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Open-label Long-term Safety Study of AT1001 (Migalastat Hydrochloride) in Participants With Fabry Disease Who Have Completed a Previous AT1001 Study

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ClinicalTrials.gov Identifier: NCT00526071
Recruitment Status : Terminated (The Sponsor (Amicus Therapeutics) terminated this study for logistical reasons.)
First Posted : September 6, 2007
Results First Posted : October 3, 2018
Last Update Posted : October 3, 2018
Sponsor:
Information provided by (Responsible Party):
Amicus Therapeutics

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Fabry Disease
Intervention Drug: migalastat HCl
Enrollment 23
Recruitment Details An open label, long-term extension study for participants who completed one of 4 preceding Phase 2 studies (FAB-CL-201 [NCT00214500], FAB-CL-202 [NCT00283959], FAB-CL-203 [NCT00283933], or FAB-CL-204 [NCT00304512]). Participants could enter this study directly upon completion of the previous study or at a later point.
Pre-assignment Details This study included a dose escalation period (DEP), in which migalastat was administered at 250 milligrams (mg) for 2 months. If there were no safety concerns the dose was increased to 500 mg for up to 10 months, depending on the date of amendment approval. Before and after the DEP, all but 1 participant (post-DEP 300 mg instead) received 150 mg.
Arm/Group Title Migalastat
Hide Arm/Group Description Participants received migalastat 150 mg given orally once every other day (QOD) before and after the DEP. During the DEP participants received 250 mg once daily (QD) for 3 days, 4 days off per week for 2 months then 500 mg QD for 3 days, 4 days off per week for up to 10 months, depending on the approval date of the protocol amendments at each site. One participant received migalastat 300 mg (QD for 3 days and 4 days off per week) until the end of the study.
Period Title: Overall Study
Started 23
Safety Population [1] 23
Pharmacodynamic (PD) Population [2] 23
Amenable Population; Men [3] 11
Amenable Population; Women [4] 5
Non-amenable Population; Men [5] 3
Non-amenable Population; Women [5] 4
Completed 17
Not Completed 6
Reason Not Completed
Adverse Event             1
Withdrawal by Subject             1
Lack of Response to Study Drug             4
[1]
All participants who received at least 1 dose of study drug
[2]
Received study drug and had a baseline measurement and at least 1 postbaseline PD measure
[3]
Amenable mutations based on the clinical trial (CT) Human Embryonic Kidney (HEK) assay
[4]
Amenable mutations based on the CT-HEK assay
[5]
Those without mutant forms of α-Gal A responsive to migalastat treatment based on the CT-HEK assay
Arm/Group Title Migalastat
Hide Arm/Group Description Participants received migalastat 150 mg given orally QOD before and after the DEP. During the DEP participants received 250 mg QD for 3 days, 4 days off per week for 2 months then 500 mg QD for 3 days, 4 days off per week for up to 10 months, depending on the approval date of the protocol amendments at each site. One participant received migalastat 300 mg (QD for 3 days and 4 days off per week) until the end of the study.
Overall Number of Baseline Participants 23
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 23 participants
43.1  (11.33)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 23 participants
Female
9
  39.1%
Male
14
  60.9%
1.Primary Outcome
Title Number Of Participants Who Experienced Severe Treatment-emergent Adverse Events (TEAEs)
Hide Description A TEAE was defined as any adverse event (AE) 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 AE was defined as an AE that was incapacitating and required medical intervention. The number of participants who experienced one or more severe TEAEs after dosing on Day 1 through End of Study (EOS) or follow-up (for participants who did not enroll in Study AT1001-041) are presented. A summary of serious and all other non-serious AEs regardless of causality is located in the Reported Adverse Events module.
Time Frame Day 1 (after dosing) through EOS (up to 56 months) or follow-up (28 days after EOS)
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
Hide Arm/Group Description:
Participants received migalastat 150 mg given orally QOD before and after the DEP. During the DEP participants received 250 mg QD for 3 days, 4 days off per week for 2 months then 500 mg QD for 3 days, 4 days off per week for up to 10 months, depending on the approval date of the protocol amendments at each site. One participant received migalastat 300 mg (QD for 3 days and 4 days off per week) until the end of the study.
Overall Number of Participants Analyzed 23
Measure Type: Count of Participants
Unit of Measure: Participants
9
  39.1%
2.Secondary Outcome
Title Absolute Change From Baseline In α-Galactosidase A (α-Gal A) Activity In Leukocytes To Month 42
Hide Description The activity of the α-Gal A enzyme was measured in leukocyte lysate by a validated fluorometric assay method, using 4-methylumbelliferone as a reference. The activity values obtained were normalized to protein (measured using a colorimetric assay). Baseline was defined as the last non-missing pre-treatment value for each participant in his or her respective preceding migalastat Phase 2 study. A negative change from Baseline indicates that α-Gal A activity decreased. α-Gal A activity levels are presented for Baseline and Month 42.
Time Frame Baseline, Month 42
Hide Outcome Measure Data
Hide Analysis Population Description
PD Population: all participants who received at least 1 dose of study drug and who had a baseline measurement and at least 1 postbaseline PD measure.
Arm/Group Title Amenable Population; Men Amenable Population; Women Non-amenable Population; Men Non-amenable Population; Women
Hide Arm/Group Description:
Amenable participants were those with mutant forms of α-Gal A determined to be responsive to migalastat treatment based on the CT-HEK assay. Migalastat was administered orally, 150 mg QOD before and after the DEP. During the DEP participants received 250 mg QD for 3 days, 4 days off per week for 2 months then 500 mg QD for 3 days, 4 days off per week for up to 10 months, depending on the approval date of the protocol amendments at each site. One participant received migalastat 300 mg (QD for 3 days and 4 days off per week) until the end of the study.
Amenable participants were those with mutant forms of α-Gal A determined to be responsive to migalastat treatment based on the CT-HEK assay. Migalastat was administered orally, 150 mg QOD before and after the DEP. During the DEP participants received 250 mg QD for 3 days, 4 days off per week for 2 months then 500 mg QD for 3 days, 4 days off per week for up to 10 months, depending on the approval date of the protocol amendments at each site.
Non-amenable participants were those without mutant forms of α-Gal A as determined by the CT-HEK assay. Migalastat was administered orally, 150 mg QOD before and after the DEP. During the DEP participants received 250 mg QD for 3 days, 4 days off per week for 2 months then 500 mg QD for 3 days, 4 days off per week for up to 10 months, depending on the approval date of the protocol amendments at each site.
Non-amenable participants were those without mutant forms of α-Gal A as determined by the CT-HEK assay. Migalastat was administered orally, 150 mg QOD before and after the DEP. During the DEP participants received 250 mg QD for 3 days, 4 days off per week for 2 months then 500 mg QD for 3 days, 4 days off per week for up to 10 months, depending on the approval date of the protocol amendments at each site.
Overall Number of Participants Analyzed 11 5 3 4
Mean (Standard Deviation)
Unit of Measure: nanomoles (nm)/hour (hr)/mg protein
Baseline Number Analyzed 11 participants 5 participants 3 participants 4 participants
2.08  (2.433) 16.84  (7.955) 0.09  (0.047) 14.62  (8.944)
Month 42 Number Analyzed 7 participants 3 participants 0 participants 4 participants
7.88  (8.691) 18.31  (14.186) 9.77  (5.071)
3.Secondary Outcome
Title Pharmacokinetics Of Migalastat As Assessed By Plasma Concentration
Hide Description The concentration of migalastat was evaluated in plasma following a dose of 250 mg and 500 mg. Blood samples were taken at trough (predose or Time 0; just prior to the third dose during a 3 day on, 4 days off dosing regimen) and at peak (3 hr postdose; after the third dose during a 3 day on, 4 days off dosing regimen) during the Day 1 (250 mg) and Month 2 (500 mg) visits. This outcome presents the lowest and highest concentrations of migalastat measured in any of the participants for predose and 3 hr postdose.
Time Frame 0 (predose on Day 1; start of DEP), 3 hr (postdose at Month 2; during DEP])
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
Hide Arm/Group Description:
Participants received migalastat 150 mg given orally QOD before and after the DEP. During the DEP participants received 250 mg QD for 3 days, 4 days off per week for 2 months then 500 mg QD for 3 days, 4 days off per week for up to 10 months, depending on the approval date of the protocol amendments at each site. One participant received migalastat 300 mg (QD for 3 days and 4 days off per week) until the end of the study.
Overall Number of Participants Analyzed 23
Measure Type: Number
Unit of Measure: nanograms/milliliter
Predose Lowest Concentration 5.94
Predose Highest Concentration 313
250 mg 3 hr Postdose Lowest Concentration 908
250 mg 3 hr Postdose Highest Concentration 5250
500 mg 3 hr Postdose Lowest Concentration 113
500 mg 3 hr Postdose Highest Concentration 8500
Time Frame Day 1 after dosing through EOS (up to 56 months) or follow-up (28 days after EOS). Follow-up was not required for participants who enrolled in Study AT1001-041.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Migalastat
Hide Arm/Group Description Participants received migalastat 150 mg given orally QOD before and after the DEP. During the DEP participants received 250 mg QD for 3 days, 4 days off per week for 2 months then 500 mg QD for 3 days, 4 days off per week for up to 10 months, depending on the approval date of the protocol amendments at each site. One participant received migalastat 300 mg (QD for 3 days and 4 days off per week) until the end of the study.
All-Cause Mortality
Migalastat
Affected / at Risk (%)
Total   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Migalastat
Affected / at Risk (%)
Total   7/23 (30.43%) 
Cardiac disorders   
Atrial Fibrillation  1  2/23 (8.70%) 
Atrial Flutter  1  1/23 (4.35%) 
Atrioventricular Block  1  1/23 (4.35%) 
Cardiac Failure Congestive  1  1/23 (4.35%) 
Ventricular Fibrillation  1  1/23 (4.35%) 
Endocrine disorders   
Hyperthyroidism  1  1/23 (4.35%) 
Gastrointestinal disorders   
Dyspepsia  1  1/23 (4.35%) 
General disorders   
Sensation of Foreign Body  1  1/23 (4.35%) 
Injury, poisoning and procedural complications   
Ankle Fracture  1  1/23 (4.35%) 
Post Procedural Haemorrhage  1  1/23 (4.35%) 
Metabolism and nutrition disorders   
Dehydration  1  1/23 (4.35%) 
Malnutrition  1  1/23 (4.35%) 
Nervous system disorders   
Transient Ischaemic Attack  1  1/23 (4.35%) 
Cerebrovascular Accident  1  1/23 (4.35%) 
Syncope  1  1/23 (4.35%) 
Respiratory, thoracic and mediastinal disorders   
Epistaxis  1  1/23 (4.35%) 
Pneumonia Aspiration  1  1/23 (4.35%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (12.1)
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Migalastat
Affected / at Risk (%)
Total   23/23 (100.00%) 
Blood and lymphatic system disorders   
Lymphadenopathy  1  2/23 (8.70%) 
Cardiac disorders   
Palpitations  1  5/23 (21.74%) 
Sinus bradycardia  1  2/23 (8.70%) 
