An open-label phase 2A study to investigate drug-drug interactions between AT1001 (migalastat hydrochloride) and agalsidase in subjects with Fabry disease.
- Conditions
- Fabry Diseasemetabolic disease10021605
- Registration Number
- NL-OMON36355
- Lead Sponsor
- Amicus Therapeutics, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 4
1. Male, diagnosed with Fabry disease and between 18 and 65 years of age, inclusive
2. Body Mass Index (BMI) between 18-35
3. Subject initiated treatment with agalsidase at least 1 month, having received at least two infusions, before Screening Visit
4. Subject*s dose level, dosing regimen and form (i.e., alfa or beta) of agalsidase have been stable (stable dose defined as not varying by more than ± 20%) for at least 1 month before Screening Visit
5. Subject has a estimated creatinine clearance * 60 mL/min at Screening; creatinine clearance to be estimated using the 4-parameter MDRD equation:
eGFR (mL/min/1.73 m2) <= 186 x (Scr)-1.154 x (Age)-0.203 x (0.742 if female) x (1.212 if African-American)
6. Subject agrees to use medically accepted methods of contraception during the study and for 30 days after study completion
7. Subject is willing and able to provide written informed consent
1. Subject has had a documented transient ischemic attack, ischemic stroke, unstable angina, or myocardial infarction within the 3 months before Screening
2. Subject has clinically significant unstable cardiac disease (e.g., cardiac disease requiring active management, such as symptomatic arrhythmia, unstable angina, or NYHA class III or IV congestive heart failure)
3. Subject has a history of allergy or sensitivity to study drug (including excipients) or other iminosugars (e.g., miglustat, miglitol)
4. Subject requires a concomitant medication prohibited by the protocol: Glyset® (miglitol), or Zavesca® (miglustat)
5. Any investigational/experimental drug or device within 30 days of Screening
6. Subject is currently being treated with or has previously received AT1001
7. Subject has any intercurrent illness or condition that may preclude the subject from fulfilling the protocol requirements or suggests to the investigator that the potential subject may have an unacceptable risk by participating in this study
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Primary Endpoints:<br /><br>* AT1001 plasma pharmacokinetic parameter values after administration of a<br /><br>single oral dose of AT1001 alone and in combination with agalsidase<br /><br>* Agalsidase plasma pharmacokinetic parameter values by measurement of *-Gal A<br /><br>enzyme levels and protein levels after agalsidase infusion alone and in<br /><br>combination with AT1001<br /><br>* Safety variables: adverse events, clinical laboratory tests, 12-Lead ECGs,<br /><br>physical examinations, vital signs and infusion reactions</p><br>
- Secondary Outcome Measures
Name Time Method <p>Secondary Endpoint:<br /><br>* Distribution of agalsidase to skin after dosing with agalsidase alone and<br /><br>agalsidase in combination with AT1001 at 24 hours and 7 days after dosing by<br /><br>measuring *-Gal A levels and protein levels<br /><br><br /><br>Exploratory Endpoints:<br /><br>* Urinary GL-3 excretion before and 14 days after each agalsidase dose<br /><br>* GL-3 in skin after dosing with agalsidase alone and agalsidase in combination<br /><br>with AT1001 at 24 hours and 7 days after dosing<br /><br>* WBC *-Gal A enzyme levels, determined before initiation of the agalsidase<br /><br>infusion and at 2, 4 and 24 hours and 7 and 14 days after dosing<br /><br>* Antibody titer (IgG) before initiation of an infusion of agalsidase<br /><br>* Plasma globotriaosylsphingosine (lyso-GB3) concentrations and urinary<br /><br>excretion of lyso-GB3 before each dose of agalsidase and 14 days after each<br /><br>dose of agalsidase</p><br>