Single Ascending Dose Study for Evaluation of Safety, Tolerability and Pharmacokinetics of L606

Study Overview
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Brief Summary
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The primary objective of this study is to evaluate the Pharmacokinetics, Safety and Tolerability of L606 (Liposomal Treprostinil) Inhalation Solution in Single Ascending Dose study design in healthy volunteers.

Detailed Description
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L606 (Liposomal Treprostinil) Inhalation Solution and dedicated inhalation system is developed by Pharmosa Biopharm Inc. intended to improve the inconvenience, as one of the greatest impediments to patient satisfaction to current inhaled treprostinil therapy. Pharmosa's liposomal technology offers sustained release of treprostinil which enable bid treatment instead of conventional qid treatment offered by current inhaled treprostinil therapy for treatment of patients with PAH (WHO Group 1).

Official Title
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A Phase I, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Single Ascending Dose of L606 for Inhalation in Healthy Subjects

Conditions
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Pulmonary Arterial Hypertension

Intervention / Treatment
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* Drug: L606 (Liposomal Treprostinil) Inhalation Solution 51ug
* Device: L606 Inhalation System
* Other: Placebo Solution


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males or females, of any race, 18 to 50 years of age, inclusive, at Screening. Body mass index between 18.5 and 32.0 kg/m2, inclusive, at Screening. In good health, determined by no clinically significant findings from medical history, physical examination, 12 lead ECG, vital sign measurements, and clinical laboratory evaluations (congenital nonhemolytic hyperbilirubinemia [eg, Gilbert's syndrome] is not acceptable) at Screening or Check in as assessed by the Investigator (or designee). Ability of the subject to generate spirometry according to minimum ATS/ERS guidance criteria. Females will not be pregnant or lactating, and females of childbearing potential and males will agree to use contraception as detailed in Section 6.6. Able to comprehend and willing to sign an ICF and to abide by the study restrictions. Agree to abstain from consuming alcohol from 72 hours prior to Check-in. Agree to refrain from strenuous exercise from 7 days prior to Check-in. Agree to abstain from consuming foods and beverages containing poppy seeds, grapefruit, or Seville oranges from 7 days prior to Check-in. Agree to abstain from consuming caffeine-containing foods and beverages from 48 hours prior to Check-in. Agree to abstain from consuming carbonated drinks (including sparkling water and soda) from 48 hours prior to Check-in and until end of study. Exclusion Criteria: Clinically relevant abnormalities identified during Screening, physical examination, 12 lead ECG, or laboratory examinations. Clinically significant history of hepatic, renal, hematological, pulmonary, cardiovascular, gastrointestinal, neurological, respiratory, endocrine, genitourinary, and/or musculoskeletal disease, glaucoma, psychiatric disorder, or any other chronic disease, whether controlled by medication or not. History of anaphylaxis, significant hypersensitivity, intolerance, or allergy to any drug compound, food, or other substance, unless deemed not clinically significant by the Investigator (or designee). History of postural hypotension, unexplained syncope, or hypertension. History of asthma, chronic obstructive pulmonary disease (COPD), or reactive airways conditions or findings consistent with asthma or COPD on spirometry testing. Blood pressure <90 mmHg systolic or <50 mmHg diastolic after supine for 5 minutes at Screening or Check in upon repeat testing. Blood pressure >150 mmHg systolic or >90 mmHg diastolic after supine for 5 minutes at Screening or Check in upon repeat testing. Pulse rate >100 bpm after supine for 5 minutes at Screening or Check-in upon repeat testing. Have a pre-existing condition that could interfere with the absorption, distribution, metabolism, or excretion of drugs. Cholecystectomy is permitted if done at least 10 days before enrollment. Use tobacco- or nicotine-containing products within 6 months prior to Check-in, or have a history of >1 pack cigarettes daily use over multiple years of smoking. History of alcoholism or drug/chemical abuse within 2 years prior to Check-in. Have