Safety, Tolerability and Pharmacokinetics of L608 in Healthy Adults

NCT ID: NCT05938946

Last Updated: 2024-10-16

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 64 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-08-30
• Study Completion Date: 2024-09-02

Brief Summary

This is a Phase I, randomized, double-blinded, placebo-controlled single ascending dose, sequential-group study to evaluate the safety, tolerability, and PK of single ascending doses of L608 inhalation in healthy volunteers.

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 PAH (WHO Group 1). 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 volunteers in Australia 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.

Conditions

Pulmonary Arterial Hypertension

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

L608 Liposomal inhalation solution

Eight subjects will be enrolled in each cohort and be randomized to receive assigned dose of L608 or placebo (6:2).

Group Type: EXPERIMENTAL

L608 Inhalation Solution

Intervention Type: DRUG

subjects will be randomized at a ratio of 1:1 (for Sentinel dosing) followed by 5:1 for rest of the cohort to receive the assigned dose of L608 or placebo

Placebo

Eight subjects will be enrolled in each cohort and be randomized to receive assigned dose of L608 or placebo (6:2).

Group Type: EXPERIMENTAL

Placebo solution

Intervention Type: DRUG

subjects will be randomized at a ratio of 1:1 (for Sentinel dosing) followed by 5:1 for rest of the cohort to receive the assigned dose of L608 or placebo

Interventions

L608 Inhalation Solution

subjects will be randomized at a ratio of 1:1 (for Sentinel dosing) followed by 5:1 for rest of the cohort to receive the assigned dose of L608 or placebo

Intervention Type: DRUG

Placebo solution

subjects will be randomized at a ratio of 1:1 (for Sentinel dosing) followed by 5:1 for rest of the cohort to receive the assigned dose of L608 or placebo

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Men and women aged between 18 and 65 (inclusive) at the time of Screening visit. Females must not be pregnant or lactating.

2. Body Mass Index (BMI) of ≥18.5 and ≤30.0 kg/m2

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.

Exclusion Criteria

1. Subjects with contraindications or sensitivity to any components of the study treatment.

2. Subjects with medical histories (within 3 months prior to Screening) or ongoing conditions of any clinically significant and/or any other medical conditions which may jeopardize the safety of the subjects and/or effect the results of the study at the Investigator's discretion.

3. Subjects with histories or active conditions of unexplained bleeding events, hemoptysis, abnormal bleeding tendencies, and/or coagulation disorders.

4. Subjects who voluntarily participate in this study and sign the informed consent form prior to any study procedures.

5. Subjects 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.

6. Subjects 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.

7. Subjects with systolic blood pressure < 90 mmHg or > 160 mmHg and/or diastolic blood pressure < 50 mmHg or > 95 mmHg at Screening or check-in visit.

8. Subjects with FEV1 less than 80% predicted, FVC ˂80% predicted, or resting oxygen saturation less than 95% at Screening or check-in visit.

9. Subjects with histories of drug or alcohol abuse within 1 year prior to subject check-in (Day -1). Regular alcohol consumption defined as > 10 standard drinks per week.

10. 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.

11. Positive results of human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV), and pregnancy test.

12. Blood donation or significant blood loss (>480 ml) within 3 months prior to Screening.

13. Subjects are pregnant or breast feeding.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Novotech (Australia) Pty Limited

INDUSTRY

Sponsor Role: collaborator

Pharmosa Biopharm Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

CMAX Clinical Research Pty Ltd

Adelaide, South Australia, Australia

Countries

Australia

Other Identifiers

PBI L608p1

Identifier Type: -

Identifier Source: org_study_id