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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

Tracking Information
First Submitted Date  ICMJE May 30, 2008
First Posted Date  ICMJE June 3, 2008
Results First Submitted Date  ICMJE July 23, 2018
Results First Posted Date  ICMJE August 17, 2018
Last Update Posted Date August 17, 2018
Actual Study Start Date  ICMJE December 8, 2008
Actual Primary Completion Date December 14, 2009   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 23, 2018)
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.
Original Primary Outcome Measures  ICMJE
 (submitted: May 30, 2008)
Treatment-emergent Adverse Events [ Time Frame: 11 weeks ]
Change History Complete list of historical versions of study NCT00688597 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: July 23, 2018)
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
Original Secondary Outcome Measures  ICMJE
 (submitted: May 30, 2008)
Change in functional parameters from Baseline to End of Study [ Time Frame: 11 weeks ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study to Evaluate the Safety of AT2220 (Duvoglustat) in Pompe Disease
Official Title  ICMJE 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
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.
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Pompe Disease
Intervention  ICMJE Drug: Duvoglustat
Powder in a bottle for dissolution in water for oral administration
Other Names:
  • Duvoglustat hydrochloride
  • 1-Deoxynojirimycin hydrochloride
  • AT2220
Study Arms  ICMJE
  • 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.
    Intervention: Drug: Duvoglustat
  • 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.
    Intervention: Drug: Duvoglustat
  • 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.
    Intervention: Drug: Duvoglustat
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: November 9, 2009)
3
Original Estimated Enrollment  ICMJE
 (submitted: May 30, 2008)
18
Actual Study Completion Date  ICMJE December 14, 2009
Actual Primary Completion Date December 14, 2009   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 74 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries Australia,   Canada,   France,   Germany,   Netherlands,   United Kingdom
 
Administrative Information
NCT Number  ICMJE NCT00688597
Other Study ID Numbers  ICMJE POM-CL-201
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Amicus Therapeutics
Study Sponsor  ICMJE Amicus Therapeutics
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Medical Monitor Clinical Research Amicus Therapeutics
PRS Account Amicus Therapeutics
Verification Date July 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP