Clinical trial NCT06155487: A Study to Investigate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics After Oral Administration of AJH-2947 in Healthy Korean and/or Caucasian Adult Male Subjects
Official title: A Randomized, Double-blind, Placebo-controlled, Single and Multiple Ascending Dose, Phase 1 Clinical Trial to Evaluate Pharmacokinetics, Pharmacodynamics, Safety and Tolerability After Oral Administration of AJH-2947 in Healthy Korean or Caucasian Male Subjects
Study type: INTERVENTIONAL
Overall status: ENROLLING_BY_INVITATION
Phase: PHASE1
Conditions: Neuropathic Pain
Diabetic Neuropathies
Post Herpetic Neuralgia
Keywords: Neuropathic Pain
TRPV1 antagonist
Phase 1
Lead sponsor: JMackem Co., Ltd
Sponsor class: INDUSTRY
Collaborators: name: Seoul National University Hospital
First posted: 2023-12-04
Enrollment: 68
Sex: MALE
Minimum age (years): 19
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: A randomized, double-blind, placebo-controlled, single and multiple ascending dose
Primary purpose: TREATMENT

Brief summary: Preliminary evaluate of pharmacokinetics, pharmacodynamics, safety and tolerability after oral administration of AJH-2947 in healthy Korean or Caucasian male subjects


Eligibility criteria: Inclusion Criteria:

1. Healthy Korean or Caucasian adult males aged 19 to 55 years old, based on the date of written consent

   \*Caucasian subjects = Individuals born in Europe, have resided in countries outside Europe for less than 10 years, and whose parents and grandparents are all of European descent.
2. Individuals with a body weight between 50.0 kg and 90.0 kg and a body mass index (BMI) ranging from 18.5 kg/m2 to less than 30.0 kg/m2

   - BMI (kg/m2) = weight (kg) / {height (m)}2
3. Individuals who agree to stay in the CTC ward until discharge and consent to the use of sunscreen until the end of the clinical trial (PSV)
4. Individuals who have heard a detailed explanation of the trial, fully understand it, voluntarily decide to participate, and provide written consent before the screening examination
5. Individuals deemed suitable by the investigator based on medical history, vital signs, 12-lead electrocardiogram (ECG), physical examination, and clinical laboratory tests performed during the screening.

Exclusion Criteria:

1. Individuals with clinically significant diseases or a history of diseases related to the liver, kidney, nervous system, immune system, respiratory system, digestive system, endocrine system, blood/tumors, cardiovascular system, urinary system, mental disorders, etc.
2. In the multiple-dose trial, individuals with skin lesions, tattoos on both forearms or show hypersensitivity or allergic reactions to capsaicin cream who may affect the pharmacodynamic evaluation of the investigational product.
3. Individuals with gastrointestinal diseases (such as gastrointestinal ulcers, gastritis, gastric spasm, gastroesophageal reflux disease, and Crohn's disease) or a history of surgery that may affect the safety and pharmacokinetic evaluation of the investigational product (excluding simple appendectomy and hernia repair)
4. Individuals with a medical history of hypersensitivity reactions to the main active ingredient or components of the investigational product or to drugs in the same class as the main active ingredient
5. Individuals with positive results for hepatitis B (HBV) test, hepatitis C (HCV) test, syphilis (RPR) test, or HIV test conducted during screening
6. Individuals who exhibited systolic blood pressure \< 80 mmHg or ≥ 140 mmHg or diastolic blood pressure \< 45 mmHg or ≥ 90 mmHg during vital sign measurements in the supine position after a rest period of at least three minutes
7. Individuals with a history of drug abuse or who tested positive for drug abuse in the urine drug screening test
8. Individuals who have taken prescription drugs or traditional herbal medicine within 2 weeks before the scheduled first dose of the investigational product or have taken any over-the-counter medicines, health-functional foods, or vitamin supplements within 1 week, or are expected to take them
9. Individuals who have participated in another clinical trial (including bioequivalence studies) within 6 months before the scheduled first dose of the investigational product
10. Individuals who donated blood within 2 months or donated blood components within 1 month, or received a blood transfusion within 1 month before the scheduled first dose of the investigational product
11. Individuals who have consumed excessive caffeine (\> 5 units/day) or cannot abstain from consuming caffeine/caffeine-containing foods (such as coffee, tea, carbonated beverages, coffee-flavored milk, energy drinks, etc.) from 3 days before the expected first dose until the end of the clinical trial (PSV)
12. Individuals who engage in persistent alcohol consumption (\> 21 units/week, 1 unit = 10 g of pure alcohol) or cannot abstain from alcohol consumption from 3 days before the expected first dose of the investigational product until the end of the clinical trial (PSV) (1 glass (250 mL) of beer (5%) = 10 g, 1 glass (50 mL) of soju (20%) = 8 g, 1 glass (125 mL) of wine (12%) = 12 g)
13. Individuals who have smoked more than 10 cigarettes/day within the last 3 months before the scheduled first dose of the investigational product or cannot quit smoking from the screening day until the end of the clinical trial (PSV)
14. Individuals who cannot refrain from consuming grapefruit-containing foods from 3 days before the expected first dose of the investigational product until the end of the clinical trial (PSV)
15. Individuals who have a pregnancy planning during the entire clinical trial and up to 90 days after the last administration of the investigational product or do not agree to use one or more medically acceptable contraceptive methods. The medically acceptable contraceptive methods are as follows:

