Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

A 12-Week Safety and Pharmacodynamic Study of AT1001 (Migalastat Hydrochloride) in Female Participants With Fabry Disease

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT00304512
Recruitment Status : Completed
First Posted : March 20, 2006
Results First Posted : September 7, 2018
Last Update Posted : October 3, 2018
Sponsor:
Information provided by (Responsible Party):
Amicus Therapeutics

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Fabry Disease
Intervention Drug: migalastat HCl
Enrollment 9
Recruitment Details  
Pre-assignment Details Before randomization, participants were stratified into 2 groups (high or low) by their baseline α-galactosidase A (α-Gal A) activity. High was defined as activity greater than 40% of normal; low was defined as activity less than or equal to 40% of normal.
Arm/Group Title Migalastat Low Dose 50 mg Migalastat Middle Dose 150 mg Migalastat High Dose 250 mg
Hide Arm/Group Description Migalastat 50 milligrams (mg) was administered orally QOD during the 12-week treatment period and then during the optional 36-week treatment extension period. Migalastat 150 mg was administered orally QOD during the 12-week treatment period and then during the optional 36-week treatment extension period. Migalastat 250 mg was administered orally QOD during the 12-week treatment period and then during the optional 36-week treatment extension period.
Period Title: Treatment Period
Started 2 4 3
Safety Population [1] 2 4 3
Pharmacokinetic (PK) Population [2] 2 4 3
Pharmacodynamic (PD) Population [3] 2 4 3
Completed 2 4 3
Not Completed 0 0 0
[1]
Received at least 1 dose of study drug
[2]
Received study drug and had at least 1 postbaseline PK parameter recorded
[3]
Received study drug and had at least 1 postbaseline PD parameter recorded
Period Title: Extension Period
Started 2 4 3
Completed 2 4 3
Not Completed 0 0 0
Arm/Group Title Migalastat Low Dose 50 mg Migalastat Middle Dose 150 mg Migalastat High Dose 250 mg Total
Hide Arm/Group Description Migalastat 50 mg was administered orally QOD during the 12-week treatment period and then during the optional 36-week treatment extension period. Migalastat 150 mg was administered orally QOD during the 12-week treatment period and then during the optional 36-week treatment extension period. Migalastat 250 mg was administered orally QOD during the 12-week treatment period and then during the optional 36-week treatment extension period. Total of all reporting groups
Overall Number of Baseline Participants 2 4 3 9
Hide Baseline Analysis Population Description
All participants who received at least 1 dose of study drug.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 2 participants 4 participants 3 participants 9 participants
49.0  (18.38) 44.8  (9.95) 44.0  (2.65) 45.4  (9.23)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 2 participants 4 participants 3 participants 9 participants
Female
2
 100.0%
4
 100.0%
3
 100.0%
9
 100.0%
Male
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1.Primary Outcome
Title Number Of Participants Who Experienced Severe Treatment-emergent Adverse Events (TEAEs)
Hide Description TEAEs were defined as any adverse event with start date on or after administration of study drug or pre-existing conditions that worsened on or after the start of the first study drug administration (on Day 1). A severe adverse event was defined as an adverse event that was incapacitating and required medical intervention. The number of participants who experienced one or more severe TEAEs after dosing on Day 1 through Week 48 is presented. A summary of serious and all other non-serious adverse events regardless of causality is located in the Reported Adverse Events module.
Time Frame Day 1 (after dosing) through Week 48
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population: all participants who received at least 1 dose of study drug.
Arm/Group Title Migalastat Low Dose 50 mg Migalastat Middle Dose 150 mg Migalastat High Dose 250 mg
Hide Arm/Group Description:
Migalastat 50 mg was administered orally QOD during the 12-week treatment period and then during the optional 36-week treatment extension period.
Migalastat 150 mg was administered orally QOD during the 12-week treatment period and then during the optional 36-week treatment extension period.
Migalastat 250 mg was administered orally QOD during the 12-week treatment period and then during the optional 36-week treatment extension period.
Overall Number of Participants Analyzed 2 4 3
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
0
   0.0%
0
   0.0%
2.Secondary Outcome
Title PK: Area Under The Concentration Versus Time Curve (AUC) After Administration Of Migalastat
Hide Description The AUC to the last measurable concentration (AUC0-t) was evaluated in plasma following a single oral dose of migalastat on Day 1 and following multiple oral doses on Day 14 (2 weeks) and Day 84 (12 weeks). All samples were collected on each dosing day.
Time Frame 0 (predose), 0.5, 1, 2, 3, 4, 5, 6, 8, and 10 hours (postdose)
Hide Outcome Measure Data
Hide Analysis Population Description
PK Population: all participants who received study drug and had at least 1 postbaseline PK parameter recorded.
Arm/Group Title Migalastat Low Dose 50 mg Migalastat Middle Dose 150 mg Migalastat High Dose 250 mg
Hide Arm/Group Description:
Migalastat 50 mg was administered orally QOD during the 12-week treatment period and then during the optional 36-week treatment extension period.
Migalastat 150 mg was administered orally QOD during the 12-week treatment period and then during the optional 36-week treatment extension period.
Migalastat 250 mg was administered orally QOD during the 12-week treatment period and then during the optional 36-week treatment extension period.
Overall Number of Participants Analyzed 2 4 3
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: nanograms*hours/milliliters (ng*hr/mL)
AUC0-t: Single Dose, Day 1
2628.9
(100.4%)
8941.6
(32.2%)
13217.2
(30.2%)
AUC0-t: Multiple Dose, Day 14
3191.6
(64.9%)
10637.9
(35.6%)
14850.6
(9.6%)
AUC0-t: Multiple Dose, Day 84
2300.3
(79.6%)
8581.9
(29.7%)
9970.3
(37.8%)
3.Secondary Outcome
Title α-Gal A Activity In Leukocytes At Baseline, Week 12, And Week 48
Hide Description Leukocytes were isolated from whole blood and lysed, and α-Gal A activity was measured using a validated fluorometric assay, with catalysis to fluorescent 4-methylumbelliferone (4-MU) as the activity measure. The activity values obtained were normalized to protein (measured using a colorimetric assay) and reported as enzyme activity (nanomole [nmol] 4-MU/hr) per mg of protein. On Day 1 of the first visit and at every visit thereafter, the samples were collected prior to dosing with migalastat. α-Gal A activity in leukocytes are presented by individual participants.
Time Frame Baseline, Week 12 (end of treatment period), Week 48 (end of extension period)
Hide Outcome Measure Data
Hide Analysis Population Description
PD Population: all participants who received study drug and had at least 1 postbaseline PD parameter recorded.
Arm/Group Title Migalastat Low Dose 50 mg Migalastat Middle Dose 150 mg Migalastat High Dose 250 mg
Hide Arm/Group Description:
Migalastat 50 mg was administered orally QOD during the 12-week treatment period and then during the optional 36-week treatment extension period.
Migalastat 150 mg was administered orally QOD during the 12-week treatment period and then during the optional 36-week treatment extension period.
Migalastat 250 mg was administered orally QOD during the 12-week treatment period and then during the optional 36-week treatment extension period.
