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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.
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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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
|
| 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. |
|
| 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. |
|
| 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. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| duvoglustat | Drug | Single oral dose |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Total GAA Activity In Skeletal Muscle | 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. | Day 3 or Day 7 |
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Inclusion Criteria:
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)
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Medical Monitor | Study Sponsor (Amicus Therapeutics, Inc) | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Phoenix | Arizona | 85018 | United States | |||
A total of 27 participants were enrolled; 25 participants completed the study. Two participants were discontinued from the study prior to assignment to a cohort: 1 participant voluntarily withdrew before receiving study drug; 1 participant was screened twice and enrolled once, and was counted twice under the total number enrolled.
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| ID | Title | Description |
|---|---|---|
| FG000 | 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 mg oral dose of duvoglustat 1 hour prior to initiation of a single rhGAA infusion. |
| FG001 | 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. |
| FG002 | 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. |
| FG003 | 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. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
All participants who were enrolled and received at least 1 dose of rhGAA or duvoglustat.
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| ID | Title | Description |
|---|---|---|
| BG000 | 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 mg oral dose of duvoglustat 1 hour prior to initiation of a single rhGAA infusion. |
| BG001 | Cohort 2, Duvoglustat 100 mg + rhGAA |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | The Safety Population included all participants who were enrolled and received at least 1 dose of rhGAA or duvoglustat. | Posted | Count of Participants | Participants | Day 1 after dosing up to Day 60 |
|
Day 1 after dosing up to Day 60
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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 mg oral dose of duvoglustat 1 hour prior to initiation of a single rhGAA infusion. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Electrocardiogram QT prolonged | Investigations | MedDRA 14.0 | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Dental caries | Gastrointestinal disorders | MedDRA 14.0 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Amicus Therapeutics | Patient Advocacy | +1-609-662-2000 | clinicaltrials@amicusrx.com |
Not provided
| ID | Term |
|---|---|
| D006009 | Glycogen Storage Disease Type II |
| ID | Term |
|---|---|
| D020140 | Lysosomal Storage Diseases, Nervous System |
| D020739 | Brain Diseases, Metabolic, Inborn |
| D001928 | Brain Diseases, Metabolic |
| D001927 | Brain Diseases |
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| ID | Term |
|---|---|
| D017485 | 1-Deoxynojirimycin |
| C509951 | GAA protein, human |
| ID | Term |
|---|---|
| D050112 | Imino Pyranoses |
| D050111 | Imino Sugars |
| D007097 | Imines |
| D009930 | Organic Chemicals |
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|
|
| rhGAA | Drug | Single intravenous infusion |
|
|
| 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 |
| Duvoglustat Concentration In Skeletal Muscle | 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. | Day 3 or Day 7 |
| Scottsdale |
| Arizona |
| 85258 |
| United States |
| Orange | California | 92868 | United States |
| Gainesville | Florida | 32610 | United States |
| Decatur | Georgia | 30033 | United States |
| Kansas City | Kansas | 66160 | United States |
| Great Falls | Montana | 59405 | United States |
| Durham | North Carolina | 27710 | United States |
| Cincinnati | Ohio | 45299 | United States |
| Portland | Oregon | 97239 | United States |
| Springfield | Virginia | 22152 | United States |
| Hamilton | Ontario | L8N 3Z5 | Canada |
| Paris | 75013 | France |
| London | Queen Square | WC1N 3BG | United Kingdom |
| Salford | M68 HD | United Kingdom |
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. |
| BG002 | 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. |
| BG003 | 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. |
| BG004 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
During Period 1, participants received a single intravenous infusion of rhGAA. During Period 2, each participant received a single 50 mg oral dose of duvoglustat 1 hour prior to initiation of a single rhGAA infusion. |
| OG001 | 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. |
| OG002 | 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. |
| OG003 | 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. |
|
|
| Primary | 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. | The Per Protocol population included all participants who successfully completed both periods. | Posted | Geometric Mean | Geometric Coefficient of Variation | nmol/mL/h | 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 |
|
|
|
| Primary | 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. | The Per Protocol population included all participants who successfully completed both periods. | Posted | Median | Full Range | h | 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 |
|
|
|
| Primary | 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. | The Per Protocol population included all participants who successfully completed both periods. | Posted | Geometric Mean | Geometric Coefficient of Variation | h | 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 |
|
|
|
| Primary | 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. | The Per Protocol population included all participants who successfully completed both periods. | Posted | Geometric Mean | Geometric Coefficient of Variation | nmol/mL/h | 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 |
|
|
|
| Primary | 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. | The Per Protocol population included all participants who successfully completed both periods. | Posted | Geometric Mean | Geometric Coefficient of Variation | h*(nmol/mL/h) | 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 | Total GAA Activity In Skeletal Muscle | 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. | The Per Protocol population included all participants who successfully completed both periods. | Posted | Geometric Mean | Geometric Coefficient of Variation | pmol/mg/h | Day 3 or Day 7 |
|
|
|
| Secondary | Duvoglustat Concentration In Skeletal Muscle | 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. | The Per Protocol population included all participants who successfully completed both periods. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/g | Day 3 or Day 7 |
|
|
|
| 0 |
| 6 |
| 5 |
| 6 |
| EG001 | 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. | 1 | 6 | 3 | 6 |
| EG002 | 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. | 0 | 6 | 4 | 6 |
| EG003 | 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. | 0 | 7 | 4 | 7 |
| Oedema peripheral | General disorders | MedDRA 14.0 | Systematic Assessment |
|
| Post procedural haematoma | Injury, poisoning and procedural complications | MedDRA 14.0 | Systematic Assessment |
|
| Procedural pain | Injury, poisoning and procedural complications | MedDRA 14.0 | Systematic Assessment |
|
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA 14.0 | Systematic Assessment |
|
| Melanocytic naevus | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 14.0 | Systematic Assessment |
|
| Dysuria | Renal and urinary disorders | MedDRA 14.0 | Systematic Assessment |
|
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 14.0 | Systematic Assessment |
|
| Dermatitis contact | Skin and subcutaneous tissue disorders | MedDRA 14.0 | Systematic Assessment |
|
| Erythema | Skin and subcutaneous tissue disorders | MedDRA 14.0 | Systematic Assessment |
|
| Hyperhidrosis | Skin and subcutaneous tissue disorders | MedDRA 14.0 | Systematic Assessment |
|
| Scar pain | Skin and subcutaneous tissue disorders | MedDRA 14.0 | Systematic Assessment |
|
| Haematoma | Vascular disorders | MedDRA 14.0 | Systematic Assessment |
|
| Palpitations | Cardiac disorders | MedDRA 14.0 | Systematic Assessment |
|
| Vertigo | Ear and labyrinth disorders | MedDRA 14.0 | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | MedDRA 14.0 | Systematic Assessment |
|
| Oral pain | Gastrointestinal disorders | MedDRA 14.0 | Systematic Assessment |
|
| Fatigue | General disorders | MedDRA 14.0 | Systematic Assessment |
|
| Nodule | General disorders | MedDRA 14.0 | Systematic Assessment |
|
| Oral candidiasis | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
|
| Otitis media | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
|
| Respiratory tract infection | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
|
| Sinusitis | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
|
| Tooth abscess | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
|
| Upper respiratory tract infection | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
|
| Urinary tract infection | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
|
| Back injury | Injury, poisoning and procedural complications | MedDRA 14.0 | Systematic Assessment |
|
| Fall | Injury, poisoning and procedural complications | MedDRA 14.0 | Systematic Assessment |
|
| Muscle strain | Injury, poisoning and procedural complications | MedDRA 14.0 | Systematic Assessment |
|
| Procedural complication | Injury, poisoning and procedural complications | MedDRA 14.0 | Systematic Assessment |
|
| Tooth fracture | Injury, poisoning and procedural complications | MedDRA 14.0 | Systematic Assessment |
|
| Weight increased | Investigations | MedDRA 14.0 | Systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 14.0 | Systematic Assessment |
|
| Neck pain | Musculoskeletal and connective tissue disorders | MedDRA 14.0 | Systematic Assessment |
|
| Ovarian neoplasm | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 14.0 | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA 14.0 | Systematic Assessment |
|
| Hyperaesthesia | Nervous system disorders | MedDRA 14.0 | Systematic Assessment |
|
| Somnolence | Nervous system disorders | MedDRA 14.0 | Systematic Assessment |
|
| Nephrolithiasis | Renal and urinary disorders | MedDRA 14.0 | Systematic Assessment |
|
| Pollakiuria | Renal and urinary disorders | MedDRA 14.0 | Systematic Assessment |
|
| Urinary incontinence | Renal and urinary disorders | MedDRA 14.0 | Systematic Assessment |
|
| Uterine enlargement | Reproductive system and breast disorders | MedDRA 14.0 | Systematic Assessment |
|
| Sinus congestion | Respiratory, thoracic and mediastinal disorders | MedDRA 14.0 | Systematic Assessment |
|
The investigator can only publish the results from this trial provided they supply the sponsor (or authorized entity) a copy of any proposed publication for review. If requested, the investigator will remove information deemed confidential or proprietary by the sponsor and will withhold publication for an additional period of time to allow the sponsor to take appropriate measures to establish and preserve its proprietary rights.
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D008661 | Metabolism, Inborn Errors |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D006008 | Glycogen Storage Disease |
| D002239 | Carbohydrate Metabolism, Inborn Errors |
| D016464 | Lysosomal Storage Diseases |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D000470 |
| Alkaloids |
| D006571 | Heterocyclic Compounds |
| D010880 | Piperidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D002241 | Carbohydrates |
| Total GAA, Period 2 |
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| rhGAA, Period 1 |
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| rhGAA, Period 2 |
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| Total GAA, Period 2 |
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| rhGAA, Period 1 |
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| rhGAA, Period 2 |
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| Total GAA, Period 2 |
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| rhGAA, Period 1 |
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| rhGAA, Period 2 |
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| Total GAA, Period 2 |
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| rhGAA, Period 1 |
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| rhGAA, Period 2 |
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| Total GAA, Period 2 |
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| rhGAA, Period 1 |
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| rhGAA, Period 2 |
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| Total GAA, Period 2, Day 3 |
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| Total GAA, Period 1, Day 7 |
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| Total GAA, Period 2, Day 7 |
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| Duvoglustat Concentration, Day 7 |
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