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Study to Evaluate a Dose of Telotristat Etiprate in Male and Female With Mild, Moderate and Severe Hepatic Insufficiency and Matched Healthy Subjects

24. januar 2019 oppdatert av: Ipsen

A Phase 1, Open-label Study to Evaluate the Single Dose Pharmacokinetics of Telotristat Etiprate in Male and Female Subjects With Mild, Moderate and Severe Hepatic Impairment and Matched Subjects With Normal Hepatic Function

The purpose of the protocol is to assess the pharmacokinetics, safety and tolerability of a single dose of telotristat etiprate in subjects with various stages of hepatic impairment compared to healthy control subjects.

Studieoversikt

Status

Fullført

Intervensjon / Behandling

Studietype

Intervensjonell

Registrering (Faktiske)

24

Fase

  • Fase 1

Kontakter og plasseringer

Denne delen inneholder kontaktinformasjon for de som utfører studien, og informasjon om hvor denne studien blir utført.

Studiesteder

      • Chisinau, Moldova, Republikken, MD-2025
        • ARENSIA Exploratory Medicine
      • Bucharest, Romania, 050159 Distr
        • ARENSIA Exploratory Medicine

Deltakelseskriterier

Forskere ser etter personer som passer til en bestemt beskrivelse, kalt kvalifikasjonskriterier. Noen eksempler på disse kriteriene er en persons generelle helsetilstand eller tidligere behandlinger.

Kvalifikasjonskriterier

Alder som er kvalifisert for studier

18 år til 70 år (Voksen, Eldre voksen)

Tar imot friske frivillige

Ja

Kjønn som er kvalifisert for studier

Alle

Beskrivelse

Inclusion Criteria:

  • Body mass index (BMI) between 18 and 34 kg/m², inclusive, at screening. BMI 35 may be accepted in case of 3-point scored ascites.
  • Minimum body weight of 50 kg.
  • Vital signs (after 5 minutes resting in a supine position) that are within study specified ranges
  • Female subjects of childbearing potential must agree to use an adequate double-barrier method of contraception during the study and for 30 days after discharge.
  • Subjects with impaired hepatic function: Clinical diagnosis of chronic hepatic disease (stable for more than 3 months) with a documented history of underlying hepatic insufficiency and no acute episodes of illness within 30 days prior to Day -1, and no significant change in disease status (ie, up to 1 point in the Child-Pugh classification) from screening to Day -1.
  • Control subjects with normal hepatic function: Clinical laboratory test results must be strictly within the normal laboratory reference ranges for liver function, and mean corpuscular volume (MCV) or, for other parameters, deemed as not clinically significant by the investigator.

Exclusion Criteria:

  • Presence of clinically significant physical, laboratory, or Electrocardiogram (ECG) findings (with the exception of those parameters that are resulting from the underlying hepatic disease) that, in the opinion of the investigator, may interfere with any aspect of study conduct or interpretation of results.
  • Clinically significant illness or disease as determined by medical history, including cardiac, pulmonary, hepatic (other than reason for their hepatic impairment), biliary, Gastrointestinal (GI), endocrinologic, or renal disorders, or cancer within the last 5 years (except localised or in situ nonmelanoma skin cancer), physical examination, clinical laboratory tests, and 12-lead ECGs.
  • Receipt of any investigational agent or study drug within 30 days or 10 half-lives, whichever is longer, prior to dosing.
  • Smoking more than 20 cigarettes (eg, 1 pack) per day or equivalent (eg, e-vapour cigarette, pipe, cigar, chewing tobacco, nicotine patch, nicotine gum); unable or unwilling to refrain from smoking and tobacco use for 2 hours prior to dosing and 4 hours after dose administration.
  • History of any serious adverse reaction or hypersensitivity to any inactive component of telotristat etiprate (ie, microcrystalline cellulose, croscarmellose sodium (disintegrant), talc, silicon dioxide, and magnesium stearate (nonbovine)).
  • Existence of any surgical or medical condition that, in the judgment of the investigator and the sponsor's, medical monitor, might interfere with the absorption, distribution, metabolism, or excretion of telotristat etiprate.
  • History of any major surgery within 6 months or anticipated surgery prior to Day -1.
  • History of renal disease or significantly abnormal kidney function test.
  • History of any active infection within 30 days prior to Day 1, if deemed clinically significant by the investigator.

Studieplan

Denne delen gir detaljer om studieplanen, inkludert hvordan studien er utformet og hva studien måler.

Hvordan er studiet utformet?

Designdetaljer

  • Primært formål: Grunnvitenskap
  • Tildeling: N/A
  • Intervensjonsmodell: Enkeltgruppeoppdrag
  • Masking: Ingen (Open Label)

Våpen og intervensjoner

Deltakergruppe / Arm
Intervensjon / Behandling
Eksperimentell: Telotristat etiprate 500 mg
1 single oral dose (2 x 250-mg tablets)

Hva måler studien?

