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Open-Label Phase 3 Long-Term Safety Study of Migalastat (AT1001-041)

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ClinicalTrials.gov Identifier: NCT01458119
Recruitment Status : Terminated (Amicus Therapeutics discontinued Study AT1001-041 for logistical reasons.)
First Posted : October 24, 2011
Results First Posted : October 2, 2018
Last Update Posted : October 2, 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 hydrochloride
Enrollment 85
Recruitment Details Eighty-five eligible participants with Fabry disease who completed treatment with migalastat in one of three previous studies (AT1001-011 [NCT00925301], AT1001-012 [NCT01218659], or FAB-CL-205 [NCT00526071]) were enrolled in this open-label extension study to enable the collection of long-term safety and efficacy data.
Pre-assignment Details  
Arm/Group Title Migalastat
Hide Arm/Group Description Participants received migalastat hydrochloride (migalastat) 150-milligram (mg) capsule (equivalent to 123 mg of migalastat) given orally once every other day (QOD) for a median duration of 23.5 months (m). Participants received an inactive reminder capsule on alternate days during the study.
Period Title: Overall Study
Started 85
Received at Least 1 Dose of Study Drug 85
Safety Population 85
Intent to Treat (ITT) Population [1] 85
ITT-Amenable Population [2] 68
Completed 65
Not Completed 20
Reason Not Completed
Physician Decision             4
Withdrawal Due to Nonamenable Mutation             1
Pregnancy             1
Death             2
Adverse Event             1
Consent Withdrawn by Participant             8
Non-compliance With Study Drug             3
[1]
Received at least 1 dose of study drug.
[2]
Amenable mutations based on Good Laboratory Practice (GLP) Human Embryonic Kidney (HEK) assay.
Arm/Group Title Migalastat
Hide Arm/Group Description Participants received migalastat 150-mg capsule given orally QOD for a median duration of 23.5 m. Participants received an inactive reminder capsule on alternate days during the study.
Overall Number of Baseline Participants 85
Hide Baseline Analysis Population Description
ITT Population: All participants who received at least 1 dose of study drug after they enrolled into this open-label extension study.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 85 participants
48.8  (12.25)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 85 participants
Female
52
  61.2%
Male
33
  38.8%
1.Primary Outcome
Title Number Of Participants Experiencing Treatment-emergent Adverse Events (TEAEs)
Hide Description An adverse event (AE) was defined as any untoward medical occurrence in a participant administered migalastat that did not necessarily have a causal relationship with the treatment. Each AE was recorded at the time of reporting; visits typically occurred every 6 months. A TEAE was defined as an AE starting on or after the first study drug administration date. Serious AEs were life-threatening or resulted in death, persistent or significant incapacitation, inpatient or prolonged hospitalization, or a congenital anomaly. The criteria for AE severity were: Mild: minimal discomfort, does not interfere with normal everyday activities; Moderate: sufficiently discomforting, interferes with normal everyday activities; Severe: prevents normal everyday activities. The number of participants experiencing TEAEs is presented for those who received migalastat treatment. A summary of serious and all other non-serious AEs regardless of causality is located in the Reported Adverse Events module.
Time Frame Baseline to End of Follow-up (30 days after the end of this 42-month study), with AE reporting occurring at each study visit, which occurred once every 6 months.
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population: All participants who received at least 1 dose of study drug after they enrolled into this open-label extension study.
Arm/Group Title Migalastat
Hide Arm/Group Description:
Participants received migalastat 150-mg capsule given orally QOD for a median duration of 23.5 m. Participants received an inactive reminder capsule on alternate days during the study.
Overall Number of Participants Analyzed 85
Measure Type: Number
Unit of Measure: participants
Participants with at least 1 TEAE 74
Participants with at least 1 serious TEAE 22
Participants discontinued due to TEAEs 1
Participants with adverse events leading to death 2
Participants with TEAEs related to study drug 14
Participants with TEAEs unrelated to study drug 60
Participants with at least 1 mild TEAE 22
Participants with at least 1 moderate TEAE 40
Participants with at least 1 severe TEAE 12
2.Secondary Outcome
Title Annualized Rate Of Change In The Estimated Glomerular Filtration Rate (eGFR)
Hide Description

The annualized rate of change of the eGFR was assessed per participant by the slope of the simple linear regression between the observed values and the assessment times. It was calculated by using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation (eGFR [CKD-EPI]) and the Modification of Diet in Renal Disease (MDRD) equation (eGFR [MDRD]). The equations are as follows:

eGFR [MDRD] = 175 * (Serum Creatinine)^–1.154 * (Age)^–0.203 * 1.212 (if black or African American) * 0.742 (if female); eGFR [CKD-EPI] = 141 * min(serum creatinine/kappa,1)^alpha * max(serum creatinine/kappa, 1)^-1.209 * 0.993^age * 1.1018(if female) * 1.159(if black or African American), where kappa is 0.7 for females and 0.9 for males, alpha is -0.329 for females and -0.411 for males, min is minimum of serum creatinine/kappa or 1, and max is the maximum of serum creatinine/kappa or 1. The number of participants with at least a Baseline and a post-Baseline value are presented.

Time Frame Baseline, Every 6 m until the End of Study (42 m)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT-Amenable Population: All participants who received at least 1 dose of study drug. Participants with mutant forms of α-Galactosidase (Gal) A determined to be amenable to migalastat based on the GLP-HEK assay are referred to as “with amenable mutations." Number of participants analyzed are those with at least a Baseline and a post-Baseline value.
Arm/Group Title Migalastat ITT-Amenable Population
Hide Arm/Group Description:
Participants received migalastat 150-mg capsule given orally QOD for a median duration of 23.5 m. Participants received an inactive reminder capsule on alternate days during the study. The ITT-amenable population included all participants who received at least 1 dose of study drug after they enrolled into this open-label extension study. Participants with mutant forms of α-Gal A determined to be amenable to migalastat treatment based on the GLP-HEK assay are referred to as "with amenable mutations."
Overall Number of Participants Analyzed 47
Mean (95% Confidence Interval)
Unit of Measure: milliliters/minute/1.73 meters^2
EGFR [CKD-EPI]
1.54
(-1.63 to 4.71)
eGFR [MDRD]
1.40
(-3.14 to 5.94)
Time Frame Baseline to End of Follow-up (30 days after the end of this 42-month study), with AE reporting occurring at each study visit, which occurred once every 6 months.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Migalastat
Hide Arm/Group Description Participants received migalastat 150-mg capsule given orally QOD for a median duration of 23.5 m. Participants received an inactive reminder capsule on alternate days during the study.
All-Cause Mortality
Migalastat
Affected / at Risk (%)
Total   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Migalastat
Affected / at Risk (%)
Total   22/85 (25.88%) 
Cardiac disorders   
Angina pectoris  1  1/85 (1.18%) 
Atrial fibrillation  1  2/85 (2.35%) 
Endocrine disorders   
Thyroid mass  1  1/85 (1.18%) 
Gastrointestinal disorders   
Abdominal pain upper  1  1/85 (1.18%) 
Hiatus hernia  1  1/85 (1.18%) 
Pancreatitis  1  1/85 (1.18%) 
General disorders   
Death  1  1/85 (1.18%) 
Device malfunction  1  1/85 (1.18%) 
Hepatobiliary disorders   
Hepatic infarction  1  1/85 (1.18%) 
Infections and infestations   
Pneumonia  1  2/85 (2.35%) 
Injury, poisoning and procedural complications   
Foot fracture  1  1/85 (1.18%) 
Musculoskeletal and connective tissue disorders   
Muscle spasms  1  1/85 (1.18%) 
Musculoskeletal chest pain  1  1/85 (1.18%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)   
Breast cancer metastatic  1  1/85 (1.18%) 
Metastatic squamous cell carcinoma  1  1/85 (1.18%) 
Papillary thyroid cancer  1  1/85 (1.18%) 
Nervous system disorders   
Brain stem ischaemia  1  1/85 (1.18%) 
Hemiplegic migraine  1  1/85 (1.18%) 
Presyncope  1  1/85 (1.18%) 
Psychiatric disorders   
Conversion disorder  1  1/85 (1.18%) 
Renal and urinary disorders   
Calculus urinary  1  1/85 (1.18%) 
Reproductive system and breast disorders   
Priapism  1  1/33 (3.03%) 
Uterine polyp  1  1/52 (1.92%) 
Skin and subcutaneous tissue disorders   
Angioedema  1  1/85 (1.18%) 
Skin lesion  1  1/85 (1.18%) 
Surgical and medical procedures   
Implantable defibrillator insertion  1  2/85 (2.35%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 16.1
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   57/85 (67.06%) 
Cardiac disorders   
Atrial fibrillation  1  7/85 (8.24%) 
Palpitations  1  5/85 (5.88%) 
Ear and labyrinth disorders   
Vertigo  1  5/85 (5.88%) 
Gastrointestinal disorders   
Abdominal distension  1  5/85 (5.88%) 
Abdominal pain upper  1  5/85 (5.88%) 
Constipation  1  6/85 (7.06%) 
Nausea  1  10/85 (11.76%) 
Diarrhoea  1  13/85 (15.29%) 
General disorders   
Fatigue  1  9/85 (10.59%) 
Oedema peripheral  1  6/85 (7.06%) 
Pain  1  5/85 (5.88%) 
Pyrexia  1  7/85 (8.24%) 
Infections and infestations   
Influenza  1  9/85 (10.59%) 
Nasopharyngitis  1  9/85 (10.59%) 
Upper respiratory tract infection  1  6/85 (7.06%) 
Urinary Tract Infection  1  8/85 (9.41%) 
Injury, poisoning and procedural complications   
Contusion  1  5/85 (5.88%) 
Musculoskeletal and connective tissue disorders   
Arthralgia  1  11/85 (12.94%) 
Back pain  1  6/85 (7.06%) 
Pain in extremity  1  11/85 (12.94%) 
Nervous system disorders   
Headache  1  11/85 (12.94%) 
Dizziness  1  9/85 (10.59%) 
Paraesthesia  1  5/85 (5.88%) 
Psychiatric disorders   
Anxiety  1  5/85 (5.88%) 
Respiratory, thoracic and mediastinal disorders   
Cough  1  6/85 (7.06%) 
Vascular disorders   
Hypertension  1  6/85 (7.06%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 16.1
The study was discontinued for logistical reasons and not due to either safety concerns or lack of efficacy. The investigators were offered participation in a similar long-term migalastat study for participants ongoing at discontinuation.
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 publish only the results from this trial, provided they supply the sponsor (or authorized entity) a copy of any proposed publication for review prior to submission for publication. If requested and prior to publication, the investigator will remove information deemed confidential or proprietary by the sponsor and will withhold publication 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: Medical Affairs
Organization: Amicus Therapeutics
Phone: +1-877-426-4287 (877-4-AMICUS)
Responsible Party: Amicus Therapeutics
ClinicalTrials.gov Identifier: NCT01458119     History of Changes
Other Study ID Numbers: AT1001-041
2011-004800-40 ( EudraCT Number )
First Submitted: October 20, 2011
First Posted: October 24, 2011
Results First Submitted: August 10, 2018
Results First Posted: October 2, 2018
Last Update Posted: October 2, 2018