Dose-Finding and Human Abuse Potential Study Of HSK3486 Injection In Nondependent, Recreational Central Nervous System Depressant Users

NCT05614544 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: HSK3486-110
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 1

Brief Summary

Part 1: To determine the doses of IV HSK3486 and propofol for use in Part 2, the abuse potential part of the study. Part 2: To evaluate the abuse potential of HSK3486 compared with propofol when administered IV to healthy nondependent, recreational CNS depressant drug users.

Conditions

General Anesthesia

Outcome Measures

Primary Outcomes (2)

• Part 1

  To determine the doses of IV HSK3486 and propofol for use in Part 2, the abuse potential part of the study

  Screening between Day -28 and Day -5; confinement period 9 days in clinic from Day -4 (admission) to 24 hours after study drug administration in period 4; follow-up 3 to 7 days after study drug administration

• Part 2

  To evaluate the abuse potential of HSK3486 compared with propofol when administered IV to healthy nondependent, recreational CNS depressant drug users

  Screening between Day -28 and Day -2; confinement period 2 days in clinic from Day -1 (admission) to 24 hours after study drug administration; follow-up 3 to 7 days after study drug administration

Secondary Outcomes (2)

• To evaluate the safety and tolerability of HSK3486 in healthy, nondependent, recreational CNS depressant drug users

  Screening between Day -28 and Day -5; confinement period 9 days in clinic from Day -4 (admission) to 24 hours after study drug administration in period 4; follow-up 3 to 7 days after study drug administration

• • To evaluate the safety and tolerability of HSK3486 compared to propofol when administered IV to healthy nondependent, recreational CNS depressant drug users

  Screening between Day -28 and Day -2; confinement period 2 days in clinic from Day -1 (admission) to 24 hours after study drug administration; follow-up 3 to 7 days after study drug administration

Study Arms (4)

Treatment A: HSK3486 dose 1

EXPERIMENTAL

Treatment A: HSK3486 dose 1 (IV bolus over 30 seconds \[+5 seconds\] from a syringe; dose to be determined in Part 1)

Drug: HSK3486

Treatment B: HSK3486 dose 2

EXPERIMENTAL

Treatment B: HSK3486 dose 2 (IV bolus over 30 seconds \[+5 seconds\] from a syringe; dose to be determined in Part 1)

Drug: HSK3486

Treatment C: Propofol

ACTIVE COMPARATOR

Treatment C: Propofol (IV bolus over 30 seconds \[+5 seconds\] from a syringe; dose to be determined in Part 1)

Drug: Propofol

Treatment D: Placebo

PLACEBO COMPARATOR

Treatment D: Placebo (Treatment A matched) (IV bolus over 30 seconds \[+5 seconds\] from a syringe)

Drug: Placebo

Interventions

HSK3486 DRUG

HSK3486 for induction of general anesthesia

Treatment A: HSK3486 dose 1; Treatment B: HSK3486 dose 2

Propofol DRUG

Propofol for induction of general anesthesia

Treatment C: Propofol

Placebo DRUG

Intralipid

Treatment D: Placebo

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Willing to participate in the study, give written informed consent, and comply with the study restrictions.
• Gender: male or female; females may be of childbearing potential, of nonchildbearing potential, or postmenopausal.
• Age: 18 years to 55 years, inclusive, at Screening.
• Body mass index (BMI): 18.0 kg/m2 to 30.0 kg/m2, inclusive.
• Weight: ≥50 kg, inclusive.
• Healthy subject, defined by the absence of evidence of any clinically significant, in the opinion of the Investigator, active or chronic disease following a detailed medical and surgical history, a complete physical examination including vital signs, 12-lead ECG, hematology, blood chemistry, serology, and urinalysis.
• Subject must be a nondependent, nontreatment-seeking recreational CNS depressant user, defined as follows:
• ≥10 lifetime nontherapeutic experiences (i.e., for psychoactive effects) with CNS depressants (e.g., benzodiazepines, barbiturates, opiates, zolpidem, zopiclone, propofol/fospropofol, gamma-hydroxybutyrate).
• ≥1 nontherapeutic use of a CNS depressant within the 8 weeks prior to Screening.
• ≥1 nontherapeutic use of benzodiazepines within the 12 months prior to Screening.
• Ability and willingness to abstain from alcohol-, caffeine-, and xanthine-containing beverages or food (e.g., coffee, tea, cola, chocolate, energy drinks) from 48 hours (2 days) prior to first admission to the CRU, throughout the entire study, and until discharge.
• All values for hematology and clinical chemistry tests of blood and urine within the normal range or show no clinically relevant deviations, as judged by the Investigator.
• Females of childbearing potential, and males with female partner(s) of childbearing potential, as judged by the Investigator, must agree to use 2 forms of contraception, 1 of which must be a barrier method, during the study and for 90 days after the last drug administration. Acceptable barrier forms of contraception are condom, cervical cap, and diaphragm. Acceptable non barrier forms of contraception for this study are an intrauterine device (IUD) including hormonal IUDs, oral contraceptives (used for ≥30 days prior to dosing any study treatment), and/or spermicide.
• For females: a negative pregnancy test at Screening and Admission.
• Postmenopausal females: defined as 12 months with no menses prior to Screening and a serum follicle stimulating hormone (FSH) \>40 IU/L at Screening.

You may not qualify if:

• An employee of the Sponsor or research site personnel directly affiliated with this study or their immediate family member (defined as a spouse, parent, child, or sibling, whether biological or legally adopted).
• Drug or alcohol dependence within the 2 years prior to Screening (except nicotine and caffeine), as defined by the Diagnostic and Statistical Manual of Mental Disorders, fourth edition, text revision (DSM IV TR), and/or has ever participated or plans to participate in a substance or alcohol rehabilitation program to treat their substance or alcohol dependence.
• Opioid dependence as judged by the Investigator after a naloxone challenge.
• Women who are pregnant, lactating, or planning to attempt to become pregnant during this study or within 90 days of last study drug administration.
• Males with female partners who are pregnant, lactating, or planning to attempt to become pregnant during this study or within 90 days of last study drug administration.
• Positive drug and alcohol screen (tetrahydrocannabinol \[THC\], morphine/opiates, methadone, oxycodone, phencyclidine, cocaine, amphetamines, methamphetamines, ecstasy, barbiturates, benzodiazepines, tricyclic antidepressants, and alcohol) at each admission to the CRU. For THC, subjects should ideally test negative. However, eligibility decision with regards to THC use will be considered on a case by case basis, at the discretion of the Investigator.
• Treatment with an investigational drug or device within 5 times the elimination half-life, if known (e.g., a marketed product) or within 30 days (if the elimination half-life is unknown) prior to first drug administration or is concurrently enrolled in any research judged not to be scientifically or medically compatible with this study. An exception may be made for subjects who participated in Part 1 of the study.
• History or presence of clinically significant abnormality (e.g., obstructive sleep apnea) as assessed by physical examination, medical history, ECG, vital signs, or laboratory values, which, in the opinion of the Investigator, would jeopardize the safety of the subject or the validity of the study results.
• Any disease which, in the opinion of the Investigator, poses an unacceptable risk to the subjects.
• Mallampati intubation score \>2.
• History of clinically significant drug allergy diagnosed by a physician. Confirmatory circumstances would include treatment with epinephrine or in an emergency department.
• Any personal or family history of issues with succinylcholine, such as malignant hyperthermia or pseudocholinesterase deficiency.
• History of allergy, adverse reaction (including significant agitation, etc.), or hypersensitivity to propofol, lidocaine, other injected anesthetic agents, or related drugs.
• History of allergy to eggs, egg products, soybeans or soy products.
• Heavy smoker (\>20 cigarettes per day) and/or is unable to abstain from smoking and/or the use of prohibited nicotine-containing products (including e-cigarettes, pipes, cigars, chewing tobacco, nicotine topical patches, nicotine gum, or nicotine lozenges) from 2 hours prior to dosing until at least 4 hours postdose during the in clinic periods.

Sponsors & Collaborators

• Haisco-USA Pharmaceuticals, Inc.: lead

Study Sites (1)

ICON (LPRA) - Salt Lake

Salt Lake City, Utah, 84124, United States

Location

MeSH Terms

Interventions

HSK3486; Propofol

Intervention Hierarchy (Ancestors)

Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: double-blind, placebo- and active-controlled 4 period, 4 way crossover design to assess the abuse potential of HSK3486
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 12, 2022
• First Posted: November 14, 2022
• Study Start: August 16, 2022
• Primary Completion: October 3, 2023
• Study Completion: October 3, 2023
• Last Updated: October 13, 2023

Record last verified: 2022-10

Locations

US (1)