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This study is a first-in-human, randomized, placebo-controlled, 4-Part, single ascending dose (SAD) and multiple ascending dose (MAD) study in healthy adult subjects and adult subjects with Classic Galactosemia.
The study is designed to assess the safety and PK of AT-007 in healthy subjects and subjects with Classic Galactosemia as well as the effect of AT-007 on biomarkers of galactose metabolism (galactose, galactitol, and other galactose metabolites) in subjects with Classic Galactosemia.
This study consists of 4 parts:
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| AT-007 | Experimental | AT-007 is a CNS and retina penetrant aldose reductase inhibitor. |
|
| Placebo Comparator | Placebo Comparator | Placebo is used as a comparator to the experimental arm. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| AT-007 | Drug | AT-007 will be administered once daily before breakfast. Up to 4 different dose cohorts in part A; up to 4 dose cohorts in part B, up to 2 dose cohorts for part C, and up to 3 dose cohorts for part D will be enrolled in the study. The starting dose in Part A will be 0.5 mg/kg as a single dose. Subsequent doses in Part A and all doses in Parts B, C, and D will be based on the results of previous cohorts and/or previous parts of the study. Part B will start after all subjects in Part A have completed the study. Cohort C1 will be conducted simultaneously with Cohort B3 and using the same dose as Cohort B2. The dose for Cohort D1 will not be higher than the dose for Cohort B2. The second and third cohorts in Part D (D2 and D3) will not start until after all subjects in Cohorts B3 and B4, respectively, have completed the study and the dose levels will not be higher than those for Cohorts B3 and B4, respectively. |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Treatment-emergent Adverse Events | To evaluate the safety and tolerability of AT-007 after administration to healthy subjects, including clinically-significant changes in clinical laboratory test results, physical examination findings, vital sign evaluations, and electrocardiogram results. | Events after 1 day of administration. |
| Number of Participants With Treatment-emergent Adverse Events | To evaluate the safety and tolerability of AT-007 after multiple ascending doses are administered to healthy subjects, including clinically-significant changes in clinical laboratory test results, physical examination findings, vital sign evaluations, and electrocardiogram results. Part B and Part C are combined. | 7 Days after Dosing |
| Number of Participants With Treatment-emergent Adverse Events | To evaluate the safety and tolerability of AT-007 after multiple doses administered to Classic Galactosemia Patients, including clinically-significant changes in clinical laboratory test results, physical examination findings, vital sign evaluations, and electrocardiogram results. | 28 Days of Dosing |
| Number of Participants With Treatment-emergent Adverse Events | To evaluate the safety and tolerability of AT-007 administered to Classic Galactosemia Patients, including clinically-significant changes in clinical laboratory test results, physical examination findings, vital sign evaluations, and electrocardiogram results. | 90 Days after Dosing |
| Measure | Description | Time Frame |
|---|---|---|
| Cmax of AT-007 | Maximum (peak) plasma drug concentration | Part A: Sampling- predose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 36, 48 hrs Parts B, C, D: Day of Last Dose for each Part- predose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 36, 48 hrs D Extension: Day 30, 60, 90- predose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 36, 48 hrs |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Robert Green, MD, MPH | Brigham and Women's Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Anaheim Clinical Trials, LLC | Anaheim | California | 92801 | United States | ||
| Atlanta Center for Medical Research |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 38988185 | Derived | Perfetti R, Bailey E, Wang S, Mills R, Mohanlal R, Shendelman S. Safety, Pharmacokinetics, and Pharmacodynamics of the New Aldose Reductase Inhibitor Govorestat (AT-007) After a Single and Multiple Doses in Participants in a Phase 1/2 Study. J Clin Pharmacol. 2024 Nov;64(11):1397-1406. doi: 10.1002/jcph.2495. Epub 2024 Jul 10. |
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| ID | Title | Description |
|---|---|---|
| FG000 | Part A Cohort 1: AT-007 0.5mg/kg | AT-007 administered once daily before breakfast as a single dose. |
| FG001 | Part A Cohort 2: AT-007 5mg/kg | AT-007 administered once daily before breakfast as a single dose. |
| FG002 | Part A Cohort 3: AT-007 10mg/kg | AT-007 administered once daily before breakfast as a single dose. |
