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
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 40
- 试验地点
- 2
- 主要终点
- Frequency and severity of TEAEs and SAEs
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
盲法说明
This is a double-blinded, single ascending dose escalation design. For Cohorts A1 and B1, after confirmation of eligibility, subjects will be randomized at a ratio of 1:1 (for sentinel dosing) followed by 5:1 for rest of the cohorts to receive the assigned dose of L608 or placebo.
Cohorts B2, B3, C1 and C2 are open-label.
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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.
排除标准
- •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 Day
- •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
- •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.
研究组 & 干预措施
L608 Liposomal inhalation suspension
Eight participants will be enrolled in each cohort and be randomized to receive assigned dose of L608 or placebo (6:2).
干预措施: L608 Liposomal inhalation suspension (Drug)
Placebo
Eight participants will be enrolled in each cohort and be randomized to receive assigned dose of L608 or placebo (6:2).
干预措施: Placebo Solution (Drug)
结局指标
主要结局
Frequency and severity of TEAEs and SAEs
时间窗: 2 weeks after administration
TEAEs: treatment emergent adverse events; SAEs: serious adverse events
Percentage of participants with DLT
时间窗: 7 days after administration
DLT: Dose-limiting toxicity
Percentage of participants with TEAEs and SAEs
时间窗: 2 weeks after administration
TEAEs: treatment emergent adverse events; SAEs: serious adverse events
次要结局
- AUC0-t(24 hours after administration)
- %AUCextrap(24 hours after administration)
- AUC0-inf(24 hours after administration)
- Cmax(24 hours after administration)
- Tmax(24 hours after administration)
- T1/2(24 hours after administration)
- CL/F(24 hours after administration)
- Vz/F(24 hours after administration)
- Cmax/D(24 hours after administration)
- λz(24 hours after administration)
- AUC0-t/D(24 hours after administration)
- AUC0-inf/D(24 hours after administration)