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A Study to Evaluate the Effect of a Single Oral Dose of ZX-7101A on the QTc Interval in Healthy Subjects (QTc-ZX-7101A)

Primary Purpose

Influenza, Human

Status
Not yet recruiting
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
ZX-7101A
Placebo
Sponsored by
Nanjing Zenshine Pharmaceuticals
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Influenza, Human

Eligibility Criteria

18 Years - 45 Years (Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria: Healthy male or female subjects, 18-45 years of age, inclusive, at the time of signing the ICF. Weight: Male weight ≥50 kg, female weight ≥45 kg, BMI between 19.0 and 28.0 kg/m2 (including cut-off value), BMI= weight (kg)/height 2 (m2). The investigator judged the subjects to be in good overall health based on their medical history, physical examination, vital signs, 12-lead electrocardiogram, laboratory tests (routine blood work, urine work, blood biochemistry, coagulation function), viral serology, and chest X-ray results (normal or abnormal test results have no clinical significance). Female subjects of childbearing potential and male subjects with a partner of childbearing potential who voluntarily signed ICF should be no fertile, sperm/egg donation for 6 months (female) or 90 days (male) from the beginning to the last dose, and voluntary use highly effective contraception (including partner) (non-drug contraception is required during the trial). Fully understand the trial content and possible adverse reactions, have the ability to communicate with researchers normally, while complying with study requirements, follow protocol procedures and restrictions, and be able to visit on time. Exclusion Criteria: Subjects with a prior or present history of clinically abnormal metabolic, liver, kidney, hematological, pulmonary, cardiovascular, gastrointestinal, urinary, endocrine, neurological, or psychiatric disease who were judged by the investigator to be unsuitable for participation in this study. Subjects with digestive tract disease or any condition that may affect drug absorption, such as a history of liver and gallbladder disease, gastrointestinal disease, gastrointestinal surgery (except appendectomy) or a history of chronic pancreatitis, idiopathic acute pancreatitis, or habitual diarrhea. Subjects with electrolyte metabolism disorders such as hyperkalemia, hypokalemia, hypermagnesia, hypomagnesia, hypercalcemia or hypocalcemia. Subjects who have a history of other risk factors for tachycardia, or a family history of a first-degree relative (i.e. biological parent, sibling, or child) of short QT syndrome, long QT syndrome, or sudden unexplained death in young age (≤40 years). Allergic constitutions (such as allergies to two or more drugs, foods, and pollen), or determined by the investigator, may be allergic to the investigational product or any component of the investigational product. Subjects who have got acute respiratory infections within 2 weeks before screening; Or have a history of fungal infection. For patients with abnormal vital signs (blood pressure, pulse rate, ear temperature) and clinically significant results, the abnormal values of each vital sign are: Body temperature (ear temperature) >37.5 ℃; Systolic blood pressure (recumbent) <90 mmHg or ≥140 mmHg;Diastolic blood pressure (lying) <50 mmHg or ≥90 mmHg; Pulse rate (lying position) <50 beats/min or >100 beats/min. QTcF interval > 450ms or < 300 ms (Fridericia's correction), or QRS>120ms. Subjects who have abnormal liver function: alanyl aminotransferase (ALT) or aspartate aminotransferase (AST) higher than the upper limit of normal or serum total bilirubin (TBIL) greater than 1.5 times the upper limit of normal, who judged clinical significance by investigators. Subjects estimate glomerular filtration rate <90 mL/min/1.73 m2. Subjects virus serological test (hepatitis B virus surface antigen, hepatitis C virus antibody, human immunodeficiency virus antibody, treponema pallidum specific antibody TPPA) positive results. Subjects with a history of drug abuse (morphine, dimethylene dioxyamphetamine, methamphetamine, THC, ketamine, cocaine) or who screened positive for drug abuse. Women who are pregnant or breastfeeding, or who test positive for blood pregnancy. Subjects who have used any P-gp or CYP inducer or inhibitor within 30 days before screening, or any prescription or Chinese herbal medicine within 4 weeks before the start of the trial, or over-the-counter or health care products (including polyvalent cations and metal supplements, etc.) within 2 weeks before the start of the trial; It should have a longer time interval if the elimination half-life is longer-at least 5 elimination half-lives for the drug. Subjects who consumed more than 14 units of alcohol per week in the 6 months prior before screening (1 unit of alcohol =360mL beer or 45mL spirits with 40% alcohol or 150mL wine) or had a positive alcohol breath test or could not abstain during the trial. Subjects who smoked more than 5 cigarettes per day in the 3 months prior before screening or habitually used nicotine-containing products or could not give up during the trial.

