Trial Outcomes & Findings for A 24-Week Safety and Pharmacodynamic Study of AT1001 (Migalastat Hydrochloride) in Participants With Fabry Disease (NCT NCT00283933)

NCT ID: NCT00283933

Last Updated: 2018-09-07

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

5 participants

Primary outcome timeframe

Day 1 (after dosing) through Week 48

Results posted on

2018-09-07

Participant Flow

Participant milestones

Participant milestones
Measure
Migalastat
Migalastat 150 milligrams (mg) was administered orally QOD during the 24-week treatment period and then during the optional 24-week extension period.
Treatment Period
STARTED
5
Treatment Period
Safety Population
5
Treatment Period
Pharmacodynamic (PD) Population
5
Treatment Period
COMPLETED
5
Treatment Period
NOT COMPLETED
0
Extension Period
STARTED
5
Extension Period
COMPLETED
5
Extension Period
NOT COMPLETED
0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

A 24-Week Safety and Pharmacodynamic Study of AT1001 (Migalastat Hydrochloride) in Participants With Fabry Disease

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Migalastat
n=5 Participants
Migalastat 150 mg was administered orally QOD during the 24-week treatment period and then during the optional 24-week extension period.
Age, Continuous
41.6 years
STANDARD_DEVIATION 9.5 • n=5 Participants
Sex: Female, Male
Female
0 Participants
n=5 Participants
Sex: Female, Male
Male
5 Participants
n=5 Participants

PRIMARY outcome

Timeframe: Day 1 (after dosing) through Week 48

Population: Safety Population: All participants who received at least 1 dose of study drug.

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.

Outcome measures

Outcome measures
Measure
Migalastat
n=5 Participants
Migalastat 150 mg was administered orally QOD during the 24-week treatment period and then during the optional 24-week extension period.
Number Of Participants Who Experienced Severe Treatment-emergent Adverse Events (TEAEs)
0 Participants

SECONDARY outcome

Timeframe: Baseline, Week 24 (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.

PBMC 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/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 leukocytes are presented by individual participants.

Outcome measures

Outcome measures
Measure
Migalastat
n=5 Participants
Migalastat 150 mg was administered orally QOD during the 24-week treatment period and then during the optional 24-week extension period.
α-Galactosidase A (α-Gal A) Activity In Peripheral Blood Mononuclear Cells (PBMC) At Baseline, Week 24, And Week 48
Participant 1: Baseline
0.05 nmol 4-MU/hr/mg protein
α-Galactosidase A (α-Gal A) Activity In Peripheral Blood Mononuclear Cells (PBMC) At Baseline, Week 24, And Week 48
Participant 1: Week 24
0.36 nmol 4-MU/hr/mg protein
α-Galactosidase A (α-Gal A) Activity In Peripheral Blood Mononuclear Cells (PBMC) At Baseline, Week 24, And Week 48
Participant 1: Week 48
0.1 nmol 4-MU/hr/mg protein
α-Galactosidase A (α-Gal A) Activity In Peripheral Blood Mononuclear Cells (PBMC) At Baseline, Week 24, And Week 48
Participant 2: Baseline
0.06 nmol 4-MU/hr/mg protein
α-Galactosidase A (α-Gal A) Activity In Peripheral Blood Mononuclear Cells (PBMC) At Baseline, Week 24, And Week 48
Participant 2: Week 24
0.13 nmol 4-MU/hr/mg protein
α-Galactosidase A (α-Gal A) Activity In Peripheral Blood Mononuclear Cells (PBMC) At Baseline, Week 24, And Week 48
Participant 2: Week 48
0.1 nmol 4-MU/hr/mg protein
α-Galactosidase A (α-Gal A) Activity In Peripheral Blood Mononuclear Cells (PBMC) At Baseline, Week 24, And Week 48
Participant 3: 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 24, And Week 48
Participant 3: Week 24
0.3 nmol 4-MU/hr/mg protein
α-Galactosidase A (α-Gal A) Activity In Peripheral Blood Mononuclear Cells (PBMC) At Baseline, Week 24, And Week 48
Participant 3: Week 48
0.33 nmol 4-MU/hr/mg protein
α-Galactosidase A (α-Gal A) Activity In Peripheral Blood Mononuclear Cells (PBMC) At Baseline, Week 24, And Week 48
Participant 4: Baseline
3.4 nmol 4-MU/hr/mg protein
α-Galactosidase A (α-Gal A) Activity In Peripheral Blood Mononuclear Cells (PBMC) At Baseline, Week 24, And Week 48
Participant 4: Week 24
10.9 nmol 4-MU/hr/mg protein
α-Galactosidase A (α-Gal A) Activity In Peripheral Blood Mononuclear Cells (PBMC) At Baseline, Week 24, And Week 48
Participant 4: Week 48
7.4 nmol 4-MU/hr/mg protein
α-Galactosidase A (α-Gal A) Activity In Peripheral Blood Mononuclear Cells (PBMC) At Baseline, Week 24, And Week 48
Participant 5: Baseline
0.18 nmol 4-MU/hr/mg protein
α-Galactosidase A (α-Gal A) Activity In Peripheral Blood Mononuclear Cells (PBMC) At Baseline, Week 24, And Week 48
Participant 5: Week 24
1.32 nmol 4-MU/hr/mg protein
α-Galactosidase A (α-Gal A) Activity In Peripheral Blood Mononuclear Cells (PBMC) At Baseline, Week 24, And Week 48
Participant 5: Week 48
0.13 nmol 4-MU/hr/mg protein