| FG003 | Part A Cohort 4: AT-007 20mg/kg | AT-007 administered once daily before breakfast as a single dose. |
| FG004 | Part A Cohort 5: AT-007 40mg/kg | AT-007 administered once daily before breakfast as a single dose. |
| FG005 | Part A: Placebo Comparator | Placebo: Matching placebo will be administered once in the morning before breakfast as a single dose |
| FG006 | Part B & C: AT-007 5mg/kg | Part B and Part C are combined with results pooled for each dose level. Healthy adult volunteers received multiple doses of AT-007 once daily for 7 days. |
| FG007 | Part B & C: AT-007 10mg/kg | Part B and Part C are combined with results pooled for each dose level. Healthy adult volunteers received multiple doses of AT-007 once daily for 7 days. |
| FG008 | Part B & C: AT-007 20mg/kg | Part B and Part C are combined with results pooled for each dose level. Healthy adult volunteers received multiple doses of AT-007 once daily for 7 days. |
| FG009 | Part B & C: AT-007 40mg/kg | Part B and Part C are combined with results pooled for each dose level. Healthy adult volunteers received multiple doses of AT-007 once daily for 7 days. |
| FG010 | Part B &C: Placebo Comparator | Part B and Part C are combined with results pooled for each dose level. Healthy adult volunteers received multiple doses of AT-007 once daily for 7 days. |
| FG011 | Part D Cohort 1: AT-007 5mg/kg | AT-007 administered as a single dose once followed by a 5-day wash followed by 28 days of dosing. |
| FG012 | Part D Cohort 1 (Placebo) Then Cohort 2 (AT-007 20mg/kg | Placebo administered as a single dose once followed by a 5-day wash followed by 28 days of dosing in Cohort 1. Then, after washout, AT-007 administered as a single dose once followed by a 5-day wash followed by 28 days of dosing in Cohort 2. |
| FG013 | Part D Cohort 1 (AT-007 5mg/kg) Then Cohort 3 (AT-007 40mg/kg) | AT-007 administered as a single dose once followed by a 5-day wash followed by 28 days of dosing for each dosing cohort after a washout between cohort dosing. |
| FG014 | Part D Cohort 1 (Placebo) Then Cohort 3 (AT-007 40mg/kg) | Placebo administered as a single dose once followed by a 5-day wash followed by 28 days of dosing in Cohort 1. After washout, AT-007 administered as a single dose once followed by a 5-day wash followed by 28 days of dosing in Cohort 3. |
| FG015 | Part D Cohort 2: AT-007 20mg/kg | AT-007 administered as a single dose once followed by a 5-day wash followed by 28 days of dosing. |
| FG016 | Part D Cohort 2 (AT-007 20mg/kg) Then Cohort 3 (AT-007 40mg/kg) | AT-007 administered as a single dose once followed by a 5-day wash followed by 28 days of dosing for each cohort with washout between cohorts. |
| FG017 | Part D Cohort 3: AT-007 40mg/kg | AT-007 administered as a single dose once followed by a 5-day wash followed by 28 days of dosing. |
| FG018 | Part D: Placebo Comparator | Placebo administered as a single dose once followed by a 5-day wash followed by 28 days of dosing. |
| FG019 | Part D Extension Cohort 1: AT-007 20mg/kg | Adults with Classic Galactosemia, daily doses of AT-007 for 90 days |
| FG020 | Part D Extension Cohort 2: 40mg/kg | Adults with Classic Galactosemia, daily doses of AT-007 for 90 days |
| FG021 | Part D Extension: Placebo Compartor | Adults with Classic Galactosemia, daily doses of placebo for 90 days |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Part A Cohort 1 |
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| Part A Cohort 2 |
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| Part A Cohort 3 |
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| Part A Cohort 4 |
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| Part A Cohort 5 |
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| Part A Placebo Comparator |
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| Part B & C AT-007 5mg/kg Cohort |
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| Part B & C AT-007 10mg/kg Cohort |
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| Part B & C AT-007 20mg/kg Cohort |
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| Part B & C AT-007 40mg/kg |
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| Part B & C Placebo Comparator |
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| Part D Cohort 1 |
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| Part D Cohort 2 |
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| Part D Cohort 3 |
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| Part D Placebo Comparator |
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| Part D Extension Cohort 1 |
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| Part D Extension Cohort 2 |
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| Part D Extension Placebo Comparator |
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| ID | Title | Description |
|---|---|---|
| BG000 | Part A Cohort 1: AT-007 0.5mg/kg | Baseline characteristics of the healthy adult subjects enrolled in Part A were well-balanced between active and placebo across all dosing cohorts. |
| BG001 | Part A Cohort 2: AT-007 5mg/kg |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median |
| 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 With Treatment-emergent Adverse Events | To evaluate the safety and tolerability of AT-007 after administration to healthy subjects, including clinically-significant changes in clinical laboratory test results, physical examination findings, vital sign evaluations, and electrocardiogram results. | All subjects dosed were analyzed. | Posted | Count of Participants | Participants | Events after 1 day of administration. |
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Part A: 1 day; Part B&C: 7 days; Part D: 32 days; Part D Extension: 90 days
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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 | Part A Cohort 1: AT-007 0.5mg/kg | Single ascending doses of orally administered AT-007 were administered to healthy adult subjects. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Liver Injury | Hepatobiliary disorders | MedDRA (Unspecified) | Non-systematic Assessment | There was 1 severe SAE of liver injury in 1 subject (20 mg/kg dosing) that was considered not related to study drug by the independent Liver Safety Adjudication Committee. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Gastrointestinal Disorders | Gastrointestinal disorders | MedDRA (Unspecified) | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Riccardo Perfetti, MD | Applied Therapeutics, Inc | 2122209226 | rperfetti@appliedtherapeutics.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Sep 3, 2021 | Feb 14, 2023 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Jul 20, 2021 | Feb 14, 2023 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D005693 | Galactosemias |
| ID | Term |
|---|---|
| D020739 | Brain Diseases, Metabolic, Inborn |
| D001928 | Brain Diseases, Metabolic |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
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| Placebo | Drug | Matching placebo will be administered once in the morning before breakfast |
|
| Tmax of AT-007 |
Time to reach maximum (peak) plasma drug concentration |
| Part A: Sampling- predose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 36, 48 hrs Parts B, C, D: Day of Last Dose for each Part- predose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 36, 48 hrs D Extension: Day 30, 60, 90- predose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 36, 48 hrs |
| t1/2 of AT-007 | Terminal elimination half life | Part A: Sequential sampling at predose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 36, and 48 hours. Parts B, C, D: Determined using Day of Last Dose for the respective Part; predose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 36, and 48 hours. |
| AUClast of AT-007 | Area under the plasma concentration-time curve from time zero to time of last quantifiable concentration | Part A: Sequential sampling at predose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 36, and 48 hours. Parts B, C, D: Determined using Day of Last Dose for the respective Part at predose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 36, and 48 hours. |
| AUCinf of AT-007 | Area under the plasma concentration-time curve from time zero extrapolated to infinity | Part A: Sequential sampling at predose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 36, and 48 hours. Part D: Determined using Day 1 with sampling at predose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 36, and 48 hours. |
| Maximal Galactitol Reduction in Plasma | Disease-Specific Biomarker in Classic Galactosemia Patients | Part D: Samples at predose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 36, and 48 hours on days 1, 12, 32. Part D Extension: Samples at predose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 36, and 48 hours on days 1, 30, 60, & 90. |
| Galactose Concentration in Plasma | Disease-Specific Biomarker in Classic Galactosemia Patients | Part D: Day 32. Part D Extension: Days 30, 60, & 90. |
| Galactose-1-Phosphate (Gal-1p) Concentration in Plasma | Disease-Specific Biomarker in Classic Galactosemia Patients | Part D: Day 32. Part D Extension: Days 30, 60, & 90. |
| Atlanta |
| Georgia |
| 30331 |
| United States |
| Brigham and Women's Hospital | Boston | Massachusetts | 02115 | United States |
| ICON Clinical Research | San Antonio | Texas | 78209 | United States |
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Baseline characteristics of the healthy adult subjects enrolled in Part A were well-balanced between active and placebo across all dosing cohorts.
| BG002 | Part A Cohort 3: AT-007 10mg/kg | Baseline characteristics of the healthy adult subjects enrolled in Part A were well-balanced between active and placebo across all dosing cohorts. |
| BG003 | Part A Cohort 4: AT-007 20mg/kg | Baseline characteristics of the healthy adult subjects enrolled in Part A were well-balanced between active and placebo across all dosing cohorts. |
| BG004 | Part A Cohort 5: AT-007 40mg/kg | Baseline characteristics of the healthy adult subjects enrolled in Part A were well-balanced between active and placebo across all dosing cohorts. |
| BG005 | Part A Placebo Comparator | Baseline characteristics of the healthy adult subjects enrolled in Part A were well-balanced between active and placebo across all dosing cohorts. |
| BG006 | Part B & C AT-007 5mg/kg Cohort | Baseline characteristics of the healthy adult subjects enrolled in Part B & C were well-balanced between active and placebo across all dosing cohorts. |
| BG007 | Part B & C AT-007 10mg/kg Cohort | Baseline characteristics of the healthy adult subjects enrolled in Part B & C were well-balanced between active and placebo across all dosing cohorts. |
| BG008 | Part B & C AT-007 20mg/kg Cohort | Baseline characteristics of the healthy adult subjects enrolled in Part B & C were well-balanced between active and placebo across all dosing cohorts. |
| BG009 | Part B & C AT-007 40mg/kg Cohort | Baseline characteristics of the healthy adult subjects enrolled in Part B & C were well-balanced between active and placebo across all dosing cohorts. |
| BG010 | Part B & C Placebo Comparator | Baseline characteristics of the healthy adult subjects enrolled in Part B & C were well-balanced between active and placebo across all dosing cohorts. |
| BG011 | Part D Cohort 1: AT-007 5mg/kg | Baseline characteristics of the adult subjects with Classic Galactosemia enrolled in Part D were well-balanced between active and placebo across all dosing cohorts. |
| BG012 | Part D Cohort 1 (Placebo) Then Cohort 2 (AT-007 20mg/kg) | Baseline characteristics of the adult subjects with Classic Galactosemia enrolled in Part D were well-balanced between active and placebo across all dosing cohorts. |
| BG013 | Part D Cohort 1 (AT-007 5mg/kg) Then Cohort 3 (AT-007 40mg/kg) | Baseline characteristics of the adult subjects with Classic Galactosemia enrolled in Part D were well-balanced between active and placebo across all dosing cohorts. |
| BG014 | Part D Cohort 1 (Placebo) Then Cohort 3 (AT-007 40mg/kg) | Baseline characteristics of the adult subjects with Classic Galactosemia enrolled in Part D were well-balanced between active and placebo across all dosing cohorts. |
| BG015 | Part D Cohort 2: AT-007 20mg/kg | Baseline characteristics of the adult subjects with Classic Galactosemia enrolled in Part D were well-balanced between active and placebo across all dosing cohorts. |
| BG016 | Part D Cohort 2 (AT-007 20mg/kg) Then Chort 3 (AT-007 40mg/kg) | Baseline characteristics of the adult subjects with Classic Galactosemia enrolled in Part D were well-balanced between active and placebo across all dosing cohorts. |
| BG017 | Part D Cohort 3: AT-007 40mg/kg | Baseline characteristics of the adult subjects with Classic Galactosemia enrolled in Part D were well-balanced between active and placebo across all dosing cohorts. |
| BG018 | Part D Placebo Comparator | Baseline characteristics of the adult subjects with Classic Galactosemia enrolled in Part D were well-balanced between active and placebo across all dosing cohorts. |
| BG019 | Part D Extension Placebo Comparator | Baseline characteristics of the adult subjects with Classic Galactosemia enrolled in Part D Extension were well-balanced between active and placebo across all dosing cohorts. |
| BG020 | Part D Extension Cohort 1: AT-007 20mg/kg | Baseline characteristics of the adult subjects with Classic Galactosemia enrolled in Part D Extension were well-balanced between active and placebo across all dosing cohorts. |
| BG021 | Part D Extension Cohort 2: AT-007 40mg/kg | Baseline characteristics of the adult subjects with Classic Galactosemia enrolled in Part D Extension were well-balanced between active and placebo across all dosing cohorts. |
| BG022 | Total | Total of all reporting groups |
| years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Region of Enrollment | Number | participants |
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| Galactitol | Galactitol is a disease specific pharmakodynamic marker in Classic Galactosemia and therefore was only collected and measured in Part D and Part D Extension. Galactitol is NOT measurable in healthy people because they do not produce it; as such and as per protocol it was not collected and not measured in healthy adults. This means that no healthy adults had galactitol measured so it is not present for Part A, Part B, or Part C. The units are ng/mL and it's measured in plasma. | Galactitol is NOT measurable in healthy people because they do not produce it; as such and as per protocol it was not collected and not measured in healthy adults. This means that no healthy adults had galactitol measured so it is not present for Part A, Part B, or Part C. | Median | Full Range | ng/mL |
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Single doses of orally administered AT-007 were administered to Healthy Adult Subjects and all TEAEs recorded.
| OG002 | Part A Cohort 3: AT-007 10mg/kg | Single doses of orally administered AT-007 were administered to Healthy Adult Subjects and all TEAEs recorded. |
| OG003 | Part A Cohort 4: AT-007 20mg/kg | Single doses of orally administered AT-007 were administered to Healthy Adult Subjects and all TEAEs recorded. |
| OG004 | Part A Cohort 5: AT-007 40mg/kg | Single doses of orally administered AT-007 were administered to Healthy Adult Subjects and all TEAEs recorded. |
| OG005 | Part A: Placebo Comparator | Single doses of orally administered matched-placebo were administered to Healthy Adult Subjects and all TEAEs recorded. |
|
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| Primary | Number of Participants With Treatment-emergent Adverse Events | To evaluate the safety and tolerability of AT-007 after multiple ascending doses are administered to healthy subjects, including clinically-significant changes in clinical laboratory test results, physical examination findings, vital sign evaluations, and electrocardiogram results. Part B and Part C are combined. | All subjects dosed were analyzed | Posted | Count of Participants | Participants | 7 Days after Dosing |
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| Primary | Number of Participants With Treatment-emergent Adverse Events | To evaluate the safety and tolerability of AT-007 after multiple doses administered to Classic Galactosemia Patients, including clinically-significant changes in clinical laboratory test results, physical examination findings, vital sign evaluations, and electrocardiogram results. | All subjects dosed were analyzed. | Posted | Count of Participants | Participants | 28 Days of Dosing |
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| Primary | Number of Participants With Treatment-emergent Adverse Events | To evaluate the safety and tolerability of AT-007 administered to Classic Galactosemia Patients, including clinically-significant changes in clinical laboratory test results, physical examination findings, vital sign evaluations, and electrocardiogram results. | All subjects dosed were analyzed. | Posted | Count of Participants | Participants | 90 Days after Dosing |
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| Secondary | Cmax of AT-007 | Maximum (peak) plasma drug concentration | Part D Extension Cohort 2 40mg/kg ended early at Day 30 as recommended by Monitoring Committee. As such, only 1 subject has D30 data available; the other subject did not have enough blood samples to calculate. | Posted | Geometric Mean | Geometric Coefficient of Variation | microgram/mL | Part A: Sampling- predose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 36, 48 hrs Parts B, C, D: Day of Last Dose for each Part- predose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 36, 48 hrs D Extension: Day 30, 60, 90- predose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 36, 48 hrs |