Primære resultatmål

Resultatmål
Tiltaksbeskrivelse
Tidsramme
Assessment of Maximum Observed Plasma Drug Concentration (Cmax) for Telotristat Ethyl and Comparison Between Each HI Group and Healthy Control Group
Tidsramme: Blood samples were collected on Day 1 (pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12 hours [h] post-dose), Day 2 (24 h), Day 3 (48 h) and Day 4 (72 h).
Blood was sampled for the purpose of determining pharmacokinetic (PK) parameters for total telotristat ethyl using a validated, specific, and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) bioanalytical method. The method was selective, linear, precise and accurate within the range from 0.5 to 500 nanograms per millilitre (ng/mL) for telotristat ethyl and the lower limit of quantification (LoQ) was 0.5 ng/mL. Results were derived by non-compartmental analysis of the plasma concentration-time profiles.
Blood samples were collected on Day 1 (pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12 hours [h] post-dose), Day 2 (24 h), Day 3 (48 h) and Day 4 (72 h).
Assessment of Time to Maximum Observed Plasma Concentration (Tmax) for Telotristat Ethyl and Comparison Between Each HI Group and Healthy Control Group
Tidsramme: Blood samples were collected on Day 1 (pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12 h post-dose), Day 2 (24 h), Day 3 (48 h) and Day 4 (72 h).
Blood was sampled for the purpose of determining PK parameters for total telotristat ethyl using a LC-MS/MS bioanalytical method. The method was selective, linear, precise and accurate within the range from 0.5 to 500 ng/mL for telotristat ethyl and the LoQ was 0.5 ng/mL. Results were derived by non-compartmental analysis of the plasma concentration-time profiles.
Blood samples were collected on Day 1 (pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12 h post-dose), Day 2 (24 h), Day 3 (48 h) and Day 4 (72 h).
Assessment of Area Under the Plasma Concentration Time Curve From 0 to Time t Corresponding to the Last Quantifiable Concentration (AUC[0-tlast]) for Telotristat Ethyl and Comparison Between Each HI Group and Healthy Control Group
Tidsramme: Blood samples were collected on Day 1 (pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12 h post-dose), Day 2 (24 h), Day 3 (48 h) and Day 4 (72 h).
Blood was sampled for the purpose of determining PK parameters for total telotristat ethyl using a LC-MS/MS bioanalytical method. The method was selective, linear, precise and accurate within the range from 0.5 to 500 ng/mL for telotristat ethyl and the LoQ was 0.5 ng/mL. Results were derived by non-compartmental analysis of the plasma concentration-time profiles.
Blood samples were collected on Day 1 (pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12 h post-dose), Day 2 (24 h), Day 3 (48 h) and Day 4 (72 h).
Assessment of Area Under the Plasma Concentration Time Curve From Time 0 to Infinity (AUC[0-inf]) for Telotristat Ethyl
Tidsramme: Blood samples were collected on Day 1 (pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12 h post-dose), Day 2 (24 h), Day 3 (48 h) and Day 4 (72 h).
Blood was sampled for the purpose of determining PK parameters for total telotristat ethyl using a LC-MS/MS bioanalytical method. The method was selective, linear, precise and accurate within the range from 0.5 to 500 ng/mL for telotristat ethyl and the LoQ was 0.5 ng/mL. Results were derived by non-compartmental analysis of the plasma concentration-time profiles. AUC(0-inf) was not determined when the apparent terminal elimination half-life (t1/2) could not be determined over a time interval equal to at least 2 times t1/2 and/or the adjusted coefficient of determination value was inferior to 0.7 and/or extrapolated AUC was greater than 20%.
Blood samples were collected on Day 1 (pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12 h post-dose), Day 2 (24 h), Day 3 (48 h) and Day 4 (72 h).
Assessment of Cmax for LP-778902 (Active Metabolite) and Comparison Between Each HI Group and Healthy Control Group
Tidsramme: Blood samples were collected on Day 1 (pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12 h post-dose), Day 2 (24 h), Day 3 (48 h) and Day 4 (72 h).
Blood was sampled for the purpose of determining PK parameters for LP-778902 (active metabolite of telotristat ethyl) using a LC-MS/MS bioanalytical method. The method was selective, linear, precise and accurate within the range from 2 to 2000 ng/mL for LP-778902 and the LoQ was 2.0 ng/mL. Results were derived by non-compartmental analysis of the plasma concentration-time profiles.
Blood samples were collected on Day 1 (pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12 h post-dose), Day 2 (24 h), Day 3 (48 h) and Day 4 (72 h).
Assessment of Tmax for LP-778902 (Active Metabolite) and Comparison Between Each Hepatic Impairment Group and Healthy Control Group and Comparison Between Each Hepatic Impairment Group and Healthy Control Group
Tidsramme: Blood samples were collected on Day 1 (pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12 h post-dose), Day 2 (24 h), Day 3 (48 h) and Day 4 (72 h).
