Safety, Tolerability and Pharmacokinetics Study of L608 in Healthy Adults

Официальное название

A Phase 1, Randomized, Double-blinded, Placebo-controlled Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Single Ascending Doses of L608 for Inhalation in Healthy Participants

Обзор

This is a single ascending dose study of L608 in healthy participants and is being conducted to evaluate the safety of L608 with dose level ranging from 10 μg to 20 μg.

Подробное описание

L608 inhalation Suspension (L608) is developed by Pharmosa Biopharm Inc. (PBI) as a new liposomal Iloprost formulation for inhalation use in the treatment of patients with WHO Group 1 PAH. As a liposomal formulation of iloprost, L608 is intended to reduce the dosing frequency, as well as provide sustained and selective release along with achieving therapeutically relevant iloprost level.

This Phase I, randomized, double-blinded, placebo-controlled study will be conducted in healthy participants in New Zealand to evaluate the safety, tolerability, and pharmacokinetic of L608.

Вмешательства

• Препарат L608 Liposomal inhalation suspension
  Participants will be randomized at a ratio of 1:1 (for sentinel dosing) followed by 5:1 for the rest of the cohort to receive the assigned dose of L608 or placebo.
• Препарат Placebo Solution
  Participants will be randomized at a ratio of 1:1 (for sentinel dosing) followed by 5:1 for the rest of the cohort to receive the assigned dose of L608 or placebo.

Первичные конечные точки

• Percentage of participants with DLT [Срок оценки: 7 days after administration]
• Percentage of participants with TEAEs and SAEs [Срок оценки: 2 weeks after administration]
• Frequency and severity of TEAEs and SAEs [Срок оценки: 2 weeks after administration]

Вторичные конечные точки (12)

• AUC0-t [Срок оценки: 24 hours after administration]
• AUC0-inf [Срок оценки: 24 hours after administration]
• %AUCextrap [Срок оценки: 24 hours after administration]
• Cmax [Срок оценки: 24 hours after administration]
• Tmax [Срок оценки: 24 hours after administration]
• T1/2 [Срок оценки: 24 hours after administration]
• CL/F [Срок оценки: 24 hours after administration]
• Vz/F [Срок оценки: 24 hours after administration]
• λz [Срок оценки: 24 hours after administration]
• Cmax/D [Срок оценки: 24 hours after administration]
• AUC0-t/D [Срок оценки: 24 hours after administration]
• AUC0-inf/D [Срок оценки: 24 hours after administration]

Критерии участия

Критерии включения

• Men and women aged between 18 and 65 (inclusive) at the time of Screening visit.
• Participants with Body Mass Index (BMI) of ≥18.5 and ≤32.0 kg/m2 and weight of at least 50 kg at Screening.
• Non-smokers or former smokers who have smoked ≤ 100 cigarettes in their lifetime and have not consumed any tobacco or tobacco-containing products for at least 3 months prior to Screening.
• Females must not be pregnant or lactating and must use acceptable, highly effective double contraception from Screening until 3 months after the last dose of the Investigational product.

Критерии исключения

• Participants with contraindications or sensitivity to any components of the study treatment.
• Participants with histories or active conditions of unexplained bleeding events, hemoptysis, abnormal bleeding tendencies, and/or coagulation disorders.
• Participants with histories or active conditions of asthma, sleep apnea, chronic obstructive pulmonary disease (COPD), pulmonary fibrosis, bronchiectasis, bronchospasm, and/or reactive airway. Subjects who have had childhood asthma which have resolved as deemed by the PI can be considered.
• Participants with histories or active conditions of myocardial infarction (MI), cerebrovascular accident (CVA), coronary artery disease (CAD), unstable angina, heart failure, significant cardiac arrhythmias, congenital or acquired valvular heart disease with clinically insignificant symptom, suspected lung congestion, and/or pulmonary arterial hypertension (PAH) causing by venous thromboembolism.
• Cohorts A1 and B1: Participants with systolic blood pressure < 90 mmHg or > 140 mmHg and/or diastolic blood pressure < 50 mmHg or > 95 mmHg at Screening or check-in visit.

Cohorts B2, B3, C1 and C2: Participants with systolic blood pressure < 110 mmHg or > 140 mmHg and/or diastolic blood pressure < 50 mmHg or > 95 mmHg at Screening, check-in visit or predose on Day1.

• Participants with FEV1 less than 80% predicted, FVC ˂ 80% predicted, or resting oxygen saturation less than 95% at Screening or check-in visit.
• Participants with histories of drug or alcohol abuse within 1 year prior to subject check-in (Day -1). Regular alcohol consumption defined as > 14 standard drinks per week for female and > 21 standard drinks per week for male.
• Consumption of products containing caffeine/methylxanthines, poppy seeds and/or alcohol within 48 hours before dosing and products containing grapefruit and/or pomelo (shown to inhibit cytochrome P450 \[CYP\] 3A4 activity) within 10 days prior to drug administration, and/or participants unwilling to refrain from consumption of alcohol from 48 hours before dosing to Day 14.
• Receipt of blood products within 2 months prior to dosing.
• Positive results of human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV), and pregnancy test.
• Blood donation or significant blood loss (>480 ml) within 3 months prior to Screening.
• Participants unwilling to refrain from strenuous exercises from 7 days prior to dosing until the EOS visit.
• Participants planning to receive a tattoo, body piercing, or undergo any invasive procedure during the study period.

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

Здоровые добровольцы: Да

Дизайн исследования

Распределение

Рандомизированное

Модель

Одна группа

Маскирование

Двойное слепое

Основная цель

Лечение

Центры проведения

Новая Зеландия · 1 центр

• NZCR Ltd (New Zealand Clinical Research) — Christchurch

Идентификаторы

NCT: NCT06429930 · PBI-L608-B12

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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