Pompe Disease
Conditions
Keywords
Amicus Therapeutics, duvoglustat, AT2220, alpha-glucosidase, alglucosidase alfa
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.
Interventions
DRUGduvoglustat
Single oral dose
DRUGrhGAA
Single intravenous infusion
Sponsors
Amicus Therapeutics
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| PK: AUC From Time 0 Extrapolated To Infinity (AUCinf) Of Total GAA And rhGAA Protein In Plasma In Participants With Pompe Disease | 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. |
| PK: Elimination Half-life (T1/2) Of Total GAA And rhGAA Protein In Plasma In Participants With Pompe Disease | 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. |
| 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 | 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. |
| Number Of Participants Who Experienced Severe Treatment-Emergent Adverse Events (TEAEs) | 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. |
| Pharmacokinetics (PK): Maximum Measured Plasma Concentration (Cmax) Of Total GAA And rhGAA Protein In Plasma In Participants With Pompe Disease | 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. |
| PK: Time To The Maximum Plasma Concentration (Tmax) Of Total GAA And rhGAA Protein In Plasma In Participants With Pompe Disease | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duvoglustat Concentration In Skeletal Muscle | 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. |
| Total GAA Activity In Skeletal Muscle | 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. |
Countries
Canada, France, United Kingdom, United States
Participant flow
Pre-assignment details
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.
Participants by arm
| Arm | Count |
|---|---|
| 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. | 6 |
| 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. | 6 |
| 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. | 6 |
| 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. | 7 |
| Total | 25 |
Baseline characteristics
| Characteristic | Cohort 1, Duvoglustat 50 mg + rhGAA | Cohort 2, Duvoglustat 100 mg + rhGAA | Cohort 3, Duvoglustat 250 mg + rhGAA | Cohort 4, Duvoglustat 600 mg + rhGAA | Total |
|---|---|---|---|---|---|
| Age, Continuous | 47.7 years STANDARD_DEVIATION 5.35 | 52.8 years STANDARD_DEVIATION 5.71 | 50.0 years STANDARD_DEVIATION 12.9 | 40.0 years STANDARD_DEVIATION 6.61 | 47.3 years STANDARD_DEVIATION 9.13 |
| Sex: Female, Male Female | 3 Participants | 3 Participants | 4 Participants | 2 Participants | 12 Participants |
| Sex: Female, Male Male | 3 Participants | 3 Participants | 2 Participants | 5 Participants | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 5 / 6 | 3 / 6 | 4 / 6 | 4 / 7 |
| serious Total, serious adverse events | 0 / 6 | 1 / 6 | 0 / 6 | 0 / 7 |
Outcome results
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.
Time frame: Day 1 after dosing up to Day 60
Population: The Safety Population included all participants who were enrolled and received at least 1 dose of rhGAA or duvoglustat.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort 1, Duvoglustat 50 mg + rhGAA | Number Of Participants Who Experienced Severe Treatment-Emergent Adverse Events (TEAEs) | 0 Participants |
| Cohort 2, Duvoglustat 100 mg + rhGAA | Number Of Participants Who Experienced Severe Treatment-Emergent Adverse Events (TEAEs) | 0 Participants |
| Cohort 3, Duvoglustat 250 mg + rhGAA | Number Of Participants Who Experienced Severe Treatment-Emergent Adverse Events (TEAEs) | 0 Participants |
| Cohort 4, Duvoglustat 600 mg + rhGAA | Number Of Participants Who Experienced Severe Treatment-Emergent Adverse Events (TEAEs) | 1 Participants |
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.
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
Population: The Per Protocol population included all participants who successfully completed both periods.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1, Duvoglustat 50 mg + rhGAA | Pharmacokinetics (PK): Maximum Measured Plasma Concentration (Cmax) Of Total GAA And rhGAA Protein In Plasma In Participants With Pompe Disease | Total GAA, Period 1 | 17269 nmol/mL/h | Geometric Coefficient of Variation 25.6 |
| Cohort 1, Duvoglustat 50 mg + rhGAA | Pharmacokinetics (PK): Maximum Measured Plasma Concentration (Cmax) Of Total GAA And rhGAA Protein In Plasma In Participants With Pompe Disease | Total GAA, Period 2 | 20539 nmol/mL/h | Geometric Coefficient of Variation 21.2 |
| Cohort 1, Duvoglustat 50 mg + rhGAA | Pharmacokinetics (PK): Maximum Measured Plasma Concentration (Cmax) Of Total GAA And rhGAA Protein In Plasma In Participants With Pompe Disease | rhGAA, Period 1 | 328660 nmol/mL/h | Geometric Coefficient of Variation 40.7 |
| Cohort 1, Duvoglustat 50 mg + rhGAA | Pharmacokinetics (PK): Maximum Measured Plasma Concentration (Cmax) Of Total GAA And rhGAA Protein In Plasma In Participants With Pompe Disease | rhGAA, Period 2 | 385475 nmol/mL/h | Geometric Coefficient of Variation 35.7 |
| Cohort 2, Duvoglustat 100 mg + rhGAA | Pharmacokinetics (PK): Maximum Measured Plasma Concentration (Cmax) Of Total GAA And rhGAA Protein In Plasma In Participants With Pompe Disease | Total GAA, Period 2 | 28607 nmol/mL/h | Geometric Coefficient of Variation 14.1 |
| Cohort 2, Duvoglustat 100 mg + rhGAA | Pharmacokinetics (PK): Maximum Measured Plasma Concentration (Cmax) Of Total GAA And rhGAA Protein In Plasma In Participants With Pompe Disease | rhGAA, Period 1 | 399622 nmol/mL/h | Geometric Coefficient of Variation 33.2 |
| Cohort 2, Duvoglustat 100 mg + rhGAA | Pharmacokinetics (PK): Maximum Measured Plasma Concentration (Cmax) Of Total GAA And rhGAA Protein In Plasma In Participants With Pompe Disease | rhGAA, Period 2 | 430738 nmol/mL/h | Geometric Coefficient of Variation 39.5 |
| Cohort 2, Duvoglustat 100 mg + rhGAA | Pharmacokinetics (PK): Maximum Measured Plasma Concentration (Cmax) Of Total GAA And rhGAA Protein In Plasma In Participants With Pompe Disease | Total GAA, Period 1 | 22785 nmol/mL/h | Geometric Coefficient of Variation 18.1 |
| Cohort 3, Duvoglustat 250 mg + rhGAA | Pharmacokinetics (PK): Maximum Measured Plasma Concentration (Cmax) Of Total GAA And rhGAA Protein In Plasma In Participants With Pompe Disease | rhGAA, Period 1 | 405543 nmol/mL/h | Geometric Coefficient of Variation 11.4 |
| Cohort 3, Duvoglustat 250 mg + rhGAA | Pharmacokinetics (PK): Maximum Measured Plasma Concentration (Cmax) Of Total GAA And rhGAA Protein In Plasma In Participants With Pompe Disease | Total GAA, Period 2 | 22651 nmol/mL/h | Geometric Coefficient of Variation 9 |
| Cohort 3, Duvoglustat 250 mg + rhGAA | Pharmacokinetics (PK): Maximum Measured Plasma Concentration (Cmax) Of Total GAA And rhGAA Protein In Plasma In Participants With Pompe Disease | rhGAA, Period 2 | 438795 nmol/mL/h | Geometric Coefficient of Variation 7 |
| Cohort 3, Duvoglustat 250 mg + rhGAA | Pharmacokinetics (PK): Maximum Measured Plasma Concentration (Cmax) Of Total GAA And rhGAA Protein In Plasma In Participants With Pompe Disease | Total GAA, Period 1 | 18986 nmol/mL/h | Geometric Coefficient of Variation 19.5 |
| Cohort 4, Duvoglustat 600 mg + rhGAA | Pharmacokinetics (PK): Maximum Measured Plasma Concentration (Cmax) Of Total GAA And rhGAA Protein In Plasma In Participants With Pompe Disease | rhGAA, Period 2 | 637571 nmol/mL/h | Geometric Coefficient of Variation 48.8 |
| Cohort 4, Duvoglustat 600 mg + rhGAA | Pharmacokinetics (PK): Maximum Measured Plasma Concentration (Cmax) Of Total GAA And rhGAA Protein In Plasma In Participants With Pompe Disease | Total GAA, Period 2 | 22989 nmol/mL/h | Geometric Coefficient of Variation 36.4 |
| Cohort 4, Duvoglustat 600 mg + rhGAA | Pharmacokinetics (PK): Maximum Measured Plasma Concentration (Cmax) Of Total GAA And rhGAA Protein In Plasma In Participants With Pompe Disease | Total GAA, Period 1 | 18980 nmol/mL/h | Geometric Coefficient of Variation 34.6 |
| Cohort 4, Duvoglustat 600 mg + rhGAA | Pharmacokinetics (PK): Maximum Measured Plasma Concentration (Cmax) Of Total GAA And rhGAA Protein In Plasma In Participants With Pompe Disease | rhGAA, Period 1 | 507294 nmol/mL/h | Geometric Coefficient of Variation 47.9 |
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.
