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

Official title

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

Overview

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.

Detailed description

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.

Interventions

• Drug H021
  H021 oral tablet.
• Drug H021 Placebo
  H021 placebo oral tablet.

Primary outcome measures

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

Secondary outcome measures (12)

• SAD Part: Area under the concentration-time curve from time zero until the last observed concentration (AUC0-t) of H021 [Time frame: 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 [Time frame: 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 [Time frame: 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 [Time frame: 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 [Time frame: 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 [Time frame: 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 [Time frame: 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 [Time frame: 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 [Time frame: 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 [Time frame: 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 [Time frame: 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 [Time frame: pre-dose (spot; within 2 hours) and 0-4, 4-8, 8-12, 12-24, and 24-48 hours post-dose]

Eligibility criteria

Inclusion criteria

• 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.

Exclusion criteria

• 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Triple blind

Primary purpose

Treatment

Study locations

Australia · 1 center

• Nucleus Network Ply Ltd. — Melbourne

Identifiers

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

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