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| Secondary | Tmax of AT-007 | Time to reach maximum (peak) plasma drug concentration | Part D Extension Cohort 2 40mg/kg ended early at Day 30 as recommended by Monitoring Committee. As such, only 1 subject has D30 data available; the other subject did not have enough blood samples to calculate. | Posted | Median | Full Range | hours | Part A: Sampling- predose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 36, 48 hrs Parts B, C, D: Day of Last Dose for each Part- predose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 36, 48 hrs D Extension: Day 30, 60, 90- predose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 36, 48 hrs |
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| Secondary | t1/2 of AT-007 | Terminal elimination half life | For Part D Extension, t1/2 was not performed so these cohorts are not presented. | Posted | Geometric Mean | Geometric Coefficient of Variation | hours | Part A: Sequential sampling at predose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 36, and 48 hours. Parts B, C, D: Determined using Day of Last Dose for the respective Part; predose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 36, and 48 hours. |
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| Secondary | AUClast of AT-007 | Area under the plasma concentration-time curve from time zero to time of last quantifiable concentration | For Part D Extension, AUClast was not performed so these cohorts are not presented. | Posted | Geometric Mean | Geometric Coefficient of Variation | microgram*hour/mL | Part A: Sequential sampling at predose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 36, and 48 hours. Parts B, C, D: Determined using Day of Last Dose for the respective Part at predose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 36, and 48 hours. |
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| Secondary | AUCinf of AT-007 | Area under the plasma concentration-time curve from time zero extrapolated to infinity | AUCinf was only calculated for all cohorts of Part A and on Day 1 of Part D. It was not calculated for Parts B, C, or D Extension so those cohorts are not presented. | Posted | Geometric Mean | Geometric Coefficient of Variation | microgram*hour/mL | Part A: Sequential sampling at predose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 36, and 48 hours. Part D: Determined using Day 1 with sampling at predose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 36, and 48 hours. |
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| Secondary | Maximal Galactitol Reduction in Plasma | Disease-Specific Biomarker in Classic Galactosemia Patients | Part D Extension Cohort 2 40mg/kg ended early at Day 30 as recommended by Monitoring Committee. As such, there are no results for this outcome measure for the Part D Extension Cohort 2 40mg/kg. | Posted | Mean | Standard Deviation | maximal change from baseline in ng/mL | Part D: Samples at predose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 36, and 48 hours on days 1, 12, 32. Part D Extension: Samples at predose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 36, and 48 hours on days 1, 30, 60, & 90. |
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| Secondary | Galactose Concentration in Plasma | Disease-Specific Biomarker in Classic Galactosemia Patients | Part D Extension Cohort 2 40mg/kg ended early at Day 30 as recommended by Monitoring Committee. As such, there are no results for this outcome measure for the Part D Extension Cohort 2 40mg/kg. Part D Extension Cohort 1 of AT-007 20mg/kg is presented for Days 30, 60, and 90. | Posted | Mean | Standard Deviation | percent change from baseline | Part D: Day 32. Part D Extension: Days 30, 60, & 90. |
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| Secondary | Galactose-1-Phosphate (Gal-1p) Concentration in Plasma | Disease-Specific Biomarker in Classic Galactosemia Patients | Part D Extension Cohort 2 40mg/kg ended early at Day 30 as recommended by Monitoring Committee. As such, there are no results for this outcome measure for the Part D Extension Cohort 2 40mg/kg. Part D Extension Cohort 1 of AT-007 20mg/kg is presented for Days 30, 60, and 90. | Posted | Mean | Standard Deviation | percent change from baseline | Part D: Day 32. Part D Extension: Days 30, 60, & 90. |
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| 0 |
| 6 |
| 0 |
| 6 |
| 1 |
| 6 |
| EG001 | Part A Cohort 2: AT-007 5mg/kg | Single ascending doses of orally administered AT-007 were administered to healthy adult subjects. | 0 | 6 | 0 | 6 | 0 | 6 |
| EG002 | Part A Cohort 3: AT-007 10mg/kg | Single ascending doses of orally administered AT-007 were administered to healthy adult subjects. | 0 | 6 | 0 | 6 | 0 | 6 |
| EG003 | Part A Cohort 4: AT-007 20mg/kg | Single ascending doses of orally administered AT-007 were administered to healthy adult subjects. | 0 | 6 | 0 | 6 | 2 | 6 |
| EG004 | Part A Cohort 5: 40mg/kg | Single ascending doses of orally administered AT-007 were administered to healthy adult subjects. | 0 | 6 | 0 | 6 | 1 | 6 |
| EG005 | Part A Placebo Comparator | Single ascending doses of orally administered matched placebo were administered to healthy adult subjects. | 0 | 10 | 0 | 10 | 2 | 10 |
| EG006 | Part B & C Cohort 1: AT-007 5mg/kg | Multiple doses of orally administered AT-007 were administered to healthy adult subjects. | 0 | 6 | 0 | 6 | 1 | 6 |
| EG007 | Part B & C Cohort 2: AT-007 10mg/kg | Multiple doses of orally administered AT-007 were administered to healthy adult subjects. | 0 | 8 | 0 | 8 | 2 | 8 |
| EG008 | Part B & C Cohort 3: AT-007 20mg/kg | Multiple doses of orally administered AT-007 were administered to healthy adult subjects. | 0 | 10 | 0 | 10 | 3 | 10 |
| EG009 | Part B & C Cohort 4: AT-007 40mg/kg | Multiple doses of orally administered AT-007 were administered to healthy adult subjects. | 0 | 9 | 0 | 9 | 1 | 9 |
| EG010 | Part B & C Placebo Comparator | Multiple doses of orally administered matched placebo were administered to healthy adult subjects. | 0 | 8 | 0 | 8 | 2 | 8 |
| EG011 | Part D Cohort 1: AT-007 5mg/kg | Multiple doses of orally administered AT-007 were administered to adult subjects with Classic Galactosemia. | 0 | 4 | 0 | 4 | 3 | 4 |
| EG012 | Part D Cohort 2: AT-007 20mg/kg | Multiple doses of orally administered AT-007 were administered to adult subjects with Classic Galactosemia. | 0 | 4 | 0 | 4 | 1 | 4 |
| EG013 | Part D Cohort 3: AT-007 40mg/kg | Multiple doses of orally administered AT-007 were administered to adult subjects with Classic Galactosemia. | 0 | 4 | 0 | 4 | 2 | 4 |
| EG014 | Part D Placebo Comparator | Multiple doses of orally administered matched placebo were administered to adult subjects with Classic Galactosemia. | 0 | 6 | 0 | 6 | 2 | 6 |
| EG015 | Part D Extension Cohort 1: 20mg/kg | Multiple doses of orally administered AT-007 were administered to adult subjects with Classic Galactosemia. | 0 | 9 | 1 | 9 | 7 | 9 |
| EG016 | Part D Extension Cohort 2: 40mg/kg | Multiple doses of orally administered AT-007 were administered to adult subjects with Classic Galactosemia. | 0 | 2 | 0 | 2 | 1 | 2 |
| EG017 | Part D Extension Placebo Comparator | Multiple doses of orally administered matched placebo were administered to adult subjects with Classic Galactosemia. | 0 | 4 | 0 | 4 | 2 | 4 |
|
| ALT Increased | Hepatobiliary disorders | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Infections/Infestations | Infections and infestations | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Musculoskelatal & Connective Tissue Disorders | Musculoskeletal and connective tissue disorders | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Nervous System | Nervous system disorders | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Injury, poisoning and procedural complications | Injury, poisoning and procedural complications | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Investigations | Investigations | MedDRA (Unspecified) | Non-systematic Assessment |
|
| General Disorders | General disorders | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Seasonal Allergies | Immune system disorders | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Reproductive System Disorder | Reproductive system and breast disorders | MedDRA (Unspecified) | Non-systematic Assessment |
|
Not provided
Not provided
| D009422 | Nervous System Diseases |
| D008661 | Metabolism, Inborn Errors |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D002239 | Carbohydrate Metabolism, Inborn Errors |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| Male |
|
| Not Hispanic or Latino |
|
| Unknown or Not Reported |
|
| Asian |
|
| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|