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A Phase 1 Study Evaluating Eliglustat's Effects on Pharmacokinetics, Safety & Tolerability of Digoxin in Healthy Adults

19 marzo 2015 aggiornato da: Genzyme, a Sanofi Company

A Single-site, Open-label, Fixed-sequence Phase 1 Study Evaluating the Effect of Eliglustat (Genz-112638) on the Pharmacokinetics and Safety and Tolerability of Digoxin in Healthy Adult Subjects

The primary objective of this study is to determine the effect of repeat oral doses of eliglustat 150 mg twice daily (BID) (or 100 mg BID for CYP2D6 poor metabolizers) on the pharmacokinetics (PK) of orally administered digoxin 0.25 mg in healthy adult subjects. This will be a single-site, open-label study in 2 staggered cohorts of healthy adult subjects. The study will comprise a screening period (between Day -45 and Day -2), treatment period 1 (Day -1 to Day 4), treatment period 2 (Day 11 to Day 18), and a safety follow-up visit (Day 24 ± 1). There will be a 10-day washout between dosing of study drug in Period 1 and Period 2. The duration of each subject's participation in the study, inclusive of the screening and follow-up visits, will be approximately 10 weeks.

Panoramica dello studio

Stato

Completato

Condizioni

Descrizione dettagliata

Cohort 1 will comprise 10 subjects and Cohort 2 will comprise 18 subjects. Initiation of treatment in Cohort 1 will occur at least 6 days prior to the start of treatment for Cohort 2. In each cohort, eligible subjects will be admitted to the clinical facility on Day -1, the day prior to the start of dosing in Period 1, and will remain in the clinic until completion of study procedures on Day 18, the last day of Period 2 (an approximately 18-night inpatient stay). In Period 1, all subjects will receive a single oral dose of digoxin 0.25 mg on Day 1. In Period 2, subjects will receive repeat oral doses of eliglustat 150 mg BID (or 100 mg BID if a CYP2D6 poor metabolizer) from Day 11 to Day 17 and a single oral dose of digoxin 0AA mg on Day 15. For Cohort 2, co-administration of digoxin and eliglustat on Day 15 will occur only after review of safety data (including telemetry data) through at least Day 16 for all subjects in Cohort 1. The decision to proceed with concomitant dosing of subjects in Cohort 2 will be at the discretion of the Investigator, with consultation of the Sponsor, as appropriate.

Tipo di studio

Interventistico

Iscrizione (Effettivo)

28

Fase

  • Fase 1

Contatti e Sedi

Questa sezione fornisce i recapiti di coloro che conducono lo studio e informazioni su dove viene condotto lo studio.

Luoghi di studio

    • Texas
      • Austin, Texas, Stati Uniti
        • PPD Phase I Clinic

Criteri di partecipazione

I ricercatori cercano persone che corrispondano a una certa descrizione, chiamata criteri di ammissibilità. Alcuni esempi di questi criteri sono le condizioni generali di salute di una persona o trattamenti precedenti.

Criteri di ammissibilità

Età idonea allo studio

Da 18 anni a 45 anni (Adulto)

Accetta volontari sani

Sessi ammissibili allo studio

Tutto

Descrizione

Inclusion Criteria:

  • The male or female subject is in good general health
  • The subject has a body weight of 50 to 100 kg (110 to 220 lb) with a body mass index (BMI) ≤32 kg/m2 at screening.
  • The subject's physical examination, laboratory, vital sign, and electrocardiogram (ECG) test results are within normal limits at screening and Day -1 or, if abnormal, are not considered clinically significant in the opinion of the Investigator.
  • The subject has been a non-smoker for at least 6 months prior to the time of providing informed consent, and is willing and able to abstain from smoking (and use of other forms of nicotine) until completion of the safety follow-up visit.
  • The subject has not used drugs of abuse for at least 6 months prior to Day -1 and is willing and able to abstain from using drugs of abuse until completion of the safety follow-up visit.
  • The subject is willing and able to abstain from alcohol for 48 hours prior to the first dose of study drug until completion of the safety follow-up visit.
  • The subject is willing and able to abstain from grapefruit and grapefruit juice for 72 hours prior to the first dose of study drug until completion of the safety follow-up visit.
  • The subject is willing and able to maintain a normal-fiber diet (i.e., to abstain from excess fiber-rich foods) for 72 hours prior to the first dose of study drug until completion of the safety follow-up visit.
  • Female subjects of childbearing potential must have a documented negative pregnancy test at screening and Day 1, and be willing to use a medically accepted form of contraception (as defined in the protocol) from screening until 30 days after the last dose of study drug. A woman of childbearing potential is defined as any female who has not been amenorrheic for at least 2 years or has not undergone a hysterectomy or surgical sterilization.

Exclusion Criteria:

  • The subject has any of the following: Clinically significant coronary artery disease including history of myocardial infarction or ongoing signs or symptoms consistent with cardiac ischemia or heart failure; clinically significant arrhythmias or conduction defect such as 2nd or 3rd degree atrioventricular (AV) block, a PR interval ≥210 msec, complete bundle branch block, prolonged QTc interval (e.g., repeated demonstration of a QTc interval ≥450 msec), or sustained ventricular tachycardia.
  • The subject has received antibiotics for any reason within 30 days prior to the first dose of study drug.
  • The subject has received any other prescription or non-prescription medication (with the exception of nonprescription-strength ibuprofen and acetaminophen) or dietary or herbal or fiber supplement within 30 days or 5 half-lives (whichever is longer) prior to the first dose of study drug without the approval of the Investigator and Genzyme.
  • The subject receives an immunization within 30 days of providing informed consent.
  • The subject has a history of hypersensitivity to digoxin or other digitalis glycosides, or has other drug allergies that are clinically significant in the opinion of the Investigator (e.g., significant rash or hives).
  • The subject has a clinically significant organic disease, including cardiovascular, renal, hepatic, gastrointestinal, pulmonary, neurologic, endocrine, metabolic, or psychiatric disease, or other medical condition such as electrolyte disorders, serious intercurrent illness, or extenuating circumstance that, in the opinion of the Investigator, precludes participation in the trial.
  • The subject has digestive disorders, including malabsorption, gastroenteritis, pancreatitis, constipation, gastroesophageal reflux disease, diverticulitis, irritable bowel syndrome, or inflammatory bowel disease (including Crohn's disease).
  • The subject has had a cholecystectomy.
  • The subject has a screening laboratory test result >2x the upper limit of normal (ULN) for any of the following liver function tests: aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma glutamyltransferase (GGT), and total bilirubin.
  • The subject tests positive for human immunodeficiency virus (HIV) antibody, hepatitis C antibody, or hepatitis B surface antigen at screening.
  • The subject tests positive for urine drugs of abuse, urine alcohol, or urine cotinine at screening.
  • The subject received an investigational product within 30 days prior to providing informed consent or plans to receive any other investigational product at any time during the course of this study.
  • The subject donated blood or blood products within 30 days prior to providing informed consent.
  • The subject's schedule or travel plans prevent the completion of all required visits.
  • The subject is scheduled for inpatient hospitalization, including elective surgery (inpatient or outpatient), during the study.
  • The subject has a history of cancer, with the exception of basal cell carcinoma.
  • The female subject of childbearing potential is pregnant or lactating.
  • The subject, in the opinion of the Investigator, is unable to adhere to the requirements of the study.

Piano di studio

Questa sezione fornisce i dettagli del piano di studio, compreso il modo in cui lo studio è progettato e ciò che lo studio sta misurando.

Come è strutturato lo studio?

Dettagli di progettazione

  • Assegnazione: Non randomizzato
  • Modello interventistico: Assegnazione parallela
  • Mascheramento: Nessuno (etichetta aperta)

Armi e interventi

Gruppo di partecipanti / Arm
Intervento / Trattamento
Comparatore attivo: digoxin
oral 0.25mg dose of digoxin (single dose) on Day 1
Sperimentale: eliglustat with digoxin
repeat oral doses of 150 mg BID (or 100 mg BID if a CYP2D6 poor metabolizer) eliglustat (Day 11 to Day 17) plus singe dose of digoxin 0.25mg on Day 15
Altri nomi:
  • Genz-112638

Cosa sta misurando lo studio?

Misure di risultato primarie

Misura del risultato
Lasso di tempo
Pharmacokinetics as measured by area under the serum concentration time curve (AUC) of digoxin alone and in combination with eliglustat
Lasso di tempo: 18 days
18 days
Pharmacokinetics as measured by maximum serum concentration (Cmax) following administration of digoxin alone and in combination with eliglustat
Lasso di tempo: 18 days
18 days

Misure di risultato secondarie

Misura del risultato
Lasso di tempo
Pharmacokinetics for digoxin as measured by the time to maximum serum concentration (Tmax) following administration of digoxin alone and in combination with eliglustat
Lasso di tempo: 18 days
18 days
Pharmacokinetics for digoxin as measured by terminal elimination half-life (T1/2) following administration of digoxin alone and in combination with eliglustat
Lasso di tempo: 18 days
18 days
Pharmacokinetics for digoxin as measured by apparent serum clearance (CL) following administration of digoxin alone and in combination with eliglustat
Lasso di tempo: 18 days
18 days
Pharmacokinetics for digoxin as measured by renal clearance (CLr) following administration of digoxin alone and in combination with eliglustat
Lasso di tempo: 18 days
18 days
Pharmacokinetics as measured by amount of digoxin excreted in the urine over 72 hours (Ae) following administration of digoxin alone and in combination with eliglustat.
Lasso di tempo: 18 days
18 days
Pharmacokinetics as measured by eliglustat trough concentrations following administration of digoxin in combination with eliglustat
Lasso di tempo: 18 days
18 days
Safety as measured by the incidence, seriousness and severity of adverse events (AEs).
Lasso di tempo: 10 weeks
10 weeks

Collaboratori e investigatori

Qui è dove troverai le persone e le organizzazioni coinvolte in questo studio.

Studiare le date dei record

Queste date tengono traccia dell'avanzamento della registrazione dello studio e dell'invio dei risultati di sintesi a ClinicalTrials.gov. I record degli studi e i risultati riportati vengono esaminati dalla National Library of Medicine (NLM) per assicurarsi che soddisfino specifici standard di controllo della qualità prima di essere pubblicati sul sito Web pubblico.

Studia le date principali

Inizio studio

1 agosto 2011

Completamento primario (Effettivo)

1 novembre 2011

Completamento dello studio (Effettivo)

1 novembre 2011

Date di iscrizione allo studio

Primo inviato

19 maggio 2011

Primo inviato che soddisfa i criteri di controllo qualità

19 maggio 2011

Primo Inserito (Stima)

23 maggio 2011

Aggiornamenti dei record di studio

Ultimo aggiornamento pubblicato (Stima)

23 marzo 2015

Ultimo aggiornamento inviato che soddisfa i criteri QC

19 marzo 2015

Ultimo verificato

1 marzo 2015

Maggiori informazioni

Termini relativi a questo studio

Queste informazioni sono state recuperate direttamente dal sito web clinicaltrials.gov senza alcuna modifica. In caso di richieste di modifica, rimozione o aggiornamento dei dettagli dello studio, contattare register@clinicaltrials.gov. Non appena verrà implementata una modifica su clinicaltrials.gov, questa verrà aggiornata automaticamente anche sul nostro sito web .

Prove cliniche su digoxin

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