a history of alcohol abuse or a history of or current impairment of organ function reasonably related to alcohol abuse. Have a history of or current evidence of abuse of licit or illicit drugs or a positive urine screen for drugs of abuse. Alcohol consumption of >21 units per week. One unit of alcohol equals 12 oz (360 mL) beer, 1.5 oz (45 mL) liquor, or 5 oz (150 mL) wine. Positive urine drug screen (including alcohol and cotinine) at Screening and/or Check-in. Positive hepatitis panel and/or positive human immunodeficiency virus test at Screening. Participation in a clinical study involving administration of an investigational drug (new chemical entity) within 30 days prior to Check-in. Use or intend to use any medications/products known to alter drug absorption, metabolism, or elimination processes, including St. John's Wort, within 30 days prior to Check-in, unless deemed acceptable by the Investigator (or designee). Use or intend to use any prescription medications/products within 14 days prior to Check-in with the exception of hormone replacement therapy, oral, implantable, transdermal, injectable, or intrauterine contraceptives, unless deemed acceptable by the Investigator (or designee). Use or intend to use slow-release medications/products considered to still be active within 14 days prior to Check-in, unless deemed acceptable by the Investigator (or designee). Use or intend to use any nonprescription medications/products or herbal supplements within 7 days prior to Check-in, unless deemed acceptable by the Investigator (or designee). Use of nonsteroidal anti inflammatory drugs or aspirin is prohibited within 14 days prior to Check-in. Receipt of blood products within 2 months prior to Check-in. Donation of blood, plasma, and platelets, or the loss of a significant volume of blood (>450 mL) within 6 weeks prior to Screening. Poor peripheral venous access. Have a history of bleeding problems or abnormal bleeding tendencies. Platelet or coagulation factor levels below the lower limit of normal, unless considered not clinically significant by the Investigator. Have previously completed or withdrawn from this study or any other study investigating treprostinil, and have previously received the investigational product. History of any recent infection within 2 weeks of Check-in. In the opinion of the Investigator (or designee), should not participate in this study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: placebo<br>placebo group | Device: L606 Inhalation System<br>* Single ascending dose<br>* Other names: Device: L606 Inhalation Solution;Other: Placebo Solution<br>* Single ascending dose<br>|
| Experimental: L606 Liposomal inhalation solution<br>Liposomal inhalation solution | Drug: L606 (Liposomal Treprostinil) Inhalation Solution 51ug<br>* Single ascending dose<br>* Other names: Drug: L606 (Liposomal Treprostinil) Inhalation Solution;Device: L606 Inhalation System<br>* Single ascending dose<br>* Other names: Device: L606 Inhalation Solution;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The number of treatment-emergent adverse events for L606 and placebo, including abnormal laboratory events | Frequency, severity and seriousness of adverse events (AE) including physical examination, incident of laboratory abnormalities, 12-lead ECG parameter and vital sign assessment | From Pre-dose to Day 10 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUC0-2hr | area under curve from time zero to 2 hours postdose | From pre-dose to 24 hours post dose | 
| AUC0-4hr | AUC from time zero to 4 hours postdose | From pre-dose to 24 hours post dose | 
| AUC0-8hr | area under curve from time zero to 8 hours postdose | From pre-dose to 24 hours post dose | 
| AUC0-12hr | area under curve from time zero to 12 hours postdose | From pre-dose to 24 hours post dose | 
| AUC0-24hr | area under curve from time zero to 24 hours postdose | From pre-dose to 24 hours post dose | 
| AUC0-tlast | AUC from time zero to the time of the last quantifiable concentration | From pre-dose to 24 hours post dose | 
| AUC0-∞ | area under curve from time zero to infinite | From pre-dose to 24 hours post dose | 
| Cmax | maximum plasma concentration | From pre-dose to 24 hours post dose | 
| tmax | time to Maximum Plasma Concentration | From pre-dose to 24 hours post dose | 
| t1/2 | time to half-life | From pre-dose to 24 hours post dose | 
| CL/F | apparent total plasma clearance | From pre-dose to 24 hours post dose | 
| Vz/F | apparent volume of distribution during terminal phase | From pre-dose to 24 hours post dose |