A Phase 1 Study of KHN702 Tablets in Healthy Subjects

Official title

A Phase 1 Study to Evaluate the Safety, Tolerability, and Pharmacokinetic Profile of Single and Multiple Doses of KHN702 Tablets in Chinese Healthy Volunteers

Overview

This study is a single-center, randomized, double-blind, placebo-controlled study divided into a Single Ascending Dose (SAD) stage and a Multiple Ascending Dose (MAD) phase. The primary objective is to evaluate the safety and tolerability of KHN702 tablets in Chinese healthy volunteers（HVs).

Detailed description

This study consists of two parts: Part 1-SAD phase and Part 2- MAD phase. There will be 7 cohorts in Part 1 and 3 cohorts in Part 2.

The SAD study will enroll approximately 54 HVs across 7 dose cohorts. All participants in Part 1 will be administered with a single oral dose of KHN702 or its matching placebo under fasted condition.

Approximately 30 HVs will be enrolled in the multiple ascending dose study. All participants in Part 2 will received KHN702 or placebo once daily for continuous 7 days (QD x 7d) in a double-blind manner.

The safety and tolerability will be evaluated by monitoring and assessment of AEs, clinical laboratory tests (hematology, urinalysis, biochemistry, coagulation, etc.), physical examination findings, etc.

Interventions

• Drug KHN702 tablet or placebo
  Subject will receive a single KHN702 tablet or matching placebo orally in fasted state.
• Drug KHN702 tablet or placebo
  All participants will receive KHN702 tablet or matching placebo orally once a day for 7 days in fasted state.

Primary outcome measures

• The incidence and severity of adverse events (AEs) [Time frame: From screening to Day 4 for Part 1, and Day 10 for Part 2.]

Secondary outcome measures (7)

• Maximum observed plasma concentration (Cmax) [Time frame: Part I: Day 1 to Day 4. Part II: Day 1 to Day 10.]
• Time to reach maximum observed concentration (Tmax) [Time frame: Part I: Day 1 to Day 4. Part II: Day 1 to Day 10.]
• Area under plasma concentration-time curve from zero to infinity (AUC0-inf) [Time frame: Part I: Day 1 to Day 4. Part II: Day 1 to Day 10.]
• Area under the plasma concentration-curve across the dosing interval (AUC0-tau) [Time frame: Day 1 to Day 10.]
• Terminal elimination half-life (t1/2) [Time frame: Part I: Day 1 to Day 4. Part II: Day 1 to Day 10.]
• Apparent total body clearance (CL/F) [Time frame: Part I: Day 1 to Day 4. Part II: Day 1 to Day 10.]
• Apparent volume of distribution during the terminal phase after extravascular administration (Vz/F) [Time frame: Part I: Day 1 to Day 4. Part II: Day 1 to Day 10.]

Eligibility criteria

Inclusion criteria

1.Age: 18 to 45 years old (inclusive), Male or female. 2.Body weight: ≥ 50 kg for male and ≥ 45 kg for female, body mass index: 19\~26 kg/m2 (inclusive).

3\. Effective contraception measures and no sperm/egg donation plan from signing the informed consent to 3 months after last dose.

4.Fully understand the procedures and sigh the informed consent. exclusion criteria：

• Have clinically significant medical history or clinical manifestations, including but not limited to the history of any clinically serious disease such as hematological system, circulatory system,digestive system, urinary system, respiratory system, central nervous system,immunology, endocrine system cardiovascular system, malignant tumors, metabolic abnormalities, or any other disease or physiological condition that may interfere with the results .
• Subjects with clinically significant abnormalities in vital signs, physical examination, 12 lead electrocardiogram, laboratory examination, abdominal color Doppler ultrasound and chest X-ray during screening period, as determined by the investigator.
• Dysphagia or history of gastrointestinal diseases, liver and kidney diseases that can affect the pharmacokinetic behavior of drugs as judged by the investigator.
• Had surgery within 3 months before screening, or planned surgery during the study period, or had surgery that would affect drug absorption, distribution, metabolism, and excretion.
• Allergic to the IMP or its excipients, or allergic to two or more other drugs, food and environment, or prone to skin rash, urticaria and other allergic symptoms.
• Allergic to natural light / UV, or phototoxic reaction after previous use of specific drugs (such as fluoroquinolones and tetracyclines).
• There are risk factors for cardiac disease, including but not limited to congenital long QT syndrome, torsade de pointes or torsade de pointes (such as hypokalemia, hypomagnesemia, family history of long QT syndrome). Currently, class IA \[such as quinidine or procainamide\] or class III \[such as amiodarone or sotalol\] antiarrhythmic drugs or other drugs known to affect QT interval are used. Or QTc interval (QTCF) corrected according to fridericia's criteria > 450 ms in males and > 470 ms in females at screening or other 12 lead ECG abnormalities with clinical significance.
• Alanine aminotransferase (ALT) and / or aspartate aminotransferase (AST) and / or total bilirubin (TBIL), or serum creatinine (CR) exceeded the upper limit of normal at screening.
• Positive test for hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibody, human immunodeficiency virus (HIV) antibody and treponema pallidum antibody at Screening.
• Systolic blood pressure ≥ 140 mmHg and / or diastolic blood pressure ≥ 90 mmHg at screening.
• Vaccinated within 30 days before screening.
• Any drugs that affects the absorption, metabolism or elimination of the drug has been used within 30 days before administration.
• Any drugs or health care products (including Chinese herbal medicine and vitamins) used within 14 days before the first administration of the study.
• Have special requirements for diet and cannot comply with the unified diet.
• Consumption of foods or juices containing alcohol or caffeine, or having strenuous exercise, or other factors affecting the absorption, distribution, metabolism, excretion of drugs with 48 hours before the first dose. Or disagree to stop drinking tea, coffee and / or caffeinated beverages and foods during the trial.
• Average daily smoking of more than 5 cigarettes within the 3 months prior to screening or refuse to abstain from smoking during the trial.
• A history of alcohol abuse or alcohol abuse within 6 months before screening (defined as an average intake of alcohol > 14 units per week, 1 unit ≈ 285 ml of beer with an alcohol content ≥ 3.5%, or 25 ml of spirits with an alcohol content ≥ 40%, or 85 ml of wines with an alcohol content ≥ 12%), or a positive alcohol test at the screening, or unable to abstain from alcohol during the trial.
• Donation of blood or significant blood loss ≥ 400 mL in 3 month prior to screening.
• Substance abuse-related disorder or a history of drug, or positive drug screen at screening and Day -1.
• Positive pregnancy test, or lactating women.
• Participate in other clinical trials within 3 months before screening (participation refers to receiving drug administration or device treatment for the trial).
• Subjects with other factors deemed ineligible to participate in the trial by the Investigator.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation

Randomized

Model

Sequential

Masking

Triple blind

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT07044960 · KHN702-30101

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