Trial Outcomes & Findings for A 12-Week Safety and Pharmacodynamic Study of AT1001 (Migalastat Hydrochloride) in Participants With Fabry Disease (NCT NCT00283959)
NCT ID: NCT00283959
Last Updated: 2018-10-31
Results Overview
TEAEs were defined as any adverse event with a 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.
COMPLETED
PHASE2
4 participants
Day 1 (after dosing) through Week 48 (end of extension period)
2018-10-31
Participant Flow
Participant milestones
| Measure |
Migalastat
Participants received migalastat 150 milligrams (mg) orally every other day (QOD) during the 12-week treatment period and the optional 36-week extension period.
|
|---|---|
|
Treatment Period
STARTED
|
4
|
|
Treatment Period
Safety Population
|
4
|
|
Treatment Period
Pharmacodynamics (PD) Population
|
4
|
|
Treatment Period
COMPLETED
|
4
|
|
Treatment Period
NOT COMPLETED
|
0
|
|
Extension Period
STARTED
|
4
|
|
Extension Period
COMPLETED
|
3
|
|
Extension Period
NOT COMPLETED
|
1
|
Reasons for withdrawal
| Measure |
Migalastat
Participants received migalastat 150 milligrams (mg) orally every other day (QOD) during the 12-week treatment period and the optional 36-week extension period.
|
|---|---|
|
Extension Period
Low Compliance
|
1
|
Baseline Characteristics
A 12-Week Safety and Pharmacodynamic Study of AT1001 (Migalastat Hydrochloride) in Participants With Fabry Disease
Baseline characteristics by cohort
| Measure |
Migalastat
n=4 Participants
Participants received migalastat 150 mg orally QOD during the 12-week treatment period and the optional 36-week extension period.
|
|---|---|
|
Age, Continuous
|
33.3 years
STANDARD_DEVIATION 21.5 • n=5 Participants
|
|
Sex: Female, Male
Female
|
0 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
4 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Day 1 (after dosing) through Week 48 (end of extension period)Population: Safety Population: all participants who received at least 1 dose of study drug.
TEAEs were defined as any adverse event with a 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.
Outcome measures
| Measure |
Migalastat
n=4 Participants
Participants received migalastat 150 mg orally QOD during the 12-week treatment period and the optional 36-week extension period.
|
|---|---|
|
Number Of Participants Who Experienced Severe Treatment-emergent Adverse Events (TEAEs)
|
1 Participants
|
SECONDARY outcome
Timeframe: Baseline, Week 12 (end of treatment period), Week 48 (end of extension period)Population: PD Population: All participants who received at least 1 dose of study drug and had at least 1 non-missing postbaseline PD parameter recorded. Participants who discontinued prior to the specified time point were not analyzed because no data were available.
PBMCs were isolated from whole blood and lysed, and α-Gal A activity was measured by 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/hour \[hr\]) 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 PBMCs are presented by individual participants. Values of "0" presented below represent α-Gal A activity levels that were below the lower limit of quantification.
Outcome measures
| Measure |
Migalastat
n=4 Participants
Participants received migalastat 150 mg orally QOD during the 12-week treatment period and the optional 36-week extension period.
|
|---|---|
|
α-Galactosidase A (α-Gal A) Activity In Peripheral Blood Mononuclear Cells (PBMC) At Baseline, Week 12, And Week 48
Participant 1 Baseline
|
0.14 nmol 4-MU/hr/mg protein
|
|
α-Galactosidase A (α-Gal A) Activity In Peripheral Blood Mononuclear Cells (PBMC) At Baseline, Week 12, And Week 48
Participant 1 Week 12
|
NA nmol 4-MU/hr/mg protein
Data for this participant were below the limit of quantification.
|
|
α-Galactosidase A (α-Gal A) Activity In Peripheral Blood Mononuclear Cells (PBMC) At Baseline, Week 12, And Week 48
Participant 1 Week 48
|
0.12 nmol 4-MU/hr/mg protein
|
|
α-Galactosidase A (α-Gal A) Activity In Peripheral Blood Mononuclear Cells (PBMC) At Baseline, Week 12, And Week 48
Participant 2 Baseline
|
0.24 nmol 4-MU/hr/mg protein
|
|
α-Galactosidase A (α-Gal A) Activity In Peripheral Blood Mononuclear Cells (PBMC) At Baseline, Week 12, And Week 48
Participant 2 Week 12
|
2.3 nmol 4-MU/hr/mg protein
|
|
α-Galactosidase A (α-Gal A) Activity In Peripheral Blood Mononuclear Cells (PBMC) At Baseline, Week 12, And Week 48
Participant 3 Baseline
|
0.21 nmol 4-MU/hr/mg protein
|
|
α-Galactosidase A (α-Gal A) Activity In Peripheral Blood Mononuclear Cells (PBMC) At Baseline, Week 12, And Week 48
Participant 3 Week 12
|
2.43 nmol 4-MU/hr/mg protein
|
|
α-Galactosidase A (α-Gal A) Activity In Peripheral Blood Mononuclear Cells (PBMC) At Baseline, Week 12, And Week 48
Participant 4 Baseline
|
0.3 nmol 4-MU/hr/mg protein
|
|
α-Galactosidase A (α-Gal A) Activity In Peripheral Blood Mononuclear Cells (PBMC) At Baseline, Week 12, And Week 48
Participant 4 Week 12
|
7.36 nmol 4-MU/hr/mg protein
|
|
α-Galactosidase A (α-Gal A) Activity In Peripheral Blood Mononuclear Cells (PBMC) At Baseline, Week 12, And Week 48
Participant 4 Week 48
|
6.06 nmol 4-MU/hr/mg protein
|
Adverse Events
Migalastat
Serious adverse events
| Measure |
Migalastat
n=4 participants at risk
Participants received migalastat 150 mg orally QOD during the 12-week treatment period and the optional 36-week extension period.