Congenital, familial and genetic disorders   
Fabry's disease  1  2/23 (8.70%) 
Ear and labyrinth disorders   
Vertigo  1  2/23 (8.70%) 
Eye disorders   
Vision blurred  1  3/23 (13.04%) 
Gastrointestinal disorders   
Abdominal pain upper  1  5/23 (21.74%) 
Diarrhoea  1  5/23 (21.74%) 
Abdominal pain  1  4/23 (17.39%) 
Gastrooesophageal reflux disease  1  4/23 (17.39%) 
Vomiting  1  4/23 (17.39%) 
Abdominal distension  1  2/23 (8.70%) 
Abdominal pain lower  1  2/23 (8.70%) 
Constipation  1  2/23 (8.70%) 
Dry mouth  1  2/23 (8.70%) 
Nausea  1  2/23 (8.70%) 
General disorders   
Fatigue  1  8/23 (34.78%) 
Oedema peripheral  1  3/23 (13.04%) 
Pyrexia  1  3/23 (13.04%) 
Asthenia  1  2/23 (8.70%) 
Chest pain  1  2/23 (8.70%) 
Influenza like illness  1  2/23 (8.70%) 
Irritability  1  2/23 (8.70%) 
Pain  1  2/23 (8.70%) 
Infections and infestations   
Influenza  1  6/23 (26.09%) 
Nasopharyngitis  1  5/23 (21.74%) 
Sinusitis  1  5/23 (21.74%) 
Upper respiratory tract infection  1  4/23 (17.39%) 
Urinary tract infection  1  4/23 (17.39%) 
Cystitis  1  2/23 (8.70%) 
Lower respiratory tract infection  1  2/23 (8.70%) 
Rhinitis  1  2/23 (8.70%) 
Injury, poisoning and procedural complications   
Fall  1  2/23 (8.70%) 
Limb injury  1  2/23 (8.70%) 
Post procedural haematuria  1  2/23 (8.70%) 
Investigations   
Alanine aminotransferase increased  1  2/23 (8.70%) 
Platelet count increased  1  2/23 (8.70%) 
Weight increased  1  2/23 (8.70%) 
Metabolism and nutrition disorders   
Vitamin d deficiency  1  2/23 (8.70%) 
Musculoskeletal and connective tissue disorders   
Arthralgia  1  9/23 (39.13%) 
Back pain  1  8/23 (34.78%) 
Pain in extremity  1  6/23 (26.09%) 
Myalgia  1  5/23 (21.74%) 
Flank pain  1  3/23 (13.04%) 
Muscle spasms  1  3/23 (13.04%) 
Joint swelling  1  2/23 (8.70%) 
Muscle twitching  1  2/23 (8.70%) 
Muscular weakness  1  2/23 (8.70%) 
Musculoskeletal chest pain  1  2/23 (8.70%) 
Musculoskeletal pain  1  2/23 (8.70%) 
Neck pain  1  2/23 (8.70%) 
Osteoarthritis  1  2/23 (8.70%) 
Nervous system disorders   
Headache  1  6/23 (26.09%) 
Dizziness  1  4/23 (17.39%) 
Paraesthesia  1  3/23 (13.04%) 
Migraine  1  2/23 (8.70%) 
Psychiatric disorders   
Insomnia  1  4/23 (17.39%) 
Depression  1  3/23 (13.04%) 
Anxiety  1  2/23 (8.70%) 
Renal and urinary disorders   
Haematuria  1  2/23 (8.70%) 
Respiratory, thoracic and mediastinal disorders   
Cough  1  3/23 (13.04%) 
Oropharyngeal pain  1  3/23 (13.04%) 
Dyspnoea  1  2/23 (8.70%) 
Epistaxis  1  2/23 (8.70%) 
Sinus congestion  1  2/23 (8.70%) 
Skin and subcutaneous tissue disorders   
Dermal cyst  1  2/23 (8.70%) 
Dry skin  1  2/23 (8.70%) 
Rash  1  2/23 (8.70%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (12.1)
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: NCT00526071     History of Changes
Other Study ID Numbers: FAB-CL-205
First Submitted: September 5, 2007
First Posted: September 6, 2007
Results First Submitted: January 9, 2018
Results First Posted: October 3, 2018
Last Update Posted: October 3, 2018