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The primary purpose of this study is to assess the effect of food upon the pharmacokinetics (PK) of SEN0014196 in subjects with Huntington disease (HD).
In addition to the pharmacokinetic endpoints, the study will assess the safety and tolerability of 100 mg once daily (qd) doses of SEN0014196 over 14 days in subjects with HD and explore potential biomarkers for use in subsequent Phase 2/3 studies.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Fasted condition | Experimental | Subjects in the Fasted group will take study drug after an overnight fast (since at least midnight). Additionally, on PK assessment days, no food will be allowed for at least 4 hours after study drug administration. |
|
| Fed condition | Experimental | Subjects in the Fed group will take study drug within 30 minutes after starting breakfast; these subjects will otherwise maintain their normal eating schedule. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| SEN0014196 | Drug | 100 mg, immediate release tablets, once daily administration |
|
| Measure | Description | Time Frame |
|---|---|---|
| To determine the effect of food on the repeated dose pharmacokinetics of SEN0014196 at 100 mg once daily in subjects with Huntington's disease | The effect of food on the PK of SEN0014196 will be evaluated for the following parameters: maximum observed plasma concentration (Cmax), time of maximum observed plasma concentration(tmax), AUC from time zero to the length of the dosing interval (tau) (AUC0-τ), AUC from time zero to the last quantifiable concentration (AUC0-last), AUC from time zero to infinity (AUC0-∞), terminal elimination half-life (t1/2), and terminal elimination rate constant (λz). | 14 Days |
| Measure | Description | Time Frame |
|---|---|---|
| Pharmacodynamics | The following PD biomarkers will be assessed: soluble huntingtin levels and huntingtin acetylation status (by enzyme-linked immunosorbent assay [ELISA] and liquid chromatography-tandem mass spectrometry [LC-MS/MS]). | 14 Days |
| To determine the safety and tolerability of repeated doses of SEN0014196 at 100 mg once daily in subjects with Huntington's disease |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Francis O Walker, MD | Wake Forest University Health Sciences | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of California San Diego | La Jolla | California | 92037-0706 | United States | ||
| University of California Davis Medical Center |
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| ID | Term |
|---|---|
| D006816 | Huntington Disease |
| D001480 | Basal Ganglia Diseases |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D003704 | Dementia |
| D002819 | Chorea |
| D020820 | Dyskinesias |
| D009069 | Movement Disorders |
| D020271 | Heredodegenerative Disorders, Nervous System |
| D019636 | Neurodegenerative Diseases |
| D030342 | Genetic Diseases, Inborn |
| D003072 | Cognition Disorders |
| D001523 | Mental Disorders |
| ID | Term |
|---|---|
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D019965 | Neurocognitive Disorders |
| D009461 | Neurologic Manifestations |
| D012816 | Signs and Symptoms |
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| ID | Term |
|---|---|
| C550547 | 6-chloro-2,3,4,9-tetrahydro-1H-carbazole-1-carboxamide |
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Safety assessments include: AEs, ECGs, vital signs, body weight and height, clinical laboratory evaluations (serum biochemistry and hematology), urinalysis, physical and neurological examinations, C-SSRS, and UHDRS. |
| 14 Days |
| Sacramento |
| California |
| 95655 |
| United States |
| Washington University | St Louis | Missouri | 63110 | United States |
| University of Rochester | Rocherster | New York | 14627 | United States |
| Wake Forest School of Medicine | Winston-Salem | North Carolina | 27157-1078 | United States |
| University of Texas Southwestern Medical Center | Dallas | Texas | 75390-8527 | United States |
| Baylor College of Medicine | Houston | Texas | 77030 | United States |
| D013568 | Pathological Conditions, Signs and Symptoms |