Clinical Study on Pharmacokinetics of FCN-437c Capsule and Its Effect on QT Interval in Healthy Subjects

A Phase I, Single-center, Randomized, Double-blind, Placebo-controlled Design to Evaluate the Pharmacokinetics and Effects on QT Interval of a Single Oral Dose of FCN-437c Capsule in Healthy Subjects.

This is a single-center, randomized, double-blind, placebo-controlled Phase I clinical trial in healthy subjects.In healthy subjects, 300mg and 400mg FCN-437c capsules were taken orally for a single time. C-QTc effect model was used to evaluate the influence of blood concentration on QT interval, and the pharmacokinetic characteristics and safety of FCN-437c were also evaluated.Based on the C-QTc effect model, this study quantitatively analyzed the relationship between ΔΔQTcF and blood concentration, and evaluated the upper limit of 90% bilateral confidence interval of ΔΔQTcF corresponding to the geometric mean of Cmax at clinically relevant dose of FCN-437c capsule.

This study plans to set up 2 dose groups, low-dose group 300mg and high-dose group 400mg.Nine healthy subjects were planned to be enrolled in each dose group, with a 2:1 ratio of placebo control.

This study was carried out in the order of dose from low to high. After the administration of the low-dose group (300mg) and the safety assessment on the fourth day after administration, the study of the high-dose group (400mg) was decided through comprehensive evaluation.

Study Overview

• Status: Completed
• Conditions: Advanced Breast Cancer
• Intervention / Treatment: Drug: Low dose group; Drug: High dose group

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100191
      • Peking University Third Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1．Healthy adult male and female subjects (not less than 1/3 of either sex); 2．18~45 years old (including boundary values)After bilateral oophorectomy; 3．The body mass index (BMI) should be between 19.0 and 26.0 kg/m2 (including boundary values), and the weight of male subjects should not be less than 50 kg and that of female subjects should not be less than 45 kg; 4．Voluntarily sign informed consent 5．The subjects were able to communicate well with the investigators and complete the test according to protocol.

Exclusion Criteria:

Patients who meet any of the following conditions are not allowed to enter this clinical study：

1. After a comprehensive physical examination, vital signs, laboratory examination (blood routine, blood biochemistry, coagulation function, urine routine) and other abnormalities and clinical significance;
2. Hyperkalemia, hypokalemia, hypermagnesia, hypomagnesemia, hypercalcemia or hypocalcemia, which is abnormal and clinically significant as determined by the investigator;
3. Abnormal 12-lead ECG results were clinically significant, QTcF≥450 ms, PR interval ≥200 ms;QRS group duration ≥120ms;
4. Hepatitis B surface antigen or hepatitis B core antibody, hepatitis C antibody, HIV antibody or syphilis antibody positive;
5. Any drug that inhibits or induces liver drug metabolism enzymes has been used within 30 days prior to the screening period
6. Use any drug known to prolong the QT interval within 30 days prior to the screening period
7. Use of any prescription, over-the-counter, herbal or food supplements, such as vitamins and calcium supplements, in the 14 days prior to the screening period;
8. A history of any clinically serious medical conditions or conditions that the investigator believes may affect the results of the study, including but not limited to circulatory, respiratory, endocrine, nervous, digestive, urinary, or blood, immune, psychiatric, or metabolic disorders;
9. Have any conditions that may affect drug absorption, such as gastrectomy, cholecystectomy, gastric bypass, duodenotomy, colectomy, history of inflammatory bowel;
10. History of organic heart disease, heart failure, myocardial infarction, angina pectoris, coronary artery bypass grafting, angioplasty, stent stenting, congestive heart failure, uncontrolled hypotension, left ventricular ejection fraction lower than the lower limit of normal location, unexplained arrhythmia, ventricular tachycardia, atrioventricular block, and prolonged QT syndromeOr have symptoms of prolongation QT syndrome and a family history (as shown by genetic evidence or by a close relative who died of sudden cardiac death at a young age);
11. Patients who have undergone any surgery within 6 months prior to the screening period;
12. Allergy, such as a known history of allergy to two or more substances;Or who may be allergic to the drug or its excipients (e.g. Lactose T80, silica, sodium stearfumarate, etc.) as determined by the investigator;
13. Binge drinking or regular drinking in the 6 months preceding the screening period, i.e. drinking more than 14 units of alcohol per week (1 unit =360mL beer or 45 mL spirits with 40% alcohol or 150 mL wine);Or positive alcohol breath test results during the screening period;
14. Use of nicotine-containing products from 3 months prior to screening to the period of study participation;
15. Those who have a history of drug abuse or drug use 3 months before the screening period;Or positive urine drug test during screening;
16. Habitual users of grapefruit juice or excessive amounts of tea, coffee and/or caffeinated beverages who were unable to abstain during the trial period;
17. Patients with a history of needle fainting and blood fainting, difficulty in blood collection or inability to tolerate venous puncture blood collection
18. Participation in any other clinical trials (including drug and device trials) within 3 months prior to the screening period;
19. Those who were vaccinated within 1 month prior to screening or planned to be vaccinated during the trial period;
20. Pregnant or lactating women;
21. Participants who planned to have children or donate sperm during the study period and six months after completion of the study, or did not agree that participants and their spouses should use strict contraceptive methods during the study period and six months after completion of the study
22. Patients who had blood loss or blood donation of up to 400 mL within 3 months prior to the screening period, or received a blood transfusion within 1 month
23. Subjects with any factors deemed unsuitable for participation in the study by the investigator.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: FCN-437c capsule; fasting oral, single dose.Specification :100mg	Drug: Low dose group; 300 mg,single dose.; Other Names: FCN-437c capsule or FCN-437c capsule Placebo; Drug: High dose group; 400 mg, single dose.; Other Names: FCN-437c capsule or FCN-437c capsule Placebo
Placebo Comparator: FCN-437c capsule Placebo; fasting oral,single dose.Specification :100mg	Drug: Low dose group; 300 mg,single dose.; Other Names: FCN-437c capsule or FCN-437c capsule Placebo; Drug: High dose group; 400 mg, single dose.; Other Names: FCN-437c capsule or FCN-437c capsule Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ΔΔQTcF	The Cmax geometric mean corresponds to the upper 90% bilateral confidence interval of ΔΔQTcF	2hours before administration and 48hours and 192hours after administration

