Clinical trial NCT06326723: Investigate the PK, Safety, and Tolerability After Single and Multiple Dose Daridorexant in Chinese Healthy Subjects
Official title: A Single-Center, Randomized, Double-Blind, Placebo-Controlled Phase 1 Clinical Study to Investigate the Pharmacokinetics, Safety, and Tolerability After Single- and Multiple-Dose Daridorexant in Chinese Healthy Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteer
Lead sponsor: Jiangsu Simcere Pharmaceutical Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2024-03-22
Enrollment: 32
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This clinical study is a single-center, randomized, double-blind, placebo-controlled Phase 1 clinical study to assess the PK characteristics and safety and tolerability of single and multiple dose daridorexant in 32 healthy adult Chinese subjects.

Detailed description: This clinical study is a single-center, randomized, double-blind, placebo-controlled Phase 1 clinical study to assess the PK characteristics and safety and tolerability of single and multiple dose daridorexant in healthy adult Chinese subjects. This study will consist of a 20-day screening period, a 1-day baseline, a 11-day in patient period, and a 27-day follow-up period. The subjects will arrive at the study site on Day -1, and the subjects will be discharged from the study site on Day11.

32 healthy subjects (18-55 years) will be randomized. Two dose levels are planned (25 mg and 50 mg). 16 healthy subjects will be randomized with a ratio of 3:1 to receive 25mg daridorexant or matched placebo and another 16 healthy subjects will be randomized with a ratio of 3:1 to receive 50mg daridorexant or matched placebo. On Day 1, each subject will receive a single dose of daridorexant or placebo in the morning under fast conditions and PK samples will be collected up to 72 h post dose. Subject will receive repeated doses of daridorexant or placebo from day 4 to day 8 (QD) in the morning under fasting conditions and PK samples will be collected up to 72 h post last dose. The final follow-up visit will be conducted on Day 38, 30 days after the last dose.

Eligibility criteria: Inclusion Criteria:

1. Ability to communicate well with the investigator in the local language, and to understand and comply with the requirements of the study. Signed informed consent in the local language prior to any study-mandated procedure.
2. Healthy Chinese male or female subjects aged between 18 and 55 years (inclusive) at screening.
3. Body Mass Index (BMI) ≥ 19 and ≤ 26 kg/m2, weight at least 45 kg for female, weight at least 50 kg for male at screening.
4. General good health at screening, with no abnormalities or abnormal clinically insignificant results based on medical history and physical examination, vital signs, laboratory tests, and 12-lead ECG performed at the time of screening. 50 bpm≤Resting heart rate (HR)≤100 bpm, 90mmHg \<systolic blood pressure\<140 mmHg or 50 mmHg\<diastolic blood pressure\<90 mmHg, ECG evidence of a QTcF interval of no more than 450 ms for male, ECG evidence of a QTcF interval of no more than 470 ms for female, (ECG monitors will be conducted for three times in five minutes, and mean values of three monitor results will be used)
5. Negative results from alcohol breath test and urine drug screen at Day -1.
6. Subjects (including male subjects) are willing to voluntarily use effective contraception from screening visit until 30 days after the end of the last dose and had no plans to become pregnant, planned parenthood or sperm/egg donation plans; Or subjects after surgical sterilization, or postmenopausal female subjects (female subjects with natural menopause ≥12 months can be considered postmenopausal; If age \<50 years by follicle stimulating hormone level confirmed)

Exclusion Criteria:

1. Previous history of fainting, collapse, syncope, orthostatic hypotension, or vasovagal reactions.
2. Intubation or repeat venipuncture is not appropriate.
3. Treatment with any prescription medications or over-the-counter medications (including herbal medicines) within 14 days prior to (first) study drug administration.
4. Have received any vaccine (including COVID-19 vaccine) prior to screening; have plan to receive vaccine (COVID-19 vaccine) during the study period or within 30 days after the last dose.
5. Not able or willing to stop treatment with moderate or strong cytochrome P450 (CYP)3A4 inhibitors, or treatment with moderate or strong CYP3A4 inducers, within 14 days prior to (first) study drug administration.
6. Not able or willing to stop consumption of grapefruit, Seville (bitter) oranges or juices from those fruits within 14 days prior to (first) study drug administration.
7. Treatment with another investigational drug within 3 months prior to screening or having participated in more than four investigational drug studies within 1 year prior to screening.
8. Use any nicotine or tobacco containing products (\>5 cigarettes/day) within 3 years prior to day 1 and inability to refrain from smoking during the study.
9. Alcohol abuse（≥ 14 standard drinks units per week; 1 unit: 285 mL beer or 25 mL spirits or 100 mL wine） within 3 years prior to day 1 and inability to refrain from taking alcohol during the study.
10. Drinking excessive tea (\>15 g tea leaves/day; 1 cup of tea contains about 3\~5 g of tea leaves) or caffeine (\>500 mg/ day, 1 cup of coffee contains about 85 mg of caffeine) and inability to refrain from drinking tea or caffeinated beverage during the study.
11. History or clinical evidence of any disease, and/or existence of any surgical or medical condition, which might interfere with the absorption, distribution, metabolism, or excretion of the study drugs (appendectomy and herniotomy allowed; cholecystectomy not allowed).
12. History of drug abuse.
13. Loss of 400 mL or more of blood, or an equivalent amount of plasma, within 3 months prior to screening.
14. Positive result to any of the following tests: HIV, hepatitis B, hepatitis C, and syphilis.
15. Known hypersensitivity to any excipients of the drug formulations.
16. Modified Swiss Narcolepsy Scale total score \< 0 at screening. History of narcolepsy or cataplexy.
17. Any surgery planned during the study period.
18. Legal incapacity or limited legal capacity at screening
19. History of tuberculosis (TB).
20. Pregnant or lactating women, or positive pregnancy test results.
21. Any suicidal ideation with intent, with or without a plan (at screening):

    Planned or unplanned any suicidal thoughts; That is, answer yes to question 4 or 5 of the Suicidal ideation section of the lifetime version C-SSRS©. Lifetime past C-SSRS© Suicidal Behavior section indicates a history of suicide attempts.
22. Any circumstances or conditions which, in the opinion of the investigator, may affect full participation in the study or compliance with the protocol.

Primary outcomes:
measure: Pharmacokinetic Endpoints1
timeFrame: Day1-Day11
measure: Pharmacokinetic Endpoints2
timeFrame: Day1-Day11
measure: Pharmacokinetic Endpoints3
timeFrame: Day1-Day11
measure: Pharmacokinetic Endpoints4
timeFrame: Day1-Day11
measure: Pharmacokinetic Endpoints5
timeFrame: Day1-Day11
measure: Pharmacokinetic Endpoints6
timeFrame: Day1-Day11
measure: Pharmacokinetic Endpoints7
timeFrame: Day1-Day11
Secondary outcomes:
measure: Safety Endpoints1
timeFrame: Day1-Day11
measure: Safety Endpoints2
timeFrame: Day1-Day11
measure: Safety Endpoints3
timeFrame: Day1-Day38
measure: Safety Endpoints4
timeFrame: Day1-Day38
measure: Safety Endpoints5
timeFrame: Day1-Day38
measure: Safety Endpoints6
timeFrame: Day1-Day38
measure: Safety Endpoints7
timeFrame: Day1-Day38
measure: Safety Endpoints8
timeFrame: Day1-Day38
Other outcomes:
Locations:
city: Nanjing
country: China
facility: Nanjing Drum Tower hospital
state: Jiangsu
Study officials:
affiliation: The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
name: Juan Li
role: PRINCIPAL_INVESTIGATOR
References: