The Safety, Tolerability and Pharmacokinetic Study of ZSP1273 in Healthy Volunteers.

NCT03679143 | Completed Phase 1

• 1 other identifier: ZSP1273-18-01
• Study Type: interventional
• Target: 103
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Influenza

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (13)

• Tmax

  UP to 5, 9, 12 days for SAD, MAD, FE part respectively

• Cmax

  UP to 5, 9, 12 days for SAD, MAD, FE part respectively

• t1/2z

  UP to 5, 9, 12 days for SAD, MAD, FE part respectively

• AUCinf（AUC0-∞）

  UP to 5, 9, 12 days for SAD, MAD, FE part respectively

• AUClast（AUC0-t）

  UP to 5, 9, 12 days for SAD, MAD, FE part respectively

Study Arms (10)

ZSP1273(single dose)-100 mg(Cohort 1)

EXPERIMENTAL

ZSP1273 100 mg /Placebo

Drug: ZSP1273 100 mg; Drug: Placebo 100 mg

ZSP1273(single dose)-200 mg(Cohort 2)

EXPERIMENTAL

ZSP1273 200mg/Placebo Enrollment into Cohort 2 will begin upon assurance of tolerance for Cohort 1.

Drug: ZSP1273 200 mg; Drug: Placebo 200 mg

ZSP1273(single dose)-400 mg(Cohort 3)

EXPERIMENTAL

ZSP1273 400mg/Placebo Enrollment into Cohort 3 will begin upon assurance of tolerance for Cohort 2.

Drug: ZSP1273 400 mg; Drug: Placebo 400 mg

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.

Drug: ZSP1273 600 mg; Drug: Placebo 600 mg

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.

Drug: ZSP1273 900 mg; Drug: Placebo 900 mg

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.

Drug: ZSP1273 1200 mg; Drug: Placebo 1200 mg

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.

Drug: ZSP1273; Drug: Placebo

ZSP1273(multiple doses)-Low Dose(Cohort 8)

EXPERIMENTAL

while fasted or fed according to the results of Cohort FE ZSP1273 /Placebo for 5 Days.

Drug: ZSP1273 Low Dose; Drug: Placebo

ZSP1273(multiple doses)-Median Dose(Cohort 9)

EXPERIMENTAL

while fasted or fed according to the results of Cohort FE ZSP1273/Placebo for 5 Days.

Drug: ZSP1273 Median Dose; Drug: Placebo

ZSP1273(multiple doses)-High Dose(Cohort 10)

EXPERIMENTAL

while fasted or fed according to the results of Cohort FE ZSP1273/Placebo for 5 Days.

Drug: ZSP1273 High Dose; Drug: Placebo

Interventions

ZSP1273 100 mg DRUG

ZSP1273 tablet administered orally once daily under fasted condition

ZSP1273(single dose)-100 mg(Cohort 1)

Placebo 100 mg DRUG

Participants will receive placebo matching to ZSP1273 orally once daily in the fasting state.

ZSP1273(single dose)-100 mg(Cohort 1)

ZSP1273 200 mg DRUG

ZSP1273 tablets administered orally once daily under fasted condition

ZSP1273(single dose)-200 mg(Cohort 2)

Placebo 200 mg DRUG

Participants will receive placebo matching to ZSP1273 orally once daily under fasted condition

ZSP1273(single dose)-200 mg(Cohort 2)

ZSP1273 400 mg DRUG

ZSP1273 tablets administered orally once daily in the fasting state

ZSP1273(single dose)-400 mg(Cohort 3)

Placebo 400 mg DRUG

Participants will receive placebo matching to ZSP1273 orally once daily in the fasting state

ZSP1273(single dose)-400 mg(Cohort 3)

ZSP1273 600 mg DRUG

ZSP1273 tablets administered orally once daily under fasted condition

ZSP1273(single dose)-600 mg(Cohort 4)

Placebo 600 mg DRUG

Participants will receive placebo matching to ZSP1273 orally once daily under fasted condition

ZSP1273(single dose)-600 mg(Cohort 4)

ZSP1273 900 mg DRUG

ZSP1273 tablets administered orally once daily in the fasting state

ZSP1273(single dose)-900 mg(Cohort 5)

Placebo 900 mg DRUG

Participants will receive placebo matching to ZSP1273 orally once daily under fasted condition

ZSP1273(single dose)-900 mg(Cohort 5)

ZSP1273 1200 mg DRUG

ZSP1273 tablets administered orally once daily in the fasting state

ZSP1273(single dose)-1200 mg(Cohort 6)

Placebo 1200 mg DRUG

Participants will receive placebo matching to ZSP1273 orally once daily in the fasting state

ZSP1273(single dose)-1200 mg(Cohort 6)

ZSP1273 DRUG

ZSP1273 tablets administered orally once daily under fasted or fed condition

ZSP1273(Food Effect)-Cohort 7

Placebo DRUG

Participants will receive placebo matching to ZSP1273 orally once daily under fasted or fed condition

ZSP1273(Food Effect)-Cohort 7

ZSP1273 Low Dose DRUG

ZSP1273 tablets administered orally once daily under fasted or fed condition for 5 Days.

ZSP1273(multiple doses)-Low Dose(Cohort 8)

ZSP1273 Median Dose DRUG

ZSP1273 tablets administered orally twice daily for 4 Days and once daily on Day 5 under fasted or fed condition.

ZSP1273(multiple doses)-Median Dose(Cohort 9)

ZSP1273 High Dose DRUG

ZSP1273 tablets administered orally twice daily for 4 Days and once daily on Day 5 under fasted or fed condition.

ZSP1273(multiple doses)-High Dose(Cohort 10)

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Subjects are required to meet the following criteria in order to be included in the trial:
• Signature of a dated Informed Consent Form (ICF) indicating that the subject has been informed of all the relevant aspects(including adverse events) of the trial prior to enrollment.
• Subjects must be willing and able to adhere to the visit schedule and protocol requirements and be available to complete the study.
• Subjects (including partners) must use reliable methods of contraception during the study and until 6 months following the last dose of investigational product.
• Males and female subjects between 18-50 years (Both inclusive).
• Body weight is no less than 50 kg in males and no less than 45 kg in females. Body mass index (BMI) 18≤BMI≤28 kg/m2; BMI is determined by the following equation: BMI = weight/height2 (kg/m2).
• Physical condition and vital signs: Normal or abnormality has no clinical significance.

You may not qualify if:

• Known hypersensitivity and/or allergy to some drugs and food, especially for the composition that is similar to the investigative product;
• The average daily smoking are more than 5 cigarettes within 3 months prior to screening.
• Known history of drug or alcohol abuse.(defined as consumption of 14 units of alcohol per week: 1 unit = 285 ml of beer; or the equivalent of 25 ml of spirit, or 100 ml of wine )
• Subjects who donated blood or bleeding profusely (\> 400 mL) in the 3 months preceding study screening.
• Dysphagia or any medical history in gastrointestinal that interferes with the absorption of drugs, include a history of frequent nausea or vomit causes by any etiology.
• History or presence of any disease or condition known to increase the risk of bleeding , eg. acute gastritis, duodenal ulcer, etc.
• Participant with any history of clinically significant skin disease such as, but not limited to, dermatitis, eczema, drug rash, psoriasis, or urticaria.
• Subjects with recent significant change in diet or exercise.
• Participated in another clinical research study and received any investigational products within 3 months prior to dosing.
• Concomitant therapy with any drugs with known hepatic enzyme-inducing or inhibiting agents prior to screening or during the study, including strong inhibitory agents and inducers that affect metabolic enzymes (see appendix 6 for specific drug information).
• Use of any prescription or over-the-counter (OTC) medications, vitamins and herbal or dietary supplements within 14 days prior to screening.
• History of having any special food (including dragon fruit, mango, grapefruit, etc.), strenuous exercises, or other factors may interfere with the absorption, distribution, metabolism, or excretion of drug within 14 days prior to screening.
• Inability to consume the food provided in the study ( a high fat, high calorie meal includes two eggs , a piece of butter bacon toast, a box of fried potatoes, and a glass of whole milk).This requirement only applies to subjects under fed condition.
• Presence of clinically significant abnormalities in ECG or QTcB\>470ms in males, or QTcB\>480ms in females.
• 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.

Sponsors & Collaborators

• Guangdong Zhongsheng Pharmaceutical Co., Ltd.: lead

Study Sites (1)

The First Hospital of Jilin University

Changchun, Jilin, 130021, China

Location

Related Publications (1)

• 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.

  PMID: 34654349 DERIVED

MeSH Terms

Conditions

Influenza, Human

Interventions

ZSP1273

Condition Hierarchy (Ancestors)

Respiratory Tract Infections; Infections; Orthomyxoviridae Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases

Study Officials

• Yanhua Ding, MD

  The First Hospital of Jilin University

  PRINCIPAL INVESTIGATOR

• Shucheng Hua, MD

  The First Hospital of Jilin University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Masking for Participant, Investigator and Clinical Research Associate
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 18, 2018
• First Posted: September 20, 2018
• Study Start: September 20, 2018
• Primary Completion: March 19, 2019
• Study Completion: April 26, 2019
• Last Updated: August 14, 2019

Record last verified: 2019-08

Locations

CN (1)