The primary objective of this study is to provide biological samples from patients with Huntington's disease to allow characterisation of the pharmacological mechanism of action of SEN0014196.
This study will establish the acute phenotypical and biological effects of repeated dose application of SEN0014196 in patients with Huntington's disease, providing biomaterials for biomarker studies (levels of circulating huntingtin, acetylation status of mutant huntingtin, innate immune markers, transcriptional profiles). Evaluation of phenotypic effects will include UHDRS scores, total functional capacity. Safety assessments will include ECG, vital signs, laboratory safety tests and physical examination.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
55
10 mg once daily administration (immediate release capsule)
100 mg once daily administration (immediate release capsule)
Once daily administration (immediate release capsule)
Universitätsklinik Ulm, Neurologie
Ulm, Germany
To determine the change from baseline of a series of pharmacodynamic markers in peripheral blood mononuclear cells
Collection of peripheral blood mononuclear cells for biomarker investigations, specifically acetylation status of mutant huntingtin, levels of circulating huntingtin, innate immune markers and transcriptional profiles
Time frame: Baseline, Day 7, Day 14, Follow-Up
To determine the safety and tolerability following repeated doses of SEN0014196 over two weeks at two dose levels in patients with Huntington's disease
Safety assessments will include ECG, vital signs, laboratory safety tests, and physical and neurological examination. Tolerability will include type and frequency of adverse events.
Time frame: Baseline, Day 7, Day 14, Follow-up
To determine the pharmacokinetics of repeated doses of SEN0014196 at two dose levels when administered over two weeks in patients with Huntington's disease
The following parameters will be assessed: 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). Gender differences. Dose proportionality.
Time frame: Baseline, Day 14
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