Chronic Pain Syndrome, Healthy Volunteers
Conditions
Keywords
Neuropathic Pain, TRPV1 antagonist, Phase 1
Brief summary
The purpose of this randomized, double-blind, placebo-controlled Phase 1 study was to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of single and multiple oral doses of AJH-2947 in healthy Korean or Caucasian adult male participants.
Interventions
DRUGAJH-2947 tablets or placebo
Administration: Oral
Sponsors
Seoul National University Hospital
JMackem Co., Ltd
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Double-blind
Intervention model description
Randomized, double-blind, placebo-controlled, sequential single- and multiple-ascending-dose cohorts.
Eligibility
Sex/Gender
MALE
Age
19 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
Healthy Korean or Caucasian adult males aged 19 to 55 years at the time of written informed consent. Caucasian participants were defined as individuals born in Europe who had resided outside Europe for less than 10 years and whose parents and grandparents were all of European descent. Body weight between 50.0 kg and 90.0 kg and body mass index (BMI) from 18.5 kg/m² to less than 30.0 kg/m². Willingness to remain in the Clinical Trial Center (CTC) until discharge and to use sunscreen until the end of the study, including the post-study visit (PSV). Ability to understand the study after receiving a detailed explanation, voluntary agreement to participate, and provision of written informed consent before any screening examination. Considered suitable for participation by the investigator based on medical history, vital signs, 12-lead electrocardiogram (ECG), physical examination, and clinical laboratory test results obtained during screening.
Exclusion criteria
Clinically significant disease or a history of disease involving the liver, kidney, nervous system, immune system, respiratory system, digestive system, endocrine system, hematologic system, cardiovascular system, urinary system, psychiatric system, or other clinically relevant body system. For the multiple-dose trial, skin lesions or tattoos on both forearms, or hypersensitivity or allergic reactions to capsaicin cream that could affect pharmacodynamic evaluation. Gastrointestinal disease, including gastrointestinal ulcer, gastritis, gastric spasm, gastroesophageal reflux disease, or Crohn's disease, or a history of surgery that could affect the safety or pharmacokinetic evaluation of the investigational product, except for simple appendectomy or hernia repair. History of hypersensitivity to the active ingredient or other components of the investigational product, or to drugs of the same class. Positive screening result for hepatitis B virus (HBV), hepatitis C virus (HCV), syphilis (RPR), or human immunodeficiency virus (HIV). Supine systolic blood pressure below 80 mmHg or at least 140 mmHg, or diastolic blood pressure below 45 mmHg or at least 90 mmHg, measured after at least 3 minutes of rest. History of drug abuse or a positive urine drug screening result. Use of prescription medication or traditional herbal medicine within 2 weeks before the scheduled first dose, or use of over-the-counter medication, health-functional food, or vitamin supplements within 1 week before the scheduled first dose, or anticipated use of any such product during the study. Participation in another clinical trial, including a bioequivalence study, within 6 months before the scheduled first dose. Donation of whole blood within 2 months, donation of blood components within 1 month, or receipt of a blood transfusion within 1 month before the scheduled first dose. Excessive caffeine consumption of more than 5 units per day or inability to abstain from caffeine or caffeine-containing foods and beverages from 3 days before the expected first dose until the end of the study, including the PSV. Persistent alcohol consumption of more than 21 units per week, with 1 unit defined as 10 g of pure alcohol, or inability to abstain from alcohol from 3 days before the expected first dose until the end of the study, including the PSV. Smoking more than 10 cigarettes per day within the 3 months before the scheduled first dose or inability to stop smoking from screening until the end of the study, including the PSV. Inability to refrain from consuming grapefruit-containing foods from 3 days before the expected first dose until the end of the study, including the PSV. Planning a pregnancy during the study or within 90 days after the last administration of the investigational product, or unwillingness to use at least one medically acceptable contraceptive method. Acceptable methods included use of an intrauterine device with a proven failure rate by the participant's spouse or partner; concurrent use of barrier contraception and oral contraceptive pills; or surgical sterilization of the participant or partner, including vasectomy, salpingectomy, tubal ligation, or hysterectomy. Considered unsuitable for participation by the investigator for any other reason, including clinical laboratory test results.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part A (SAD): Maximum observed plasma concentration (Cmax) | Day 1 to Day 7 | To characterize the Cmax of AJH-2947 following a single oral dose under fed or fasted conditions. |
| Part A (SAD): Area under the concentration-time curve to the last quantifiable concentration (AUClast) | Day 1 to Day 7 | To characterize the AUClast of AJH-2947 following a single oral dose under fed or fasted conditions. |
| Part A (SAD): Area under the concentration-time curve extrapolated to infinity (AUCinf) | Day 1 to Day 7 | To characterize the AUCinf of AJH-2947 following a single oral dose under fed or fasted conditions. |
| Part B (MAD): Maximum observed plasma concentration following the first dose (Cmax) | Day 1 to Day 2 | To characterize the maximum observed plasma concentration (Cmax) of AJH-2947 following the first dose. |
| Part B (MAD): Area under the concentration-time curve over the dosing interval following the first dose (AUCtau) | Day 1 to Day 2 | To characterize the area under the plasma concentration-time curve over the dosing interval following the first oral dose (AUCtau) of AJH-2947. |
| Part B (MAD): Maximum observed plasma concentration at steady state (Cmax,ss) | Day 7 to Day 8 | To characterize the maximum observed plasma concentration at steady state (Cmax,ss) of AJH-2947 following once-daily oral administration for 7 consecutive days. |
| Part B (MAD): Area under the concentration-time curve over the dosing interval at steady state (AUCtau,ss) | Day 7 to Day 8 | To characterize the area under the plasma concentration-time curve over the dosing interval at steady state (AUCtau,ss) of AJH-2947 following once-daily oral administration for 7 consecutive days. |
| Number of participants with AEs, SAEs, and clinically significant safety findings | From signing informed consent through the post-study visit (up to Day 18) | To assess safety and tolerability based on adverse events, vital signs, 12-lead ECGs, clinical laboratory tests, and physical examinations. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part B (MAD): Heat pain threshold | Predose (Day -1), Day 1, and Day 7 | Heat pain threshold was defined as the temperature at which the participant first perceived pain during thermal stimulation of non-sensitized and capsaicin-sensitized skin. The cutoff temperature was 50°C. |
| Part B (MAD): Heat pain tolerance | Predose (Day -1), Day 1, and Day 7 | Heat pain tolerance was defined as the maximum temperature that the participant could tolerate during thermal stimulation of non-sensitized and capsaicin-sensitized skin. The cutoff temperature was 50°C. |
Countries
South Korea
Contacts
PRINCIPAL_INVESTIGATORSeung-Hwan Lee, MD. Ph.D
Seoul National University Clinical Trials Center
Outcome results
None listed