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
adverse events	The number, frequency and incidence of adverse events	Trial period to day 21 after administration
Physical examination	Descriptive statistics on physical examination indicators visited and their changes from baseline	From 1 day before administration to 21 days after administration
Axillary temperature	Descriptive statistics of vital signs at each visit and their change from baseline	From 2.0 hours before administration to 21 days after administration
blood pressure	Descriptive statistics of vital signs at each visit and their change from baseline	From 2.0 hours before administration to 21 days after administration
pulse	Descriptive statistics of vital signs at each visit and their change from baseline	From 2.0 hours before administration to 21 days after administration
Ecg monitoring and electrocardiogram	QTcF	Trial period to day 21 after administration
laboratory examination	Descriptive statistics were collected for each laboratory indicator visited and its change from baseline	Trial period to day 21 after administration
Plasma concentration and pharmacokinetic parameters	Cmax	60 minutes before dosing to day 9 after dosing
Plasma concentration and pharmacokinetic parameters	AUC0-t	60 minutes before dosing to day 9 after dosing
Plasma concentration and pharmacokinetic parameters	AUC0-∞	60 minutes before dosing to day 9 after dosing
Plasma concentration and pharmacokinetic parameters	Tmax	60 minutes before dosing to day 9 after dosing
Plasma concentration and pharmacokinetic parameters	T1/2	60 minutes before dosing to day 9 after dosing
Plasma concentration and pharmacokinetic parameters	CL/F	60 minutes before dosing to day 9 after dosing
Plasma concentration and pharmacokinetic parameters	VZ/F	60 minutes before dosing to day 9 after dosing
Plasma concentration and pharmacokinetic parameters	MRT	60 minutes before dosing to day 9 after dosing
Plasma concentration and pharmacokinetic parameters	AUC_%Extrap	60 minutes before dosing to day 9 after dosing

Collaborators and Investigators

• Sponsor: Ahon Pharmaceutical Co., Ltd.
• Investigators: Principal Investigator: Haiyan Li, MD, Peking University Third Hospital

Study record dates

Study Major Dates

• Study Start (Actual): November 11, 2022
• Primary Completion (Actual): February 8, 2023
• Study Completion (Actual): February 8, 2023

Study Registration Dates

• First Submitted: February 18, 2024
• First Submitted That Met QC Criteria: February 26, 2024
• First Posted (Estimated): March 4, 2024

Study Record Updates

• Last Update Posted (Estimated): March 4, 2024
• Last Update Submitted That Met QC Criteria: February 26, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: QT interval
• Other Study ID Numbers: FCN-437c-CP-004

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No