Blood was sampled for the purpose of determining PK parameters for LP-778902 (active metabolite of telotristat ethyl) using a LC-MS/MS bioanalytical method. The method was selective, linear, precise and accurate within the range from 2 to 2000 ng/mL for LP-778902 and the LoQ was 2.0 ng/mL. Results were derived by non-compartmental analysis of the plasma concentration-time profiles.
Blood samples were collected on Day 1 (pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12 h post-dose), Day 2 (24 h), Day 3 (48 h) and Day 4 (72 h).
Assessment of AUC(0-tlast) for LP-778902 (Active Metabolite) and Comparison Between Each Hepatic Impairment Group and Healthy Control Group
Tidsramme: Blood samples were collected on Day 1 (pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12 h post-dose), Day 2 (24 h), Day 3 (48 h) and Day 4 (72 h).
Blood was sampled for the purpose of determining PK parameters for LP-778902 (active metabolite of telotristat ethyl) using a LC-MS/MS bioanalytical method. The method was selective, linear, precise and accurate within the range from 2 to 2000 ng/mL for LP-778902 and the LoQ was 2.0 ng/mL. Results were derived by non-compartmental analysis of the plasma concentration-time profiles.
Blood samples were collected on Day 1 (pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12 h post-dose), Day 2 (24 h), Day 3 (48 h) and Day 4 (72 h).
Assessment of AUC(0-inf) for LP-778902 (Active Metabolite) and Comparison Between Each HI Group and Healthy Control Group
Tidsramme: Blood samples were collected on Day 1 (pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12 h post-dose), Day 2 (24 h), Day 3 (48 h) and Day 4 (72 h).
Blood was sampled for the purpose of determining PK parameters for LP-778902 (active metabolite of telotristat ethyl) using a LC-MS/MS bioanalytical method. The method was selective, linear, precise and accurate within the range from 2 to 2000 ng/mL for LP-778902 and the LoQ was 2.0 ng/mL. Results were derived by non-compartmental analysis of the plasma concentration-time profiles. AUC(0-inf) was not determined when terminal half-life (t1/2) could not be determined over a time interval equal to at least 2 times t1/2 and/or the adjusted coefficient of determination value was inferior to 0.7 and/or extrapolated AUC was greater than 20%.
Blood samples were collected on Day 1 (pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12 h post-dose), Day 2 (24 h), Day 3 (48 h) and Day 4 (72 h).
Assessment of t1/2 for Telotristat Ethyl and LP-778902 (Active Metabolite)
Tidsramme: Blood samples were collected on Day 1 (pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12 h post-dose), Day 2 (24 h), Day 3 (48 h) and Day 4 (72 h).
Blood was sampled for the purpose of determining PK parameters for total telotristat ethyl and its active metabolite LP-778902 using a LC-MS/MS bioanalytical method. The method was selective, linear, precise and accurate within the range from 0.5 to 500 ng/mL for telotristat ethyl and from 2 to 2000 ng/mL for LP-778902. The LoQ for telotristat ethyl and its metabolite LP-778902 were 0.5 ng/mL and 2.0 ng/mL, respectively.
Blood samples were collected on Day 1 (pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12 h post-dose), Day 2 (24 h), Day 3 (48 h) and Day 4 (72 h).
Assessment of Apparent Terminal Elimination Rate Constant (λz) for Telotristat Ethyl and LP-778902 (Active Metabolite)
Tidsramme: Blood samples were collected on Day 1 (pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12 h post-dose), Day 2 (24 h), Day 3 (48 h) and Day 4 (72 h).
Blood was sampled for the purpose of determining PK parameters for total telotristat ethyl and its active metabolite LP-778902 using a LC-MS/MS bioanalytical method. The method was selective, linear, precise and accurate within the range from 0.5 to 500 ng/mL for telotristat ethyl and from 2 to 2000 ng/mL for LP-778902. The LoQ for telotristat ethyl and its metabolite LP-778902 were 0.5 ng/mL and 2.0 ng/mL, respectively.
Blood samples were collected on Day 1 (pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12 h post-dose), Day 2 (24 h), Day 3 (48 h) and Day 4 (72 h).

Samarbeidspartnere og etterforskere

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Sponsor

Studierekorddatoer

Disse datoene sporer fremdriften for innsending av studieposter og sammendragsresultater til ClinicalTrials.gov. Studieposter og rapporterte resultater gjennomgås av National Library of Medicine (NLM) for å sikre at de oppfyller spesifikke kvalitetskontrollstandarder før de legges ut på det offentlige nettstedet.

Studer hoveddatoer

Studiestart

1. februar 2016

Primær fullføring (Faktiske)

1. juli 2016

Studiet fullført (Faktiske)

1. juli 2016

Datoer for studieregistrering

Først innsendt

5. februar 2016

Først innsendt som oppfylte QC-kriteriene

11. februar 2016

Først lagt ut (Anslag)

17. februar 2016

Oppdateringer av studieposter

Sist oppdatering lagt ut (Faktiske)

25. januar 2019

Siste oppdatering sendt inn som oppfylte QC-kriteriene

24. januar 2019

Sist bekreftet

1. januar 2019

Mer informasjon

Begreper knyttet til denne studien

Ytterligere relevante MeSH-vilkår

Andre studie-ID-numre

  • D-FR-01017-001
  • 2015-004120-64 (EudraCT-nummer)

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