This study will consist of 2 parts: Part Ⅰ-in healthy adult subjects, Part Ⅱ-in adult patients with schizophrenia
Part Ⅰ was designed as single-center, randomized, double-blind, placebo-controlled, dose-escalation trial to assess the safety, tolerability, pharmacokinetics (PK) of multiple doses of VV119 in Chinese healthy adult subjects. Part Ⅱ was designed as multicenter, randomized, double-blind, placebo-controlled, dose-escalation trial to assess the safety, tolerability, pharmacokinetics (PK) and efficacy of multiple doses of VV119 in adult patients with schizophrenia.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
40
VV119 0.5 mg Group:2 subjects will receive VV119 Placebo 0.5 mg, orally once daily for 14 days. VV119 1 mg Group:2 subjects will receive VV119 Placebo 1 mg, orally once daily for 14 days.
VV119 0.5 mg Group:6 subjects will receive VV119 0.5 mg, orally once daily for 14 days. VV119 1 mg Group:6 subjects will receive VV119 1 mg, orally once daily for 14 days.
VV119 2 mg Group:6 subjects will receive 2 0.5mgVV119 capsules on the first four days, then take 1 2mgVV119 capsules and 1 0.5mg VV119 Placebo from the fifth day to the 28th day, orally once daily, VV119 4 mg Group:6 subjects will receive 2 0.5mgVV119 capsules on the first four days, take 1 2mgVV119 capsules and 1 0.5mg VV119 Placebo from the fifth day to the seventh day , then 2 2mgVV119 capsules and 1 0.5mg VV119 Placebo from the eighth day to the 28th day ,orally once daily, VV119 6 mg Group:6 subjects will receive 2 0.5mgVV119 capsules on the first three days,take 1 2mgVV119 capsules and 1 0.5mg VV119 Placebo from the forth day to the fifth day , take 2 2mgVV119 capsules and 1 0.5mg VV119 Placebo from the sixth day to the seventh day , then 3 2mgVV119 capsules and 1 0.5mg VV119 Placebo from the eighth day to the 28th day ,orally once daily.
Beijing Anding Hospital of Capital Medical University
Beijing, Beijing Municipality, China
RECRUITINGBeijing Anding Hospital of Capital Medical University
Beijing, Beijing Municipality, China
RECRUITINGBeijing Huilongguan Hospital
Beijing, Beijing Municipality, China
Incidence of Treatment-Emergent Adverse Events
Incidence of Treatment-Emergent Adverse Events
Time frame: Baseline to 15 days after the last administration
Cmax
maximum observed plasma concentration of VV119 and the main metabolites
Time frame: Baseline to 360 hours after the last administration
area under the plasma concentration time curve from time zero to the last (AUC0-t)
area under the plasma concentration time curve from time zero to the last of VV119 and the main metabolites
Time frame: Baseline to 360 hours after the last administration
AUC0-∞
area under the plasma concentration time curve from time zero to infinity of VV119 and the main metabolites
Time frame: Baseline to 360 hours after the last administration
Tmax
time at which Cmax occurs of VV119 and the main metabolites of VV119 and the main metabolites
Time frame: Baseline to 360 hours after the last administration
t1/2
half-life of elimination of VV119 and the main metabolites
Time frame: Baseline to 360 hours after the last administration
Apparent Clearance Rate(CL/F)
apparent clearance of VV119 and the main metabolites
Time frame: Baseline to 360 hours after the last administration
Vd/F
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VV119 2 mg Group:2 subjects will receive 1 0.5mgVV119 capsules and 1 0.5mg VV119 Placebo on the first four days, then take 1 2mgVV119 Placebo and 1 0.5mg VV119 capsules from the fifth day to the 28th day, orally once daily, VV119 4 mg Group:2 subjects will receive 1 0.5mgVV119 capsules and 1 0.5mg VV119 Placebo on the first four days, take 1 2mgVV119 Placebo and 1 0.5mg VV119 capsules from the fifth day to the seventh day , then 2 2mgVV119 Placebo and 1 0.5mg VV119 capsules from the eighth day to the 28th day ,orally once daily, VV119 6 mg Group:2 subjects will receive 1 0.5mgVV119 capsules and 1 0.5mg VV119 Placebo on the first three days, take 1 2mgVV119 Placebo and 1 0.5mg VV119 capsules from the forth day to the fifth day ,take 2 2mgVV119 capsules and 1 0.5mg VV119 Placebo from the sixth day to the seventh day, then 3 2mgVV119 Placebo and 1 0.5mg VV119 capsules from the eighth day to the 28th day ,orally once daily.
Xi'an Mental Health Center
Xi’an, Shanxi, China
RECRUITINGapparent volume of distribution during the terminal phase of VV119 and the main metabolites
Time frame: Baseline to 360 hours after the last administration
Ke
elimination rate constant of VV119 and the main metabolites
Time frame: Baseline to 360 hours after the last administration
AUC0-24h
area under the plasma concentration time curve from time zero to 24h of VV119 and the main metabolites
Time frame: Baseline to 360 hours after the last administration
mean Resident Time
mean Resident Time from time zero to infinity/the last of VV119 and the main metabolites
Time frame: Baseline to 360 hours after the last administration
Positive and Negative Syndrome Scale (PANSS)
Change from Baseline in Positive and Negative Syndrome Scale in part Ⅱ。 The PANSS measures symptom severity of participants with schizophrenia and contains 7 positive symptom scales,7negative system scales, and 16 general psychopathology symptom scales. Participants are rated from 1 to 7 on each symptom scale with a total minimum score of 30 and a maximum score of 210. A decrease in PANSS total score correlates with an improvement in schizophrenia symptoms.
Time frame: Day-1,Day14,Day28 and Day42
PANSS Positive subscale score
Change from Baseline in PANSS Positive subscale score in part Ⅱ PANSS-Positive: Assessment of positive symptoms. Minimum value:7, maximum value:49, the higher scores mean a worse outcome.
Time frame: Day-1, Day14, Day28 and Day42
PANSS Negative subscale score
Change from Baseline in PANSS Negative subscale score in part Ⅱ。 PANSS-negative: Assessment of negative symptoms. Minimum value:7, maximum value:49, the higher scores mean a worse outcome.
Time frame: Day-1, Day14, Day28 and Day42
Treatment response rate
Positive and Negative Syndrome Scale (PANSS) Response rate, Defined as a 50% or Greater Improvement from Baseline in PANSS Total Score in part Ⅱ
Time frame: Day-1,Day14, Day28 and Day42
Clinical Global Impression-Severity (CGI-S)
Change from Baseline in Clinical Global Impression-Severity in part Ⅱ。 The CGI-S rating scale is a 7-point global assessment that measures the clinician's impression of the severity of illness exhibited by a participant. A rating of 1 is equivalent to "Normal, not at all ill" and a rating of 7 is equivalent to "Among the most extremely ill participants". Negative change from baseline scores indicate improvement in the severity of illness.
Time frame: Day-14, Day28 and Day42
Rac
Accumulation Ratio of VV119
Time frame: Baseline to 360 hours after the last administration