Drug-drug Interaction Study

NCT01380743 | Completed Phase 2 Results DMC

• 1 other identifier: AT2220-010
• Study Type: interventional
• Target: 25
• Locations: 4 countries
• Sites: 15

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.

Conditions

Pompe Disease

Keywords

Amicus Therapeutics; duvoglustat; AT2220; alpha-glucosidase; alglucosidase alfa

Outcome Measures

Primary Outcomes (6)

• Number Of Participants Who Experienced Severe Treatment-Emergent Adverse Events (TEAEs)

  A TEAE was defined as an adverse event (AE) with an onset date on or after the first dose of investigational medicinal product (IMP), or an AE with an onset date before the first dose date that worsened in severity after the first dose date. A severe AE was defined as an AE that was incapacitating and required medical intervention. The number of participants who experienced 1 or more severe TEAEs after dosing on Day 1 up to Day 60 (includes end of study follow-up period) is reported. A summary of serious and all other non-serious AEs, regardless of causality, is located in the Reported Adverse Events module.

  Day 1 after dosing up to Day 60

• Pharmacokinetics (PK): Maximum Measured Plasma Concentration (Cmax) Of Total GAA And rhGAA Protein In Plasma In Participants With Pompe Disease

  The Cmax of total GAA and rhGAA protein in plasma was measured after a single rhGAA intravenous infusion and after pre-administration of single ascending oral doses of duvoglustat. During Treatment Period 1, participants received a single intravenous infusion of rhGAA. During Treatment Period 2, participants received a single oral dose of duvoglustat 1 hour before initiation of a single rhGAA intravenous infusion. PK samples were taken at time points 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.

  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

• PK: Time To The Maximum Plasma Concentration (Tmax) Of Total GAA And rhGAA Protein In Plasma In Participants With Pompe Disease

  The Tmax of total GAA and rhGAA protein in plasma was measured after a single rhGAA intravenous infusion and after pre-administration of single ascending oral doses of duvoglustat. During Treatment Period 1, participants received a single intravenous infusion of rhGAA. During Treatment Period 2, participants received a single oral dose of duvoglustat 1 hour before initiation of a single rhGAA intravenous infusion. PK samples were taken at time points 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.

  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

• PK: Elimination Half-life (T1/2) Of Total GAA And rhGAA Protein In Plasma In Participants With Pompe Disease

  The T1/2 of total GAA and rhGAA protein in plasma was measured after a single rhGAA intravenous infusion and after pre-administration of single ascending oral doses of duvoglustat. During Treatment Period 1, participants received a single intravenous infusion of rhGAA. During Treatment Period 2, participants received a single oral dose of duvoglustat 1 hour before initiation of a single rhGAA intravenous infusion. PK samples were taken at time points 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. Values presented are arithmetic mean (percent coefficient of variation, \[CV%\]). The number of participants analyzed for some cohorts are reduced because the terminal phase of the concentration profile for these participants was not estimable.

  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

• 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

  The AUC0-t of total GAA and rhGAA protein in plasma was measured after a single rhGAA intravenous infusion and after pre-administration of single ascending oral doses of duvoglustat. During Treatment Period 1, participants received a single intravenous infusion of rhGAA. During Treatment Period 2, participants received a single oral dose of duvoglustat 1 hour before initiation of a single rhGAA intravenous infusion. PK samples were taken at time points 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.

  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

• PK: AUC From Time 0 Extrapolated To Infinity (AUCinf) Of Total GAA And rhGAA Protein In Plasma In Participants With Pompe Disease

  The AUCinf of total GAA and rhGAA protein in plasma was measured after a single rhGAA intravenous infusion and after pre-administration of single ascending oral doses of duvoglustat. During Treatment Period 1, participants received a single intravenous infusion of rhGAA. During Treatment Period 2, participants received a single oral dose of duvoglustat 1 hour before initiation of a single rhGAA intravenous infusion. PK samples were taken at time points 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. The number of participants analyzed for some cohorts are reduced because the terminal phase of the concentration profile for these participants was not estimable.