Sites / Locations

  • Huashan Hospital affiliated to Fudan University

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Placebo Comparator

Arm Label

80mg group

160mg group

Placebo group

Arm Description

D1, two 40mg tablets and two placebo tablets

D1, four 40mg tablets

D1, 4 placebo tablets

Outcomes

Primary Outcome Measures

ΔΔQTc -Placebo-corrected, baseline-adjusted QTc interval (ΔΔQTc)
Placebo-corrected, baseline-adjusted QTc interval (ΔΔQTc) at designed time after single oral administration of ZX-7101A tablets 80mg and 160mg in healthy Chinese adults. ΔΔQTc:The change of QTc interval from baseline value (ΔQTc) at each time point after administration was calculated, and then the difference of ΔQTc between the experimental group and the placebo group at each time point was calculated(ΔΔQTc).

Secondary Outcome Measures

T wave
T-wave morphology,or absence
PK parameters
Cmax of prodrug ZX-7101A and active metabolite ZX-7101 (mother drug)
TEAE
Rate of Treatment-Emergent Adverse Events(TEAE)
U wave
U-wave presence and absence
PK parameters
AUC0-t of prodrug ZX-7101A and active metabolite ZX-7101 (mother drug)
PK parameters
AUCinf of prodrug ZX-7101A and active metabolite ZX-7101 (mother drug)
PK parameters
Tmax of prodrug ZX-7101A and active metabolite ZX-7101 (mother drug)

Full Information

First Posted
June 14, 2023
Last Updated
July 20, 2023
Sponsor
Nanjing Zenshine Pharmaceuticals
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1. Study Identification

Unique Protocol Identification Number
NCT05955027
Brief Title
A Study to Evaluate the Effect of a Single Oral Dose of ZX-7101A on the QTc Interval in Healthy Subjects
Acronym
QTc-ZX-7101A
Official Title
A Study to Evaluate the Effect of a Single Oral Dose of ZX-7101A on the QTc Interval in Healthy Subjects
Study Type
Interventional

2. Study Status

Record Verification Date
June 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
August 15, 2023 (Anticipated)
Primary Completion Date
March 7, 2024 (Anticipated)
Study Completion Date
May 7, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Nanjing Zenshine Pharmaceuticals

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
The purpose of this study is to evaluate the effect of a single oral dose of ZX-7101A on the QTc interval in healthy subjects.
Detailed Description
Day 1, Oral fasting administration of ZX-7101A tablets 80mg, 160mg and placebo, 6 visit periods were set from days 2 to 15(Day2, Day3, Day5, Day7, Day10, Day15)

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Influenza, Human

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
The investigational drug and the investigational drug placebo shall be provided by the sponsoring unit or its designated unit; Ensure that the placebo looks, tastes, and weighs similar to the test drug and marked for clinical trials; The test drug and placebo shall be blinded by the sponsor or its designated unit for each trial group.
Allocation
Randomized
Enrollment
24 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
80mg group
Arm Type
Experimental
Arm Description
D1, two 40mg tablets and two placebo tablets
Arm Title
160mg group
Arm Type
Experimental
Arm Description
D1, four 40mg tablets
Arm Title
Placebo group
Arm Type
Placebo Comparator
Arm Description
D1, 4 placebo tablets
Intervention Type
Drug
Intervention Name(s)
ZX-7101A
Intervention Description
a drug to treat influenza, oral
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
placebo control, oral
Primary Outcome Measure Information:
Title
ΔΔQTc -Placebo-corrected, baseline-adjusted QTc interval (ΔΔQTc)
Description
Placebo-corrected, baseline-adjusted QTc interval (ΔΔQTc) at designed time after single oral administration of ZX-7101A tablets 80mg and 160mg in healthy Chinese adults. ΔΔQTc:The change of QTc interval from baseline value (ΔQTc) at each time point after administration was calculated, and then the difference of ΔQTc between the experimental group and the placebo group at each time point was calculated(ΔΔQTc).
Time Frame
Day1, Day2, Day3, Day5, Day7, Day10, Day15
Secondary Outcome Measure Information:
Title
T wave
Description
T-wave morphology,or absence
Time Frame
Day1, Day2, Day3, Day5, Day7, Day10, Day15
Title
PK parameters
Description
Cmax of prodrug ZX-7101A and active metabolite ZX-7101 (mother drug)
Time Frame
Day1, Day2, Day3, Day5, Day7, Day10, Day15
Title
TEAE
Description
Rate of Treatment-Emergent Adverse Events(TEAE)
Time Frame
Day1, Day2, Day3, Day5, Day7, Day10, Day15
Title
U wave
Description
U-wave presence and absence
Time Frame
Day1, Day2, Day3, Day5, Day7, Day10, Day15
Title
PK parameters
Description
AUC0-t of prodrug ZX-7101A and active metabolite ZX-7101 (mother drug)
Time Frame
Day1, Day2, Day3, Day5, Day7, Day10, Day15
Title
PK parameters
Description
AUCinf of prodrug ZX-7101A and active metabolite ZX-7101 (mother drug)
Time Frame
Day1, Day2, Day3, Day5, Day7, Day10, Day15
Title
PK parameters
Description
Tmax of prodrug ZX-7101A and active metabolite ZX-7101 (mother drug)
Time Frame
Day1, Day2, Day3, Day5, Day7, Day10, Day15

