A Study to Evaluate the Pharmacokinetics (PK) and Safety of a Single Dose of Treprostinil Palmitil Inhalation Powder (TPIP) in Participants With Normal Hepatic Function and Participants With Hepatic Impairment

Official title

An Open-label, Phase 1 Trial to Evaluate the Pharmacokinetics and Safety of a Single Dose of 80 μg Treprostinil Palmitil Inhalation Powder in Participants With Normal Hepatic Function and Participants With Hepatic Impairment

Overview

The primary purpose of the study is to determine the effect of mild, moderate, and severe hepatic impairment on the PK of total treprostinil palmitil (TP) and treprostinil (TRE) following a single dose of 80 micrograms (μg) TPIP, when compared to normal hepatic function.

Interventions

• Drug Treprostinil Palmitil Inhalation Powder
  Oral inhalation using a dry powder inhaler device.

Primary outcome measures

• Area Under the Concentration-Time Curve From Time Zero to Infinity (AUCinf) of Treprostinil Palmitil (TP) and Treprostinil (TRE) [Time frame: Pre-dose and at multiple timepoints post-dose up to Day 3]
• Area Under the Concentration-Time Curve From Time Zero to Last Quantifiable Concentration (AUClast) of TP and TRE [Time frame: Pre-dose and at multiple timepoints post-dose up to Day 3]
• Maximum Observed Plasma Concentration (Cmax) of TP and TRE [Time frame: Pre-dose and at multiple timepoints post-dose up to Day 3]
• Apparent Total Clearance (CL/F) of TP and TRE [Time frame: Pre-dose and at multiple timepoints post-dose up to Day 3]
• Apparent Terminal Elimination Half-Life (t1/2) of TP and TRE [Time frame: Pre-dose and at multiple timepoints post-dose up to Day 3]
• Time to Maximum Observed Concentration (Tmax) of TP and TRE [Time frame: Pre-dose and at multiple timepoints post-dose up to Day 3]
• Apparent Volume of Distribution (Vz/F) of TP and TRE [Time frame: Pre-dose and at multiple timepoints post-dose up to Day 3]

Secondary outcome measures (2)

• Fraction Unbound (Fu) of TRE [Time frame: Pre-dose and at multiple timepoints post-dose on Days 1 and 2]
• Number of Participants Who Experienced At Least One Adverse Event (AE) [Time frame: Up to Day 7]

Eligibility criteria

Inclusion criteria

• Body mass index between 18.0 and 40.0 kilograms per square meter (kg/m\^2), inclusive.

Inclusion Criteria for Participants with Normal Hepatic Function

• In good health, as determined by no clinically significant findings from medical history, physical examination, 12-lead electrocardiogram (ECG), and vital signs measurements, and clinical laboratory assessments (congenital nonhemolytic hyperbilirubinemia \[eg, suspicion of Gilbert's syndrome based on total and direct bilirubin\] is not acceptable) at screening and check-in, as assessed by the investigator (or designee).

Inclusion Criteria for Participants With Hepatic Impairment:

• Diagnosis of chronic (>6 months), stable hepatic impairment with no clinically significant changes within 30 days prior to dosing, as determined by medical history.
• Participants with type 2 diabetes mellitus may be included, if they have:

• glycosylated hemoglobin A1C ≤8.5% at screening
• fasting blood glucose ≤240 milligrams per deciliter (mg/dL), while participant is using their normal diabetes medication, at screening and check-in.

Exclusion criteria

• History of stomach or intestinal surgery or resection that would potentially alter absorption and/or excretion of orally administered drugs (uncomplicated appendectomy, cholecystectomy, and hernia repair are allowed).
• Use or intend to use any moderate or strong inducers or inhibitors of CYP2C8 or CYP2C9 within 30 days prior to dosing.
• Participation in a clinical trial involving administration of an investigational medicinal product (IMP) (new chemical entity) in the past 30 days or 5 half-lives of that drug (if known) prior to dosing, whichever is longer.

Exclusion Criteria for Participants with Normal Hepatic Function

• Significant history or clinical manifestation of any metabolic, allergic, dermatological, hepatic, renal, hematological, pulmonary, cardiovascular, gastrointestinal, neurological, respiratory, endocrine, or psychiatric disorder, as determined by the investigator (or designee).
• Positive hepatitis panel and/or positive human immunodeficiency virus test. Participants whose results are compatible with prior immunization may be included.
• Positive urine drug screen at screening or positive alcohol test result or positive urine drug screen at check-in. Results that are compatible with marijuana use are not exclusionary.

Exclusion Criteria for Participants With Hepatic Impairment:

• Current organ transplant or waiting for organ transplant scheduled to occur during the trial.
• Hospitalization for hepatic encephalopathy within 3 months prior to dosing.
• Encephalopathy ≥Grade 2.
• History of drug/chemical abuse within 1 year prior to check-in. Marijuana use is not exclusionary.

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation

Non-randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT07643155 · INS1009-104

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