  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 (2)

• Total GAA Activity In Skeletal Muscle

  Day 3 or Day 7

• Duvoglustat Concentration In Skeletal Muscle

  Day 3 or Day 7

Study Arms (4)

Cohort 1, Duvoglustat 50 mg + rhGAA

EXPERIMENTAL

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.

Drug: duvoglustat; Drug: rhGAA

Cohort 2, Duvoglustat 100 mg + rhGAA

EXPERIMENTAL

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.

Drug: duvoglustat; Drug: rhGAA

Cohort 3, Duvoglustat 250 mg + rhGAA

EXPERIMENTAL

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.

Drug: duvoglustat; Drug: rhGAA

Cohort 4, Duvoglustat 600 mg + rhGAA

EXPERIMENTAL

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.

Drug: duvoglustat; Drug: rhGAA

Interventions

duvoglustat DRUG

Single oral dose

Also known as: AT2220, duvoglustat hydrochloride

Cohort 1, Duvoglustat 50 mg + rhGAA; Cohort 2, Duvoglustat 100 mg + rhGAA; Cohort 3, Duvoglustat 250 mg + rhGAA; Cohort 4, Duvoglustat 600 mg + rhGAA

rhGAA DRUG

Single intravenous infusion

Also known as: alglucosidase alfa, recombinant human alpha-glucosidase, Myozyme, Lumizyme

Cohort 1, Duvoglustat 50 mg + rhGAA; Cohort 2, Duvoglustat 100 mg + rhGAA; Cohort 3, Duvoglustat 250 mg + rhGAA; Cohort 4, Duvoglustat 600 mg + rhGAA

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Amicus Therapeutics: lead

Study Sites (15)

Unknown Facility

Phoenix, Arizona, 85018, United States

Location

Unknown Facility

Scottsdale, Arizona, 85258, United States

Location

Unknown Facility

Orange, California, 92868, United States

Location

Unknown Facility

Gainesville, Florida, 32610, United States

Location

Unknown Facility

Decatur, Georgia, 30033, United States

Location

Unknown Facility

Kansas City, Kansas, 66160, United States

Location

Unknown Facility

Great Falls, Montana, 59405, United States

Location

Unknown Facility

Durham, North Carolina, 27710, United States

Location

Unknown Facility

Cincinnati, Ohio, 45299, United States

Location

Unknown Facility

Portland, Oregon, 97239, United States

Location

Unknown Facility

Springfield, Virginia, 22152, United States

Location

Unknown Facility

Hamilton, Ontario, L8N 3Z5, Canada

Location

Unknown Facility

Paris, 75013, France

Location

Unknown Facility

London, Queen Square, WC1N 3BG, United Kingdom

Location

Unknown Facility

Salford, M68 HD, United Kingdom

Location

MeSH Terms

Conditions

Glycogen Storage Disease Type II

Interventions

1-Deoxynojirimycin; GAA protein, human

Condition Hierarchy (Ancestors)

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; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Glycogen Storage Disease; Carbohydrate Metabolism, Inborn Errors; Lysosomal Storage Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Imino Pyranoses; Imino Sugars; Imines; Organic Chemicals; Alkaloids; Heterocyclic Compounds; Piperidines; Heterocyclic Compounds, 1-Ring; Carbohydrates

Results Point of Contact

• Title: Amicus Therapeutics
• Organization: Patient Advocacy

clinicaltrials@amicusrx.com

+1-609-662-2000

Study Officials

• Medical Monitor

  Study Sponsor (Amicus Therapeutics, Inc)

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 23, 2011
• First Posted: June 27, 2011
• Study Start: October 31, 2011
• Primary Completion: January 4, 2013
• Study Completion: January 4, 2013
• Last Updated: June 26, 2025
• Results First Posted: August 17, 2018

Record last verified: 2025-06

Locations

CA (1); FR (1); US (11); GB (2)