A Study to Assess the Relative Bioavailability After a Single Inhalation Administration of Treprostinil Palmitil Inhalation Powder (TPIP) Formulation 2 (F2) to TPIP Formulation 3 (F3) in Healthy Participants

A Phase 1, Open-Label, Randomized, 3-Group, Crossover Study to Assess the Relative Bioavailability After a Single Inhalation Administration of TPIP Formulation 2 (F2) to TPIP Formulation 3 (F3) in Healthy Participants

The primary objective of this study is to determine the relative bioavailability of treprostinil (TRE) between the TPIP F2 and TPIP F3 at 3 capsule strengths, dose A, dose B, and dose C, in healthy participants following a single inhalation of TPIP dose.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers
• Intervention / Treatment: Drug: TPIP F2; Drug: TPIP F3

• Study Type: Interventional
• Enrollment (Actual): 42
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Utah
    • Salt Lake City, Utah, United States, 84124
      • USA001

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria

• Body mass index (BMI): 18.0 to 32.0 kilogram per square metre (kg/m^2), inclusive, at screening.
• Weight: ≥50 kg (kilograms), inclusive, at screening.
• Must be a nonsmoker (no use of tobacco or nicotine products) and/or has not used chewing tobacco for at least 1 month prior to screening.
• Participants must be able to inhale study treatment using a dry powder inhaler.
• All medication (including over-the-counter medication, health supplements such as St. John's wort extract) must have been stopped at least 14 days prior to clinical site admission. An exception is made for acetaminophen, which is allowed up to admission to the clinical facility. Female participants may continue to use hormonal contraceptives throughout the study.

Exclusion Criteria

• Female participants who are pregnant, nursing, or planning to become pregnant during the study.
• Participant has a positive serology test result for human immunodeficiency virus 1 or 2, hepatitis C virus antibodies, or hepatitis B surface antigen or hepatitis B core antibodies at screening. A positive result for hepatitis C virus antibodies will be allowed, if the participant has documented proof of prior, successful treatment.
• History of malignancy within 5 years prior to screening, with exception of completely treated in situ carcinoma of the cervix, and completely treated non-metastatic squamous cell or basal cell carcinoma of the skin.
• Use of drugs that inhibit or induce Cytochrome P2C8 (CYP2C8) within 3 weeks prior to first dose until follow-up visit.
• Participant has received any study drug in another investigational study within 30 days of screening or less than 5 times the drug's half-life, whichever is longer.
• QT interval corrected for heart rate using Fridericia's formula (QTcF) > 450 milliseconds (ms).

• The participant had active liver disease or hepatic dysfunction at screening or admission, manifested as:

  • Elevated liver function test results (Alanine Aminotransferase [ALT] or Aspartate Aminotransferase [AST] > 2 × Upper Limit of Normal [ULN])
  • Bilirubin > 1.5 × ULN (isolated bilirubin > 1.5 × ULN; ULN is acceptable if bilirubin is fractionated and direct bilirubin < 35%)
  • Known hepatic or biliary abnormalities (excluding Gilbert's syndrome or asymptomatic gallstones)
• Participant has a platelet count less than lower limit of normal and/or a history of abnormal bleeding or bruising.
• Participant has a history of alcohol or drug abuse within 3 months before screening or excessive alcohol consumption (i.e., > 21 units/week for males, > 14 units/week for females) (1 unit is equal to approximately 1/2 pint [200 milliliters (mL)] of beer, 1 small glass [100 mL] of wine, or 1 measure [25 mL] of spirits).

Note: Other protocol defined inclusion/exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: TPIP Dose A; Participants will receive single dose of TPIP F2 or F3 on Day 1 in treatment period 1 followed by single dose of TPIP F3 or F2 on Day 1 in treatment period 2. Both treatment periods are separated by 7-day washout period.	Drug: TPIP F2; Inhalation using a capsule-based dry powder inhaler device.; Other Names: INS1009; Drug: TPIP F3; Inhalation using a capsule-based dry powder inhaler device.; Other Names: INS1009
Experimental: TPIP Dose B; Participants will receive single dose of TPIP F2 or F3 on Day 1 in treatment period 1 followed by single dose of TPIP F3 or F2 on Day 1 in treatment period 2. Both treatment periods are separated by 7-day washout period.	Drug: TPIP F2; Inhalation using a capsule-based dry powder inhaler device.; Other Names: INS1009; Drug: TPIP F3; Inhalation using a capsule-based dry powder inhaler device.; Other Names: INS1009
Experimental: TPIP Dose C; Participants will receive single dose of TPIP F2 or F3 on Day 1 in treatment period 1 followed by single dose of TPIP F3 or F2 on Day 1 in treatment period 2. Both treatment periods are separated by 7-day washout period.	Drug: TPIP F2; Inhalation using a capsule-based dry powder inhaler device.; Other Names: INS1009; Drug: TPIP F3; Inhalation using a capsule-based dry powder inhaler device.; Other Names: INS1009

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Maximum Observed Plasma Concentration (Cmax) of Treprostinil (TRE)	Pre-dose and post-dose at multiple timepoints up to Day 10
Area Under Plasma Concentration-Time Curve From 0 to Last Time Point With Quantifiable Concentration (AUClast) of TRE	Pre-dose and post-dose at multiple timepoints up to Day 10
Area Under Plasma Concentration-Time Curve From 0 to Infinity (AUCinf) of TRE	Pre-dose and post-dose at multiple timepoints up to Day 10

Secondary Outcome Measures

Outcome Measure	Time Frame
Time to Reach Maximum Observed Plasma Concentration (Tmax) of TRE	Pre-dose and post-dose at multiple timepoints up to Day 10
Terminal Elimination Half-Life (t1/2) of TRE	Pre-dose and post-dose at multiple timepoints up to Day 10
Apparent Clearance Following Inhalation Administration (CL/F) of TRE	Pre-dose and post-dose at multiple timepoints up to Day 10
Apparent Volume of Distribution at Terminal Phase (Vz/F) of TRE	Pre-dose and post-dose at multiple timepoints up to Day 10
Dose-Normalized Area Under the Concentration-Time Curve From Time 0 Extrapolated to Infinity (AUCinf/D) of TRE	Pre-dose and post-dose at multiple timepoints up to Day 10
Dose-Normalized Area Under the Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable (AUClast/D) of TRE	Pre-dose and post-dose at multiple timepoints up to Day 10
Dose-Normalized Cmax and Calculated as Cmax/Dose of TRE	Pre-dose and post-dose at multiple timepoints up to Day 10
Number of Participants Who Experienced at Least One Treatment Emergent Adverse Event (TEAEs)	Up to Day 17

Collaborators and Investigators

• Sponsor: Insmed Incorporated

Study record dates

Study Major Dates

• Study Start (Actual): August 19, 2025
• Primary Completion (Actual): October 25, 2025
• Study Completion (Actual): November 3, 2025

Study Registration Dates

• First Submitted: July 28, 2025
• First Submitted That Met QC Criteria: July 28, 2025
• First Posted (Actual): August 3, 2025

Study Record Updates

• Last Update Posted (Actual): November 21, 2025
• Last Update Submitted That Met QC Criteria: November 20, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Respiration Disorders; Respiratory Aspiration
• Other Study ID Numbers: INS1009-103

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No