Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
This is a single center,double-blind,randomized,parallel design, single and multiple dose trial to evaluate the pharmacokinetics(PK), safety and tolerability of ZSP1273,and the effect of food on ZSP1273 Pharmacokinetics.
The study will be divided in 3 parts :
Study Part I(Single Ascending Dosing, SAD) will be a single ascending dose to be run at a maximum of 6 dose levels. Subjects included in this part of the study will receive only one dose level to limit the exposure to ZSP1273. Four subjects are planned to be included in the first group while 10 subjects are enrolled in every following cohort.
Study Part II(Multiple Ascending Dosing, MAD) will start after completion of some Cohorts of Study Part I. Study Part II will be a multiple ascending dose to be run at a maximum of 3 dose levels. Subjects included in this part of the study will receive only one dose level. This part also enrolls 10 subjects in every cohort.
Study Part III(Food Effect study, FE) will consists of 2 periods,and subjects will receive a single dose ranged from 100-600mg on fasting and postprandial states respectively. There will be a 7-day wash out period between treatment periods.A total of 12 to 18 subjects will be included.
All the 3 parts will be run in healthy subjects.
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| ZSP1273(single dose)-100 mg(Cohort 1) | Experimental | ZSP1273 100 mg /Placebo |
|
| ZSP1273(single dose)-200 mg(Cohort 2) | Experimental | ZSP1273 200mg/Placebo Enrollment into Cohort 2 will begin upon assurance of tolerance for Cohort 1. |
|
| ZSP1273(single dose)-400 mg(Cohort 3) | Experimental | ZSP1273 400mg/Placebo Enrollment into Cohort 3 will begin upon assurance of tolerance for Cohort 2. |
|
| ZSP1273(single dose)-600 mg(Cohort 4) | Experimental | ZSP1273 600 mg/Placebo Enrollment into Cohort 4 will begin upon assurance of tolerance for Cohort 3. |
|
| ZSP1273(single dose)-900 mg(Cohort 5) | Experimental | Drug:ZSP1273 900 mg/Placebo 900mg; Enrollment into Cohort 5 will begin upon assurance of tolerance for Cohort 4. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| ZSP1273 100 mg | Drug | ZSP1273 tablet administered orally once daily under fasted condition |
|
| Measure | Description | Time Frame |
|---|---|---|
| Number and severity of treatment-emergent adverse events (TEAEs) and Serious Adverse Events(SAE) | Number of participants with TEAEs as assessed by CTCAE v5.0. | At day 5, 9, 12 days post first dosing for SAD, MAD, FE part respectively |
| Measure | Description | Time Frame |
|---|---|---|
| Tmax | The time after dosing when Cmax occurs (Tmax) | UP to 5, 9, 12 days for SAD, MAD, FE part respectively |
| Cmax | Maximum concentration (Cmax) |
Not provided
Inclusion Criteria:
Subjects are required to meet the following criteria in order to be included in the trial:
Exclusion Criteria:
Eligible subjects must not meet any of the following exclusion criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Yanhua Ding, MD | The First Hospital of Jilin University | Principal Investigator |
| Shucheng Hua, MD | The First Hospital of Jilin University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| The First Hospital of Jilin University | Changchun | Jilin | 130021 | China |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 34654349 | Derived | Hu Y, Li H, Wu M, Zhang H, Ding Y, Peng Y, Li X, Yu Z. Single and multiple dose pharmacokinetics and safety of ZSP1273, an RNA polymerase PB2 protein inhibitor of the influenza A virus: a phase 1 double-blind study in healthy subjects. Expert Opin Investig Drugs. 2021 Nov;30(11):1159-1167. doi: 10.1080/13543784.2021.1994944. Epub 2021 Nov 1. |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Masking for Participant, Investigator and Clinical Research Associate
| ZSP1273(single dose)-1200 mg(Cohort 6) | Experimental | ZSP1273 1200 mg/Placebo Enrollment into Cohort 6 will begin upon assurance of tolerance for Cohort 5. |
|
| ZSP1273(Food Effect)-Cohort 7 | Experimental | Drug:ZSP1273 /Placebo; Period 1 (Day1 to Day5): Subjects receive ZSP1273/Placebo under the fasting or fed condition ,respectively on Day1. Period 2 (Day 8 to Day12): Subjects receive ZSP1273/Placebo under the fed or fasting condition, respectively on Day 8. |
|
| ZSP1273(multiple doses)-Low Dose(Cohort 8) | Experimental | while fasted or fed according to the results of Cohort FE ZSP1273 /Placebo for 5 Days. |
|
| ZSP1273(multiple doses)-Median Dose(Cohort 9) | Experimental | while fasted or fed according to the results of Cohort FE ZSP1273/Placebo for 5 Days. |
|
| ZSP1273(multiple doses)-High Dose(Cohort 10) | Experimental | while fasted or fed according to the results of Cohort FE ZSP1273/Placebo for 5 Days. |
|
| Placebo 100 mg | Drug | Participants will receive placebo matching to ZSP1273 orally once daily in the fasting state. |
|
| ZSP1273 200 mg | Drug | ZSP1273 tablets administered orally once daily under fasted condition |
|
| Placebo 200 mg | Drug | Participants will receive placebo matching to ZSP1273 orally once daily under fasted condition |
|
| ZSP1273 400 mg | Drug | ZSP1273 tablets administered orally once daily in the fasting state |
|
| Placebo 400 mg | Drug | Participants will receive placebo matching to ZSP1273 orally once daily in the fasting state |
|
| ZSP1273 600 mg | Drug | ZSP1273 tablets administered orally once daily under fasted condition |
|
| Placebo 600 mg | Drug | Participants will receive placebo matching to ZSP1273 orally once daily under fasted condition |
|
| ZSP1273 900 mg | Drug | ZSP1273 tablets administered orally once daily in the fasting state |
|
| Placebo 900 mg | Drug | Participants will receive placebo matching to ZSP1273 orally once daily under fasted condition |
|
| ZSP1273 1200 mg | Drug | ZSP1273 tablets administered orally once daily in the fasting state |
|
| Placebo 1200 mg | Drug | Participants will receive placebo matching to ZSP1273 orally once daily in the fasting state |
|
| ZSP1273 | Drug | ZSP1273 tablets administered orally once daily under fasted or fed condition |
|
| Placebo | Drug | Participants will receive placebo matching to ZSP1273 orally once daily under fasted or fed condition |
|
| ZSP1273 Low Dose | Drug | ZSP1273 tablets administered orally once daily under fasted or fed condition for 5 Days. |
|
| Placebo | Drug | Participants will receive placebo matching to ZSP1273 orally once daily under fasted or fed condition for 5 Days. |
|
| ZSP1273 Median Dose | Drug | ZSP1273 tablets administered orally twice daily for 4 Days and once daily on Day 5 under fasted or fed condition. |
|
| Placebo | Drug | Participants will receive placebo matching to ZSP1273 orally twice daily for 4 Days and once daily on Day 5 under fasted or fed condition. |
|
| ZSP1273 High Dose | Drug | ZSP1273 tablets administered orally twice daily for 4 Days and once daily on Day 5 under fasted or fed condition. |
|
| Placebo | Drug | Participants will receive placebo matching to ZSP1273 orally twice daily for 4 Days and once daily on Day 5 under fasted or fed condition. |
|
| UP to 5, 9, 12 days for SAD, MAD, FE part respectively |
| t1/2z | t1/2z is defined as the time to decline half of the drug concentration in plasma. | UP to 5, 9, 12 days for SAD, MAD, FE part respectively |
| AUCinf(AUC0-∞) | Area under the curve extrapolated until time is infinity (AUCinf) | UP to 5, 9, 12 days for SAD, MAD, FE part respectively |
| AUClast(AUC0-t) | AUClast is defined as the concentration of drug from time zero to the last quantifiable concentration. | UP to 5, 9, 12 days for SAD, MAD, FE part respectively |
| CL/F | CL/F is defined as the ratio of total clearance(Cl) to bioavailability(F). | UP to 5, 9, 12 days for SAD, MAD, FE part respectively |
| λz | λz is defined as the ratio between the elimination of compound per unit time and the total amount of compound. | UP to 5, 9, 12 days for SAD, MAD, FE part respectively |
| CLr | CLr is defined as how many milliliters of plasma in which some substance can be completely eliminated in the unit time (per minute) of two kidneys. | UP to 5, 9, 12 days for SAD, MAD, FE part respectively |
| Food Effect PK Parameter: Fe0-t | Fe0-t is defined as the cumulative excretion rate of the drug in urine and feces. | UP to 12 days |
| Food Effect PK Parameter: Ae | Ae is defined as the amount of unchanged drug excreted in urine or faeces after administration. | UP to 12 days |
| Multiple-dose plasma PK parameter: Rac of ZSP1273 at steady state | Rac (Accumulation Index) is defined as the ratio between AUC0-XX in Day XX and AUC0-XX in Day1 | Up to 9 days |
| Multiple-dose plasma PK parameter: DF of ZSP1273 at steady state | DF is defined as the percentage of fluctuation in steady state is 100 * (Cmax, ss - Cmin, ss)/Cavg, ss. | Up to 9 days |
| Multiple-dose plasma PK parameter: Cmin of ZSP1273 at steady state | Cmin is defined as the minimum observed concentration of drug in plasma at steady state. | Up to 9 days |
| ID | Term |
|---|---|
| D007251 | Influenza, Human |
| ID | Term |
|---|---|
| D012141 | Respiratory Tract Infections |
| D007239 | Infections |
| D009976 | Orthomyxoviridae Infections |
| D012327 | RNA Virus Infections |
| D014777 | Virus Diseases |
| D012140 | Respiratory Tract Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| C000721066 | ZSP1273 |
Not provided
Not provided
Not provided