Single-Ascending Dose Study to Assess the Safety, Tolerability, and Pharmacokinetics of YJ001 in Healthy Volunteers

NCT05451667 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: YJ001-102
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I, randomized, double-blind, placebo controlled study is to investigate the safety, tolerability and pharmacokinetics (PK) of topically administered YJ001 in a single-ascending dose (SAD) fashion in healthy volunteers between 18 to 55 years of age, to establish the dosage range for spray use, and to provide a dosage regimen for Phase I multiple-ascending dose (MAD) study in healthy subjects. The study is to enroll 4 cohorts, the doses of which are 148, 296, 552 and 828 mg, with the option to enroll 2 additional cohorts (8 subjects for each cohort) without requiring a protocol amendment. Subjects will be screened between Day -28 and Day -2 and will be admitted to the clinic on Day -1. Subjects will be housed within the clinic from Day -1 through Day 8 and will be discharged on Day 8 after all scheduled study procedures have been completed.

Conditions

Safety and Tolerability

Outcome Measures

Primary Outcomes (2)

• Incidence of adverse events and significant laboratory abnormality

  If ≥ 2 subjects assigned to YJ001 in a cohort experience any of the following: 1. A Grade ≥ 2 adverse event. 2. A Grade ≥ 2 clinically significant laboratory abnormality.

  Day -28 to Day 8

• Systemic exposure of the 4 analytes to be assayed

  If ≥ 1 subject meets/exceeds the exposure limits for any of YJ001 and its metabolites (YJ001-A, YJ001-B, and/or YJ001-C) or if subjects are expected to exceed the specific exposure limits for any analyte at a next planned dose level.

  Day 1 to Day 8

Study Arms (4)

Cohort 1 (6 active, 2 placebo)

EXPERIMENTAL

148 mg

Drug: YJ001 for Spray Use; Drug: Placebo of YJ001 for Spray Use

Cohort 2 (6 active, 2 placebo)

EXPERIMENTAL

296 mg

Drug: YJ001 for Spray Use; Drug: Placebo of YJ001 for Spray Use

Cohort 3 (6 active, 2 placebo)

EXPERIMENTAL

552 mg

Drug: YJ001 for Spray Use; Drug: Placebo of YJ001 for Spray Use

Cohort 4 (6 active, 2 placebo)

EXPERIMENTAL

828 mg

Drug: YJ001 for Spray Use; Drug: Placebo of YJ001 for Spray Use

Interventions

YJ001 for Spray Use DRUG

YJ001 (active ingredient)

Also known as: YJ001

Cohort 1 (6 active, 2 placebo); Cohort 2 (6 active, 2 placebo); Cohort 3 (6 active, 2 placebo); Cohort 4 (6 active, 2 placebo)

Placebo of YJ001 for Spray Use DRUG

Hydroxypropyl Methylcellulose

Also known as: Hydroxypropyl Methylcellulose

Cohort 1 (6 active, 2 placebo); Cohort 2 (6 active, 2 placebo); Cohort 3 (6 active, 2 placebo); Cohort 4 (6 active, 2 placebo)

Eligibility Criteria

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

You may qualify if:

• Male or female, between the ages of 18-55 years at screening, both inclusive.
• Subjects voluntarily consenting for participation in the study and have signed informed consent document. Subjects are required to understand verbal and/or written English or any other language in which a certified translation of the informed consent is available.
• The body weight of male and female should be ≥ 50.0 and ≥ 45.0 kg, respectively; have a body mass index (BMI) between 19.0 to 32.0 kg/m2 (both inclusive) at screening, calculated as weight (kg)/height2 (m2). Subjects must have two feet. Each foot must have five digits. Each foot must have at least total surface area of 450 cm2 measured from below the ankle to the toes including both dorsum and plantar areas.
• Medical history without any clinically significant pathology/surgery in the last 6 months.
• Resting supine blood pressure 90-140 (systolic)/60-90 (diastolic) mmHg, a resting pulse rate of 45-100 beats per minute at screening.
• Calculated creatinine clearance should be within the normal range using Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) Creatinine Based Equation1.
• Computerized 12-lead ECG recording without signs of clinically significant pathology or showing no clinically significant deviation as judged by the Investigator at screening and pre-dose.
• Subjects with either C-reactive protein of up to 3.0 mg/L or Hemoglobin A1C of up to 5.9%.
• Males must not to donate sperm until 90 days after last dose of study drug and must be willing to use a condom during heterosexual activity for up to 90 days after the application of the study drug.
• Females must be either postmenopausal for at least 1 year, surgically sterile (bilateral tubal ligation \[including clip, cauterization methods and coil\], bilateral oophorectomy or hysterectomy, and needs to be confirmed follicle stimulating hormone \[FSH\] level \>40 IU/L), or of childbearing potential either practicing true abstinence or practicing 2 effective means of contraception for 3 weeks prior to study drug administration, and until 28 days after study drug administration:
• Intrauterine device (IUD) or IUD hormone-releasing system.
• Combined estrogen and progestogen containing hormonal contraception (oral, intravaginal, or transdermal) associated with inhibition of ovulation.
• Progesterone-only hormonal contraception (oral, injectable, implantable) associated with inhibition of ovulation.
• Intrauterine hormone-releasing system.
• Double-barrier method (condoms, contraceptive sponge, diaphragm, or vaginal ring with spermicide).

You may not qualify if:

• Current participation in another investigational drug or device study or treated with an investigational drug within 30 days or 5 half-lives, whichever is longer, before dosing.
• History/evidence of clinically relevant pathology related to cardiovascular (CVS), central nervous system (CNS), respiratory tract, gastrointestinal (GI), endocrinology, immunology, hematology, or any other systemic disorder/major surgeries within the last 6 months that in the opinion of the Investigator would confound subject's participation and follow-up in the clinical trial.
• History of clinically significant drug, food allergy, skin allergy, or sensitivity to drugs of the same class (e.g., 5-aminosalicylic acid, sulfasalazine, and salicylates) or known hypersensitivity to YJ001 or any of its components.
• History of asthma. Adults with history of benign (resolved) childhood asthma may be included.
• Consumed more than 28 units of ethanol per week at any time in the 6 months before dosing (1 unit of ethanol is equivalent to 12 ounces of beer, 5 ounces of wine, or 1.5 ounces of spirits) or history of drug or alcohol abuse within the 6 months or evidence of such abuse as indicated by inquiry, medical history or the laboratory assays conducted during screening.
• Positive screening or check-in alcohol/drugs of abuse/cotinine screen.
• Positive test results for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at Screening. SARS-CoV-2 testing will be either NP or nasal swab PCR performed at Day -4, and in accordance with Centers for Disease Control and Prevention (CDC), FDA and local health authorities at the time of enrollment for this study. Participants not willing to comply with Pharmaron's COVID 19 policy.
• Female volunteers who are pregnant or lactating.
• Systemic or topical use of aspirin or salicylic acid containing products or sulfasalazine/salicylic acid derivatives within 14 days of study drug dosing.
• Use of other prescription and non-prescription medications (with the exception of oral contraceptives, combined estrogen and progestogen containing hormonal contraception and progestogen-only hormonal contraception), including nonsteroidal anti-inflammatory drugs, NSAIDs (i.e., ibuprofen), blood thinners, or sucralfate or herbal preparations within 14 days or 5 half-lives (whichever is longer) before study drug dosing, or use of an over-the-counter medication, vitamins, or supplements (including fish liver oils) within 14 days before study drug dosing.
• Any subject who has received any known hepatic or renal clearance (CLr) altering agents (e.g., erythromycin, cimetidine, barbiturates, phenothiazines, or herbal/plant-derived preparations such as St. John's Wort, etc.) for a period of 30 days prior to the dose of study medication.
• Positive screen on Hepatitis B, Hepatitis C, or Human immunodeficiency virus (HIV) at the time of screening evaluations.
• Unwilling to stay in the clinical unit for the required duration as per the protocol or consume the standard meal to be provided as per the protocol.
• History of blood donation of more than 500 mL in the last 2 months prior to screening.
• Consumption of xanthine containing food or beverages (like tea, coffee, chocolates, or cola drinks) 24 hours prior to dosing.

Sponsors & Collaborators

• Yuejia Pharmaceuticals (USA), Inc.: lead
• Zhejiang Yuejia Pharmaceuticals Co., Ltd.: collaborator

Study Sites (1)

Pharmaron CPC, Inc.

Baltimore, Maryland, 21201, United States

Location

MeSH Terms

Interventions

Hypromellose Derivatives

Intervention Hierarchy (Ancestors)

Cellulose; Glucans; Biopolymers; Polymers; Macromolecular Substances; Polysaccharides; Carbohydrates; Biomedical and Dental Materials; Manufactured Materials; Technology, Industry, and Agriculture

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double-blinded with regard to the study treatment that subjects receive, without the Investigator, the Sponsor, or the subjects being aware of whether YJ001 or the placebo is administered. All decisions concerning dose escalation will be made in a blinded manner by the safety review committee (SRC).
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 28, 2022
• First Posted: July 11, 2022
• Study Start: August 15, 2022
• Primary Completion: December 20, 2022
• Study Completion: December 20, 2022
• Last Updated: January 4, 2023

Record last verified: 2023-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)