Safety, Tolerability and Pharmacokinetics Study of L608 in Healthy Adults

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

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.

Study Overview

• Status: Recruiting
• Conditions: Healthy Adult Participants
• Intervention / Treatment: Drug: Placebo Solution; Drug: L608 Liposomal inhalation suspension

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.

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Pei Kan, PhD; Phone Number: 102 +886-2-2782-7561; Email: peikan@pharmosa.com.tw
• Study Contact Backup: Name: Sydney Chuang; Phone Number: 110 +886-2-2782-7561; Email: sydney@pharmosa.com.tw

Study Locations

• New Zealand
  • Christchurch, New Zealand, 8011
    • Recruiting
    • NZCR Ltd (New Zealand Clinical Research)
    • Contact: Christopher John Wynne; Phone Number: +64 3 372-9477; Email: chris.wynne@nzcr.co.nz

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Key Inclusion Criteria:

1. Men and women aged between 18 and 65 (inclusive) at the time of Screening visit.
2. Participants with Body Mass Index (BMI) of ≥18.5 and ≤32.0 kg/m2 and weight of at least 50 kg at Screening.
3. 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.
4. 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 Exclusion Criteria:

1. Participants with contraindications or sensitivity to any components of the study treatment.
2. Participants with histories or active conditions of unexplained bleeding events, hemoptysis, abnormal bleeding tendencies, and/or coagulation disorders.
3. 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.
4. 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.

5. 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.

6. Participants with FEV1 less than 80% predicted, FVC ˂ 80% predicted, or resting oxygen saturation less than 95% at Screening or check-in visit.
7. 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.
8. 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.
9. Receipt of blood products within 2 months prior to dosing.
10. Positive results of human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV), and pregnancy test.
11. Blood donation or significant blood loss (>480 ml) within 3 months prior to Screening.
12. Participants unwilling to refrain from strenuous exercises from 7 days prior to dosing until the EOS visit.
13. Participants planning to receive a tattoo, body piercing, or undergo any invasive procedure during the study period.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Eight participants will be enrolled in each cohort and be randomized to receive assigned dose of L608 or placebo (6:2).	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.
Experimental: 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).	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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of participants with DLT	DLT: Dose-limiting toxicity	7 days after administration
Percentage of participants with TEAEs and SAEs	TEAEs: treatment emergent adverse events; SAEs: serious adverse events	2 weeks after administration
Frequency and severity of TEAEs and SAEs	TEAEs: treatment emergent adverse events; SAEs: serious adverse events	2 weeks after administration

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AUC0-t	Area under the plasma concentration-time curve from time 0 to the last quantifiable concentration	24 hours after administration
AUC0-inf	Area under the plasma concentration-time curve from time 0 to infinity	24 hours after administration
%AUCextrap	AUC extrapolated from the last measurable concentration to infinity as a percentage of total AUC	24 hours after administration
Cmax	Maximum observed plasma concentration	24 hours after administration
Tmax	Time to reach the maximum observed plasma concentration	24 hours after administration
T1/2	Apparent plasma terminal elimination half-life	24 hours after administration
CL/F	Apparent total plasma clearance	24 hours after administration
Vz/F	Apparent volume of distribution during the terminal phase	24 hours after administration
λz	Terminal elimination rate constant	24 hours after administration
Cmax/D	Dose-normalized Cmax.	24 hours after administration
AUC0-t/D	Dose-normalized AUC0-t.	24 hours after administration
AUC0-inf/D	Dose-normalized AUC0-inf.	24 hours after administration

Collaborators and Investigators

• Sponsor: Pharmosa Biopharm Inc.
• Collaborators: Novotech (Australia) Pty Limited

Study record dates

Study Major Dates

• Study Start (Actual): April 11, 2025
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: May 21, 2024
• First Submitted That Met QC Criteria: May 21, 2024
• First Posted (Actual): May 28, 2024

Study Record Updates

• Last Update Posted (Actual): July 22, 2026
• Last Update Submitted That Met QC Criteria: July 21, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Keywords: Respiratory Tract Diseases; Lung Diseases; Pulmonary Arterial Hypertension; Pharmaceutical Solutions; Hypertension, Pulmonary
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Hypertension; Pulmonary Arterial Hypertension; Lung Diseases; Respiratory Tract Diseases; Hypertension, Pulmonary; Pharmaceutical Solutions
• Other Study ID Numbers: PBI-L608-B12

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No