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
45 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Healthy male or female subjects, 18-45 years of age, inclusive, at the time of signing the ICF. Weight: Male weight ≥50 kg, female weight ≥45 kg, BMI between 19.0 and 28.0 kg/m2 (including cut-off value), BMI= weight (kg)/height 2 (m2). The investigator judged the subjects to be in good overall health based on their medical history, physical examination, vital signs, 12-lead electrocardiogram, laboratory tests (routine blood work, urine work, blood biochemistry, coagulation function), viral serology, and chest X-ray results (normal or abnormal test results have no clinical significance). Female subjects of childbearing potential and male subjects with a partner of childbearing potential who voluntarily signed ICF should be no fertile, sperm/egg donation for 6 months (female) or 90 days (male) from the beginning to the last dose, and voluntary use highly effective contraception (including partner) (non-drug contraception is required during the trial). Fully understand the trial content and possible adverse reactions, have the ability to communicate with researchers normally, while complying with study requirements, follow protocol procedures and restrictions, and be able to visit on time. Exclusion Criteria: Subjects with a prior or present history of clinically abnormal metabolic, liver, kidney, hematological, pulmonary, cardiovascular, gastrointestinal, urinary, endocrine, neurological, or psychiatric disease who were judged by the investigator to be unsuitable for participation in this study. Subjects with digestive tract disease or any condition that may affect drug absorption, such as a history of liver and gallbladder disease, gastrointestinal disease, gastrointestinal surgery (except appendectomy) or a history of chronic pancreatitis, idiopathic acute pancreatitis, or habitual diarrhea. Subjects with electrolyte metabolism disorders such as hyperkalemia, hypokalemia, hypermagnesia, hypomagnesia, hypercalcemia or hypocalcemia. Subjects who have a history of other risk factors for tachycardia, or a family history of a first-degree relative (i.e. biological parent, sibling, or child) of short QT syndrome, long QT syndrome, or sudden unexplained death in young age (≤40 years). Allergic constitutions (such as allergies to two or more drugs, foods, and pollen), or determined by the investigator, may be allergic to the investigational product or any component of the investigational product. Subjects who have got acute respiratory infections within 2 weeks before screening; Or have a history of fungal infection. For patients with abnormal vital signs (blood pressure, pulse rate, ear temperature) and clinically significant results, the abnormal values of each vital sign are: Body temperature (ear temperature) >37.5 ℃; Systolic blood pressure (recumbent) <90 mmHg or ≥140 mmHg;Diastolic blood pressure (lying) <50 mmHg or ≥90 mmHg; Pulse rate (lying position) <50 beats/min or >100 beats/min. QTcF interval > 450ms or < 300 ms (Fridericia's correction), or QRS>120ms. Subjects who have abnormal liver function: alanyl aminotransferase (ALT) or aspartate aminotransferase (AST) higher than the upper limit of normal or serum total bilirubin (TBIL) greater than 1.5 times the upper limit of normal, who judged clinical significance by investigators. Subjects estimate glomerular filtration rate <90 mL/min/1.73 m2. Subjects virus serological test (hepatitis B virus surface antigen, hepatitis C virus antibody, human immunodeficiency virus antibody, treponema pallidum specific antibody TPPA) positive results. Subjects with a history of drug abuse (morphine, dimethylene dioxyamphetamine, methamphetamine, THC, ketamine, cocaine) or who screened positive for drug abuse. Women who are pregnant or breastfeeding, or who test positive for blood pregnancy. Subjects who have used any P-gp or CYP inducer or inhibitor within 30 days before screening, or any prescription or Chinese herbal medicine within 4 weeks before the start of the trial, or over-the-counter or health care products (including polyvalent cations and metal supplements, etc.) within 2 weeks before the start of the trial; It should have a longer time interval if the elimination half-life is longer-at least 5 elimination half-lives for the drug. Subjects who consumed more than 14 units of alcohol per week in the 6 months prior before screening (1 unit of alcohol =360mL beer or 45mL spirits with 40% alcohol or 150mL wine) or had a positive alcohol breath test or could not abstain during the trial. Subjects who smoked more than 5 cigarettes per day in the 3 months prior before screening or habitually used nicotine-containing products or could not give up during the trial.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Zhang Jing, Doctor
Phone
52887926
Email
Zhangj_fudan@163.com
First Name & Middle Initial & Last Name or Official Title & Degree
Xi Yue Wen, Doctor
Facility Information:
Facility Name
Huashan Hospital affiliated to Fudan University
City
Shanghai
State/Province
Shanghai
Country
China

12. IPD Sharing Statement

Plan to Share IPD
No

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A Study to Evaluate the Effect of a Single Oral Dose of ZX-7101A on the QTc Interval in Healthy Subjects

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