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A Study of AT1001 (Migalastat Hydrochloride) in Participants With Fabry Disease

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ClinicalTrials.gov Identifier: NCT00214500
Recruitment Status : Completed
First Posted : September 22, 2005
Results First Posted : September 7, 2018
Last Update Posted : October 30, 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 9
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Migalastat
Hide Arm/Group Description

Migalastat was administered orally during the 12-week treatment period and then during the optional 2 treatment extension periods.

Treatment Period:

  • Migalastat 25 milligrams (mg) twice a day (BID) for Weeks 1 and 2 (Day 1 through the morning dose on Day 14).
  • Migalastat 100 mg BID for Weeks 3 and 4 (Day 15 through the morning dose on Day 28).
  • Migalastat 250 mg BID for Weeks 5 and 6 (Day 29 through the morning dose on Day 42).
  • Migalastat 25 mg BID for Weeks 6 to 12 (Days 43 to 84).

Extension Period:

  • Migalastat 25 mg BID for Weeks 12 through 48.
  • Migalastat 50 mg once a day (QD) for Weeks 48 through 96.
Period Title: Treatment Period
Started [1] 9 [2]
Safety Population [2] 9
Pharmacokinetic (PK) Population [3] 9
Pharmacodynamic (PD) Population [4] 9
Completed 8
Not Completed 1
Reason Not Completed
Adverse Event             1
[1]
6 additional participants were dosed screen failures and are not included
[2]
All eligible-enrolled participants who received at least 1 dose of study drug
[3]
Received study drug and had at least 1 postbaseline PK parameter recorded
[4]
Received study drug on Day 1 and had a non-missing baseline and postbaseline PD parameter recorded
Period Title: Extension Period
Started 8
Completed 6
Not Completed 2
Reason Not Completed
Withdrawal by Subject             2
Arm/Group Title Migalastat
Hide Arm/Group Description

Migalastat was administered orally during the 12-week treatment period and then during the optional 2 treatment extension periods.

Treatment Period:

  • Migalastat 25 mg BID for Weeks 1 and 2 (Day 1 through the morning dose on Day 14).
  • Migalastat 100 mg BID for Weeks 3 and 4 (Day 15 through the morning dose on Day 28).
  • Migalastat 250 mg BID for Weeks 5 and 6 (Day 29 through the morning dose on Day 42).
  • Migalastat 25 mg BID for Weeks 6 to 12 (Days 43 to 84).

Extension Period:

  • Migalastat 25 mg BID for Weeks 12 through 48.
  • Migalastat 50 mg QD for Weeks 48 through 96.
Overall Number of Baseline Participants 9
Hide Baseline Analysis Population Description
Eligible-enrolled participants who received at least 1 dose of study drug. 6 participants were dosed screen failures, and were not included in safety, PK, or PD analyses.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 9 participants
36.7  (13.0)
Age, Customized   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 9 participants
17 years
1
  11.1%
18 to 55 years
7
  77.8%
58 years
1
  11.1%
[1]
Measure Description: 2 participants (aged 17 and 58) did not meet the age inclusion criterion but were granted approval by the Sponsor for enrollment before migalastat was administered.
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 9 participants
Female
0
   0.0%
Male
9
 100.0%
1.Primary Outcome
Title Number Of Participants Who Experienced Severe Treatment-emergent Adverse Events (TEAEs)
Hide Description 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 96 is presented. A summary of serious and all other non-serious adverse events regardless of causality is located in the Reported Adverse Events module.
Time Frame Day 1 (after dosing) through Week 96
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population: all eligible-enrolled participants who received at least 1 dose of study drug. 6 participants were dosed screen failures, and were not included in the safety analysis.
Arm/Group Title Migalastat
Hide Arm/Group Description:

Migalastat was administered orally during the 12-week treatment period and then during the optional 2 treatment extension periods.

Treatment Period:

  • Migalastat 25 mg BID for Weeks 1 and 2 (Day 1 through the morning dose on Day 14).
  • Migalastat 100 mg BID for Weeks 3 and 4 (Day 15 through the morning dose on Day 28).
  • Migalastat 250 mg BID for Weeks 5 and 6 (Day 29 through the morning dose on Day 42).
  • Migalastat 25 mg BID for Weeks 6 to 12 (Days 43 to 84).

Extension Period:

  • Migalastat 25 mg BID for Weeks 12 through 48.
  • Migalastat 50 mg QD for Weeks 48 through 96.
Overall Number of Participants Analyzed 9
Measure Type: Count of Participants
Unit of Measure: Participants
2
  22.2%
2.Secondary Outcome
Title PK: Area Under The Concentration Versus Time Curve (AUC) After Administration Of Migalastat
Hide Description The AUC from time zero to 12 hours (hr) postdose (AUC0-12) was evaluated in plasma following a single dose of migalastat 25, 100, and 250 mg on Days 1, 15, and 29, respectively. In addition, AUC0-12 was assessed following multiple doses (14 days) of migalastat 25, 100, and 250 mg on Days 14, 28, and 42, respectively.
Time Frame 0 (predose), 0.5, 1, 2, 3, 4, 5, 6, 8, and 10 hr (postdose)
Hide Outcome Measure Data
Hide Analysis Population Description
PK Population: all eligible-enrolled participants who received study drug and had at least 1 postbaseline PK parameter recorded. One participant discontinued prior to receiving doses of migalastat 100 and 250 mg.
Arm/Group Title Migalastat 25 mg Migalastat 100 mg Migalastat 250 mg
Hide Arm/Group Description:
Migalastat was administered orally. Migalastat 25 mg BID for Weeks 1 and 2 (Day 1 through the morning dose on Day 14).
Migalastat was administered orally. Migalastat 100 mg BID for Weeks 3 and 4 (Day 15 through the morning dose on Day 28).
Migalastat was administered orally. Migalastat 250 mg BID for Weeks 5 and 6 (Day 29 through the morning dose on Day 42).
Overall Number of Participants Analyzed 9 8 8
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: nanograms*hr/milliliters (ng*hr/mL)
AUC0-12: Single Dose
1052.96
(29.9%)
4217.95
(32.0%)
10880.66
(32.4%)
AUC0-12: Multiple Dose
1360.69
(32.9%)
5643.50
(25.3%)
12244.47
(26.0%)
3.Secondary Outcome
Title α-Galactosidase A (α-Gal A) Activity In Leukocytes At Baseline, Week 12, And Week 96
Hide Description Leukocytes 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/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.
Time Frame Baseline, Week 12 (end of treatment period), Week 96 (end of extension period)
Hide Outcome Measure Data
Hide Analysis Population Description
PD Population: all eligible-enrolled participants who received at least 1 dose of study drug on Day 1, and who had a non-missing baseline and 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.
Arm/Group Title Migalastat
Hide Arm/Group Description:

Migalastat was administered orally during the 12-week treatment period and then during the optional 2 treatment extension periods.

Treatment Period:

  • Migalastat 25 mg BID for Weeks 1 and 2 (Day 1 through the morning dose on Day 14).
  • Migalastat 100 mg BID for Weeks 3 and 4 (Day 15 through the morning dose on Day 28).
  • Migalastat 250 mg BID for Weeks 5 and 6 (Day 29 through the morning dose on Day 42).
  • Migalastat 25 mg BID for Weeks 6 to 12 (Days 43 to 84).

Extension Period:

  • Migalastat 25 mg BID for Weeks 12 through 48.
  • Migalastat 50 mg QD for Weeks 48 through 96.
Overall Number of Participants Analyzed 9
Measure Type: Number
Unit of Measure: nmol 4-MU/hr/mg protein
Participant 1: Baseline Number Analyzed 1 participants
5.2
Participant 1: Week 12 Number Analyzed 1 participants
17.4
Participant 1: Week 96 Number Analyzed 1 participants
20.3
Participant 2: Baseline Number Analyzed 1 participants
4.7
Participant 2: Week 12 Number Analyzed 1 participants
24.6
Participant 2: Week 96 Number Analyzed 1 participants
22.8
Participant 3: Baseline Number Analyzed 1 participants
6.6
Participant 3: Week 12 Number Analyzed 1 participants
24.6
Participant 3: Week 96 Number Analyzed 1 participants
20.3
Participant 4: Baseline Number Analyzed 1 participants
1.0
Participant 4: Week 12 Number Analyzed 1 participants
14.8
Participant 4: Week 96 Number Analyzed 1 participants
12.8
Participant 5: Baseline Number Analyzed 1 participants
10.7
Participant 5: Week 12 Number Analyzed 0 participants
Participant 5: Week 96 Number Analyzed 0 participants
Participant 6: Baseline Number Analyzed 1 participants
0.9
Participant 6: Week 12 Number Analyzed 1 participants
3.9
Participant 6: Week 96 Number Analyzed 1 participants
1.9
Participant 7: Baseline Number Analyzed 1 participants
0.0
Participant 7: Week 12 Number Analyzed 1 participants
0.4
Participant 7: Week 96 Number Analyzed 0 participants
Participant 8: Baseline Number Analyzed 1 participants
0.1
Participant 8: Week 12 Number Analyzed 1 participants
0.9
Participant 8: Week 96 Number Analyzed 0 participants
Participant 9: Baseline Number Analyzed 1 participants
0.2
Participant 9: Week 12 Number Analyzed 1 participants
0.3
Participant 9: Week 96 Number Analyzed 1 participants
0.2
Time Frame Day 1 after dosing through Week 96 (end of extension period)
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Migalastat
Hide Arm/Group Description

Migalastat was administered orally during the 12-week treatment period and then during the optional 2 treatment extension periods.

Treatment Period:

  • Migalastat 25 mg BID for Weeks 1 and 2 (Day 1 through the morning dose on Day 14).
  • Migalastat 100 mg BID for Weeks 3 and 4 (Day 15 through the morning dose on Day 28).
  • Migalastat 250 mg BID for Weeks 5 and 6 (Day 29 through the morning dose on Day 42).
  • Migalastat 25 mg BID for Weeks 6 to 12 (Days 43 to 84).

Extension Period:

  • Migalastat 25 mg BID for Weeks 12 through 48.
  • Migalastat 50 mg QD for Weeks 48 through 96.
All-Cause Mortality
Migalastat
Affected / at Risk (%)
Total   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Migalastat
Affected / at Risk (%)
Total   0/9 (0.00%) 
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   9/9 (100.00%) 
Cardiac disorders   
Arrhythmia  1  1/9 (11.11%) 
Ear and labyrinth disorders   
Deafness  1  1/9 (11.11%) 
Ear pain  1  1/9 (11.11%) 
Vertigo  1  2/9 (22.22%) 
Gastrointestinal disorders   
Abdominal pain upper  1  2/9 (22.22%) 
Constipation  1  1/9 (11.11%) 
Diarrhoea  1  2/9 (22.22%) 
Dry mouth  1  2/9 (22.22%) 
Dyspepsia  1  1/9 (11.11%) 
Gingival pain  1  1/9 (11.11%) 
Nausea  1  4/9 (44.44%) 
Odynophagia  1  1/9 (11.11%) 
Oral pain  1  1/9 (11.11%) 
General disorders   
Fatigue  1  1/9 (11.11%) 
Hunger  1  1/9 (11.11%) 
Influenza like illness  1  1/9 (11.11%) 
Oedema peripheral  1  1/9 (11.11%) 
Pain  1  2/9 (22.22%) 
Pyrexia  1  1/9 (11.11%) 
Thirst  1  1/9 (11.11%) 
Infections and infestations   
Giardiasis  1  1/9 (11.11%) 
Nasopharyngitis  1  1/9 (11.11%) 
Respiratory tract infection  1  1/9 (11.11%) 
Tinea versicolour  1  1/9 (11.11%) 
Urinary tract infection  1  1/9 (11.11%) 
Injury, poisoning and procedural complications   
Femur fracture  1  1/9 (11.11%) 
Investigations   
Blood bilirubin increased  1  1/9 (11.11%) 
Blood creatine phosphokinase increased  1  1/9 (11.11%) 
Blood glucose increased  1  1/9 (11.11%) 
Musculoskeletal and connective tissue disorders   
Back pain  1  2/9 (22.22%) 
Chest wall pain  1  1/9 (11.11%) 
Groin pain  1  1/9 (11.11%) 
Muscle spasms  1  1/9 (11.11%) 
Musculoskeletal pain  1  1/9 (11.11%) 
Myalgia  1  2/9 (22.22%) 
Pain in extremity  1  2/9 (22.22%) 
Shoulder pain  1  1/9 (11.11%) 
Nervous system disorders   
Headache  1  5/9 (55.56%) 
Psychiatric disorders   
Bipolar disorder  1  1/9 (11.11%) 
Insomnia  1  2/9 (22.22%) 
Libido decreased  1  1/9 (11.11%) 
Renal and urinary disorders   
Dysuria  1  1/9 (11.11%) 
Haematuria  1  1/9 (11.11%) 
Micturition urgency  1  1/9 (11.11%) 
Respiratory, thoracic and mediastinal disorders   
Asthma  1  1/9 (11.11%) 
Cough  1  1/9 (11.11%) 
Epistaxis  1  1/9 (11.11%) 
Nasal congestion  1  1/9 (11.11%) 
Pharyngolaryngeal pain  1  1/9 (11.11%) 
Pleuritic pain  1  1/9 (11.11%) 
Respiratory tract irritation  1  1/9 (11.11%) 
Upper respiratory tract congestion  1  1/9 (11.11%) 
Skin and subcutaneous tissue disorders   
Angiokeratoma  1  1/9 (11.11%) 
Hyperhidrosis  1  1/9 (11.11%) 
Vascular disorders   
Hypertension  1  1/9 (11.11%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 8.0
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: NCT00214500     History of Changes
Obsolete Identifiers: NCT00231036
Other Study ID Numbers: FAB-CL-201 (AA1565520)
First Submitted: September 13, 2005
First Posted: September 22, 2005
Results First Submitted: August 10, 2018
Results First Posted: September 7, 2018
Last Update Posted: October 30, 2018