Safety, Tolerability and Pharmacokinetics of L608 in Healthy Adults

NCT05938946 | Completed Phase 1 DMC

• 1 other identifier: PBI L608p1
• Study Type: interventional
• Target: 64
• Locations: 1 country
• Sites: 1

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.

Conditions

Pulmonary Arterial Hypertension

Outcome Measures

Primary Outcomes (3)

• The incidence of dose limiting toxicity (DLT)

  The percentage of subjects with dose limiting toxicity (DLT) within 14 days after dosing

  Baseline to Day 14

• The incidence of treatment emergent adverse events (TEAEs) and serious adverse events (SAEs)

  The percentage of subjects with treatment emergent adverse events (TEAEs) and serious adverse events (SAEs) within 21 days after dosing.

  Baseline to Day 21

• Frequency and severity of treatment emergent adverse events (TEAEs) and serious adverse events (SAEs)

  The frequency and severity of treatment emergent adverse events (TEAEs) and serious adverse events (SAEs) within 21 days after dosing.

  Baseline to Day 21

Secondary Outcomes (9)

• AUC0-t

  Baseline to 24 hours

• AUC0-∞

  Baseline to 24 hours

• %AUCextrap

  Baseline to 24 hours

• Cmax

  Baseline to 24 hours

• Tmax

  Baseline to 24 hours

Study Arms (2)

L608 Liposomal inhalation solution

EXPERIMENTAL

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

Drug: L608 Inhalation Solution

Placebo

EXPERIMENTAL

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

Drug: Placebo solution

Interventions

L608 Inhalation Solution 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

L608 Liposomal inhalation solution

Placebo solution 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

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Men and women aged between 18 and 65 (inclusive) at the time of Screening visit. Females must not be pregnant or lactating.
• Body Mass Index (BMI) of ≥18.5 and ≤30.0 kg/m2
• 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.

You may not qualify if:

• Subjects with contraindications or sensitivity to any components of the study treatment.
• 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.
• Subjects with histories or active conditions of unexplained bleeding events, hemoptysis, abnormal bleeding tendencies, and/or coagulation disorders.
• Subjects who voluntarily participate in this study and sign the informed consent form prior to any study procedures.
• 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.
• 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.
• 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.
• Subjects with FEV1 less than 80% predicted, FVC ˂80% predicted, or resting oxygen saturation less than 95% at Screening or check-in visit.
• 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.
• 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.
• 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.
• Subjects are pregnant or breast feeding.

Sponsors & Collaborators

• Pharmosa Biopharm Inc.: lead
• Novotech (Australia) Pty Limited: collaborator

Study Sites (1)

CMAX Clinical Research Pty Ltd

Adelaide, South Australia, SA 5000, Australia

Location

MeSH Terms

Conditions

Pulmonary Arterial Hypertension

Condition Hierarchy (Ancestors)

Hypertension, Pulmonary; Lung Diseases; Respiratory Tract Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: This is a double-blinded, single ascending dose escalation design. 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
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Randomized, Placebo-controlled, double-blinded, single ascending dose escalation

Study Record Dates

• First Submitted: June 9, 2023
• First Posted: July 11, 2023
• Study Start: August 30, 2023
• Primary Completion: September 2, 2024
• Study Completion: September 2, 2024
• Last Updated: October 16, 2024

Record last verified: 2024-10

Locations

AU (1)