The primary objective of this study is to assess the safety and tolerability of single and multiple oral administered doses of HS-10380 in Chinese healthy subjects.
This is a phase I, randomized, double-blinded, placebo-controlled, both single ascending doses (SAD) study and multiple ascending dose (MAD) clinical trial to assess the safety, tolerability, and pharmacokinetics of HS-10380 in Chinese healthy subjects. There will be four phases in SAD and MAD study: a 2-week screening phase, a 1-day baseline phase, a double-blind treatment phase, and a 1-week post-treatment (follow-up) phase.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
76
Shanghai Mental Health Center
Shanghai, Shanghai Municipality, China
RECRUITINGNumber of Subjects Experiencing Adverse Events (AEs)
AE include adverse events (AEs) and serious adverse events (SAEs)
Time frame: Baseline to end of follow-up (a maximum of 20 days)
Changes from baseline in laboratory tests
Laboratory tests include blood routine, urine routine, blood biochemistry, coagulation function, thyroid function and serum prolactin;
Time frame: Baseline to end of follow-up (a maximum of 20 days)
Changes from baseline in vital signs
Vital signs include respiration, pulse, blood pressure, body temperature and SpO2
Time frame: Baseline to end of follow-up (a maximum of 20 days)
Change from baseline in Electrocardiogram (ECG)
ECG parameters including heart rate, PR interval, RR interval and QTcF, etc.
Time frame: Baseline to end of follow-up (a maximum of 20 days)
Change from baseline in weight (kg)
Time frame: Baseline to end of follow-up (a maximum of 20 days)
Change from baseline in physical examination
Including general condition, heart, chest and abdomen, skin and mucous membranes, lymph node examination, etc.
Time frame: Baseline to end of follow-up (a maximum of 20 days)
Change from baseline in Simpson-Angus Scale (SAS) score
The SAS is a 10-item testing instrument used to evaluate drug-related extrapyramidal syndromes. The following items are included in the SAS: gait, arm dropping, shoulder shaking, elbow rigidity, wrist rigidity, leg pendulousness, head dropping, glabella reflex, tremor, and salivation. Total score ranges from 0 to 40 with a higher score indicating increased severity.
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Time frame: Baseline to end of follow-up (a maximum of 20 days)
Change from baseline in Abnormal Involuntary Movement Scale (AIMS) score
AIMS is a rating scale measuring involuntary movements known as tardive dyskinesia, that sometimes develop as a side effect of long-term treatment with antipsychotic medications. The AIMS score was calculated as the sum of questions 1 through 7 of the AIMS instrument, which includes assessments of involuntary movements in the face, lips, jaw, tongue, upper and lower extremities, and neck/shoulders/hips. Each item is rated on a five-point scale of severity from 0-4 with 0 (none), 1 (minimal), 2 (mild), 3 (moderate), 4 (severe). Total scores range from 0 to 28.
Time frame: Baseline to end of follow-up (a maximum of 20 days)
Change from baseline in Barnes Akathisia Rating Scale (BARS) score
BAS is a rating scale that is administered by physicians to assess the severity of drug-induced akathisia, which is a movement disorder characterized by a feeling of inner restlessness and a compelling need to be in constant motion, as well as by actions such as rocking while standing or sitting, lifting the feet as if marching on the spot, and crossing and uncrossing the legs while sitting. The following subcategories are scored: objective akathisia, subjective awareness of restlessness and subjective distress related to restlessness and are rated on a 4-point scale from 0-3. In addition, the global clinical assessment of akathisia uses a 6-point scale ranging from 0-5. Total score ranges from 0 to 14 with a higher score indicating increased severity.
Time frame: Baseline to end of follow-up (a maximum of 20 days)
Maximum plasma concentration (Cmax) of single-dose HS-10380 administration
Time frame: Up to 120 hours post-dose
Time of the Maximum Concentration (Tmax) of single-dose HS-10380 administration
Time frame: Up to 120 hours post-dose
Terminal rate constant (λz) of single-dose HS-10380 administration
Time frame: Up to 120 hours post-dose
Elimination half-life (t1/2) of single-dose HS-10380 administration
Time frame: Up to 120 hours post-dose
Area under the concentration-time curve from time zero (pre-dose) to last time of quantifiable concentration (AUC0-t) of single-dose HS-10380 administration
Time frame: Up to 120 hours post-dose
Area under the concentration-time curve from time zero (pre-dose) extrapolated to infinite time (AUC0-∞) of single-dose HS-10380 administration
Time frame: Up to 120 hours post-dose
Apparent clearance (CL/F) of single-dose HS-10380 administration
Time frame: Up to 120 hours post-dose
Apparent volume of distribution (Vd/F) of single-dose HS-10380 administration
Time frame: Up to 120 hours post-dose
Mean retention time (MRT) of single-dose HS-10380 administration
Time frame: Up to 120 hours post-dose
Maximum plasma concentration (Cmax) of first HS-10380 administration
Time frame: Up to 12 days
Time of the Maximum Concentration (Tmax) of first HS-10380 administration
Time frame: Up to 12 days
Area under the plasma concentration-time curve from time zero to 24 hours (AUC0-24) first HS-10380 administration
Time frame: Up to 24 hours
Maximum concentration at steady state (Css, max) of multiple-dose HS-10380 administration
Time frame: Up to 12 days
Time of the maximum concentration at steady state (Tss, max) of multiple-dose HS-10380 administration
Time frame: Up to 12 days
Minimum concentration at steady state (Css, min) of multiple-dose HS-10380 administration
Time frame: Up to 12 days
Area under the concentration-time curve at steady state (AUCss) of multiple-dose HS-10380 administration
Time frame: Up to 12 days
Accumulation ratio (RAC) after multiple doses
Time frame: Up to 12 days