A Study to Evaluate the Safety, Tolerability and Pharmacokinetics of Treprostinil Palmitil Inhalation Powder (TPIP) in Healthy Participants

Study Overview
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Brief Summary
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The primary purpose of this study is to evaluate the safety and tolerability of single and multiple doses of treprostinil palmitil inhalation powder in healthy participants.

Official Title
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A Phase 1, Randomized, Single and Multiple Ascending Dose Study to Evaluate the Safety, Tolerability, And Pharmacokinetics of Treprostinil Palmitil Inhalation Powder in Healthy Volunteers

Conditions
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Healthy Volunteers

Intervention / Treatment
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* Drug: Treprostinil Palmitil Inhalation Powder
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The participant is considered by the investigator to be in good general health as determined by medical history, physical examination findings, vital sign measurements, 12-lead electrocardiogram (ECG) results, and clinical laboratory test results within normal limits or considered not clinically significant by the investigator, at screening. Exclusion Criteria: The participant has an allergy, documented hypersensitivity, or contraindication to the ingredients or to any of the excipients of treprostinil palmitil inhalation powder or treprostinil. The participant has used any prescription (excluding hormonal birth control) or over-the-counter medications, including herbal or nutritional supplements, within 14 days before the first dose of study drug and throughout the study. The participant has a history of anaphylaxis, previously documented hypersensitivity reaction to any drug. The participant has had a surgical procedure that required general anesthesia (or equivalent) within 90 days prior to screening. The participant has a body mass index <19.0 or >32.0 kilograms per square meter (kg/m^2) at screening. The participant has a history of syncope not due to dehydration or vasovagal syncope (eg, congenital cardiac arrhythmias such as Wolff-Parkinson-White syndrome, nodal tachycardia, ventricular tachycardia, etc). The participant has active liver disease or hepatic dysfunction at screening or check-in visits. The participant has a history of human immunodeficiency virus (HIV) infection. The participant has a history of abnormal bleeding or bruising. The participant has a history of malignancy in the past 5 years, with exception of nonmelanoma skin cancer. The participant has a current history (within the past 12 months) of substance and/or alcohol abuse. The participant is a current user of cigarettes (average of ≥1 cigarette/day) or e-cigarettes within 30 days prior to screening. The participant has a positive test result for drugs of abuse, alcohol, or cotinine (indicating active current smoking) at screening or before the first dose of study drug or throughout the study. Note: Other inclusion/exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 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: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part A (SAD Cohort 1): TPIP<br>Participants in the single ascending dose (SAD) Cohort 1 received a single dose of TPIP at Dose A, Dose B, or Dose C by oral inhalation on Day 1. | Drug: Treprostinil Palmitil Inhalation Powder<br>* Oral inhalation using a Plastiape capsule-based dry powder inhaler.<br>* Other names: INS1009;|
| Experimental: Part A (SAD Cohort 2): TPIP or Placebo<br>Participants in SAD Cohort 2 received a single dose of TPIP at Dose D or matching placebo by oral inhalation on Day 1. | Drug: Treprostinil Palmitil Inhalation Powder<br>* Oral inhalation using a Plastiape capsule-based dry powder inhaler.<br>* Other names: INS1009;Drug: Placebo<br>* Oral placebo inhalation using a Plastiape capsule-based dry powder inhaler.<br>|
| Experimental: Part A (SAD Cohort 3): TPIP or Placebo<br>Participants in SAD Cohort 3 received a single dose of TPIP at Dose E or matching placebo by oral inhalation on Day 1. | Drug: Treprostinil Palmitil Inhalation Powder<br>* Oral inhalation using a Plastiape capsule-based dry powder inhaler.<br>* Other names: INS1009;Drug: Placebo<br>* Oral placebo inhalation using a Plastiape capsule-based dry powder inhaler.<br>|
| Experimental: Part B (MAD Cohort 1): TPIP or Placebo<br>Participants in the multiple ascending dose (MAD) Cohort 1 received TPIP at Dose B, Dose C or matching placebo, once daily (QD) by oral inhalation on Days 1 through 7. | Drug: Treprostinil Palmitil Inhalation Powder<br>* Oral inhalation using a Plastiape capsule-based dry powder inhaler.<br>* Other names: INS1009;Drug: Placebo<br>* Oral placebo inhalation using a Plastiape capsule-based dry powder inhaler.<br>|
| Experimental: Part B (MAD Cohort 2): TPIP or Placebo<br>Participants in MAD Cohort 2 received TPIP up to Dose D or matching placebo, QD by oral inhalation on Days 1 through 7. | Drug: Treprostinil Palmitil Inhalation Powder<br>* Oral inhalation using a Plastiape capsule-based dry powder inhaler.<br>* Other names: INS1009;Drug: Placebo<br>* Oral placebo inhalation using a Plastiape capsule-based dry powder inhaler.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Parts A and B: Number of Participants who Experienced an Adverse Event (AE) | Safety and tolerability of single and multiple doses of treprostinil inhalation powder will be determined in healthy participants. | Up to Day 31 in Part A and Day 37 in Part B | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Parts A and B: Area Under the Plasma Concentration Versus Time Curve (AUC) of Treprostinil | Pharmacokinetics of treprostinil following a single and multiple doses will be assessed in healthy participants. | Part A: Predose and at multiple time points postdose up to Day 4; Part B: Predose and at multiple time points postdose up to Day 10 | 
| Parts A and B: Area Under the Plasma Concentration Versus Time Curve (AUC) of Treprostinil Palmitil | Pharmacokinetics of treprostinil palmitil following a single and multiple doses will be assessed in healthy participants. | Part A: Predose and at multiple time points postdose up to Day 4; Part B: Predose and at multiple time points postdose up to Day 10 |