A Study of NHL907 in Healthy Adult Participants

Официальное название

A Randomized, Double-Blind, Placebo-Controlled, Multiple Ascending Dose Study to Assess Safety, Tolerability, and Pharmacokinetics of NHL907 Combination Drug Following Multiple Oral Doses in Healthy Adult Participants

Обзор

The goal of this study is to evaluate the safety, tolerability and pharmacokinetics of NHL907 when administered as multiple oral doses in healthy adult participants.

Вмешательства

• Препарат NHL907
  Investigational product NHL907
• Препарат Placebo
  NHL907 matching placebo

Первичные конечные точки

• Number of Participants with Treatment Emergent Adverse Events [Срок оценки: Baseline to 7 days after the last dose (Day 14)]

Вторичные конечные точки (12)

• Cmax: Maximum observed plasma concentration [Срок оценки: Day 1, Day 7]
• Tmax: Time of occurrence of Cmax [Срок оценки: Day 1, Day 7]
• AUC0-24: Area under the concentration-time curve from 0 to 24 hours [Срок оценки: Day 1, Day 7]
• AUC0-inf: Area under the concentration-time curve from 0 to infinity [Срок оценки: Day 1, Day 7]
• Cmax/dose: Cmax normalized by dose [Срок оценки: Day 1, Day 7]
• CL/F: Apparent total clearance [Срок оценки: Day 1, Day 7]
• Vz/F: Apparent volume of distribution [Срок оценки: Day 1, Day 7]
• AUC0-24/dose: AUC0-24 normalized by dose [Срок оценки: Day 1, Day 7]
• AUC0-inf/dose: AUC0-inf normalized by dose [Срок оценки: Day 1, Day 7]
• t1/2: Apparent terminal elimination half-life [Срок оценки: Day 1, Day 7]
• Ctrough: Trough plasma concentration [Срок оценки: Day 4-7]
• RA Cmax: Observed accumulation ratio based on Cmax [Срок оценки: Day 7 to Day 1]

Критерии участия

Критерии включения

• Healthy adult male and female participants aged between 18 and 60 years of age, inclusive.
• Has a body mass index (BMI) between ≥ 18 and ≤ 32 kg/m2 inclusive, with body weight ≥ 50 kg at Screening.
• Able and willing to understand and sign the informed consent form, communicate meaningfully with study personnel, and comply with all study restrictions, procedures, laboratory tests, and other study requirements.
• In good health, determined by the Investigator on the basis of medical history, physical examination, vital signs, Screening laboratory results, Screening ECG, and mental status.
• Participants of non-childbearing potential should be congenitally or surgically sterile or in a menopausal state as confirmed by follicle-stimulating hormone (FSH) concentrations (≥ 40 IU/L at Screening).
• Female participants with childbearing potential must agree to use accepted contraceptive regimens from time of Screening, during the study, and for at least 60 days after end of study.
• Male participants with the potential to father a child must agree to abstain from sperm donation and to use accepted contraceptive regimens from Screening, during the study, and for at least 90 days after end of study.
• Participants should agree to refrain from donating blood for at least 30 days after end of study.

Критерии исключения

If an individual meets any of the following criteria, they will be ineligible for this study:

• History or evidence of clinically significant disorders and deemed not suitable to participants in the study by the Principal Investigator or delegate.
• History or presence of any gastrointestinal (GI) disease (except for Gilbert's syndrome or cholecystectomy) or condition that could compromise the participant safety and/or absorption of the study drug, including irritable bowel disease, known untreated helicobacter pylori infection, abnormal gastric emptying, dyspepsia, GI ulcers, GI bleeding, or GI surgeries within 6 months before Screening.
• Have a known hypersensitivity to any component of the IP formulation or related derivatives of each component.
• Have abnormalities in resting vital signs at Screening, on Day -1, or on Day 1 prior to dosing.
• History of or ongoing cardiac abnormalities as assessed during Screening, including abnormal and clinically relevant ECG changes, considered by the Investigator.
• History of smoking in the past 90 days before Screening which is defined as more than the equivalent of 5 cigarettes weekly (including alternative nicotine products such as cigars, e-cigarettes, chewing tobacco, etc.); and /or have a positive urine test for cotinine at Screening or Baseline, or unable to abstain from smoking starting from at least 3 days before Screening, or Day -1 / check-in until end of study.
• History of illicit or prescription drug abuse or addiction within 1 year of Screening, or positive urine drug screen at Screening or Baseline. Participants who used a THC / CBD product within 30 days before Screening and added a deterrent from any use before that are excluded.
• History of alcohol abuse (unless fully recovered with no use of alcohol within the 12 months prior to Screening), which is defined as exceeding an average weekly intake of 21 standard drinks for males or 14 standard drinks for females (1 standard drink is equivalent to 5 ounces \[150 mL\] of wine or 12 ounces \[360 mL\] of beer or 1.5 ounces \[45 mL\] of hard liquor); or positive alcohol breath test at Screening or Baseline; incapable to refrain from consuming alcohol starting from at least 48 h prior to Day 1 / check-in until end of study.
• Has participated in any interventional trial or drug investigation or device investigation (including placebo) within 30 days, or 5 half-lives of the IP, whichever is longer, prior to Screening or has the intention to participate in another trial during the present study.
• Have received vaccines within 14 days and within 60 days for live-attenuated vaccines before screening.
• Have any medical condition(s) screened by the Investigator and determined to be ineligible or have any acute illness within 7 days prior to Day 1 will be excluded or may be considered for the next cohort if still within their screening window.
• Have clinical safety laboratory parameters at Screening (serum chemistry and lipid panel, hematology, coagulation, and urinalysis) that are outside the normal limits and are considered clinically significant in the opinion of the Investigator and the Sponsor's MM (e.g., LFTs / bilirubin ≥ 1.5 ULN and eGFR ≤ 60 ml/min/1.73 m2). Participants with elevated unconjugated bilirubin (Gilbert's syndrome) are not excluded.
• History of suicidal ideations or suicide attempts, including current instances of either case or any "yes" response to C-SSRS at screening.
• The participant is pregnant, lactating, or planning to become pregnant within 6 months of being discharged from the trial.
• Use of any prescription medicine within 2 weeks, or over the counter (OTC) medicine, herbal remedy, or nutritional supplement, or within 5 half-lives of any drugs, whichever is longer prior to dosing, except for vitamins and occasional use of paracetamol / acetaminophen (≤ 2 g/day; no more than 3 consecutive days) which will be reviewed by the PI and the Sponsor's MM for determination of acceptability.
• Have undergone surgery within 90 days before Screening, or have surgery planned during the study period or within 90 days after the last dose or has previously undergone any surgery that may affect drug absorption, distribution, metabolism, or excretion during the study.
• Blood donation or loss of ≥ 450 mL of blood within 90 days before dosing or receiving a blood transfusion within 90 days before dosing. Platelet/Plasma donation is prohibited within 30 days before Screening and until at least 30 days after study completion.
• Positive hepatitis B virus (HBsAg), hepatitis B core antibody (HBcAb), hepatitis C virus (HCV-Ab), human immunodeficiency virus (HIV-1 and HIV-2), or syphilis at Screening.
• History of malignancy, with the exception of non-melanoma skin cancer or curatively treated cancer that has not been in full remission for ≥ 5 years, without evidence of recurrence.
• Have any special dietary requirements that may include CYP2D6 inhibitors, e.g., grapefruit, bitter citrus products, tonic water, or any other requirement that would prevent compliance with study standardized meals.
• History of dysphagia or difficulty swallowing tablets / capsules.
• Unable or unwilling to comply with the lifestyle guidelines and evaluations detailed in this protocol, for the duration of the study or have a situation or condition that, in the opinion of the Investigator, may interfere with participation in the study.
• Participants who cannot perform venous blood sampling (i.e., poor venous access or vasovagal response to injection).
• Any other circumstances or laboratory abnormalities that, in the Investigator's judgement, may result in an unacceptable increase in risk to the participant, or impair the participant's ability to participate in and complete the study, or could preclude the evaluation of the participant's response.
• Have any clinically significant abnormality on physical examination at Screening, on Day -1, or on Day 1 prior to dosing which in the opinion of the Investigator would exclude them from the study.
• History of a severe allergic reaction to any drug or multiple food / drug allergies.
• Heavy caffeine drinker (> 5 cups or glasses of caffeinated beverages, e.g., coffee, tea, cola per day).
• Have any condition which, in the judgement of the Investigator, would prevent the participant from completing the study or complying with study procedures and requirements.

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

Здоровые добровольцы: Да

Дизайн исследования

Распределение

Рандомизированное

Модель

Последовательный дизайн

Маскирование

Тройное слепое

Основная цель

Лечение

Центры проведения

Австралия · 1 центр

• CMAX Clinical Research Pty Ltd — Adelaide

Идентификаторы

NCT: NCT07580924 · NHL907-101

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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