Drug-drug Interaction Study

Amicus Therapeutics

Status and phase: Completed; Phase 2

Conditions: Pompe Disease

Treatments: Drug: rhGAA; Drug: duvoglustat

Study type: Interventional

Funder types: Industry

Identifiers

NCT01380743

AT2220-010

Details and patient eligibility

About

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.

Full 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.

Enrollment: 25 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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25 participants in 4 patient groups

Cohort 1, Duvoglustat 50 mg + rhGAA

Experimental group

Description:

During Period 1, participants received a single intravenous infusion of rhGAA. During Period 2, each participant received a single 50 milligram (mg) oral dose of duvoglustat 1 hour prior to initiation of a single rhGAA infusion. Participants were on a stable regimen and dose of rhGAA for at least 3 months before screening.

Treatment:

Drug: duvoglustat

Drug: rhGAA

Cohort 2, Duvoglustat 100 mg + rhGAA

Experimental group

Description:

During Period 1, participants received a single intravenous infusion of rhGAA. During Period 2, each participant received a single 100 mg oral dose of duvoglustat 1 hour prior to initiation of a single rhGAA infusion. Participants were on a stable regimen and dose of rhGAA for at least 3 months before screening.

Treatment:

Drug: duvoglustat

Drug: rhGAA

Cohort 3, Duvoglustat 250 mg + rhGAA

Experimental group

Description:

During Period 1, participants received a single intravenous infusion of rhGAA. During Period 2, each participant received a single 250 mg oral dose of duvoglustat 1 hour prior to initiation of a single rhGAA infusion. Participants were on a stable regimen and dose of rhGAA for at least 3 months before screening.

Treatment:

Drug: duvoglustat

Drug: rhGAA

Cohort 4, Duvoglustat 600 mg + rhGAA

Experimental group

Description:

During Period 1, participants received a single intravenous infusion of rhGAA. During Period 2, each participant received a single 600 mg oral dose of duvoglustat 1 hour prior to initiation of a single rhGAA infusion. Participants were on a stable regimen and dose of rhGAA for at least 3 months before screening.

Treatment:

Drug: duvoglustat

Drug: rhGAA