A Phase 1 Study Evaluating Eliglustat's Effects on Pharmacokinetics, Safety & Tolerability of Digoxin in Healthy Adults
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
Study Overview
Status
Status
Conditions
Conditions
Intervention / Treatment
Intervention / Treatment
Detailed Description
Study Type
Study Type
Enrollment (Actual)
Enrollment
Phase
Phase
- Phase 1
Contacts and Locations
Study Locations
-
-
Texas
-
Austin, Texas, United States
- PPD Phase I Clinic
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-
Participation Criteria
Eligibility Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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.
Study Plan
How is the study designed?
Design Details
- Allocation: Non-Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Number of Arms
Arms and Interventions
Participant Group / ArmParticipant Group / Arm |
Intervention / TreatmentIntervention / Treatment |
|---|---|
|
Active Comparator: digoxin
|
oral 0.25mg dose of digoxin (single dose) on Day 1
|
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Experimental: eliglustat with digoxin
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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
Other Names:
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What is the study measuring?
Primary Outcome Measures
Primary Outcome Measures
Outcome Measure |
Time Frame |
|---|---|
|
Pharmacokinetics as measured by area under the serum concentration time curve (AUC) of digoxin alone and in combination with eliglustat
Time Frame: 18 days
|
18 days
|
|
Pharmacokinetics as measured by maximum serum concentration (Cmax) following administration of digoxin alone and in combination with eliglustat
Time Frame: 18 days
|
18 days
|
Secondary Outcome Measures
Secondary Outcome Measures
Outcome Measure |
Time Frame |
|---|---|
|
Pharmacokinetics for digoxin as measured by the time to maximum serum concentration (Tmax) following administration of digoxin alone and in combination with eliglustat
Time Frame: 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
Time Frame: 18 days
|
18 days
|
|
Pharmacokinetics for digoxin as measured by apparent serum clearance (CL) following administration of digoxin alone and in combination with eliglustat
Time Frame: 18 days
|
18 days
|
|
Pharmacokinetics for digoxin as measured by renal clearance (CLr) following administration of digoxin alone and in combination with eliglustat
Time Frame: 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.
Time Frame: 18 days
|
18 days
|
|
Pharmacokinetics as measured by eliglustat trough concentrations following administration of digoxin in combination with eliglustat
Time Frame: 18 days
|
18 days
|
|
Safety as measured by the incidence, seriousness and severity of adverse events (AEs).
Time Frame: 10 weeks
|
10 weeks
|
Collaborators and Investigators
Sponsor
Sponsor
Study record dates
Study Major Dates
Study Start
Study Start
Primary Completion (Actual)
Primary Completion
Study Completion (Actual)
Study Completion
Study Registration Dates
First Submitted
First Submitted
First Submitted That Met QC Criteria
First Submitted That Met QC Criteria
First Posted (Estimate)
First Posted
Study Record Updates
Last Update Posted (Estimate)
Last Update Posted
Last Update Submitted That Met QC Criteria
Last Update Submitted That Met QC Criteria
Last Verified
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
Other Study ID Numbers
- GZGD03610
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