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
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
Studieoversikt
Status
Status
Forhold
Forhold
Intervensjon / Behandling
Intervensjon / Behandling
Studietype
Studietype
Registrering (Antatt)
Registrering
Fase
Fase
- Fase 1
Kontakter og plasseringer
Studiekontakt
Studiekontakt
- Navn: Insmed Medical Information
- Telefonnummer: 18444467633
- E-post: medicalinformation@insmed.com
Studiesteder
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California
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Lake Forest, California, Forente stater, 92630
- Rekruttering
- USA004
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San Dimas, California, Forente stater, 91773
- Rekruttering
- USA003
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Florida
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Orlando, Florida, Forente stater, 32809
- Rekruttering
- USA002
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Texas
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San Antonio, Texas, Forente stater, 78215
- Rekruttering
- USA001
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Deltakelseskriterier
Kvalifikasjonskriterier
Kvalifikasjonskriterier
Alder som er kvalifisert for studier
- Voksen
- Eldre voksen
Tar imot friske frivillige
Beskrivelse
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.
Studieplan
Hvordan er studiet utformet?
Designdetaljer
- Primært formål: Behandling
- Tildeling: Ikke-randomisert
- Intervensjonsmodell: Parallell tildeling
- Masking: Ingen (Open Label)
Antall våpen
Våpen og intervensjoner
Deltakergruppe / ArmDeltakergruppe / Arm |
Intervensjon / BehandlingIntervensjon / Behandling |
|---|---|
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Eksperimentell: Group 1: Treprostinil Palmitil Inhalation Powder
Healthy participants with normal hepatic function will receive a single dose of TPIP on Day 1.
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Oral inhalation using a dry powder inhaler device.
Andre navn:
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Eksperimentell: Group 2: Treprostinil Palmitil Inhalation Powder
Participants with mild hepatic impairment (classified based on the numerical Child-Pugh total score of 5 to 6) will receive a single dose of TPIP on Day 1.
|
Oral inhalation using a dry powder inhaler device.
Andre navn:
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Eksperimentell: Group 3: Treprostinil Palmitil Inhalation Powder
Participants with moderate hepatic impairment (classified based on the numerical Child-Pugh total score of 7 to 9) will receive a single dose of TPIP on Day 1.
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Oral inhalation using a dry powder inhaler device.
Andre navn:
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Eksperimentell: Group 4: Treprostinil Palmitil Inhalation Powder
Participants with severe hepatic impairment (classified based on the numerical Child-Pugh total score of 10 to 15) will receive a single dose of TPIP on Day 1.
|
Oral inhalation using a dry powder inhaler device.
Andre navn:
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Hva måler studien?
Primære resultatmål
Primære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
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Area Under the Concentration-Time Curve From Time Zero to Infinity (AUCinf) of Treprostinil Palmitil (TP) and Treprostinil (TRE)
Tidsramme: Pre-dose and at multiple timepoints post-dose up to Day 3
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Determination of the effect of mild, moderate, and severe hepatic impairment on the PK of TP and TRE following a single dose of TPIP, when compared to normal hepatic function.
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Pre-dose and at multiple timepoints post-dose up to Day 3
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Area Under the Concentration-Time Curve From Time Zero to Last Quantifiable Concentration (AUClast) of TP and TRE
Tidsramme: Pre-dose and at multiple timepoints post-dose up to Day 3
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Determination of the effect of mild, moderate, and severe hepatic impairment on the PK of TP and TRE following a single dose of TPIP, when compared to normal hepatic function.
|
Pre-dose and at multiple timepoints post-dose up to Day 3
|
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Maximum Observed Plasma Concentration (Cmax) of TP and TRE
Tidsramme: Pre-dose and at multiple timepoints post-dose up to Day 3
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Determination of the effect of mild, moderate, and severe hepatic impairment on the PK of TP and TRE following a single dose of TPIP, when compared to normal hepatic function.
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Pre-dose and at multiple timepoints post-dose up to Day 3
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Apparent Total Clearance (CL/F) of TP and TRE
Tidsramme: Pre-dose and at multiple timepoints post-dose up to Day 3
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Determination of the effect of mild, moderate, and severe hepatic impairment on the PK of TP and TRE following a single dose of TPIP, when compared to normal hepatic function.
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Pre-dose and at multiple timepoints post-dose up to Day 3
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Apparent Terminal Elimination Half-Life (t1/2) of TP and TRE
Tidsramme: Pre-dose and at multiple timepoints post-dose up to Day 3
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Determination of the effect of mild, moderate, and severe hepatic impairment on the PK of TP and TRE following a single dose of TPIP, when compared to normal hepatic function.
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Pre-dose and at multiple timepoints post-dose up to Day 3
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Time to Maximum Observed Concentration (Tmax) of TP and TRE
Tidsramme: Pre-dose and at multiple timepoints post-dose up to Day 3
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Determination of the effect of mild, moderate, and severe hepatic impairment on the PK of TP and TRE following a single dose of TPIP, when compared to normal hepatic function.
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Pre-dose and at multiple timepoints post-dose up to Day 3
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Apparent Volume of Distribution (Vz/F) of TP and TRE
Tidsramme: Pre-dose and at multiple timepoints post-dose up to Day 3
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Determination of the effect of mild, moderate, and severe hepatic impairment on the PK of TP and TRE following a single dose of TPIP, when compared to normal hepatic function.
|
Pre-dose and at multiple timepoints post-dose up to Day 3
|
Sekundære resultatmål
Sekundære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
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Fraction Unbound (Fu) of TRE
Tidsramme: Pre-dose and at multiple timepoints post-dose on Days 1 and 2
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Determination of the effect of mild, moderate, and severe hepatic impairment on the unbound PK of TRE following a single dose of TPIP, when compared to normal hepatic function.
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Pre-dose and at multiple timepoints post-dose on Days 1 and 2
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Number of Participants Who Experienced At Least One Adverse Event (AE)
Tidsramme: Up to Day 7
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Evaluation of safety and tolerability of a single dose of TPIP in participants with mild, moderate, and severe hepatic impairment and normal hepatic function.
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Up to Day 7
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Samarbeidspartnere og etterforskere
Sponsor
Sponsor
Etterforskere
Etterforskere
- Studieleder: Study Director, Insmed Incorporated
Studierekorddatoer
Studer hoveddatoer
Studiestart (Faktiske)
Studiestart
Primær fullføring (Antatt)
Primær fullføring
Studiet fullført (Antatt)
Studiet fullført
Datoer for studieregistrering
Først innsendt
Først innsendt
Først innsendt som oppfylte QC-kriteriene
Først innsendt som oppfylte QC-kriteriene
Først lagt ut (Faktiske)
Først lagt ut
Oppdateringer av studieposter
Sist oppdatering lagt ut (Faktiske)
Sist oppdatering lagt ut
Siste oppdatering sendt inn som oppfylte QC-kriteriene
Siste oppdatering sendt inn som oppfylte QC-kriteriene
Sist bekreftet
Sist bekreftet
Mer informasjon
Begreper knyttet til denne studien
Andre studie-ID-numre
Andre studie-ID-numre
- INS1009-104
Plan for individuelle deltakerdata (IPD)
Planlegger du å dele individuelle deltakerdata (IPD)?
Legemiddel- og utstyrsinformasjon, studiedokumenter
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