Adverse Events

Migalastat

Serious events: 0 serious events
Other events: 5 other events
Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure
Migalastat
n=5 participants at risk
Migalastat 150 mg was administered orally QOD during the 24-week treatment period and then during the optional 24-week extension period.
Cardiac disorders
Ventricular tachycardia
20.0%
1/5 • Day 1 after dosing through Week 48 (end of extension period)
Gastrointestinal disorders
Diarrhoea
20.0%
1/5 • Day 1 after dosing through Week 48 (end of extension period)
Infections and infestations
Gastroenteritis
20.0%
1/5 • Day 1 after dosing through Week 48 (end of extension period)
Infections and infestations
Nasopharyngitis
20.0%
1/5 • Day 1 after dosing through Week 48 (end of extension period)
Investigations
Gamma-glutamyltransferase increased
20.0%
1/5 • Day 1 after dosing through Week 48 (end of extension period)
Metabolism and nutrition disorders
Gout
20.0%
1/5 • Day 1 after dosing through Week 48 (end of extension period)
Musculoskeletal and connective tissue disorders
Arthralgia
20.0%
1/5 • Day 1 after dosing through Week 48 (end of extension period)
Musculoskeletal and connective tissue disorders
Bursitis
20.0%
1/5 • Day 1 after dosing through Week 48 (end of extension period)
Musculoskeletal and connective tissue disorders
Joint swelling
20.0%
1/5 • Day 1 after dosing through Week 48 (end of extension period)
Renal and urinary disorders
Haematuria
20.0%
1/5 • Day 1 after dosing through Week 48 (end of extension period)
Renal and urinary disorders
Proteinuria
40.0%
2/5 • Day 1 after dosing through Week 48 (end of extension period)
Reproductive system and breast disorders
Scrotal mass
20.0%
1/5 • Day 1 after dosing through Week 48 (end of extension period)
Skin and subcutaneous tissue disorders
Pruritis
20.0%
1/5 • Day 1 after dosing through Week 48 (end of extension period)
Injury, poisoning and procedural complications
Contusion
20.0%
1/5 • Day 1 after dosing through Week 48 (end of extension period)
Injury, poisoning and procedural complications
Muscle strain
20.0%
1/5 • Day 1 after dosing through Week 48 (end of extension period)
Nervous system disorders
Dizziness
20.0%
1/5 • Day 1 after dosing through Week 48 (end of extension period)
Nervous system disorders
Headache
40.0%
2/5 • Day 1 after dosing through Week 48 (end of extension period)
Respiratory, thoracic and mediastinal disorders
Cough
20.0%
1/5 • Day 1 after dosing through Week 48 (end of extension period)

Additional Information

Amicus Therapeutics

Medical Affairs

Phone: +1-877-426-4287 (877-4-AMICUS)

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