|
|---|---|
|
Cardiac disorders
Atrioventricular block
|
25.0%
1/4 • Day 1 after dosing through Week 48 (end of extension period).
|
Other adverse events
| Measure |
Migalastat
n=4 participants at risk
Participants received migalastat 150 mg orally QOD during the 12-week treatment period and the optional 36-week extension period.
|
|---|---|
|
Cardiac disorders
Atrial Fibrillation
|
25.0%
1/4 • Day 1 after dosing through Week 48 (end of extension period).
|
|
Gastrointestinal disorders
Abdominal Pain Upper
|
50.0%
2/4 • Day 1 after dosing through Week 48 (end of extension period).
|
|
Gastrointestinal disorders
Diarrhoea
|
25.0%
1/4 • Day 1 after dosing through Week 48 (end of extension period).
|
|
Gastrointestinal disorders
Nausea
|
25.0%
1/4 • Day 1 after dosing through Week 48 (end of extension period).
|
|
General disorders
Oedema Peripheral
|
25.0%
1/4 • Day 1 after dosing through Week 48 (end of extension period).
|
|
General disorders
Pyrexia
|
25.0%
1/4 • Day 1 after dosing through Week 48 (end of extension period).
|
|
Cardiac disorders
Bifascicular block
|
25.0%
1/4 • Day 1 after dosing through Week 48 (end of extension period).
|
|
Cardiac disorders
Bundle branch block left
|
25.0%
1/4 • Day 1 after dosing through Week 48 (end of extension period).
|
|
Gastrointestinal disorders
Abdominal discomfort
|
25.0%
1/4 • Day 1 after dosing through Week 48 (end of extension period).
|
|
Gastrointestinal disorders
Abdominal distension
|
25.0%
1/4 • Day 1 after dosing through Week 48 (end of extension period).
|
|
Gastrointestinal disorders
Dyspepsia
|
25.0%
1/4 • Day 1 after dosing through Week 48 (end of extension period).
|
|
General disorders
Fatigue
|
25.0%
1/4 • Day 1 after dosing through Week 48 (end of extension period).
|
|
General disorders
Pain
|
25.0%
1/4 • Day 1 after dosing through Week 48 (end of extension period).
|
|
Infections and infestations
Nasopharyngitis
|
25.0%
1/4 • Day 1 after dosing through Week 48 (end of extension period).
|
|
Investigations
Blood thyroid stimulating hormone increased
|
25.0%
1/4 • Day 1 after dosing through Week 48 (end of extension period).
|
|
Investigations
QRS axis abnormal
|
25.0%
1/4 • Day 1 after dosing through Week 48 (end of extension period).
|
|
Investigations
Venous pressure jugular increased
|
25.0%
1/4 • Day 1 after dosing through Week 48 (end of extension period).
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal stiffness
|
25.0%
1/4 • Day 1 after dosing through Week 48 (end of extension period).
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
25.0%
1/4 • Day 1 after dosing through Week 48 (end of extension period).
|
|
Psychiatric disorders
Nervousness
|
25.0%
1/4 • Day 1 after dosing through Week 48 (end of extension period).
|
|
Renal and urinary disorders
Proteinuria
|
25.0%
1/4 • Day 1 after dosing through Week 48 (end of extension period).
|
|
Renal and urinary disorders
Renal pain
|
25.0%
1/4 • Day 1 after dosing through Week 48 (end of extension period).
|
|
Skin and subcutaneous tissue disorders
Nail discolouration
|
25.0%
1/4 • Day 1 after dosing through Week 48 (end of extension period).
|
|
Vascular disorders
Poor peripheral circulation
|
25.0%
1/4 • Day 1 after dosing through Week 48 (end of extension period).
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee 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.
- Publication restrictions are in place
Restriction type: OTHER