A Study of Single and Multiple Ascending Doses of H021 in Healthy Participants

Официальное название

A Phase 1, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Single and Multiple Ascending Doses of H021 in Healthy Participants

Обзор

The primary purpose of this study is to evaluate the safety and tolerability of H021 tablets following oral administration of single and multiple ascending doses in healthy participants.

Подробное описание

This is a single center, Phase 1, randomized, double-blind, placebo controlled, sequential single ascending dose/multiple ascending dose (SAD/MAD) study, with a food-effect arm. The study will be divided into two parts:

* SAD cohorts, with food-effect evaluation * MAD cohorts The two parts will be completed sequentially but with partial overlapping. The MAD phase can start once safety, tolerability, and pharmacokinetic data from the SAD phase show that single doses of at least 25 mg are acceptable. If the 25 mg dose will be not reached in the SAD phase, the Safety Review Committee (SRC) will set a new starting dose.

Вмешательства

• Препарат H021
  H021 oral tablet.
• Препарат H021 Placebo
  H021 placebo oral tablet.

Первичные конечные точки

• Number of Participants with Adverse Events (AEs) [Срок оценки: Up to final follow-up (SAD Part: up to 8 days: MAD Part: up to 14 days)]

Вторичные конечные точки (12)

• SAD Part: Area under the concentration-time curve from time zero until the last observed concentration (AUC0-t) of H021 [Срок оценки: pre-dose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, and 48 hours post-dose]
• SAD Part: Area under the concentration-time curve from time zero to infinity (AUC0-infinity) of H021 [Срок оценки: pre-dose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, and 48 hours post-dose]
• SAD Part: Maximal observed concentration (Cmax) of H021 [Срок оценки: pre-dose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, and 48 hours post-dose]
• SAD Part: Time to Reach Cmax (Tmax) of H021 [Срок оценки: pre-dose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, and 48 hours post-dose]
• SAD Part: Lag Time (Tlag) of H021 [Срок оценки: pre-dose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, and 48 hours post-dose]
• SAD Part: Residual area of H021 [Срок оценки: pre-dose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24), and 48 hours post-dose]
• SAD Part: Terminal elimination half-life (T1/2 el) of H021 [Срок оценки: pre-dose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, and 48 hours post-dose]
• SAD Part: Terminal elimination rate constant (Kel) of H021 [Срок оценки: pre-dose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, and 48 hours post-dose]
• SAD Part: Apparent clearance (CL/F) of H021 [Срок оценки: pre-dose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, and 48 hours post-dose]
• SAD Part: Apparent volume of distribution (Vz/F) of H021 [Срок оценки: pre-dose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, and 48 hours post-dose]
• SAD Part: Cumulative Urinary Excretion From Time Zero to Time t (Ae0-t) of H021 [Срок оценки: pre-dose (spot; within 2 hours) and 0-4, 4-8, 8-12, 12-24, and 24-48 hours post-dose]
• SAD Part: Maximal Rate of Urinary Excretion (Rmax) of H021 [Срок оценки: pre-dose (spot; within 2 hours) and 0-4, 4-8, 8-12, 12-24, and 24-48 hours post-dose]

Критерии участия

Критерии включения

• Male or female, non-smoker (no use of tobacco or nicotine products within 3 months prior to screening), greater than and equal to (>=) 18 and less than and equal to (<=) 55 years of age, with body mass index (BMI) greater than (>)18.5 and less than (<) 32.0 kilograms per square meter (kg/m\^2).
• Healthy as defined by:

• the absence of clinically significant illness and surgery within 4 weeks prior to study drug administration.
• the absence of clinically significant history of neurological, endocrine, cardiovascular, respiratory, hematological, immunological, psychiatric, gastrointestinal, renal, hepatic, and metabolic disease.
• Female participants of non-childbearing potential must be:

• post-menopausal (spontaneous amenorrhea for at least 12 months prior to dosing) with confirmation by documented follicle-stimulating hormone (FSH) levels >=40 milli-international units per milliliter (mIU/mL); or
• surgically sterile (bilateral oophorectomy, bilateral salpingectomy, hysterectomy, or bilateral tubal occlusion) at least 3 months prior to dosing.
• Participants must be willing not to donate sperm for 90 days or ova (egg) for 6 months after the last dose.
• Sexually active females of childbearing potential and non-sterile males must be willing to use an acceptable contraceptive method throughout the study.
• Able to understand the study procedures and provide signed informed consent to participate in the study.

Критерии исключения

• Any clinically significant abnormal finding at physical examination.
• Clinically significant abnormal laboratory test results including biochemistry, hematology, urinalysis, and coagulation results, or positive serology test results for hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibody, or human immunodeficiency virus (HIV) antigen and antibody, or QuantiFERON®-TB test at screening.
• Positive pregnancy test or lactating female participant.
• Positive urine drug screen, urine cotinine test, or alcohol breath test at screening or Day -1.
• History of significant allergic reactions (example, anaphylactic reaction, hypersensitivity, angioedema) to any drug.
• Clinically significant ECG abnormalities or vital signs abnormalities (systolic blood pressure lower than 90 or over 140 millimetres of mercury (mmHg), diastolic blood pressure lower than 40 or over 90 mmHg, heart rate less than 40 or over 100 beats per minute (bpm), respiratory rate less than 10 or over 22 bpm), or oxygen saturation less than 95 percent (%) oxygen at screening.
• History of drug abuse within 1 year prior to screening as determined by the investigator.
• History of alcohol abuse within 1 year prior to screening or regular use of alcohol within 1 month prior to screening that exceeds 10 units of alcohol per week for women and men (1 unit = 375 \[milliliter\] mL of beer 3.5%, 100 mL of wine 13.5%, or 30 mL of distilled alcohol 40%).
• History of active tuberculosis or presence of active or latent tuberculosis. Previous latent tuberculosis that has been treated and is no longer active is not exclusionary.
• History of clinically significant opportunistic infection (example, invasive candidiasis or pneumocystis pneumonia).
• History of serious local infection (example, cellulitis, abscess) or systemic infection (example, septicemia) within 3 months prior to screening.
• Presence of fever (body temperature greater than (>) 37.5 degrees Celsius (°C) (example, a fever associated with a symptomatic viral or bacterial infection) within 2 weeks prior to dosing.
• Use of medications within the timeframes specified.
• Participation in a clinical research study involving the administration of an investigational or marketed drug or device within 30 days prior to the first dosing, administration of a biological product in the context of a clinical research study within 90 days prior to the first dosing, or simultaneous participation in an investigational study involving no drug or device administration.
• Donation of plasma within 7 days prior to dosing or donation or loss of 500 mL or more of whole blood within 8 weeks prior to dosing.
• Any reason which, in the opinion of the Investigator, would prevent the participant from participating in 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

Тройное слепое

Основная цель

Лечение

Центры проведения

Австралия · 1 центр

• Nucleus Network Ply Ltd. — Melbourne

Идентификаторы

NCT: NCT06627556 · KFP-2024-H021-HW-101

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