Overall Number of Participants Analyzed 2 4 3
Measure Type: Number
Unit of Measure: nmol 4-MU/hr/mg protein
Participant 1: Baseline Number Analyzed 1 participants 0 participants 0 participants
13.4
Participant 1: Week 12 Number Analyzed 1 participants 0 participants 0 participants
2.46
Participant 1: Week 48 Number Analyzed 1 participants 0 participants 0 participants
26
Participant 2: Baseline Number Analyzed 1 participants 0 participants 0 participants
24.5
Participant 2: Week 12 Number Analyzed 1 participants 0 participants 0 participants
35.8
Participant 2: Week 48 Number Analyzed 1 participants 0 participants 0 participants
39.6
Participant 3: Baseline Number Analyzed 0 participants 1 participants 0 participants
25.1
Participant 3: Week 12 Number Analyzed 0 participants 1 participants 0 participants
4.15
Participant 3: Week 48 Number Analyzed 0 participants 1 participants 0 participants
NA [1] 
Participant 4: Baseline Number Analyzed 0 participants 1 participants 0 participants
6.39
Participant 4: Week 12 Number Analyzed 0 participants 1 participants 0 participants
18.4
Participant 4: Week 48 Number Analyzed 0 participants 1 participants 0 participants
16.1
Participant 5: Baseline Number Analyzed 0 participants 1 participants 0 participants
17.3
Participant 5: Week 12 Number Analyzed 0 participants 1 participants 0 participants
5.85
Participant 5: Week 48 Number Analyzed 0 participants 1 participants 0 participants
22.2
Participant 6: Baseline Number Analyzed 0 participants 1 participants 0 participants
24.6
Participant 6: Week 12 Number Analyzed 0 participants 1 participants 0 participants
12.6
Participant 6: Week 48 Number Analyzed 0 participants 1 participants 0 participants
46.5
Participant 7: Baseline Number Analyzed 0 participants 0 participants 1 participants
3.25
Participant 7: Week 12 Number Analyzed 0 participants 0 participants 1 participants
6.56
Participant 7: Week 48 Number Analyzed 0 participants 0 participants 1 participants
4.83
Participant 8: Baseline Number Analyzed 0 participants 0 participants 1 participants
14.7
Participant 8: Week 12 Number Analyzed 0 participants 0 participants 1 participants
23.3
Participant 8: Week 48 Number Analyzed 0 participants 0 participants 1 participants
29.2
Participant 9: Baseline Number Analyzed 0 participants 0 participants 1 participants
13.1
Participant 9: Week 12 Number Analyzed 0 participants 0 participants 1 participants
8.86
Participant 9: Week 48 Number Analyzed 0 participants 0 participants 1 participants
7.58
[1]
The 4-MU concentration at this time point was below the limit of quantitation
Time Frame Day 1 after dosing through Week 48 (end of extension period)
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Migalastat Low Dose 50 mg Migalastat Middle Dose 150 mg Migalastat High Dose 250 mg
Hide Arm/Group Description Migalastat 50 mg was administered orally QOD during the 12-week treatment period and then during the optional 36-week treatment extension period. Migalastat 150 mg was administered orally QOD during the 12-week treatment period and then during the optional 36-week treatment extension period. Migalastat 250 mg was administered orally QOD during the 12-week treatment period and then during the optional 36-week treatment extension period.
All-Cause Mortality
Migalastat Low Dose 50 mg Migalastat Middle Dose 150 mg Migalastat High Dose 250 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Migalastat Low Dose 50 mg Migalastat Middle Dose 150 mg Migalastat High Dose 250 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/2 (0.00%)   1/4 (25.00%)   0/3 (0.00%) 
Musculoskeletal and connective tissue disorders       
Musculoskeletal chest pain  1  0/2 (0.00%)  1/4 (25.00%)  0/3 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (8.0)
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Migalastat Low Dose 50 mg Migalastat Middle Dose 150 mg Migalastat High Dose 250 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   2/2 (100.00%)   4/4 (100.00%)   3/3 (100.00%) 
Blood and lymphatic system disorders       
Anaemia  1  0/2 (0.00%)  1/4 (25.00%)  0/3 (0.00%) 
Eosinophilia  1  0/2 (0.00%)  1/4 (25.00%)  0/3 (0.00%) 
Cardiac disorders       
Atrial fibrillation  1  0/2 (0.00%)  0/4 (0.00%)  1/3 (33.33%) 
Atrioventricular block  1  0/2 (0.00%)  1/4 (25.00%)  0/3 (0.00%) 
Bifascicular block  1  0/2 (0.00%)  1/4 (25.00%)  0/3 (0.00%) 
Cardiomegaly  1  0/2 (0.00%)  0/4 (0.00%)  1/3 (33.33%) 
Cardiomyopathy  1  0/2 (0.00%)  1/4 (25.00%)  0/3 (0.00%) 
Diastolic dysfunction  1  0/2 (0.00%)  0/4 (0.00%)  1/3 (33.33%) 
Mitral valve calcification  1  0/2 (0.00%)  0/4 (0.00%)  1/3 (33.33%) 
Myocardial ischaemia  1  0/2 (0.00%)  1/4 (25.00%)  0/3 (0.00%) 
Sinus arrhythmia  1  1/2 (50.00%)  0/4 (0.00%)  0/3 (0.00%) 
Ventricular hypertrophy  1  0/2 (0.00%)  1/4 (25.00%)  0/3 (0.00%) 
Congenital, familial and genetic disorders       
Fabry's disease  1  0/2 (0.00%)  1/4 (25.00%)  0/3 (0.00%) 
Eye disorders       
Visual acuity reduced  1  0/2 (0.00%)  0/4 (0.00%)  1/3 (33.33%) 
Gastrointestinal disorders       
Abdominal discomfort  1  1/2 (50.00%)  0/4 (0.00%)  0/3 (0.00%) 
Abdominal mass  1  0/2 (0.00%)  0/4 (0.00%)  1/3 (33.33%) 
Abdominal pain  1  1/2 (50.00%)  1/4 (25.00%)  0/3 (0.00%) 
Constipation  1  0/2 (0.00%)  0/4 (0.00%)  1/3 (33.33%) 
Diarrhoea  1  1/2 (50.00%)  0/4 (0.00%)  0/3 (0.00%) 
Nausea  1  1/2 (50.00%)  0/4 (0.00%)  0/3 (0.00%) 
Vomiting  1  1/2 (50.00%)  1/4 (25.00%)  0/3 (0.00%) 
General disorders       
Chest Pain  1  0/2 (0.00%)  1/4 (25.00%)  0/3 (0.00%) 
Chills  1  0/2 (0.00%)  1/4 (25.00%)  0/3 (0.00%) 
Face oedema  1  1/2 (50.00%)  0/4 (0.00%)  0/3 (0.00%) 
Fatigue  1  0/2 (0.00%)  1/4 (25.00%)  0/3 (0.00%) 
Feeling abnormal  1  0/2 (0.00%)  0/4 (0.00%)  1/3 (33.33%) 
Oedema peripheral  1  1/2 (50.00%)  1/4 (25.00%)  0/3 (0.00%) 
Pyrexia  1  0/2 (0.00%)  1/4 (25.00%)  0/3 (0.00%) 
Infections and infestations       
Bronchitis  1  0/2 (0.00%)  0/4 (0.00%)  1/3 (33.33%) 
Bronchitis acute  1  1/2 (50.00%)  0/4 (0.00%)  0/3 (0.00%) 
Fungal infection  1  0/2 (0.00%)  0/4 (0.00%)  1/3 (33.33%) 
Impetigo  1  0/2 (0.00%)  1/4 (25.00%)  0/3 (0.00%) 
Influenza  1  1/2 (50.00%)  0/4 (0.00%)  0/3 (0.00%) 
Nasopharyngitis  1  1/2 (50.00%)  1/4 (25.00%)  0/3 (0.00%) 
Sinusitis  1  1/2 (50.00%)  0/4 (0.00%)  0/3 (0.00%) 
Viral infection  1  0/2 (0.00%)  0/4 (0.00%)  1/3 (33.33%) 
Injury, poisoning and procedural complications       
Ankle fracture  1  1/2 (50.00%)  0/4 (0.00%)  0/3 (0.00%) 
Subcutaneous haematoma  1  1/2 (50.00%)  0/4 (0.00%)  0/3 (0.00%) 
Investigations       
Atrial pressure increased  1  0/2 (0.00%)  0/4 (0.00%)  1/3 (33.33%) 
Blood glucose increased  1  0/2 (0.00%)  0/4 (0.00%)  1/3 (33.33%) 
Blood urine present  1  0/2 (0.00%)  0/4 (0.00%)  1/3 (33.33%) 
C-reactive protein increased  1  1/2 (50.00%)  1/4 (25.00%)  0/3 (0.00%) 
Cardiac murmur  1  0/2 (0.00%)  1/4 (25.00%)  0/3 (0.00%) 
Echocardiogram abnormal  1  0/2 (0.00%)  0/4 (0.00%)  1/3 (33.33%) 
Electrocardiogram abnormal  1  1/2 (50.00%)  1/4 (25.00%)  1/3 (33.33%) 
Electrocardiogram PR shortened  1  0/2 (0.00%)  0/4 (0.00%)  1/3 (33.33%) 
Nuclear magnetic resonance imaging abnormal  1  0/2 (0.00%)  1/4 (25.00%)  0/3 (0.00%) 
Nuclear magnetic resonance imaging brain abnormal  1  0/2 (0.00%)  0/4 (0.00%)  1/3 (33.33%) 
QRS axis abnormal  1  0/2 (0.00%)  1/4 (25.00%)  0/3 (0.00%) 
Musculoskeletal and connective tissue disorders       
Arthralgia  1  1/2 (50.00%)  2/4 (50.00%)  0/3 (0.00%) 
Back pain  1  0/2 (0.00%)  0/4 (0.00%)  1/3 (33.33%) 
Flank pain  1  1/2 (50.00%)  0/4 (0.00%)  0/3 (0.00%) 
Neck mass  1  0/2 (0.00%)  1/4 (25.00%)  0/3 (0.00%) 
Pain in extremity  1  0/2 (0.00%)  2/4 (50.00%)  0/3 (0.00%) 
Nervous system disorders       
Carotid artery stenosis  1  0/2 (0.00%)  1/4 (25.00%)  0/3 (0.00%) 
Cerebral Artery occlusion  1  0/2 (0.00%)  1/4 (25.00%)  0/3 (0.00%) 
Dizziness  1  0/2 (0.00%)  1/4 (25.00%)  0/3 (0.00%) 
Gliosis  1  0/2 (0.00%)  1/4 (25.00%)  0/3 (0.00%) 
Headache  1  1/2 (50.00%)  3/4 (75.00%)  0/3 (0.00%) 
Lethargy  1  0/2 (0.00%)  1/4 (25.00%)  0/3 (0.00%) 
Memory impairment  1  0/2 (0.00%)  0/4 (0.00%)  1/3 (33.33%) 
Vertebral artery stenosis  1  0/2 (0.00%)  1/4 (25.00%)  0/3 (0.00%) 
Psychiatric disorders       
Anxiety  1  0/2 (0.00%)  0/4 (0.00%)  1/3 (33.33%) 
Depressed mood  1  0/2 (0.00%)  0/4 (0.00%)  1/3 (33.33%) 
Renal and urinary disorders       
Dysuria  1  1/2 (50.00%)  0/4 (0.00%)  0/3 (0.00%) 
Proteinuria  1  0/2 (0.00%)  1/4 (25.00%)  0/3 (0.00%) 
Respiratory, thoracic and mediastinal disorders       
Cough  1  0/2 (0.00%)  1/4 (25.00%)  0/3 (0.00%) 
Pulmonary hypertension  1  0/2 (0.00%)  0/4 (0.00%)  1/3 (33.33%) 
Skin and subcutaneous tissue disorders       
Rash  1  0/2 (0.00%)  1/4 (25.00%)  0/3 (0.00%) 
Rash macular  1  0/2 (0.00%)  1/4 (25.00%)  0/3 (0.00%) 
Vascular disorders       
Aortic stenosis  1  0/2 (0.00%)  0/4 (0.00%)  1/3 (33.33%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (8.0)
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The investigator can only publish the results from this trial provided they supply the sponsor (or authorized entity) a copy of any proposed publication for review. If requested, the investigator will remove information deemed confidential or proprietary by the sponsor and will withhold publication for an additional period of time to allow the sponsor to take appropriate measures to establish and preserve its proprietary rights.
Results Point of Contact
Name/Title: Amicus Therapeutics
Organization: Medical Affairs
Phone: +1-877-426-4287 (877-4-AMICUS)
Responsible Party: Amicus Therapeutics
ClinicalTrials.gov Identifier: NCT00304512     History of Changes
Other Study ID Numbers: FAB-CL-204
First Submitted: March 17, 2006
First Posted: March 20, 2006
Results First Submitted: August 10, 2018
Results First Posted: September 7, 2018
Last Update Posted: October 3, 2018