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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| FCN-437c capsule | Experimental | fasting oral, single dose.Specification :100mg |
|
| FCN-437c capsule Placebo | Placebo Comparator | fasting oral,single dose.Specification :100mg |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Low dose group | Drug | 300 mg,single dose. |
|
| 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 |
| 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 |
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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:
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| Name | Affiliation | Role |
|---|---|---|
| Haiyan Li, MD | Peking University Third Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Peking University Third Hospital | Beijing | Beijing Municipality | 100191 | China |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 39188943 | Derived | Zhao L, Sun Y, Yang X, Tian L, Li L, Wang F, Niu X, Diao L, Li H. No QTc prolongation with CDK 4/6 inhibitor FCN-437c: results of a concentration-QTc analysis from a dedicated study in adult healthy subjects. Front Pharmacol. 2024 Aug 12;15:1433663. doi: 10.3389/fphar.2024.1433663. eCollection 2024. |
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| ID | Term |
|---|---|
| D044382 | Population Groups |
| C000722927 | FCN-437c |
| ID | Term |
|---|---|
| D003710 | Demography |
| D011154 | Population Characteristics |
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| High dose group | Drug | 400 mg, single dose. |
|
|
| 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 |