Clinical trial NCT01380743: Drug-drug Interaction Study
Official title: An Open-Label, Multi-Center, International Study to Investigate Drug-Drug Interactions Between AT2220 and Alglucosidase Alfa in Patients With Pompe Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Pompe Disease
Keywords: Amicus Therapeutics
duvoglustat
AT2220
alpha-glucosidase
alglucosidase alfa
Lead sponsor: Amicus Therapeutics
Sponsor class: INDUSTRY
First posted: 2011-06-27
Enrollment: 25
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study evaluates drug-drug interactions between AT2220 (duvoglustat) and recombinant human alpha-glucosidase (rhGAA, also known as alglucosidase alfa) in participants with Pompe Disease.

Detailed description: This was a multi-center, international, open-label, two-period, fixed-sequence crossover study to evaluate the safety and pharmacokinetic effect of single ascending doses of duvoglustat on rhGAA administered 1 hour before initiation of a single rhGAA infusion. During Period 1, participants received a single intravenous infusion of rhGAA. During Period 2, each participant received a single oral dose of duvoglustat 1 hour prior to initiation of a single rhGAA infusion.

Eligibility criteria: Inclusion Criteria:

* Male or female, diagnosed with Pompe disease and between 18 and 65 years of age, inclusive
* Participant has been on a stable regimen and dose of rhGAA for at least 3 months before screening (stable regimen defined as currently receiving rhGAA every 2 weeks and stable dose defined as not varying by more than ± 10%)
* Participant has an estimated glomerular filtration rate (eGFR) ≥ 50 mL/min at Screening; eGFR to be estimated using the 4-parameter Modification of Diet in Renal Disease (MDRD) equation:

eGFR (mL/min/1.73 m\^2) = 175 x (Scr)\^(-1.154) x (Age)\^(-0.203) x (0.742 if female) x (1.212 if African-American)

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

Exclusion Criteria:

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

Primary outcomes:
measure: Number Of Participants Who Experienced Severe Treatment-Emergent Adverse Events (TEAEs)
timeFrame: Day 1 after dosing up to Day 60
measure: Pharmacokinetics (PK): Maximum Measured Plasma Concentration (Cmax) Of Total GAA And rhGAA Protein In Plasma In Participants With Pompe Disease
timeFrame: Predose, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, and 24 hours, and 3 or 7 days postdose during Periods 1 and 2, and 24 to 30 days postdose during Period 2
measure: PK: Time To The Maximum Plasma Concentration (Tmax) Of Total GAA And rhGAA Protein In Plasma In Participants With Pompe Disease
timeFrame: Predose, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, and 24 hours, and 3 or 7 days postdose during Periods 1 and 2, and 24 to 30 days postdose during Period 2
measure: PK: Elimination Half-life (T1/2) Of Total GAA And rhGAA Protein In Plasma In Participants With Pompe Disease
timeFrame: Predose, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, and 24 hours, and 3 or 7 days postdose during Periods 1 and 2, and 24 to 30 days postdose during Period 2
measure: PK: Area Under The Plasma Concentration Versus Time Curve From Time 0 To The Time Of The Last Measurable Concentration (AUC0-t) Of Total GAA And rhGAA Protein In Plasma In Participants With Pompe Disease
timeFrame: Predose, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, and 24 hours, and 3 or 7 days postdose during Periods 1 and 2, and 24 to 30 days postdose during Period 2
measure: PK: AUC From Time 0 Extrapolated To Infinity (AUCinf) Of Total GAA And rhGAA Protein In Plasma In Participants With Pompe Disease
timeFrame: Predose, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, and 24 hours, and 3 or 7 days postdose during Periods 1 and 2, and 24 to 30 days postdose during Period 2
Secondary outcomes:
measure: Total GAA Activity In Skeletal Muscle
timeFrame: Day 3 or Day 7
measure: Duvoglustat Concentration In Skeletal Muscle
timeFrame: Day 3 or Day 7
Other outcomes:
Locations:
city: Phoenix
country: United States
state: Arizona
city: Scottsdale
country: United States
state: Arizona
city: Orange
country: United States
state: California
city: Gainesville
country: United States
state: Florida
city: Decatur
country: United States
state: Georgia
city: Kansas City
country: United States
state: Kansas
city: Great Falls
country: United States
state: Montana
city: Durham
country: United States
state: North Carolina
city: Cincinnati
country: United States
state: Ohio
city: Portland
country: United States
state: Oregon
city: Springfield
country: United States
state: Virginia
city: Hamilton
country: Canada
state: Ontario
city: Paris
country: France
city: London
country: United Kingdom
state: Queen Square
city: Salford
country: United Kingdom
Study officials:
affiliation: Study Sponsor (Amicus Therapeutics, Inc)
name: Medical Monitor
role: STUDY_DIRECTOR
References: