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document
Safety , pharmacokinetics , pharmacogenomics and QT concentration-effect modelling of the SirT1 inhibitor selisistat in healthy volunteers . AIM Selisistat ( SEN0014196 ) , a first-in-class SirT1 inhibitor , is being developed as a disease-modifying therapy for Huntington 's disease . This first-in-human study investigated the safety , pharmacokinetics and pharmacogenomics of single and multiple doses of selisistat in healthy male and female subjects . METHOD In this double-blind , randomized , placebo-controlled study , seven cohorts of eight subjects received a single dose of selisistat at dose levels of 5 , 25 , 75 , 150 , 300 and 600 mg and four cohorts of eight subjects were administered 100 , 200 and 300 mg once daily for 7 days . Blood sampling and safety assessments were conducted throughout the study . RESULTS Selisistat was rapidly absorbed and systemic exposure increased in proportion to dose in the 5-300 mg range . Steady-state plasma concentrations were achieved within 4 days of repeated dosing . The incidence of drug related adverse events showed no correlation with dose level or number of doses received and was comparable with the placebo group . No serious adverse events were reported and no subjects were withdrawn due to adverse events . There were no trends in clinical laboratory parameters or vital signs . No trends in heart rate or ECG parameters , including the QTc interval and T-wave morphology , were observed . There were no findings in physical or neurological examinations or postural control . Transcriptional alteration was observed in peripheral blood . CONCLUSION Selisistat was safe and well tolerated by healthy male and female subjects after single doses up to 600 mg and multiple doses up to 300 mg day ( -1 ) .
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Intervention_Pharmacological
SirT1 inhibitor selisistat
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Intervention_Pharmacological
Selisistat
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Intervention_Pharmacological
selisistat
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Intervention_Control
placebo-controlled
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Intervention_Pharmacological
selisistat
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Intervention_Pharmacological
Selisistat
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Intervention_Control
placebo
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Intervention_Pharmacological
Selisistat
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Outcome_Physical
Safety , pharmacokinetics , pharmacogenomics and QT concentration-effect modelling
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Outcome_Other
safety assessments
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Outcome_Other
Steady-state plasma concentrations
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Outcome_Adverse-effects
adverse events
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Outcome_Adverse-effects
adverse events
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Outcome_Physical
heart rate
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Outcome_Physical
ECG parameters , including the QTc interval and T-wave morphology
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Participant_Condition
healthy volunteers .
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Participant_Condition
Huntington 's disease .
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Participant_Sex
male
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Participant_Sex
female
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Participant_Sample-size
seven cohorts of eight
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Participant_Sample-size
four
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Participant_Sex
male
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Participant_Sex
female