The purpose of this study is to assess the safety, tolerability and pharmacokinetics (PK) of NH102 when administered as multiple oral dose at escalating dose levels in healthy participants.
The drug being tested in this study is called NH102. NH102 is being tested to treat people who have depression. This study will look at the safety, tolerability and PK of NH102 in healthy participants. The study may enroll up to 30-40 participants. Participants will be randomly assigned within each cohort to receive NH102 or placebo which will remain undisclosed to the participants and study doctor during the study (unless there is an urgent medical need). The study consists of four dose groups: 3 mg (fixed dose), 10 mg (fixed dose), 15 mg (starting at 6 mg, then escalated to 10 mg, and finally to 15 mg), and 20 mg (starting at 10 mg, then escalated to 15 mg, and finally to 20 mg). Each group enrolls 10 subjects, with 8 receiving NH102 and 2 receiving placebo. For the third and fourth dose groups (15 mg and 20 mg) that follow a titration dosing regimen, each includes 2 sentinel subjects (both male). The two sentinel subjects may be dosed simultaneously. Only after both sentinel subjects complete all 17 doses (with a single dose administered on Day 9) and are observed for at least 24 hours, along with preliminary confirmation of safety, may the remaining subjects in the same dose group proceed with dosing.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
40
Shanghai Mental Health Center
Shanghai, Shanghai Municipality, China
Number of participants with adverse events
Time frame: Baseline up to Day 9 ( the 3 mg and 10mg dose groups) or Day 10 (the 15 mg and 20 mg dose groups)
Number of participants with change in laboratory parameters following treatment administration
The laboratory parameters include hematology, clinical chemistry, coagulation and urinalysis.
Time frame: Baseline up to Day 9 ( the 3 mg and 10mg dose groups) or Day 10 (the 15 mg and 20 mg dose groups)
Number of participants with change in vital sign measurements following treatment adminstration
The items of vital sign include blood pressure, heart rate, body temperature and respiratory rate.
Time frame: Baseline up to Day 9 ( the 3 mg and 10mg dose groups) or Day 10 (the 15 mg and 20 mg dose groups)
Number of participants with change in physical examination following treatment administration
Time frame: Baseline up to Day 9 ( the 3 mg and 10mg dose groups) or Day 10 (the 15 mg and 20 mg dose groups)
Number of participants with change in 12-lead ECG following treatment administration
Time frame: Baseline up to Day 9 ( the 3 mg and 10mg dose groups) or Day 10 (the 15 mg and 20 mg dose groups)
Number of participants with change in Columbia-suicide severity rating scale (C-SSRS) score
Time frame: Baseline up to Day 9 ( the 3 mg and 10mg dose groups) or Day 10 (the 15 mg and 20 mg dose groups)
Plasma PK parameters-Maximum plasma concentration (Cmax) after single-dose administration
Time frame: From pre-dose to 12 hours (before the second administration on Day 1)
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Plasma PK Parameters-Time for maximum plasma concentration (Tmax)
Time frame: From pre-dose to 12 hours (before the second administration on Day 1), and from pre-dose on Day 7 to 48 hours (Day 9) for the 3 mg and 10 mg dose groups, or from pre-dose on Day 9 to 24 hours (Day 10) for the 15 mg and 20 mg dose groups.
Plasma PK Parameters-Area Under Curve from zero to 24 hours (AUC0-12h)
Time frame: From pre-dose to 12 hours (before the second administration on Day 1)
Plasma PK Parameters-Maximum observed drug concentration at steady state (Cmax,ss)
Time frame: From pre-dose on Day 7 to 48 hours (Day 9) for the 3 mg and 10 mg dose groups, or from pre-dose on Day 9 to 24 hours (Day 10) for the 15 mg and 20 mg dose groups.
Plasma PK Parameters-Minimum observed drug concentration at steady state (Cmin,ss)
Time frame: From pre-dose on Day 7 to 48 hours (Day 9) for the 3 mg and 10 mg dose groups, or from pre-dose on Day 9 to 24 hours (Day 10) for the 15 mg and 20 mg dose groups.
Plasma PK-Parameters-Average drug concentration at steady state (Cav,ss)
Time frame: From pre-dose on Day 7 to 48 hours (Day 9) for the 3 mg and 10 mg dose groups, or from pre-dose on Day 9 to 24 hours (Day 10) for the 15 mg and 20 mg dose groups.
Plasma PK Parameters-Area Under Curve from time zero to the last time point with a measurable concentration (AUC0-t)
Time frame: From pre-dose on Day 7 to 48 hours (Day 9) for the 3 mg and 10 mg dose groups, or from pre-dose on Day 9 to 24 hours (Day 10) for the 15 mg and 20 mg dose groups.
Plasma PK Parameters-Area Under Curve from zero to infinity (AUC0-∞)
Time frame: From pre-dose on Day 7 to 48 hours (Day 9) for the 3 mg and 10 mg dose groups, or from pre-dose on Day 9 to 24 hours (Day 10) for the 15 mg and 20 mg dose groups.
Plasma PK Parameters-Area Under Curve over a dosing interval at steady state (AUCss)
Time frame: From pre-dose on Day 7 to 48 hours (Day 9) for the 3 mg and 10 mg dose groups, or from pre-dose on Day 9 to 24 hours (Day 10) for the 15 mg and 20 mg dose groups.
Plasma PK Parameters-Apparent total body clearance at steady state after extravascular administration (CLss/F)
Time frame: From pre-dose on Day 7 to 48 hours (Day 9) for the 3 mg and 10 mg dose groups, or from pre-dose on Day 9 to 24 hours (Day 10) for the 15 mg and 20 mg dose groups.
Plasma PK Parameters-Trough drug concentration (Ctrough)
Time frame: From pre-dose on Day 7 to 48 hours (Day 9) for the 3 mg and 10 mg dose groups, or from pre-dose on Day 9 to 24 hours (Day 10) for the 15 mg and 20 mg dose groups.
Plasma PK Parameters-Degree of Fluctuation (DF)
Time frame: From pre-dose on Day 7 to 48 hours (Day 9) for the 3 mg and 10 mg dose groups, or from pre-dose on Day 9 to 24 hours (Day 10) for the 15 mg and 20 mg dose groups.
Plasma PK Parameters-Terminal elimination rate constant (λz)
Time frame: From pre-dose on Day 7 to 48 hours (Day 9) for the 3 mg and 10 mg dose groups, or from pre-dose on Day 9 to 24 hours (Day 10) for the 15 mg and 20 mg dose groups.
Plasma PK Parameters-Relative bioavailability based on AUC [Ra(AUC)]
Time frame: From pre-dose on Day 7 to 48 hours (Day 9) for the 3 mg and 10 mg dose groups, or from pre-dose on Day 9 to 24 hours (Day 10) for the 15 mg and 20 mg dose groups.
Plasma PK Parameters-Terminal half-life (t1/2z)
Time frame: From pre-dose on Day 7 to 48 hours (Day 9) for the 3 mg and 10 mg dose groups, or from pre-dose on Day 9 to 24 hours (Day 10) for the 15 mg and 20 mg dose groups.
Plasma PK Parameters-Apparent volume of distribution during the terminal phase after extravascular administration (Vz/F)
Time frame: From pre-dose on Day 7 to 48 hours (Day 9) for the 3 mg and 10 mg dose groups, or from pre-dose on Day 9 to 24 hours (Day 10) for the 15 mg and 20 mg dose groups.