Safety, Tolerability, and Pharmacokinetics of MCAM in Healthy Adult Participants

Официальное название

A Phase 1, First-In-Human, Placebo-Controlled Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Single Ascending Doses of MCAM in Randomized Healthy Adult Participants (Double-Blind)

Обзор

The goal of this clinical trial is to test the safety and to see if there are any side effects of the investigational drug, MCAM. The main aim is to measure blood levels of the study drug after oral administration. Researchers will compare the active study drug to a placebo to test for any differences between the two groups. Participants will be screened for up to 28 days before starting study treatment. Following the screening visit, participants will be admitted to a clinic for 4 days for treatment with either the study drug or placebo. They will attend a follow-up visit on Days 5 and 7 and participate in a follow-up phone call on Day 8. Three different doses will be tested to find the highest safe dose.

Подробное описание

A Single ascending dose (SAD) will be administered to evaluate safety, tolerability and pharmacokinetics (PK) of MCAM.

MCAM will be dosed orally to healthy adult participants at one of 3 dose levels: 3, 10, or 30 mg or a matching placebo.

Вмешательства

• Другое Placebo
  A 1% methylcellulose solution will be dosed orally using an amber syringe to maintain blinding.
• Препарат MCAM
  MCAM will be dosed orally as a 3, 10, or 30 mg suspension in an amber syringe to maintain blinding.

Первичные конечные точки

• Single Ascending Dose (SAD): Cmax [Срок оценки: Baseline to 96 hours]
• SAD: Tmax [Срок оценки: Baseline to 96 hours]
• SAD: T1/2 [Срок оценки: Baseline to 96 hours]
• SAD: Area under the curve from 0-24 hours [Срок оценки: Baseline to 96 hours]
• SAD: Area under the curve from 0-t [Срок оценки: Baseline to 96 hours]
• SAD: Area under the curve from 0-infinity [Срок оценки: Baseline to 96 hours]

Критерии участия

Критерии включения

• Is willing and able to provide informed consent and comply with all protocol requirements
• Is aged ≥18 years and ≤55 years at time of informed consent
• Has a body mass index (BMI) between 18.0 and 32.0 kg/m2 and body weight (BW) not lower than 50 kg
• Participant is a nonsmoker (for at least 3 months prior to Screening) and does not use tobacco-containing products (including but not limited to cigarettes, pipes, cigars, chewing tobacco, or nicotine patch or gum)
• Has Blood pressure (BP) and Heart rate (HR) within the normal range at the Screening visit after 5 minutes in a seated position:

• Systolic BP between 90 and 145 mmHg
• Diastolic BP between 60 and 90 mmHg
• HR between 60 and 90 beats per minute
• Electrocardiogram (ECG) is normal based on 12-lead ECG assessment at Screening:

• ECG PR interval between 120 and 200 ms
• ECG QRS interval <100 ms
• ECG QT interval (corrected) (QTc) with Fridericia formula (QTcF) <450 ms and no history of additional risk factors for Torsades de pointes (TdP)
• No sign of any sinus node dysfunction
• Has clinical laboratory parameters (hematology \[including coagulation\], clinical chemistry, and urinalysis) within normal ranges. Individual values out of the normal range may be acceptable if judged clinically insignificant by an Investigator.
• Has not been dosed in an interventional clinical drug trial within 30 days prior to screening or within 5 half-lives of the last dose of study drug, whichever is longer.
• If female, participants who are not of childbearing potential should be surgically sterile (e.g., have undergone hysterectomy, bilateral oophorectomy, bilateral salpingectomy, or tubal ligation/occlusion) or in a post-menopausal state (at least one year without menses). Female participants of childbearing potential will use a highly effective (i.e., failure rate of <1%) method of contraception throughout the study and for at least five half-lives following MCAM dosing. Methods of contraception that are considered to be highly effective with a failure rate of <1% that are appropriate for this study include the following: a) intrauterine device (IUD)/intrauterine system (IUS); b) implantable rod; c) bilateral tubal occlusion; d) complete abstinence from sexual intercourse; and e) infertile male partner (e.g., vasectomized \[with documented evidence of azoospermia\], permanently sterile following bilateral orchidectomy, or any other documented cause of infertility).
• If female, must have a negative serum or urine pregnancy test at Screening and a negative serum or urine test at Admission (day 1)
• Male participants who report surgical sterilization will be required to confirm sterility by post-vasectomy semen analysis (PVSA). Participants in whom PVSA confirmation cannot be obtained will be required to use a double-barrier method (e.g., condom with spermicide), same as for the rest of the male participants, or agree to remain abstinent from heterosexual intercourse at the time of Screening, during the study, and for at least five half-lives following MCAM dosing.
• If male, participants must agree not to donate sperm for the duration of the study and for 90 days after the last dose of study drug.

Критерии исключения

• Any significant acute or chronic medical illness
• Any history of cancer within 5 years of enrollment, with the exception of fully resected skin basal cell carcinoma
• Any major hospitalization or surgery 3 months prior to study drug administration
• Has donated or experienced a blood loss of 500 mL or more within 56 days prior to Screening or has donated plasma within 7 days prior to Screening
• Poor venous access assessed at Screening
• Has ever participated or plans to participate in a substance or alcohol rehabilitation program to treat their substance or alcohol dependence. If participation in a rehabilitation program was court-mandated as part of a plea agreement, entry may be permissible at an Investigator's discretion
• Any history of substance use disorder) as defined in the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5; e.g. a score of ≥2, within a 12-month period) or recent use of an opioid-containing product (e.g., codeine) within 6 months prior to study drug administration
• History of, or currently diagnosed with, any clinically significant psychiatric disorder (based on the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition \[DSM-5\] and Mini International Neuropsychiatric Interview \[MINI\] criteria), which in the opinion of an Investigator could interfere with study participation or study data collection
• History of any suicidal ideation within the past 6 months or a lifetime history of suicidal behavior, as assessed by the Columbia-Suicide Severity Rating Scale (C-SSRS)
• Any neurological, renal, cardiac, hepatic, or other medical condition that could interfere with study assessments as determined by and Investigator, or Sponsor
• Any significant illness or infection, as determined by an Investigator or Sponsor, within the prior 30 days
• Positive urine alcohol or urine drug screen for substance of abuse at Screening
• Must not be physically dependent on opioids, as demonstrated by successful completion of the naloxone challenge
• Known hypersensitivity to any component of the MCAM drug product, naloxone, or placebo
• Use of any prescription or over-the-counter medications (such as antacids, vitamins, minerals, dietary/herbal preparations, St. John's Wort, and nutritional supplements) within 14 days prior to Screening or 5 half-lives prior to the study
• Positive screen for hepatitis B surface antigen (HBsAg), Hepatitis C (HCV) antibody, or HIV-1 and HIV-2 antibodies
• Have a procedure planned that would require the use of opioids for pain management within at least 2 weeks after the conclusion of the study (participants may be resistant to opioids for two weeks or longer after study participation)
• Is likely, in the opinion of an Investigator, to be non-compliant or uncooperative with study procedures for any reason
• If female, are pregnant, nursing, or planning to become pregnant during the study

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Да

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Двойное слепое

Основная цель

Фундаментальное исследование

Центры проведения

США · 1 центр

• Dr. Vince Clinical Research — Overland Park

Идентификаторы

NCT: NCT07602335 · UTHSCSA-MCAM-101 · U01DA060704

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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