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This study was a single-center, randomized, double-blind, placebo-controlled study divided into a Single Ascending Dose (SAD) stage and a Multiple Ascending Dose (MAD) stage. The primary objective was to evaluate the safety and tolerability of KH607 tablets in Chinese healthy volunteers.
This study consists of two parts: Part 1-SAD phase and Part 2- MAD phase. There will be eight cohorts in Part 1 and three cohorts in Part 2 of this study.
The SAD study will enroll approximately 58 HVs across 8 dose cohorts. The dose cohorts will include the following dose levels: 2 mg, 5 mg, 10 mg, 20 mg, 30 mg, 40 mg, 50mg and 60 mg. All participants in Part 1 will be administered with a single oral dose of KH607 or its matching placebo under fasted condition.
Approximately 30 HVs will be enrolled in the multiple ascending dose study. The dose cohorts will include the following dose levels: 10 mg, 20 mg, 30 mg.At each cohort, 10 subjects will be randomized in a ratio of 8:2 to be receive KH607 or placebo once daily for continuous 7 days (QDx7d) in a double-blind manner.
Additionally, this study will explore the effect of food on the PK of a single oral administration of KH607 in one selected SAD cohort.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| KH607 Cohort 1 | Experimental | Subject received a single KH607 tablets dose of 2mg KH607 tablets or matching placebo. |
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| KH607 Cohort 2 | Experimental | Subject received a single KH607 tablets dose of 5mg KH607 tablets or matching placebo. |
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| KH607 Cohort 3 | Experimental | Subject received a single KH607 tablets dose of 10mg KH607 tablets or matching placebo. |
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| KH607 Cohort 4 | Experimental | Subject received a single KH607 tablets dose of 20mg KH607 tablets or matching placebo. |
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| KH607 Cohort 5 | Experimental | Subject received a single KH607 tablets dose of 30mg KH607 tablets or matching placebo. |
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| KH607 Cohort 6 | Experimental |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 2mg KH607 tablets | Drug | Subject receive KH607 tablets or placebo orally single dose. |
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| Measure | Description | Time Frame |
|---|---|---|
| 12-lead ECGs | Using a standard 12-lead ECG machine that automatically calculates heart rate and measures PR interval, RR interval, QRS interval, QT interval and QTc interval. ECGs will be reviewed by the Investigator on an ongoing basis as safety assessments. | Screening up to Part 1 Days, Part 2 Day14. |
| Physical Examination | Screening up to Part 1 Days, Part 2 Day14. | |
| 12-lead ECGs | Using a standard 12-lead ECG machine that automatically calculate heart rate and measures PR interval, RR interval, QRS interval, QT interval, QTc interval. ECGs will be reviewed by the Investigator on an ongoing basis as safety assessments. | Screening up to Part 2 Day14. |
| Stanford Sleepiness Scale | Participants rate their current sleepiness on a scale of 1 to 7, where scale of 1 indicates feeling active, vital, alert, or wide awake. Scale of 7 indicates no longer fighting sleep, sleep onset soon, and having dream-like thoughts. | Screening up to Part 1 Day3,Part 2 Day14. |
| Modified Observer's Assessment of Alertness/Sedation scale | The MOAA/S ranges from 0 to 5, with a score of 5 defined as awake or minimally sedated, and a score of 0 defined as general anaesthesia. | Screening up to Part 1 Day3,Part 2 Day14. |
| Measure | Description | Time Frame |
|---|---|---|
| Columbia-Suicide Severity Rating Scale | The C-SSRS scale consists of three subscales: suicidal ideation, intensity of ideation and suicidal behavior. | Screening up to Part 1 Day3,Part 2 Day14. |
| Observed maximum plasma concentration (Cmax) |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Ling Song | Contact | 028-81258178 | 022516@cnkh.com |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Beijing Anding Hospital Affiliated to Capital Medical University | Recruiting | Beijing | China |
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Subject received a single KH607 tablets dose of 40mg KH607 tablets or matching placebo.
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| KH607 Cohort 7 | Experimental | Subject received a single KH607 tablets dose of 50mg KH607 tablets or matching placebo. |
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| KH607 Cohort 8 | Experimental | Subject received a single KH607 tablets dose of 60mg KH607 tablets or matching placebo. |
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| KH607 Cohort 9 | Experimental | Subject received 10mg KH607 or matching placebo, oncely daily from Day 1 to Day 7. |
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| KH607 Cohort 10 | Experimental | Subjects receive 20mg KH607 or matching placebo, once daily from Day 1 to Day 7. |
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| KH607 Cohort 11 | Experimental | Subjects receive 30mg KH607 or matching placebo, once daily from Day 1 to Day 7. |
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| 5mg KH607 tablets |
| Drug |
Subject receive KH607 tablets or placebo orally single dose. |
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| 10mg KH607 tablets | Drug | Subject receive KH607 tablets or placebo orally single dose or multiple doses. |
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| 20mg KH607 tablets | Drug | Subject receive KH607 tablets or placebo orally single dose or multiple doses. |
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| 30mg KH607 tablets | Drug | Subject receive KH607 tablets or placebo orally single dose or multiple doses. |
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| 40mg KH607 tablets | Drug | Subject receive KH607 tablets or placebo orally single dose. |
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| 50mg KH607 tablets | Drug | Subject receive KH607 tablets or placebo orally single dose. |
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| 60mg KH607 tablets | Drug | Subject receive KH607 tablets or placebo orally single dose. |
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| Up to 48 hours after dosing in Part 1. |
| Time to reach maximum plasma concentration (Tmax) | Up to 48 hours after dosing in Part 1. |
| Elimination Halflife (T1/2) | Up to 48 hours after dosing in Part 1. |
| Area under the concentration-time curve from time zero to last time of quantifiable concentration(AUC0-t) | Up to 48 hours after dosing in Part 1. |
| Apparent Distribution Volume (Vd) | Up to 48 hours after dosing in Part 1. |
| Apparent Total Plasma Clearance (CL) | Up to 48 hours after dosing in Part 1. |
| Elimination Rate Constant (Kel) | Up to 48 hours after dosing in Part 1. |
| Mean Residence Time(MRT) | Up to 48 hours after dosing in Part 1. |
| Steady-state valley concentration(Css,min) | Up to 24 hours after Day7 dosing in Part 2. |
| Steady-state peak concentration(Css,max) | Up to 24 hours after Day7 dosing in Part 2. |
| Mean steady-state blood concentration(Css,av) | Up to 24 hours after Day7 dosing in Part 2. |
| Steady state area under the curve(AUC0-tau) | Up to 24 hours after Day7 dosing in Part 2. |
| Accumulation Index(Rac) | Up to 24 hours after Day7 dosing in Part 2. |