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Trial record 60 of 103 for:    Pompe Disease

Drug-drug Interaction Study

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ClinicalTrials.gov Identifier: NCT01380743
Recruitment Status : Completed
First Posted : June 27, 2011
Results First Posted : August 17, 2018
Last Update Posted : October 2, 2018
Sponsor:
Information provided by (Responsible Party):
Amicus Therapeutics

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.

Condition or disease Intervention/treatment Phase
Pompe Disease Drug: duvoglustat Drug: rhGAA Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 25 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open-Label, Multi-Center, International Study to Investigate Drug-Drug Interactions Between AT2220 and Alglucosidase Alfa in Patients With Pompe Disease
Actual Study Start Date : October 31, 2011
Actual Primary Completion Date : January 4, 2013
Actual Study Completion Date : January 4, 2013


Arm Intervention/treatment
Experimental: Cohort 1, Duvoglustat 50 mg + rhGAA

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
Single oral dose
Other Names:
  • AT2220
  • duvoglustat hydrochloride

Drug: rhGAA
Single intravenous infusion
Other Names:
  • alglucosidase alfa
  • recombinant human alpha-glucosidase
  • Myozyme
  • Lumizyme

Experimental: Cohort 2, Duvoglustat 100 mg + rhGAA

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
Single oral dose
Other Names:
  • AT2220
  • duvoglustat hydrochloride

Drug: rhGAA
Single intravenous infusion
Other Names:
  • alglucosidase alfa
  • recombinant human alpha-glucosidase
  • Myozyme
  • Lumizyme

Experimental: Cohort 3, Duvoglustat 250 mg + rhGAA

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
Single oral dose
Other Names:
  • AT2220
  • duvoglustat hydrochloride

Drug: rhGAA
Single intravenous infusion
Other Names:
  • alglucosidase alfa
  • recombinant human alpha-glucosidase
  • Myozyme
  • Lumizyme

Experimental: Cohort 4, Duvoglustat 600 mg + rhGAA

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
Single oral dose
Other Names:
  • AT2220
  • duvoglustat hydrochloride

Drug: rhGAA
Single intravenous infusion
Other Names:
  • alglucosidase alfa
  • recombinant human alpha-glucosidase
  • Myozyme
  • Lumizyme




Primary Outcome Measures :
  1. Number Of Participants Who Experienced Severe Treatment-Emergent Adverse Events (TEAEs) [ Time Frame: Day 1 after dosing up to Day 60 ]

    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.


  2. Pharmacokinetics (PK): Maximum Measured Plasma Concentration (Cmax) Of Total GAA And rhGAA Protein In Plasma In Participants With Pompe Disease [ Time Frame: 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 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.


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


  4. PK: Elimination Half-life (T1/2) Of Total GAA And rhGAA Protein In Plasma In Participants With Pompe Disease [ Time Frame: 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 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.


  5. 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 [ Time Frame: 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 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.


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



Secondary Outcome Measures :
  1. Total GAA Activity In Skeletal Muscle [ Time Frame: Day 3 or Day 7 ]
    The total GAA activity in skeletal muscle was measured after a single intravenous administration of rhGAA alone and after pre-administration of single ascending oral doses of duvoglustat. Participants were assessed using skeletal muscle biopsies at either Day 3 or Day 7 during Treatment Periods 1 and 2.

  2. Duvoglustat Concentration In Skeletal Muscle [ Time Frame: Day 3 or Day 7 ]

    The concentration of duvoglustat in skeletal muscle tissue homogenate was measured after pre-administration of single ascending oral doses of duvoglustat during Treatment Period 2. Participants had skeletal muscle biopsies at either Day 3 or Day 7 during Treatment Period 2.

    Three participants were excluded from this analysis due to the following reasons: treatment sequence was inadvertently switched due to study site error, follow-up biopsy sample could not be conclusively identified, or muscle biopsies were mislabeled at the clinical site.

    Values presented are arithmetic mean (percent coefficient of variation, [CV%]) because of the prevalence of participants with values below the limit of quantification. Concentrations below the limit of quantification were treated as zero.




Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01380743


Locations
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United States, Arizona
Phoenix, Arizona, United States, 85018
Scottsdale, Arizona, United States, 85258
United States, California
Orange, California, United States, 92868
United States, Florida
Gainesville, Florida, United States, 32610
United States, Georgia
Decatur, Georgia, United States, 30033
United States, Kansas
Kansas City, Kansas, United States, 66160
United States, Montana
Great Falls, Montana, United States, 59405
United States, North Carolina
Durham, North Carolina, United States, 27710
United States, Ohio
Cincinnati, Ohio, United States, 45299
United States, Oregon
Portland, Oregon, United States, 97239
United States, Virginia
Springfield, Virginia, United States, 22152
Canada, Ontario
Hamilton, Ontario, Canada, L8N 3Z5
France
Paris, France, 75013
United Kingdom
London, Queen Square, United Kingdom, WC1N 3BG
Salford, United Kingdom, M68 HD
Sponsors and Collaborators
Amicus Therapeutics
Investigators
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Study Director: Medical Monitor Study Sponsor (Amicus Therapeutics, Inc)

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Responsible Party: Amicus Therapeutics
ClinicalTrials.gov Identifier: NCT01380743     History of Changes
Other Study ID Numbers: AT2220-010
First Posted: June 27, 2011    Key Record Dates
Results First Posted: August 17, 2018
Last Update Posted: October 2, 2018
Last Verified: September 2018

Keywords provided by Amicus Therapeutics:
Amicus Therapeutics
duvoglustat
AT2220
alpha-glucosidase
alglucosidase alfa

Additional relevant MeSH terms:
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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
Genetic Diseases, Inborn
Glycogen Storage Disease
Lysosomal Storage Diseases
Metabolic Diseases
Metabolism, Inborn Errors
Carbohydrate Metabolism, Inborn Errors
1-Deoxynojirimycin
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action