Safety, Tolerability and Pharmacokinetics Study of L608 in Healthy Adults
- Conditions
- Pulmonary Arterial Hypertension
- Interventions
- Drug: Placebo Solution
- Registration Number
- NCT06429930
- Lead Sponsor
- Pharmosa Biopharm Inc.
- Brief Summary
This is the second single ascending dose study of L608 in healthy participants and is being conducted to evaluate the safety of L608 with higher dose levels, starting from 20 μg and escalating up to a planned maximum dose of 110 μg.
- Detailed Description
L608 inhalation Solution (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. Meanwhile, L608 is expected to mitigate burst release related local irritation and systemic side effects (e.g., hypotension due to plasma peak) in clinical practice.
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. The dose escalation design is applied in this study. The sentinel dosing design will be applied for all cohorts.
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 56
- 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.
Key
- 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.
- 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.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description L608 Liposomal inhalation solution L608 Liposomal inhalation solution Eight participants will be enrolled in each cohort and be randomized to receive assigned dose of L608 or placebo (6:2). Placebo Placebo Solution Eight participants will be enrolled in each cohort and be randomized to receive assigned dose of L608 or placebo (6:2).
- Primary Outcome Measures
Name Time Method Frequency and severity of TEAEs and SAEs 2 weeks after administration TEAEs: treatment emergent adverse events; SAEs: serious adverse events
Percentage of participants with DLT 7 days after administration DLT: Dose-limiting toxicity
Percentage of participants with TEAEs and SAEs 2 weeks after administration TEAEs: treatment emergent adverse events; SAEs: serious adverse events
- Secondary Outcome Measures
Name Time Method Cmax 24 hours after administration Maximum observed plasma concentration
AUC0-t 24 hours after administration Area under the plasma concentration-time curve from time 0 to the last quantifiable concentration
%AUCextrap 24 hours after administration AUC extrapolated from the last measurable concentration to infinity as a percentage of total AUC
AUC0-inf 24 hours after administration Area under the plasma concentration-time curve from time 0 to infinity
Tmax 24 hours after administration Time to reach the maximum observed plasma concentration
T1/2 24 hours after administration Apparent plasma terminal elimination half-life
CL/F 24 hours after administration Apparent total plasma clearance
Vz/F 24 hours after administration Apparent volume of distribution during the terminal phase
Cmax/D 24 hours after administration Dose-normalized Cmax.
λz 24 hours after administration Terminal elimination rate constant
AUC0-t/D 24 hours after administration Dose-normalized AUC0-t.
AUC0-inf/D 24 hours after administration Dose-normalized AUC0-inf.
Trial Locations
- Locations (1)
NZCR Ltd (New Zealand Clinical Research)
🇳🇿Christchurch, New Zealand