A Study to Investigate the Safety, Tolerability and Pharmacokinetics of TESP-0401 in Healthy Participants

Официальное название

A Phase 1 Randomised, Double-blind, Placebo-controlled, Parallel Group, Single Ascending Dose (Part A) and Multiple Ascending Dose (Part B) Study to Assess the Safety, Tolerability and Pharmacokinetics of IV Infusion of TESP-0401 in Healthy Participants

Обзор

The goal of this intervention study is to evaluate the safety and tolerability of TESP-0401, and to understand how the body processes TESP-0401, in healthy participants after single and multiple doses. The study aims to answer the following questions: 1. What are the safety, tolerability, and pharmacokinetic characteristics of a single dose of TESP-0401 in healthy participants? 2. What are the safety, tolerability, and pharmacokinetic characteristics of multiple doses of TESP-0401 in healthy participants? This study will be a randomized, placebo controlled study.

Вмешательства

• Препарат TESP-0401
  IV infusion, single administration, over 60 minutes, in a fasted state
• Препарат Placebo
  IV infusion of placebo, once, over 60 minutes, in a fasted state
• Препарат TESP-0401
  IV infusion, QD for 7 days, over 60 minutes, in a fasted state
• Препарат Placebo
  IV infusion of placebo, QD for 7 days, over 60 minutes, in a fasted state

Первичные конечные точки

• Number of participants with SAEs, TEAEs, with abnormal clinical laboratory tests results, abnormal vital signs, abnormal ECG readings and abnormal physical examination findings [Срок оценки: up to 8 days after the last dose]

Вторичные конечные точки (7)

• Maximum concentration of the drug (Cmax) following single and multiple doses of TESP-0401 in healthy participants [Срок оценки: up to 9 days]
• Time to peak concentration (Tmax) following single and multiple doses of TESP-0401 in healthy participants [Срок оценки: up to 9 days]
• Clearance (CL) following single and multiple doses of TESP-0401 in healthy participants [Срок оценки: up to 9 days]
• Elimination half-life (t1/2) following single and multiple doses of TESP-0401 in healthy participants [Срок оценки: up to 9 days]
• Volume of distribution (Vd) following single and multiple doses of TESP-0401 in healthy participants. [Срок оценки: up to 9 days]
• Area under the curve (AUC) - AUC0-24h, AUC0-last, AUC0-inf following single and multiple doses of TESP-0401 in healthy participants. [Срок оценки: up to 9 days]
• Accumulation ratio (AR) following single and multiple doses of TESP-0401 in healthy participants. [Срок оценки: up to 9 days]

Критерии участия

Критерии включения

• Participants who are healthy as determined no clinically significant findings by the PI/delegate in medical evaluation including medical history, physical examination, laboratory tests, vital signs and 12-lead ECG.
• Systolic blood pressure (SBP) ≥110 mmHg at screening measured after at least 10 minutes of rest in the supine position, and on the dosing day prior to administration of study intervention measured after at least 1 hour of rest in the supine position.
• Resting heart rate ≥50 bpm at screening and on the dosing day prior to administration of study intervention, measured after at least 10 minutes of rest in the supine position.
• BMI within the range 18 to 32 kg/m2
• Male participants who refrain from donating sperms and either remain abstinent from sexual intercourse or agree to use protocol-required contraception.
• Female participants who are not pregnant or breastfeeding and are of non-childbearing potential, or if of childbearing potential, agree to use protocol-required contraception and not to donate ova.
• Participants able to provide signed informed consent form.
• Agree to abstain from smoking cigarettes or equivalent nicotine-containing products from 7 days prior to study drug administration through to the end of study visit.
• Willing and able to adhere to study restrictions and to be confined at the CRU.

Критерии исключения

• History or presence of cardiovascular, respiratory including resolved childhood asthma, hepatic, renal, gastrointestinal including cholecystectomy, endocrinological, haematological, immunological, psychiatric including history of depression/anxiety or neurological disorders including migraine capable of (as judged by the PI/delegate) significantly altering the absorption, metabolism, or elimination of drugs; constituting a risk when taking the study intervention; or interfering with the interpretation of data.
• History of clinically significant hypersensitivity or allergic reactions (e.g. anaphylaxis, angioedema, or severe cutaneous reactions) to any drug or excipient, including components of the study intervention, or a history of multiple drug allergies, which in the opinion of the investigator would place the participant at increased risk or contraindicate participation in the study.
• Abnormal blood pressure determined clinically significant by the PI/delegate.
• Symptomatic herpes zoster within 3 months prior to screening.
• Evidence of active or latent tuberculosis (TB) as documented by medical history, and TB testing consisting of a positive (not indeterminate) TB test such as QuantiFERON-R TB Gold Plus test.
• Lymphoma, leukemia, or any malignancy within the past 5 years except for basal cell or squamous epithelial carcinomas of the skin that have been resected with no evidence of metastatic disease for 3 years.
• Breast cancer within the past 10 years.
• QTc > 450 msec for male participants or > 470 msec for female participants.
• eGFR (CKD-EPI method) <80 mL/min/1.73 m2
• Alanine transaminase (ALT) or aspartate transaminase (AST) > 1.5 x upper limit of normal (ULN).
• Total bilirubin > 1.5 x ULN
• Current or chronic history of liver disease. This includes but is not limited to hepatitis virus infections, drug- or alcohol-related liver disease, steatotic liver disease,autoimmune hepatitis, haemochromatosis, Wilson's disease, α-1 antitrypsin deficiency, primary biliary cholangitis, primary sclerosing cholangitis, or any other liver disease considered clinically significant by the PI/delegate.
• Presence of hepatitis B surface antigen (HBsAg) at screening.
• Positive hepatitis C antibody test result at screening unless hepatitis C virus ribonucleic acid (HCV-RNA) negative test is documented.
• Individuals with Gilbert syndrome.
• Past or intended use of over-the-counter or prescription medication, including herbal medications, within 30 days or 5 half-lives (whichever is longer) prior to dosing or during the study.
• Live vaccine(s) within 1 month prior to screening, or plans to receive such vaccines during the study.
• Participant who has donated blood (or blood products) or experienced a significant blood loss in excess of 450 mL within 30 days prior to screening, or who plans to donate blood during the study period.
• Receiving or has received any investigational drug (small molecule) or is currently using an investigational device, within 14 days prior to study Day 1, or within 5 elimination half-lives prior to study Day 1 (whichever is longer).
• Use of any investigational biologic (eg, monoclonal antibody) ≤ 6 months prior to study Day 1.
• Positive drug/alcohol screen at Screening or Day -1.
• Positive cotinine test at admission to the CRU on Day -1.
• Positive human immunodeficiency virus (HIV) antibody test.
• Regular alcohol consumption within 6 months prior to the study defined as: an average weekly intake of > 10 units for males or > 10 units for females.
• History of consuming 5 or more cigarettes or equivalent nicotine-containing products per week within the last 6 months.
• Known history of drug or alcohol abuse within 1 year of Screening.
• Sensitivity to heparin or heparin-induced thrombocytopenia.
• Any other medical condition or social circumstance, which in the opinion of the PI/delegate would impede compliance with or hinder completion of 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

Четверное слепое

Основная цель

Лечение

Центры проведения

Австралия · 1 центр

• Novatrials — Charlestown

Идентификаторы

NCT: NCT07658638 · TESP-0401-001

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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