief of 7 all influenza symptoms
Part 2: Symptom remission is defined as a score of 0 (asymptomatic) or 1 (mild) for all seven influenza symptoms assessed by the subject on the subject diary card. And lasts for at least 21.5 hours (approximately 24 hours-10%)
Time frame: Part 2: Baseline, Day 1 up to Day 15
Proportion of all subjects with remission of influenza symptoms
Part 2: Proportion of subjects with remission of all influenza symptoms at each visit and each evaluation time point (unit: %);
Time frame: Part 2: Baseline, Day 1 up to Day 15
Influenza virus RNA clearance time (in hours)
Part 2: The time to influenza RNA clearance in hours was defined as the time from the start of study treatment to the first time influenza RNA was below the lower limit of quantification (as measured by RT-PCR).
Time frame: Part 2: Baseline, Day1, Day2, Day3, Day5, Day9, Day15
Time for influenza virus titer to become negative
Part 2: Time for influenza virus titer to become negative (in hours)
Time frame: Part 2: Baseline, Day1, Day2, Day3, Day5, Day9, Day15
Changes in influenza RNA and virus titers
Changes from baseline in RT-PCR-determined influenza RNA (log10 viral copies per milliliter) and virus titers (log10TCID50 per milliliter) at each visit.
Time frame: Part 2: Baseline, Day1, Day2, Day3, Day5, Day9, Day15
Influenza virus RNA
Proportion of subjects positive for influenza virus RNA by RT-PCR and with detectable virus titers at each visit (%)
Time frame: Part 2: Baseline, Day1, Day2, Day3, Day5, Day9, Day15