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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT00304512




Registration number
NCT00304512
Ethics application status
Date submitted
17/03/2006
Date registered
20/03/2006
Date last updated
3/10/2018

Titles & IDs
Public title
A 12-Week Safety and Pharmacodynamic Study of AT1001 (Migalastat Hydrochloride) in Female Participants With Fabry Disease
Scientific title
A Phase 2, Open-Label, Multiple Dose Level, 12-Week Study to Evaluate the Safety, Tolerability, and Pharmacodynamics of AT1001 in Female Patients With Fabry Disease
Secondary ID [1] 0 0
FAB-CL-204
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Fabry Disease 0 0
Condition category
Condition code
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders
Metabolic and Endocrine 0 0 0 0
Metabolic disorders
Metabolic and Endocrine 0 0 0 0
Other metabolic disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Experimental: Migalastat Low Dose 50 mg - Migalastat 50 mg was administered orally QOD during the 12-week treatment period and then during the optional 36-week treatment extension period.

Experimental: Migalastat Middle Dose 150 mg - Migalastat 150 mg was administered orally QOD during the 12-week treatment period and then during the optional 36-week treatment extension period.

Experimental: Migalastat High Dose 250 mg - Migalastat 250 mg was administered orally QOD during the 12-week treatment period and then during the optional 36-week treatment extension period.
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number Of Participants Who Experienced Severe Treatment-emergent Adverse Events (TEAEs)
Timepoint [1] 0 0
Day 1 (after dosing) through Week 48
Secondary outcome [1] 0 0
PK: Area Under The Concentration Versus Time Curve (AUC) After Administration Of Migalastat
Timepoint [1] 0 0
0 (predose), 0.5, 1, 2, 3, 4, 5, 6, 8, and 10 hours (postdose)
Secondary outcome [2] 0 0
a-Gal A Activity In Leukocytes At Baseline, Week 12, And Week 48
Timepoint [2] 0 0
Baseline, Week 12 (end of treatment period), Week 48 (end of extension period)

Eligibility
Key inclusion criteria
* Females between 18 and 65 years of age (inclusive)
* Heterozygous for Fabry disease
* Had a confirmed diagnosis of Fabry disease with a documented missense gene mutation (individual or familial)
* Had enhanceable enzyme activity based on in vitro tests
* Were naïve to enzyme replacement therapy (ERT) and other therapies, except for palliative therapies for the signs and symptoms of Fabry disease, or stopped ERT for at least 18 weeks
* Had end organ dysfunction, even minimal, demonstrated by abnormal electrocardiogram (ECG) or evidence of left ventricular hypertrophy documented by echocardiogram or by cardiac biopsy; or renal insufficiency documented by common clinical assessments such as creatinine and glomerular filtration rate or by renal biopsy; or brain tissue dysfunction as documented by evidence of stroke (clinically or imaging); or peripheral nervous tissue dysfunction documented by complaints of intolerance to heat or cold, decreased vibratory sense and proprioception, decreased ability to perspire, or acroparesthesia.
* Were willing to undergo 2 renal and 3 skin biopsies
* Agreed to be sexually abstinent or practice an effective method of contraception when engaging in sexual activity during the course of the study and for a period of 30 days following their completion of the study for women of childbearing potential.
* Were willing and able to provide written informed consent
Minimum age
18 Years
Maximum age
65 Years
Sex
Females
Can healthy volunteers participate?
No
Key exclusion criteria
* Pregnant or lactating
* History of organ transplant
* History of significant disease other than Fabry disease (for example, end-stage renal disease; Class III or IV heart disease [per the New York Heart Association classification]; current diagnosis of cancer, except for basal cell carcinoma of the skin; diabetes [unless hemoglobin A1c =8]; or neurological disease that would have impaired the participant's ability to participate in the study)
* Serum creatinine >176 micromoles/liter on Day -2
* Screening 12-lead ECG demonstrating corrected QT interval >450 milliseconds
* Pacemaker or other contraindication for magnetic resonance imaging scanning
* Taking a medication prohibited by the protocol: Fabrazyme® (agalsidase beta), Replagal™ (agalsidase alfa), Glyset® (miglitol), Zavesca® (miglustat), or any experimental therapy for any indication
* Participated in a previous clinical trial in the last 30 days
* Any other condition which, in the opinion of the investigator would jeopardize the safety of the participant or impact the validity of the study results.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
7/09/2006
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
9/05/2008
Sample size
Target
Accrual to date
Final
9
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
- Parkville
Recruitment postcode(s) [1] 0 0
3050 - Parkville
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Georgia
Country [2] 0 0
Brazil
State/province [2] 0 0
Porto Alegre
Country [3] 0 0
Canada
State/province [3] 0 0
Montréal
Country [4] 0 0
France
State/province [4] 0 0
Paris
Country [5] 0 0
United Kingdom
State/province [5] 0 0
Salford

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Amicus Therapeutics
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Study to evaluate the safety, tolerability, and pharmacodynamics of migalastat hydrochloride (HCl) (migalastat) in participants with Fabry disease.
Trial website
https://clinicaltrials.gov/study/NCT00304512
Trial related presentations / publications
Benjamin ER, Della Valle MC, Wu X, Katz E, Pruthi F, Bond S, Bronfin B, Williams H, Yu J, Bichet DG, Germain DP, Giugliani R, Hughes D, Schiffmann R, Wilcox WR, Desnick RJ, Kirk J, Barth J, Barlow C, Valenzano KJ, Castelli J, Lockhart DJ. The validation of pharmacogenetics for the identification of Fabry patients to be treated with migalastat. Genet Med. 2017 Apr;19(4):430-438. doi: 10.1038/gim.2016.122. Epub 2016 Sep 22.
Giugliani R, Waldek S, Germain DP, Nicholls K, Bichet DG, Simosky JK, Bragat AC, Castelli JP, Benjamin ER, Boudes PF. A Phase 2 study of migalastat hydrochloride in females with Fabry disease: selection of population, safety and pharmacodynamic effects. Mol Genet Metab. 2013 May;109(1):86-92. doi: 10.1016/j.ymgme.2013.01.009. Epub 2013 Jan 26.
Public notes

Contacts
Principal investigator
Name 0 0
Medical Monitor, Clinical Research
Address 0 0
Amicus Therapeutics
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT00304512