Clinical trial NCT00688597: Study to Evaluate the Safety of AT2220 (Duvoglustat) in Pompe Disease
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Pompe Disease
Keywords: Amicus Therapeutics
Duvoglustat
AT2220
Lead sponsor: Amicus Therapeutics
Sponsor class: INDUSTRY
First posted: 2008-06-03
Enrollment: 3
Sex: ALL
Minimum age (years): 18
Maximum age (years): 74
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: Proportion Of Participants Experiencing Severe Treatment-emergent Adverse Events (TEAEs)
timeFrame: Baseline, Week 11
Secondary outcomes:
measure: Change In 6-minute Walk Test (6MWT) From Baseline To End Of Study
timeFrame: Baseline, Week 11
Other outcomes:
Locations:
city: Decatur
country: United States
state: Georgia
Study officials:
affiliation: Amicus Therapeutics
name: Medical Monitor Clinical Research
role: STUDY_DIRECTOR
References: