## Protocol Section
### Identification Module
**NCT ID:** NCT06429930

**Brief Title:** 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

#### Organization Study ID Info
**ID:** PBI-L608-B12
#### Organization
**Class:** INDUSTRY
**Full Name:** Pharmosa Biopharm Inc.
### Status Module
#### Completion Date
**Date:** 2025-09-30

**Type:** ESTIMATED

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2024-05-28

**Type:** ACTUAL

**Last Update Submit Date:** 2024-05-21

**Overall Status:** NOT_YET_RECRUITING

#### Primary Completion Date
**Date:** 2025-08-14

**Type:** ESTIMATED

#### Start Date
**Date:** 2024-09-01

**Type:** ESTIMATED

**Status Verified Date:** 2024-05

#### Study First Post Date
**Date:** 2024-05-28
**Type:** ACTUAL
**Study First Submit Date:** 2024-05-21
**Study First Submit QC Date:** 2024-05-21
### Sponsor Collaborators Module

#### Collaborators

**Class:** UNKNOWN

**Name:** Novotech (New Zealand) Limited

#### Lead Sponsor

**Class:** INDUSTRY

**Name:** Pharmosa Biopharm Inc.

#### Responsible Party

**Type:** SPONSOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** False

### Description Module

**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.

### Conditions Module

**Conditions:**

- Pulmonary Arterial Hypertension

**Keywords:**

- Pulmonary Arterial Hypertension

- Hypertension, Pulmonary

- Lung Diseases

- Respiratory Tract Diseases

- Pharmaceutical Solutions

### Design Module

#### Design Info

**Allocation:** RANDOMIZED

**Intervention Model:** SINGLE_GROUP

**Intervention Model Description:** Randomized, Placebo-controlled, double-blinded, single ascending dose escalation

##### Masking Info

**Masking:** DOUBLE

**Masking Description:** 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.

**Who Masked:**

- PARTICIPANT

- INVESTIGATOR

**Primary Purpose:** TREATMENT

#### Enrollment Info

**Count:** 56

**Type:** ESTIMATED

**Phases:**

- PHASE1

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

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

**Intervention Names:**

- Drug: L608 Liposomal inhalation solution

**Label:** L608 Liposomal inhalation solution

**Type:** EXPERIMENTAL

#### Arm Group 2

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

**Intervention Names:**

- Drug: Placebo Solution

**Label:** Placebo

**Type:** PLACEBO_COMPARATOR

### Interventions

#### Intervention 1

**Arm Group Labels:**

- L608 Liposomal inhalation solution

**Description:** 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.

**Name:** L608 Liposomal inhalation solution

**Type:** DRUG

#### Intervention 2

**Arm Group Labels:**

- Placebo

**Description:** 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.

**Name:** Placebo Solution

**Type:** DRUG

### Outcomes Module

#### Primary Outcomes

**Description:** DLT: Dose-limiting toxicity

**Measure:** Percentage of participants with DLT

**Time Frame:** 7 days after administration

**Description:** TEAEs: treatment emergent adverse events; SAEs: serious adverse events

**Measure:** Percentage of participants with TEAEs and SAEs

**Time Frame:** 2 weeks after administration

**Description:** TEAEs: treatment emergent adverse events; SAEs: serious adverse events

**Measure:** Frequency and severity of TEAEs and SAEs

**Time Frame:** 2 weeks after administration

#### Secondary Outcomes

**Description:** Area under the plasma concentration-time curve from time 0 to the last quantifiable concentration

**Measure:** AUC0-t

**Time Frame:** 24 hours after administration

**Description:** Area under the plasma concentration-time curve from time 0 to infinity

**Measure:** AUC0-inf

**Time Frame:** 24 hours after administration

**Description:** AUC extrapolated from the last measurable concentration to infinity as a percentage of total AUC

**Measure:** %AUCextrap

**Time Frame:** 24 hours after administration

