Safety, Tolerability and Pharmacokinetics Study of L608 in Healthy Adults

Official title

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

Overview

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.

Detailed description

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.

Interventions

• Drug 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.
• Drug 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.

Primary outcome measures

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

Secondary outcome measures (12)

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

Eligibility criteria

Inclusion criteria

• 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.

Exclusion criteria

• 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation

Randomized

Model

Single group

Masking

Double blind

Primary purpose

Treatment

Study locations

New Zealand · 1 center

• NZCR Ltd (New Zealand Clinical Research) — Christchurch

Identifiers

NCT: NCT06429930 · PBI-L608-B12

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