Safety, Tolerability and Pharmacokinetics Study of L608 in Healthy Adults

Pulmonary Arterial Hypertension Clinical Trial

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06429930
• Other study ID #: PBI-L608-B12
• Status: Not yet recruiting
• Phase: Phase 1
• Start date: September 1, 2024
• Est. completion date: September 30, 2025

Study information

• Verified date: May 2024
• Source: Pharmosa Biopharm Inc.
• Contact: Pei Kan, PhD
• Phone: +886-2-2782-7561
• Email: peikan[@]pharmosa.com.tw
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 56
• Est. completion date: September 30, 2025
• Est. primary completion date: August 14, 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• Hypertension
• Pulmonary Arterial Hypertension

Intervention

Drug:
• L608 Liposomal inhalation 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.
• 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.

Locations

Country	Name	City	State
New Zealand	NZCR Ltd (New Zealand Clinical Research)	Christchurch

Sponsors (2)

Lead Sponsor	Collaborator
Pharmosa Biopharm Inc.	Novotech (New Zealand) Limited

Country where clinical trial is conducted

New Zealand, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of participants with DLT	DLT: Dose-limiting toxicity	7 days after administration
Primary	Percentage of participants with TEAEs and SAEs	TEAEs: treatment emergent adverse events; SAEs: serious adverse events	2 weeks after administration
Primary	Frequency and severity of TEAEs and SAEs	TEAEs: treatment emergent adverse events; SAEs: serious adverse events	2 weeks after administration
Secondary	AUC0-t	Area under the plasma concentration-time curve from time 0 to the last quantifiable concentration	24 hours after administration
Secondary	AUC0-inf	Area under the plasma concentration-time curve from time 0 to infinity	24 hours after administration
Secondary	%AUCextrap	AUC extrapolated from the last measurable concentration to infinity as a percentage of total AUC	24 hours after administration
Secondary	Cmax	Maximum observed plasma concentration	24 hours after administration
Secondary	Tmax	Time to reach the maximum observed plasma concentration	24 hours after administration
Secondary	T1/2	Apparent plasma terminal elimination half-life	24 hours after administration
Secondary	CL/F	Apparent total plasma clearance	24 hours after administration
Secondary	Vz/F	Apparent volume of distribution during the terminal phase	24 hours after administration
Secondary	?z	Terminal elimination rate constant	24 hours after administration
Secondary	Cmax/D	Dose-normalized Cmax.	24 hours after administration
Secondary	AUC0-t/D	Dose-normalized AUC0-t.	24 hours after administration
Secondary	AUC0-inf/D	Dose-normalized AUC0-inf.	24 hours after administration