**Description:** Maximum observed plasma concentration

**Measure:** Cmax

**Time Frame:** 24 hours after administration

**Description:** Time to reach the maximum observed plasma concentration

**Measure:** Tmax

**Time Frame:** 24 hours after administration

**Description:** Apparent plasma terminal elimination half-life

**Measure:** T1/2

**Time Frame:** 24 hours after administration

**Description:** Apparent total plasma clearance

**Measure:** CL/F

**Time Frame:** 24 hours after administration

**Description:** Apparent volume of distribution during the terminal phase

**Measure:** Vz/F

**Time Frame:** 24 hours after administration

**Description:** Terminal elimination rate constant

**Measure:** λz

**Time Frame:** 24 hours after administration

**Description:** Dose-normalized Cmax.

**Measure:** Cmax/D

**Time Frame:** 24 hours after administration

**Description:** Dose-normalized AUC0-t.

**Measure:** AUC0-t/D

**Time Frame:** 24 hours after administration

**Description:** Dose-normalized AUC0-inf.

**Measure:** AUC0-inf/D

**Time Frame:** 24 hours after administration

### Eligibility Module

**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.

**Healthy Volunteers:** True

**Maximum Age:** 65 Years

**Minimum Age:** 18 Years

**Sex:** ALL

**Standard Ages:**

- ADULT

- OLDER_ADULT

### Contacts Locations Module

#### Central Contacts

**Contact 1:**

**Email:** peikan@pharmosa.com.tw

**Name:** Pei Kan, PhD

**Phone:** +886-2-2782-7561

**Phone Ext:** 102

**Role:** CONTACT

**Contact 2:**

**Email:** sydney@pharmosa.com.tw

**Name:** Sydney Chuang

**Phone:** +886-2-2782-7561

**Phone Ext:** 110

**Role:** CONTACT

#### Locations

**Location 1:**

**City:** Christchurch

**Contacts:**

***Contact 1:***

- **Email:** chris.wynne@nzcr.co.nz

- **Name:** Christopher John Wynne

- **Phone:** +64 3 372-9477

- **Role:** CONTACT

**Country:** New Zealand

**Facility:** NZCR Ltd (New Zealand Clinical Research)

**Zip:** 8011

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000014652

- Term: Vascular Diseases

- ID: D000002318

- Term: Cardiovascular Diseases

- ID: D000006976

- Term: Hypertension, Pulmonary

- ID: D000008171

- Term: Lung Diseases

- ID: D000012140

- Term: Respiratory Tract Diseases

### Condition Browse Module - Browse Branches

- Abbrev: BC14

- Name: Heart and Blood Diseases

- Abbrev: All

- Name: All Conditions

- Abbrev: BC08

- Name: Respiratory Tract (Lung and Bronchial) Diseases

- Abbrev: BC23

- Name: Symptoms and General Pathology

- Abbrev: Rare

- Name: Rare Diseases

### Condition Browse Module - Browse Leaves

- ID: M10024

- Name: Hypertension

- Relevance: HIGH

- As Found: Hypertension

- ID: M11168

- Name: Lung Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M27137

- Name: Respiratory Aspiration

- Relevance: LOW

- As Found: Unknown

- ID: M2261

- Name: Pulmonary Arterial Hypertension

- Relevance: HIGH

- As Found: Pulmonary Arterial Hypertension

- ID: M10027

- Name: Hypertension, Pulmonary

- Relevance: LOW

- As Found: Unknown

- ID: M14977

- Name: Respiratory Tract Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M17400

- Name: Vascular Diseases

- Relevance: LOW

- As Found: Unknown

- ID: T4807

- Name: Pulmonary Arterial Hypertension

- Relevance: HIGH

- As Found: Pulmonary Arterial Hypertension

### Condition Browse Module - Meshes

- ID: D000081029

- Term: Pulmonary Arterial Hypertension

- ID: D000006973

- Term: Hypertension

### Intervention Browse Module - Browse Branches

- Abbrev: PhSol

- Name: Pharmaceutical Solutions

- Abbrev: All

- Name: All Drugs and Chemicals

### Intervention Browse Module - Browse Leaves

- ID: M21860

- Name: Pharmaceutical Solutions

- Relevance: HIGH

- As Found: Procedure

### Intervention Browse Module - Meshes

- ID: D000019999

- Term: Pharmaceutical Solutions

### Misc Info Module

- Version Holder: 2024-05-31
