Drug-drug Interaction Study - Full Text View

Purpose

This study will look at Drug-Drug Interactions Between AT2220 (duvoglustat hydrochloride) and alglucosidase alfa (ERT) in Patients with Pompe Disease.

Condition	Intervention	Phase
Pompe Disease	Drug: duvoglustat hydrochloride	Phase 2

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Pharmacokinetics Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	An Open-Label, Multi-Center, Study to Investigate Drug-Drug Interactions Between AT2220 (Duvoglustat Hydrochloride) and Alglucosidase Alfa in Patients With Pompe Disease

Resource links provided by NLM:

Genetics Home Reference related topics: glycogen storage disease type IX Pompe disease Schindler disease succinic semialdehyde dehydrogenase deficiency

MedlinePlus related topics: Drug Reactions

U.S. FDA Resources

Further study details as provided by Amicus Therapeutics:

Primary Outcome Measures:

Safety [ Time Frame: 3 months ] [ Designated as safety issue: Yes ]
adverse events (AE) (including infusion reactions), clinical laboratory tests (hematology, urinalysis, serum chemistry including creatine kinase, LDH, alkaline phosphatase, ALT and AST), urine glucose tetrasaccharides (Hex4), 12-lead ECGs, physical examinations, vital signs, and muscle strength tests
Pharmacokinetics [ Time Frame: 1 month ] [ Designated as safety issue: No ]
Plasma GAA Cmax and AUC for enzyme activity after an alglucosidase alfa infusion alone and after pre-administration of single ascending doses of AT2220; total protein concentration will also be evaluated for each infusion

Secondary Outcome Measures:

GAA activity in muscle [ Time Frame: Day 3 or Day 7 ] [ Designated as safety issue: No ]
GAA levels in skeletal muscle at Day 3 or Day 7 after a single intravenous administration of alglucosidase alfa alone and in combination with single ascending oral doses of AT2220 by measuring GAA enzyme activity and protein levels
AT2220 concentration in muscle [ Time Frame: Day 3 or Day 7 ] [ Designated as safety issue: No ]
The concentration of AT2220 in skeletal muscle tissue homogenate on Day 3 or Day 7 after pre-administration of single ascending oral doses of AT2220 in Period 2.

Estimated Enrollment:	22
Study Start Date:	October 2011
Estimated Study Completion Date:	December 2012
Estimated Primary Completion Date:	October 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Cohort 1	Drug: duvoglustat hydrochloride Single oral dose Other Name: AT2220
Experimental: Cohort 2	Drug: duvoglustat hydrochloride Single oral dose Other Name: AT2220
Experimental: Cohort 3	Drug: duvoglustat hydrochloride Single oral dose Other Name: AT2220
Experimental: Cohort 4	Drug: duvoglustat hydrochloride Single oral dose Other Name: AT2220

Detailed Description:

This will be a multi-center, international, open-label, two-period, fixed-sequence crossover study to evaluate the safety and pharmacokinetic effect of single ascending doses of AT2220 on GAA administered 1 hour before initiation of a single alglucosidase alfa infusion. During Period 1 subjects will receive a single intravenous infusion of alglucosidase alfa. During Period 2, each subject will receive one single oral dose of AT2220 one hour prior to initiation of a single alglucosidase alfa infusion.

Eligibility

Ages Eligible for Study:	18 Years to 65 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Male or female, diagnosed with Pompe disease and between 18 and 65 years of age, inclusive
Subject has been on a stable regimen and dose of alglucosidase alfa or at least 3 month before screening (stable regimen defined as currently receiving alglucosidase alfa every 2 weeks and stable dose defined as not varying by more than ± 10%)
Subject has an estimated creatinine clearance ≥ 50 mL/min at Screening; eGFR to be estimated using the 4-parameter MDRD equation:

eGFR (mL/min/1.73 m2) = 175 x (Scr)-1.154 x (Age)-0.203 x (0.742 if female) x (1.212 if African-American)

Male and female subjects of childbearing potential agree to use medically accepted methods of contraception during the study and for 30 days after study completion
Subject is willing and able to provide written informed consent and is able to comply with all study procedures

Exclusion Criteria:

Subject has had a documented transient ischemic attack, ischemic stroke, unstable angina or myocardial infarction within the 3 months before Screening
Subject has clinically significant unstable cardiac disease (e.g., cardiac disease requiring active management, such as symptomatic arrhythmia, unstable angina or NYHA class III or IV congestive heart failure)
Subject requiring mechanical ventilation or is confined to a wheelchair
Subject has a history of allergy or sensitivity to study drug (including excipients) or other iminosugars (e.g., miglustat, miglitol)
Subject is pregnant or breastfeeding
Subject tests positive for hepatitis B surface antigen or hepatitis C antibody
Subject has received any investigational/experimental drug or device within 30 days of Screening
Subject has any intercurrent illness or condition that may preclude the subject from fulfilling the protocol requirements or suggests to the investigator that the potential subject may have an unacceptable risk by participating in this study

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01380743

Locations

United States, Arizona
Phoenix Neurological Associates, Ltd
Phoenix, Arizona, United States, 85018
Neuromuscular Research Center
Scottsdale, Arizona, United States, 85258
United States, California
University of California Irvine - Neuromuscular Program
Orange, California, United States, 92868
United States, Florida
University of Florida, Department of Pediatrics, Powell Gene Therapy Center
Gainsville, Florida, United States, 32610
United States, Georgia
Emory University
Decatur, Georgia, United States, 30033
United States, Kansas
University of Kansas Medical Center
Kansas City, Kansas, United States, 66160
United States, Montana
Great Falls Clinic
Great Falls, Montana, United States, 59405
United States, North Carolina
Duke University Medical Center
Durham, North Carolina, United States, 27710
United States, Ohio
Cincinnati Children's Hospital Medical Center - Dept of Human Genetics
Cincinnati, Ohio, United States, 45299
United States, Oregon
Oregon Health & Science University
Portland, Oregon, United States, 97239
United States, Virginia
LSD Research and Treatment Center, CFCT
Springfield, Virginia, United States, 22152
Canada, Ontario
McMaster University Medical Center
Hamilton, Ontario, Canada, L8N 3Z5
France
Hospital la Salpetriere Institut de Myologie
Paris, France, 75013
United Kingdom
National Hospital for Neurology and Neurosurgery
London, Queen Square, United Kingdom, WC1N 3BG
Salford Royal NHS Trust Hope Hospital
Salford, United Kingdom, M68 HD

Sponsors and Collaborators

Amicus Therapeutics

Investigators

Study Director:

Medical Monitor

Study Sponsor

More Information

No publications provided

Responsible Party:	Amicus Therapeutics
ClinicalTrials.gov Identifier:	NCT01380743 History of Changes
Other Study ID Numbers:	AT2220-010
Study First Received:	June 23, 2011
Last Updated:	October 22, 2012
Health Authority:	United States: Food and Drug Administration Canada: Health Canada

Keywords provided by Amicus Therapeutics:

Pompe disease

Additional relevant MeSH terms:

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

Metabolism, Inborn Errors
Genetic Diseases, Inborn
Glycogen Storage Disease
Carbohydrate Metabolism, Inborn Errors
Lysosomal Storage Diseases
Metabolic Diseases

ClinicalTrials.gov processed this record on May 16, 2013