Clinical trial NCT06429930: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Pulmonary Arterial Hypertension
Keywords: Pulmonary Arterial Hypertension
Hypertension, Pulmonary
Lung Diseases
Respiratory Tract Diseases
Pharmaceutical Solutions
Lead sponsor: Pharmosa Biopharm Inc.
Sponsor class: INDUSTRY
Collaborators: name: Novotech (Australia) Pty Limited
First posted: 2024-05-28
Enrollment: 56
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Intervention model description: Randomized, Placebo-controlled, double-blinded, single ascending dose escalation
Primary purpose: TREATMENT

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.

Eligibility criteria: 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. 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.
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.

Primary outcomes:
measure: Percentage of participants with DLT
timeFrame: 7 days after administration
measure: Percentage of participants with TEAEs and SAEs
timeFrame: 2 weeks after administration
measure: Frequency and severity of TEAEs and SAEs
timeFrame: 2 weeks after administration
Secondary outcomes:
measure: AUC0-t
timeFrame: 24 hours after administration
measure: AUC0-inf
timeFrame: 24 hours after administration
measure: %AUCextrap
timeFrame: 24 hours after administration
measure: Cmax
timeFrame: 24 hours after administration
measure: Tmax
timeFrame: 24 hours after administration
measure: T1/2
timeFrame: 24 hours after administration
measure: CL/F
timeFrame: 24 hours after administration
measure: Vz/F
timeFrame: 24 hours after administration
measure: λz
timeFrame: 24 hours after administration
measure: Cmax/D
timeFrame: 24 hours after administration
measure: AUC0-t/D
timeFrame: 24 hours after administration
measure: AUC0-inf/D
timeFrame: 24 hours after administration
Other outcomes:
Locations:
city: Christchurch
country: New Zealand
facility: NZCR Ltd (New Zealand Clinical Research)
Study officials:
References: