Trial Outcomes & Findings for Open-Label Phase 3 Long-Term Safety Study of Migalastat (NCT NCT01458119)
NCT ID: NCT01458119
Last Updated: 2018-10-02
Results Overview
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.
Recruitment status
TERMINATED
Study phase
PHASE3
Target enrollment
85 participants
Primary outcome timeframe
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.
Results posted on
2018-10-02
Participant Flow
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.
Participant milestones
| Measure |
Migalastat
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.
|
|---|---|
|
Overall Study
STARTED
|
85
|
|
Overall Study
Received at Least 1 Dose of Study Drug
|
85
|
|
Overall Study
Safety Population
|
85
|
|
Overall Study
Intent to Treat (ITT) Population
|
85
|
|
Overall Study
ITT-Amenable Population
|
68
|
|
Overall Study
COMPLETED
|
65
|
|
Overall Study
NOT COMPLETED
|
20
|
Reasons for withdrawal
| Measure |
Migalastat
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.
|
|---|---|
|
Overall Study
Physician Decision
|
4
|
|
Overall Study
Withdrawal Due to Nonamenable Mutation
|
1
|
|
Overall Study
Pregnancy
|
1
|
|
Overall Study
Death
|
2
|
|
Overall Study
Adverse Event
|
1
|
|
Overall Study
Consent Withdrawn by Participant
|
8
|
|
Overall Study
Non-compliance With Study Drug
|
3
|
Baseline Characteristics
Open-Label Phase 3 Long-Term Safety Study of Migalastat
Baseline characteristics by cohort
| Measure |
Migalastat
n=85 Participants
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.
|
|---|---|
|
Age, Continuous
|
48.8 years
STANDARD_DEVIATION 12.25 • n=5 Participants
|
|
Sex: Female, Male
Female
|
52 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
33 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 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.Population: Safety Population: All participants who received at least 1 dose of study drug after they enrolled into this open-label extension study.
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.
Outcome measures
| Measure |
Migalastat
n=85 Participants
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.
|
|---|---|
|
Number Of Participants Experiencing Treatment-emergent Adverse Events (TEAEs)
Participants with at least 1 TEAE
|
74 participants
|
|
Number Of Participants Experiencing Treatment-emergent Adverse Events (TEAEs)
Participants with at least 1 serious TEAE
|
22 participants
|
|
Number Of Participants Experiencing Treatment-emergent Adverse Events (TEAEs)
Participants discontinued due to TEAEs
|
1 participants
|
|
Number Of Participants Experiencing Treatment-emergent Adverse Events (TEAEs)
Participants with adverse events leading to death
|
2 participants
|
|
Number Of Participants Experiencing Treatment-emergent Adverse Events (TEAEs)
Participants with TEAEs related to study drug
|
14 participants
|
|
Number Of Participants Experiencing Treatment-emergent Adverse Events (TEAEs)
Participants with TEAEs unrelated to study drug
|
60 participants
|
|
Number Of Participants Experiencing Treatment-emergent Adverse Events (TEAEs)
Participants with at least 1 mild TEAE
|
22 participants
|
|
Number Of Participants Experiencing Treatment-emergent Adverse Events (TEAEs)
Participants with at least 1 moderate TEAE
|
40 participants
|
|
Number Of Participants Experiencing Treatment-emergent Adverse Events (TEAEs)
Participants with at least 1 severe TEAE
|
12 participants
|
SECONDARY outcome
Timeframe: Baseline, Every 6 m until the End of Study (42 m)Population: 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.
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.
Outcome measures
| Measure |
Migalastat
n=47 Participants
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.
|
|---|---|
|
Annualized Rate Of Change In The Estimated Glomerular Filtration Rate (eGFR)
EGFR [CKD-EPI]
|
1.54 milliliters/minute/1.73 meters^2
Interval -1.63 to 4.71
|
|
Annualized Rate Of Change In The Estimated Glomerular Filtration Rate (eGFR)
eGFR [MDRD]
|
1.40 milliliters/minute/1.73 meters^2
Interval -3.14 to 5.94
|
Adverse Events
Migalastat
Serious events: 22 serious events
Other events: 57 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Migalastat
n=85 participants at risk
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.
|
|---|---|
|
Reproductive system and breast disorders
Priapism
|
3.0%
1/33 • 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.
|
|
Reproductive system and breast disorders
Uterine polyp
|
1.9%
1/52 • 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.
|
|
Injury, poisoning and procedural complications
Foot fracture
|
1.2%
1/85 • 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.
|
|
Surgical and medical procedures
Implantable defibrillator insertion
|
2.4%
2/85 • 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.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast cancer metastatic
|
1.2%
1/85 • 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.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastatic squamous cell carcinoma
|
1.2%
1/85 • 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.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Papillary thyroid cancer
|
1.2%
1/85 • 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.
|
|
General disorders
Death
|
1.2%
1/85 • 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.
|
|
General disorders
Device malfunction
|
1.2%
1/85 • 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.
|
|
Psychiatric disorders
Conversion disorder
|
1.2%
1/85 • 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.
|
|
Cardiac disorders
Angina pectoris
|
1.2%
1/85 • 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.
|
|
Cardiac disorders
Atrial fibrillation
|
2.4%
2/85 • 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.
|
|
Nervous system disorders
Brain stem ischaemia
|
1.2%
1/85 • 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.
|
|
Nervous system disorders
Hemiplegic migraine
|
1.2%
1/85 • 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.
|
|
Nervous system disorders
Presyncope
|
1.2%
1/85 • 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.
|
|
Gastrointestinal disorders
Abdominal pain upper
|
1.2%
1/85 • 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.
|
|
Gastrointestinal disorders
Hiatus hernia
|
1.2%
1/85 • 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.
|
|
Gastrointestinal disorders
Pancreatitis
|
1.2%
1/85 • 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.
|
|
Hepatobiliary disorders
Hepatic infarction
|
1.2%
1/85 • 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.
|
|
Renal and urinary disorders
Calculus urinary
|
1.2%
1/85 • 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.
|
|
Skin and subcutaneous tissue disorders
Angioedema
|
1.2%
1/85 • 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.
|
|
Skin and subcutaneous tissue disorders
Skin lesion
|
1.2%
1/85 • 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.
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
1.2%
1/85 • 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.
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal chest pain
|
1.2%
1/85 • 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.
|
|
Endocrine disorders
Thyroid mass
|
1.2%
1/85 • 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.
|
|
Infections and infestations
Pneumonia
|
2.4%
2/85 • 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.
|
Other adverse events
| Measure |
Migalastat
n=85 participants at risk
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.
|
|---|---|
|
Vascular disorders
Hypertension
|
7.1%
6/85 • 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.
|
|
Injury, poisoning and procedural complications
Contusion
|
5.9%
5/85 • 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.
|
|
Cardiac disorders
Atrial fibrillation
|
8.2%
7/85 • 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.
|
|
Cardiac disorders
Palpitations
|
5.9%
5/85 • 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.
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
7.1%
6/85 • 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.
|
|
Nervous system disorders
Headache
|
12.9%
11/85 • 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.
|
|
Nervous system disorders
Dizziness
|
10.6%
9/85 • 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.
|
|
Nervous system disorders
Paraesthesia
|
5.9%
5/85 • 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.
|
|
General disorders
Fatigue
|
10.6%
9/85 • 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.
|
|
General disorders
Oedema peripheral
|
7.1%
6/85 • 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.
|
|
General disorders
Pain
|
5.9%
5/85 • 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.
|
|
General disorders
Pyrexia
|
8.2%
7/85 • 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.
|
|
Ear and labyrinth disorders
Vertigo
|
5.9%
5/85 • 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.
|
|
Psychiatric disorders
Anxiety
|
5.9%
5/85 • 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.
|
|
Gastrointestinal disorders
Abdominal distension
|
5.9%
5/85 • 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.
|
|
Gastrointestinal disorders
Abdominal pain upper
|
5.9%
5/85 • 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.
|
|
Gastrointestinal disorders
Constipation
|
7.1%
6/85 • 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.
|
|
Gastrointestinal disorders
Nausea
|
11.8%
10/85 • 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.
|
|
Gastrointestinal disorders
Diarrhoea
|
15.3%
13/85 • 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.
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
12.9%
11/85 • 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.
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
7.1%
6/85 • 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.
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
12.9%
11/85 • 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.
|
|
Infections and infestations
Influenza
|
10.6%
9/85 • 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.
|
|
Infections and infestations
Nasopharyngitis
|
10.6%
9/85 • 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.
|
|
Infections and infestations
Upper respiratory tract infection
|
7.1%
6/85 • 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.
|
|
Infections and infestations
Urinary Tract Infection
|
9.4%
8/85 • 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.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee 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.
- Publication restrictions are in place
Restriction type: OTHER