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Study to Evaluate the Safety of AT2220 (Duvoglustat) in Pompe Disease

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ClinicalTrials.gov Identifier: NCT00688597
Recruitment Status : Terminated (Per protocol, 3 sequential dose cohorts were planned. Study discontinued by Sponsor based upon serious adverse events in first 2 of 3 participants in Cohort 1.)
First Posted : June 3, 2008
Results First Posted : August 17, 2018
Last Update Posted : August 17, 2018
Sponsor:
Information provided by (Responsible Party):
Amicus Therapeutics

Brief Summary:
The main purpose of this study was to determine the safety and tolerability of 3 different doses of duvoglustat (AT2220) in participants affected by Pompe disease. The study also evaluated the effects of duvoglustat on functional parameters in Pompe disease.

Condition or disease Intervention/treatment Phase
Pompe Disease Drug: Duvoglustat Phase 2

Detailed Description:

This was a Phase 2, open-label study in participants with Pompe disease, a lysosomal storage disorder. Duvoglustat is designed to act as a pharmacological chaperone of alpha-glucosidase, in order to restore enzyme activity. This study consisted of a 28-day screening period, an 11-week treatment period, and a 1-week follow-up period. Three dosing regimens of oral duvoglustat were to be evaluated (Cohort 1: 2.5 g daily for 3 days, followed by no study drug for 4 days; Cohort 2: 5 g daily for 3 days, followed by no study drug for 4 days; Cohort 3: 5 g daily for 7 days, followed by no study drug for 7 days).

Participants meeting all eligibility criteria underwent physical examination, electrocardiogram, spirometry, muscular strength test, functional muscle test, 6-minute walk test (when appropriate), laboratory tests, magnetic resonance imaging, and muscle (needle) biopsy. Quality of life was assessed via the 36-Item Short Form Health Survey questionnaire. Functional ability and level of handicap was assessed by Rotterdam handicap scale.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 3 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open-Label, Multicenter Study to Evaluate the Safety, Tolerability, Pharmacodynamics, and Pharmacokinetics of Three Dosing Regimens of Oral AT2220 in Patients With Pompe Disease
Actual Study Start Date : December 8, 2008
Actual Primary Completion Date : December 14, 2009
Actual Study Completion Date : December 14, 2009


Arm Intervention/treatment
Experimental: Cohort 1
Regimen 1: Low-dose duvoglustat (2.5 grams [g]) once a day (QD) for 3 days, followed by no drug for 4 days, for 11 weeks.
Drug: Duvoglustat
Powder in a bottle for dissolution in water for oral administration
Other Names:
  • Duvoglustat hydrochloride
  • 1-Deoxynojirimycin hydrochloride
  • AT2220

Experimental: Cohort 2
Regimen 1: High-dose duvoglustat (5.0 g) QD for 3 days, followed by no drug for 4 days, for 11 weeks.
Drug: Duvoglustat
Powder in a bottle for dissolution in water for oral administration
Other Names:
  • Duvoglustat hydrochloride
  • 1-Deoxynojirimycin hydrochloride
  • AT2220

Experimental: Cohort 3
Regimen 2: High-dose duvoglustat (5.0 g) QD for 7 days, followed by no drug for 7 days, for 11 weeks.
Drug: Duvoglustat
Powder in a bottle for dissolution in water for oral administration
Other Names:
  • Duvoglustat hydrochloride
  • 1-Deoxynojirimycin hydrochloride
  • AT2220




Primary Outcome Measures :
  1. Proportion Of Participants Experiencing Severe Treatment-emergent Adverse Events (TEAEs) [ Time Frame: Baseline, Week 11 ]
    The number of participants experiencing severe TEAEs is presented for participants who received duvoglustat treatment in this open-label study. The duration of duvoglustat exposure for Cohort 1 ranged from 2 to 24 days, and their exposure ranged from a total of 7,500 to 32,500 milligrams of duvoglustat. An adverse event (AE) refers to any unfavorable and unintended sign, symptom, syndrome, or illness that develops or worsens during the period of observation in the clinical study. The following guideline was used to grade the intensity of an AE: mild, the AE is easily tolerated and does not interfere with daily activity; moderate, the AE interferes with the daily activity but the participant is still able to function; severe, the AE is incapacitating and requires medical intervention. A summary of serious and all other non-serious AEs regardless of causality is located in the Reported Adverse Events module.


Secondary Outcome Measures :
  1. Change In 6-minute Walk Test (6MWT) From Baseline To End Of Study [ Time Frame: Baseline, Week 11 ]
    The 6MWT (American Thoracic Society standards) was evaluated in ambulatory participants at screening, baseline, and to the end of the study. It was a standardized test that measured the distance in meters (m) covered over a 6-minute walk. Reference equations used (for 6MWT distance in healthy adults) included: (height in centimeters [cm], weight in kilograms [kg]) 6MWT distance for men = [7.57 × height (cm)] - [5.02 × age] - [1.76 × weight (kg)] - 309 m; 6MWT distance for women = [2.11 × height (cm)] - [5.78 × age] - [2.29 × weight (kg)] + 667 m



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 74 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male or female, 18 to 74 years of age inclusive
  • Diagnosis of Pompe disease based on clinical assessment, enzyme assay, and/or genotyping. Confirmatory genotyping will be performed on all participants who are screened for the study
  • Naïve to enzyme replacement therapy (ERT) or has not received ERT in the 3 months prior to screening
  • Willing not to initiate ERT or other prohibited treatment during study participation
  • Functional grade for arms and/or legs ≥2 OR sitting forced vital capacity ≥30% and <80% of predicted value, reproducible between screening and baseline (±15%)
  • Participants of reproductive potential agree to use reliable methods of contraception during the study
  • Participant or legal representative is willing and able to provide written informed consent

Exclusion Criteria:

  • Any intercurrent condition that may preclude accurate interpretation of study data
  • Obstructive pulmonary disease
  • Invasive ventilatory support
  • Use of noninvasive ventilatory support >8 hours/day while awake
  • History of QTc prolongation >450 milliseconds (msec) for males and >470 msec for females
  • History of allergy or sensitivity to the study drug, including any prior serious adverse reaction to iminosugars (such as miglustat or miglitol)
  • Pregnancy or breast-feeding
  • Current or recent drug or alcohol abuse
  • Treatment with another investigational drug within 30 days of study start
  • Use of prohibited medications ≤3 months prior to screening
  • Otherwise unsuitable for the study in the opinion of the Investigator

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00688597


Locations
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United States, Georgia
Decatur, Georgia, United States, 30033
Sponsors and Collaborators
Amicus Therapeutics
Investigators
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Study Director: Medical Monitor Clinical Research Amicus Therapeutics

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Responsible Party: Amicus Therapeutics
ClinicalTrials.gov Identifier: NCT00688597     History of Changes
Other Study ID Numbers: POM-CL-201
First Posted: June 3, 2008    Key Record Dates
Results First Posted: August 17, 2018
Last Update Posted: August 17, 2018
Last Verified: July 2018
Keywords provided by Amicus Therapeutics:
Amicus Therapeutics
Duvoglustat
AT2220
Additional relevant MeSH terms:
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Glycogen Storage Disease Type II
Lysosomal Storage Diseases, Nervous System
Brain Diseases, Metabolic, Inborn
Brain Diseases, Metabolic
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Genetic Diseases, Inborn
Glycogen Storage Disease
Lysosomal Storage Diseases
Metabolic Diseases
Metabolism, Inborn Errors
Carbohydrate Metabolism, Inborn Errors
1-Deoxynojirimycin
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action