Phase 1 Study of KH607 Tablets

A Phase 1 Study to Evaluate the Safety, Tolerability, and Pharmacokinetic Profile of Single and Multiple Doses of KH607 Tablets in Chinese Healthy Volunteers

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.

Study Overview

• Status: Recruiting
• Conditions: Healthy
• Intervention / Treatment: Drug: 2mg KH607 tablets; Drug: 5mg KH607 tablets; Drug: 10mg KH607 tablets; Drug: 20mg KH607 tablets; Drug: 30mg KH607 tablets; Drug: 40mg KH607 tablets; Drug: 50mg KH607 tablets; Drug: 60mg KH607 tablets

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 88
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Ling Song; Phone Number: 028-81258178; Email: 022516@cnkh.com

Study Locations

• China
  • Beijing, China
    • Recruiting
    • Beijing Anding Hospital Affiliated to Capital Medical University
    • Contact: Gang Wang, Medical Doctor

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Adult, male and female volunteers, 18 to 55 years of age, inclusive.
2. Male weight ≥ 50kg, female weight ≥ 45kg, and body mass index ≥ 19 to ≤ 28 kg/m2 at the screening period.

Exclusion Criteria:

1. Vulnerable groups include the Investigator and his or her immediate family members (spouse, parents, children, siblings), non-immediate family members involved in the study, or individuals who may be participating under coercion or undue influence.
2. Subjects whose C-SSRS suggests that they are at risk for suicide at the screening period, or with the risk for suicide based on the Investigator's clinical judgment, or with a history of suicidal or self-harming behavior.
3. Subjects with SSS ≥3 or MOAA/S ≤4 during the screening period.
4. Subjects with a history of surgery for gastrointestinal disorders or current GI disorders that may interfere with drug absorption, or who have undergone major surgery within the 3 months prior to the screening period.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

11

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: KH607 Cohort 1; Subject received a single KH607 tablets dose of 2mg KH607 tablets or matching placebo.	Drug: 2mg KH607 tablets; Subject receive KH607 tablets or placebo orally single dose.
Experimental: KH607 Cohort 2; Subject received a single KH607 tablets dose of 5mg KH607 tablets or matching placebo.	Drug: 5mg KH607 tablets; Subject receive KH607 tablets or placebo orally single dose.
Experimental: KH607 Cohort 3; Subject received a single KH607 tablets dose of 10mg KH607 tablets or matching placebo.	Drug: 10mg KH607 tablets; Subject receive KH607 tablets or placebo orally single dose or multiple doses.
Experimental: KH607 Cohort 4; Subject received a single KH607 tablets dose of 20mg KH607 tablets or matching placebo.	Drug: 20mg KH607 tablets; Subject receive KH607 tablets or placebo orally single dose or multiple doses.
Experimental: KH607 Cohort 5; Subject received a single KH607 tablets dose of 30mg KH607 tablets or matching placebo.	Drug: 30mg KH607 tablets; Subject receive KH607 tablets or placebo orally single dose or multiple doses.
Experimental: KH607 Cohort 6; Subject received a single KH607 tablets dose of 40mg KH607 tablets or matching placebo.	Drug: 40mg KH607 tablets; Subject receive KH607 tablets or placebo orally single dose.
Experimental: KH607 Cohort 7; Subject received a single KH607 tablets dose of 50mg KH607 tablets or matching placebo.	Drug: 50mg KH607 tablets; Subject receive KH607 tablets or placebo orally single dose.
Experimental: KH607 Cohort 8; Subject received a single KH607 tablets dose of 60mg KH607 tablets or matching placebo.	Drug: 60mg KH607 tablets; Subject receive KH607 tablets or placebo orally single dose.
Experimental: KH607 Cohort 9; Subject received 10mg KH607 or matching placebo, oncely daily from Day 1 to Day 7.	Drug: 10mg KH607 tablets; Subject receive KH607 tablets or placebo orally single dose or multiple doses.
Experimental: KH607 Cohort 10; Subjects receive 20mg KH607 or matching placebo, once daily from Day 1 to Day 7.	Drug: 20mg KH607 tablets; Subject receive KH607 tablets or placebo orally single dose or multiple doses.
Experimental: KH607 Cohort 11; Subjects receive 30mg KH607 or matching placebo, once daily from Day 1 to Day 7.	Drug: 30mg KH607 tablets; Subject receive KH607 tablets or placebo orally single dose or multiple doses.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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.
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.
Physical Examination		Screening up to Part 1 Days, Part 2 Day14.

Secondary Outcome Measures

Outcome Measure	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)		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.

Collaborators and Investigators

• Sponsor: Chengdu Kanghong Pharmaceutical Group Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): October 21, 2023
• Primary Completion (Estimated): October 30, 2024
• Study Completion (Estimated): October 30, 2024

Study Registration Dates

• First Submitted: January 4, 2024
• First Submitted That Met QC Criteria: April 26, 2024
• First Posted (Actual): May 1, 2024

Study Record Updates

• Last Update Posted (Actual): May 7, 2024
• Last Update Submitted That Met QC Criteria: May 6, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Other Study ID Numbers: KH607-30101

Drug and device information, study documents

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