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
Population: The Per Protocol population included all participants who successfully completed both periods.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1, Duvoglustat 50 mg + rhGAA | 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 | Total GAA, Period 1 | 108578 nmol/mL/h | Geometric Coefficient of Variation 24.1 |
| Cohort 1, Duvoglustat 50 mg + rhGAA | 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 | Total GAA, Period 2 | 159994 nmol/mL/h | Geometric Coefficient of Variation 18.1 |
| Cohort 1, Duvoglustat 50 mg + rhGAA | 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 | rhGAA, Period 1 | 1891079 nmol/mL/h | Geometric Coefficient of Variation 35.6 |
| Cohort 1, Duvoglustat 50 mg + rhGAA | 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 | rhGAA, Period 2 | 2914884 nmol/mL/h | Geometric Coefficient of Variation 49.2 |
| Cohort 2, Duvoglustat 100 mg + rhGAA | 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 | Total GAA, Period 2 | 226198 nmol/mL/h | Geometric Coefficient of Variation 25.4 |
| Cohort 2, Duvoglustat 100 mg + rhGAA | 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 | rhGAA, Period 1 | 2227356 nmol/mL/h | Geometric Coefficient of Variation 62.8 |
| Cohort 2, Duvoglustat 100 mg + rhGAA | 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 | rhGAA, Period 2 | 3466263 nmol/mL/h | Geometric Coefficient of Variation 59.5 |
| Cohort 2, Duvoglustat 100 mg + rhGAA | 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 | Total GAA, Period 1 | 141515 nmol/mL/h | Geometric Coefficient of Variation 27.9 |
| Cohort 3, Duvoglustat 250 mg + rhGAA | 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 | rhGAA, Period 1 | 2248866 nmol/mL/h | Geometric Coefficient of Variation 24.7 |
| Cohort 3, Duvoglustat 250 mg + rhGAA | 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 | Total GAA, Period 2 | 201044 nmol/mL/h | Geometric Coefficient of Variation 8.3 |
| Cohort 3, Duvoglustat 250 mg + rhGAA | 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 | rhGAA, Period 2 | 3618948 nmol/mL/h | Geometric Coefficient of Variation 26.4 |
| Cohort 3, Duvoglustat 250 mg + rhGAA | 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 | Total GAA, Period 1 | 107489 nmol/mL/h | Geometric Coefficient of Variation 21.7 |
| Cohort 4, Duvoglustat 600 mg + rhGAA | 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 | rhGAA, Period 2 | 5293233 nmol/mL/h | Geometric Coefficient of Variation 68.2 |
| Cohort 4, Duvoglustat 600 mg + rhGAA | 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 | Total GAA, Period 2 | 228413 nmol/mL/h | Geometric Coefficient of Variation 38.4 |
| Cohort 4, Duvoglustat 600 mg + rhGAA | 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 | Total GAA, Period 1 | 118483 nmol/mL/h | Geometric Coefficient of Variation 43.1 |
| Cohort 4, Duvoglustat 600 mg + rhGAA | 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 | rhGAA, Period 1 | 2326168 nmol/mL/h | Geometric Coefficient of Variation 55.5 |
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.
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
Population: The Per Protocol population included all participants who successfully completed both periods.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1, Duvoglustat 50 mg + rhGAA | PK: AUC From Time 0 Extrapolated To Infinity (AUCinf) Of Total GAA And rhGAA Protein In Plasma In Participants With Pompe Disease | Total GAA, Period 2 | 165983 h*(nmol/mL/h) | Geometric Coefficient of Variation 19.1 |
| Cohort 1, Duvoglustat 50 mg + rhGAA | PK: AUC From Time 0 Extrapolated To Infinity (AUCinf) Of Total GAA And rhGAA Protein In Plasma In Participants With Pompe Disease | rhGAA, Period 1 | 2274897 h*(nmol/mL/h) | Geometric Coefficient of Variation 35.5 |
| Cohort 1, Duvoglustat 50 mg + rhGAA | PK: AUC From Time 0 Extrapolated To Infinity (AUCinf) Of Total GAA And rhGAA Protein In Plasma In Participants With Pompe Disease | rhGAA, Period 2 | 3603068 h*(nmol/mL/h) | Geometric Coefficient of Variation 37.4 |
| Cohort 1, Duvoglustat 50 mg + rhGAA | PK: AUC From Time 0 Extrapolated To Infinity (AUCinf) Of Total GAA And rhGAA Protein In Plasma In Participants With Pompe Disease | Total GAA, Period 1 | 110388 h*(nmol/mL/h) | Geometric Coefficient of Variation 24.5 |
| Cohort 2, Duvoglustat 100 mg + rhGAA | PK: AUC From Time 0 Extrapolated To Infinity (AUCinf) Of Total GAA And rhGAA Protein In Plasma In Participants With Pompe Disease | rhGAA, Period 2 | 3427088 h*(nmol/mL/h) | Geometric Coefficient of Variation 71.1 |
| Cohort 2, Duvoglustat 100 mg + rhGAA | PK: AUC From Time 0 Extrapolated To Infinity (AUCinf) Of Total GAA And rhGAA Protein In Plasma In Participants With Pompe Disease | rhGAA, Period 1 | 2232099 h*(nmol/mL/h) | Geometric Coefficient of Variation 54 |
| Cohort 2, Duvoglustat 100 mg + rhGAA | PK: AUC From Time 0 Extrapolated To Infinity (AUCinf) Of Total GAA And rhGAA Protein In Plasma In Participants With Pompe Disease | Total GAA, Period 1 | 144056 h*(nmol/mL/h) | Geometric Coefficient of Variation 28.6 |
| Cohort 2, Duvoglustat 100 mg + rhGAA | PK: AUC From Time 0 Extrapolated To Infinity (AUCinf) Of Total GAA And rhGAA Protein In Plasma In Participants With Pompe Disease | Total GAA, Period 2 | 237613 h*(nmol/mL/h) | Geometric Coefficient of Variation 27.6 |
| Cohort 3, Duvoglustat 250 mg + rhGAA | PK: AUC From Time 0 Extrapolated To Infinity (AUCinf) Of Total GAA And rhGAA Protein In Plasma In Participants With Pompe Disease | Total GAA, Period 2 | 215276 h*(nmol/mL/h) | Geometric Coefficient of Variation 9.5 |
| Cohort 3, Duvoglustat 250 mg + rhGAA | PK: AUC From Time 0 Extrapolated To Infinity (AUCinf) Of Total GAA And rhGAA Protein In Plasma In Participants With Pompe Disease | Total GAA, Period 1 | 108862 h*(nmol/mL/h) | Geometric Coefficient of Variation 22.1 |
| Cohort 3, Duvoglustat 250 mg + rhGAA | PK: AUC From Time 0 Extrapolated To Infinity (AUCinf) Of Total GAA And rhGAA Protein In Plasma In Participants With Pompe Disease | rhGAA, Period 1 | 2468980 h*(nmol/mL/h) | Geometric Coefficient of Variation 26.4 |
| Cohort 3, Duvoglustat 250 mg + rhGAA | PK: AUC From Time 0 Extrapolated To Infinity (AUCinf) Of Total GAA And rhGAA Protein In Plasma In Participants With Pompe Disease | rhGAA, Period 2 | 4602726 h*(nmol/mL/h) | Geometric Coefficient of Variation 31.3 |
| Cohort 4, Duvoglustat 600 mg + rhGAA | PK: AUC From Time 0 Extrapolated To Infinity (AUCinf) Of Total GAA And rhGAA Protein In Plasma In Participants With Pompe Disease | rhGAA, Period 1 | 2452414 h*(nmol/mL/h) | Geometric Coefficient of Variation 70.5 |
| Cohort 4, Duvoglustat 600 mg + rhGAA | PK: AUC From Time 0 Extrapolated To Infinity (AUCinf) Of Total GAA And rhGAA Protein In Plasma In Participants With Pompe Disease | rhGAA, Period 2 | 6691323 h*(nmol/mL/h) | Geometric Coefficient of Variation 46.6 |
| Cohort 4, Duvoglustat 600 mg + rhGAA | PK: AUC From Time 0 Extrapolated To Infinity (AUCinf) Of Total GAA And rhGAA Protein In Plasma In Participants With Pompe Disease | Total GAA, Period 1 | 120604 h*(nmol/mL/h) | Geometric Coefficient of Variation 44.3 |
| Cohort 4, Duvoglustat 600 mg + rhGAA | PK: AUC From Time 0 Extrapolated To Infinity (AUCinf) Of Total GAA And rhGAA Protein In Plasma In Participants With Pompe Disease | Total GAA, Period 2 | 254074 h*(nmol/mL/h) | Geometric Coefficient of Variation 42 |
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.
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
Population: The Per Protocol population included all participants who successfully completed both periods.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1, Duvoglustat 50 mg + rhGAA | PK: Elimination Half-life (T1/2) Of Total GAA And rhGAA Protein In Plasma In Participants With Pompe Disease | Total GAA, Period 1 | 3.81 h | Geometric Coefficient of Variation 12.7 |
| Cohort 1, Duvoglustat 50 mg + rhGAA | PK: Elimination Half-life (T1/2) Of Total GAA And rhGAA Protein In Plasma In Participants With Pompe Disease | Total GAA, Period 2 | 4.42 h | Geometric Coefficient of Variation 16.9 |
| Cohort 1, Duvoglustat 50 mg + rhGAA | PK: Elimination Half-life (T1/2) Of Total GAA And rhGAA Protein In Plasma In Participants With Pompe Disease | rhGAA, Period 1 | 3.31 h | Geometric Coefficient of Variation 39.6 |
| Cohort 1, Duvoglustat 50 mg + rhGAA | PK: Elimination Half-life (T1/2) Of Total GAA And rhGAA Protein In Plasma In Participants With Pompe Disease | rhGAA, Period 2 | 4.43 h | Geometric Coefficient of Variation 38.1 |
| Cohort 2, Duvoglustat 100 mg + rhGAA | PK: Elimination Half-life (T1/2) Of Total GAA And rhGAA Protein In Plasma In Participants With Pompe Disease | Total GAA, Period 2 | 4.77 h | Geometric Coefficient of Variation 14.2 |
| Cohort 2, Duvoglustat 100 mg + rhGAA | PK: Elimination Half-life (T1/2) Of Total GAA And rhGAA Protein In Plasma In Participants With Pompe Disease | rhGAA, Period 1 | 2.33 h | Geometric Coefficient of Variation 59.5 |
| Cohort 2, Duvoglustat 100 mg + rhGAA | PK: Elimination Half-life (T1/2) Of Total GAA And rhGAA Protein In Plasma In Participants With Pompe Disease | rhGAA, Period 2 | 5.76 h | Geometric Coefficient of Variation 55.6 |
| Cohort 2, Duvoglustat 100 mg + rhGAA | PK: Elimination Half-life (T1/2) Of Total GAA And rhGAA Protein In Plasma In Participants With Pompe Disease | Total GAA, Period 1 | 3.82 h | Geometric Coefficient of Variation 17.7 |
| Cohort 3, Duvoglustat 250 mg + rhGAA | PK: Elimination Half-life (T1/2) Of Total GAA And rhGAA Protein In Plasma In Participants With Pompe Disease | rhGAA, Period 1 | 1.89 h | Geometric Coefficient of Variation 46.9 |
| Cohort 3, Duvoglustat 250 mg + rhGAA | PK: Elimination Half-life (T1/2) Of Total GAA And rhGAA Protein In Plasma In Participants With Pompe Disease | Total GAA, Period 2 | 5.36 h | Geometric Coefficient of Variation 26 |
| Cohort 3, Duvoglustat 250 mg + rhGAA | PK: Elimination Half-life (T1/2) Of Total GAA And rhGAA Protein In Plasma In Participants With Pompe Disease | rhGAA, Period 2 | 4.23 h | Geometric Coefficient of Variation 52.3 |
| Cohort 3, Duvoglustat 250 mg + rhGAA | PK: Elimination Half-life (T1/2) Of Total GAA And rhGAA Protein In Plasma In Participants With Pompe Disease | Total GAA, Period 1 | 3.56 h | Geometric Coefficient of Variation 13.7 |
| Cohort 4, Duvoglustat 600 mg + rhGAA | PK: Elimination Half-life (T1/2) Of Total GAA And rhGAA Protein In Plasma In Participants With Pompe Disease | rhGAA, Period 2 | 5.71 h | Geometric Coefficient of Variation 45.6 |
| Cohort 4, Duvoglustat 600 mg + rhGAA | PK: Elimination Half-life (T1/2) Of Total GAA And rhGAA Protein In Plasma In Participants With Pompe Disease | Total GAA, Period 2 | 6.33 h | Geometric Coefficient of Variation 22.8 |
| Cohort 4, Duvoglustat 600 mg + rhGAA | PK: Elimination Half-life (T1/2) Of Total GAA And rhGAA Protein In Plasma In Participants With Pompe Disease | Total GAA, Period 1 | 3.70 h | Geometric Coefficient of Variation 19.9 |
| Cohort 4, Duvoglustat 600 mg + rhGAA | PK: Elimination Half-life (T1/2) Of Total GAA And rhGAA Protein In Plasma In Participants With Pompe Disease | rhGAA, Period 1 | 2.33 h | Geometric Coefficient of Variation 54.3 |
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.
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
Population: The Per Protocol population included all participants who successfully completed both periods.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Cohort 1, Duvoglustat 50 mg + rhGAA | PK: Time To The Maximum Plasma Concentration (Tmax) Of Total GAA And rhGAA Protein In Plasma In Participants With Pompe Disease | Total GAA, Period 1 | 4.74 h |
| Cohort 1, Duvoglustat 50 mg + rhGAA | PK: Time To The Maximum Plasma Concentration (Tmax) Of Total GAA And rhGAA Protein In Plasma In Participants With Pompe Disease | Total GAA, Period 2 | 4.51 h |
| Cohort 1, Duvoglustat 50 mg + rhGAA | PK: Time To The Maximum Plasma Concentration (Tmax) Of Total GAA And rhGAA Protein In Plasma In Participants With Pompe Disease | rhGAA, Period 1 | 4.98 h |
| Cohort 1, Duvoglustat 50 mg + rhGAA | PK: Time To The Maximum Plasma Concentration (Tmax) Of Total GAA And rhGAA Protein In Plasma In Participants With Pompe Disease | rhGAA, Period 2 | 4.98 h |
| Cohort 2, Duvoglustat 100 mg + rhGAA | PK: Time To The Maximum Plasma Concentration (Tmax) Of Total GAA And rhGAA Protein In Plasma In Participants With Pompe Disease | Total GAA, Period 2 | 4.00 h |
| Cohort 2, Duvoglustat 100 mg + rhGAA | PK: Time To The Maximum Plasma Concentration (Tmax) Of Total GAA And rhGAA Protein In Plasma In Participants With Pompe Disease | rhGAA, Period 1 | 4.01 h |
| Cohort 2, Duvoglustat 100 mg + rhGAA | PK: Time To The Maximum Plasma Concentration (Tmax) Of Total GAA And rhGAA Protein In Plasma In Participants With Pompe Disease | rhGAA, Period 2 | 4.00 h |
| Cohort 2, Duvoglustat 100 mg + rhGAA | PK: Time To The Maximum Plasma Concentration (Tmax) Of Total GAA And rhGAA Protein In Plasma In Participants With Pompe Disease | Total GAA, Period 1 | 4.00 h |
| Cohort 3, Duvoglustat 250 mg + rhGAA | PK: Time To The Maximum Plasma Concentration (Tmax) Of Total GAA And rhGAA Protein In Plasma In Participants With Pompe Disease | rhGAA, Period 1 | 4.01 h |
| Cohort 3, Duvoglustat 250 mg + rhGAA | PK: Time To The Maximum Plasma Concentration (Tmax) Of Total GAA And rhGAA Protein In Plasma In Participants With Pompe Disease | Total GAA, Period 2 | 4.00 h |
| Cohort 3, Duvoglustat 250 mg + rhGAA | PK: Time To The Maximum Plasma Concentration (Tmax) Of Total GAA And rhGAA Protein In Plasma In Participants With Pompe Disease | rhGAA, Period 2 | 4.50 h |
| Cohort 3, Duvoglustat 250 mg + rhGAA | PK: Time To The Maximum Plasma Concentration (Tmax) Of Total GAA And rhGAA Protein In Plasma In Participants With Pompe Disease | Total GAA, Period 1 | 4.00 h |
| Cohort 4, Duvoglustat 600 mg + rhGAA | PK: Time To The Maximum Plasma Concentration (Tmax) Of Total GAA And rhGAA Protein In Plasma In Participants With Pompe Disease | rhGAA, Period 2 | 4.00 h |
| Cohort 4, Duvoglustat 600 mg + rhGAA | PK: Time To The Maximum Plasma Concentration (Tmax) Of Total GAA And rhGAA Protein In Plasma In Participants With Pompe Disease | Total GAA, Period 2 | 4.00 h |
| Cohort 4, Duvoglustat 600 mg + rhGAA | PK: Time To The Maximum Plasma Concentration (Tmax) Of Total GAA And rhGAA Protein In Plasma In Participants With Pompe Disease | Total GAA, Period 1 | 4.00 h |
| Cohort 4, Duvoglustat 600 mg + rhGAA | PK: Time To The Maximum Plasma Concentration (Tmax) Of Total GAA And rhGAA Protein In Plasma In Participants With Pompe Disease | rhGAA, Period 1 | 4.00 h |
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.
Time frame: Day 3 or Day 7
Population: The Per Protocol population included all participants who successfully completed both periods.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1, Duvoglustat 50 mg + rhGAA | Duvoglustat Concentration In Skeletal Muscle | Duvoglustat Concentration, Day 3 | 0 ng/g | — |
| Cohort 1, Duvoglustat 50 mg + rhGAA | Duvoglustat Concentration In Skeletal Muscle | Duvoglustat Concentration, Day 7 | 8.7 ng/g | Geometric Coefficient of Variation 68 |
| Cohort 2, Duvoglustat 100 mg + rhGAA | Duvoglustat Concentration In Skeletal Muscle | Duvoglustat Concentration, Day 7 | 0 ng/g | — |
| Cohort 2, Duvoglustat 100 mg + rhGAA | Duvoglustat Concentration In Skeletal Muscle | Duvoglustat Concentration, Day 3 | 5.9 ng/g | Geometric Coefficient of Variation 173 |
| Cohort 3, Duvoglustat 250 mg + rhGAA | Duvoglustat Concentration In Skeletal Muscle | Duvoglustat Concentration, Day 3 | 38.8 ng/g | Geometric Coefficient of Variation 87 |
| Cohort 3, Duvoglustat 250 mg + rhGAA | Duvoglustat Concentration In Skeletal Muscle | Duvoglustat Concentration, Day 7 | 28.0 ng/g | Geometric Coefficient of Variation 0.5 |
| Cohort 4, Duvoglustat 600 mg + rhGAA | Duvoglustat Concentration In Skeletal Muscle | Duvoglustat Concentration, Day 3 | 83.6 ng/g | — |
| Cohort 4, Duvoglustat 600 mg + rhGAA | Duvoglustat Concentration In Skeletal Muscle | Duvoglustat Concentration, Day 7 | 54.1 ng/g | Geometric Coefficient of Variation 25 |
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.
Time frame: Day 3 or Day 7
Population: The Per Protocol population included all participants who successfully completed both periods.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1, Duvoglustat 50 mg + rhGAA | Total GAA Activity In Skeletal Muscle | Total GAA, Period 1, Day 3 | 1409 pmol/mg/h | Geometric Coefficient of Variation 130 |
| Cohort 1, Duvoglustat 50 mg + rhGAA | Total GAA Activity In Skeletal Muscle | Total GAA, Period 2, Day 3 | 1952 pmol/mg/h | Geometric Coefficient of Variation 8 |
| Cohort 1, Duvoglustat 50 mg + rhGAA | Total GAA Activity In Skeletal Muscle | Total GAA, Period 1, Day 7 | 1216 pmol/mg/h | Geometric Coefficient of Variation 24 |
| Cohort 1, Duvoglustat 50 mg + rhGAA | Total GAA Activity In Skeletal Muscle | Total GAA, Period 2, Day 7 | 1197 pmol/mg/h | Geometric Coefficient of Variation 18 |
| Cohort 2, Duvoglustat 100 mg + rhGAA | Total GAA Activity In Skeletal Muscle | Total GAA, Period 2, Day 3 | 2320 pmol/mg/h | Geometric Coefficient of Variation 77 |
| Cohort 2, Duvoglustat 100 mg + rhGAA | Total GAA Activity In Skeletal Muscle | Total GAA, Period 1, Day 7 | 861 pmol/mg/h | Geometric Coefficient of Variation 16 |
| Cohort 2, Duvoglustat 100 mg + rhGAA | Total GAA Activity In Skeletal Muscle | Total GAA, Period 2, Day 7 | 1064 pmol/mg/h | Geometric Coefficient of Variation 39 |
| Cohort 2, Duvoglustat 100 mg + rhGAA | Total GAA Activity In Skeletal Muscle | Total GAA, Period 1, Day 3 | 1926 pmol/mg/h | Geometric Coefficient of Variation 67 |
| Cohort 3, Duvoglustat 250 mg + rhGAA | Total GAA Activity In Skeletal Muscle | Total GAA, Period 1, Day 7 | NA pmol/mg/h | Geometric Coefficient of Variation 91 |
| Cohort 3, Duvoglustat 250 mg + rhGAA | Total GAA Activity In Skeletal Muscle | Total GAA, Period 2, Day 3 | 2746 pmol/mg/h | Geometric Coefficient of Variation 35 |
| Cohort 3, Duvoglustat 250 mg + rhGAA | Total GAA Activity In Skeletal Muscle | Total GAA, Period 2, Day 7 | 1690 pmol/mg/h | Geometric Coefficient of Variation 22 |
| Cohort 3, Duvoglustat 250 mg + rhGAA | Total GAA Activity In Skeletal Muscle | Total GAA, Period 1, Day 3 | 2622 pmol/mg/h | Geometric Coefficient of Variation 14 |
| Cohort 4, Duvoglustat 600 mg + rhGAA | Total GAA Activity In Skeletal Muscle | Total GAA, Period 2, Day 7 | 1085 pmol/mg/h | Geometric Coefficient of Variation 14 |
| Cohort 4, Duvoglustat 600 mg + rhGAA | Total GAA Activity In Skeletal Muscle | Total GAA, Period 2, Day 3 | 2710 pmol/mg/h | Geometric Coefficient of Variation 37 |
| Cohort 4, Duvoglustat 600 mg + rhGAA | Total GAA Activity In Skeletal Muscle | Total GAA, Period 1, Day 3 | 1887 pmol/mg/h | Geometric Coefficient of Variation 47 |
| Cohort 4, Duvoglustat 600 mg + rhGAA | Total GAA Activity In Skeletal Muscle | Total GAA, Period 1, Day 7 | 916 pmol/mg/h | Geometric Coefficient of Variation 25 |