    ① Use of an intrauterine device with a proven failure rate by the spouse (or partner)

    ② Concurrent use of barrier contraception (male or female) and oral contraceptive pills

    ③ Self or partner's surgical sterilization (vasectomy, salpingectomy / tubal ligation, hysterectomy)
16. Individuals deemed ineligible for participation in the clinical trial by the investigator based on other reasons, including results of clinical laboratory tests

Primary outcomes:
measure: Part A (SAD): Plasma concentrations of AJH-2947
timeFrame: Day 1 to Day 5
measure: Part A (SAD): Urine concentrations of AJH-2947
timeFrame: Day 1 to Day 4
measure: Part A (SAD): Maximum observed concentration [Cmax]
timeFrame: Day 1 to Day 5
measure: Part A (SAD): Area under concentration curve from time 0 to the last quantifiable concentration [AUClast]
timeFrame: Day 1 to Day 5
measure: Part A (SAD): Time to reach peak or maximum observed concentration [Tmax]
timeFrame: Day 1 to Day 5
measure: Part B (MAD): Plasma concentrations of AJH-2947
timeFrame: Day 1 to Day 18
measure: Part B (MAD): Maximum observed concentration [Cmax]
timeFrame: Day 1 to Day 18
measure: Part B (MAD): The partial area from dosing time to dosing time plus dosing interval [AUCτ]
timeFrame: Day 1 to Day 18
measure: Part B (MAD): Time of maximum observed concentration [Tmax]
timeFrame: Day 1 to Day 18
measure: Part B (MAD): Maximum observed concentration occurring at time Tmax,ss [Cmax,ss]
timeFrame: Day 1 to Day 18
measure: Part B (MAD): At steady state, the partial area from dosing time to dosing time plus dosing interval [AUCτ,ss]
timeFrame: Day 1 to Day 18
measure: Part B (MAD): Heat pain Threshold (The temperature at which the subject first perceives pain, ℃)
timeFrame: Predose, Day 1, Day 7, and Day 8
measure: Part B (MAD): Heat pain tolerance (The Maximum temperature that the subject can tolerate, ℃)
timeFrame: Predose, Day 1, Day 7, and Day 8
Secondary outcomes:
measure: Part A (SAD): Number of participants with adverse events (AE)
timeFrame: Day -1, Day 1 to day 12 (last visit)
measure: Part A (SAD): Number of participants with serious adverse events (SAE)
timeFrame: Day -1, Day 1 to day 18 (last visit)
measure: Part B (MAD): Number of participants with AE
timeFrame: Day -1, Day 1 to day 18 (last visit)
measure: Part B (MAD): Number of participants with SAE
timeFrame: Day -1, Day 1 to day 18 (last visit)
Other outcomes:
Locations:
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
Study officials:
affiliation: Seoul National University Clinical Trials Center
name: Seung-Hwan Lee, MD. Ph.D
role: PRINCIPAL_INVESTIGATOR
References: