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The goal of this clinical trial is evaluate the safety, pharmacokinetics, and pharmacodynamics of NS-079 with its main metabolite (NS-079-M1) in healthy participants. The main questions it aims to answer are:
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| NS-079 Arm 1 | Experimental | NS-079 SAD Dose 1 |
|
| NS-079 Arm 2 | Experimental | NS-079 SAD Dose 2 |
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| NS-079 Arm 3 | Experimental | NS-079 SAD Dose 3 |
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| NS-079 Arm 4 | Experimental | NS-079 SAD Dose 4 |
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| NS-079 Arm 5 | Experimental | NS-079 SAD Dose 5 |
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| NS-079 Arm 6 | Experimental | NS-079 MAD Dose 1 |
|
| NS-079 Arm 7 |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Placebo | Drug | NS-079 matching placebo |
|
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants with Treatment-Related Adverse Events | for SAD, day 1-4; for MAD, day 1-14, for DDI, day1-30 | |
| Main pharmacokinetic parameters | Cmax | for SAD, day 1-4; for MAD, day 1-14, for DDI, day1-30 |
| Main pharmacokinetic parameters | Cmax,ss | for MAD, day 1-14 |
| Main pharmacokinetic parameters | NS-079-M1/NS-079 AUC ratio as an in vivo CYP2D6 fm biomarker | For DDI, Day 1- 30 |
| Main urine pharmacokinetic parameters | Ae | For SAD, Day 1-4; for DDI, day 1-30 |
| Main pharmacokinetic parameters | NS-079-M1/NS-079 Ae ratio | For DDI, day 1-30 |
| Main pharmacokinetic parameters | AUC0-∞ | for SAD, day 1-4; for MAD, day 1-14, for DDI, day1-30 |
| Main pharmacokinetic parameters | AUC0-t | for SAD, day 1-4; for MAD, day 1-14, for DDI, day1-30 |
| Main pharmacokinetic parameters |
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Inclusion Criteria
Exclusion Criteria
Known hypersensitivity or allergy to the investigational product, its excipients, or any of its components, or a history of clinically significant allergic reactions that, in the opinion of the investigator/delegate, may place the participant at increased risk.
Known hypersensitivity to or severe intolerance of paroxetine or any SSRI (including serotonin syndrome or discontinuation syndrome) (for Part 3 [DDI] only).
Unable to refrain from all known CYP2D6 substrate medications (including over-the-counter (OTC) medications such as dextromethorphan-containing cough and cold preparations) during paroxetine dosing (for Part 3 [DDI] only). Final clinical judgment on individual concomitant medications remains with the investigator/delegate.
Individuals with a history of intolerance to venipuncture or venous catheterization (e.g., recurrent syncope during blood draws or significant needle phobia) that, in the opinion of the investigator/delegate, may interfere with the study procedures.
Positive serologic test results for hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (Anti-HCV) or human immunodeficiency virus antibody (Anti-HIV) at Screening.
Average daily smoking of more than 5 cigarettes per day in the 3 months prior to Screening, or inability or unwillingness to abstain from the use of tobacco or nicotine-containing products (including cigarettes, e-cigarettes, vaping products, and nicotine replacement products) from 48 hours prior to the first dose through completion of the final safety follow-up visit.
Excessive alcohol consumption, defined as average weekly alcohol intake exceeding 14 units during the 4 weeks prior to Screening (1 unit ≈10 g of pure alcohol; 1 alcohol unit is equal to 375ml 3.5% beer, 100 mL of wine, or 30 mL of 40% spirit), unwillingness or inability to abstain from alcohol and alcohol-containing products from 48 hours prior to the first dose through the completion of the final safety follow-up visit, or a positive alcohol breath test at Screening or upon admission to the clinical unit. (A repeat test may be performed once per timepoint at the investigator/delegate's discretion).
Excessive consumption of caffeinated beverages (e.g., coffee, tea, energy drinks), defined as an average of >8 cups/day (1 cup ≈ 250 mL) within 3 months prior to screening, or unwillingness or inability to refrain from caffeinated beverages from 48 hours prior to the first dose through the end of the inpatient confinement phase.
Unwillingness or inability to abstain from grapefruit or grapefruit containing products, Seville (bitter) oranges, or pomelo/pomelo-containing products from 7 days prior to the first dose through the end of the inpatient confinement phase.
Use of classic psychedelics or hallucinogenic substances with primary 5-HT2A agonist activity (e.g., lysergic acid diethylamide [LSD], psilocybin/magic mushrooms, dimethyltryptamine [DMT], ayahuasca, mescaline) on 5 or more occasions lifetime, or any use within 5 years prior to Screening.
Current or past substance use disorder (including alcohol or drugs of abuse) within the 12 months prior to Screening, as judged by the investigator/delegate; use of ketamine or phencyclidine (PCP) for recreational or non-prescribed purposes within 12 months prior to Screening; use of cannabis within 6 weeks prior to Screening; use of other illicit drugs or non-prescribed psychoactive substances (including but not limited to MDMA, cocaine, opiates, amphetamines) within 4 weeks prior to Screening; or a positive drug of abuse urine screen at Screening or upon admission. Single or occasional use prior to the applicable washout period may be permitted at the investigator/delegate's discretion, provided the urine drug screen is negative. A repeat drug screen may be performed once per timepoint at the investigator/delegate's discretion.
History or presence of the following conditions:
Family history of a psychotic disorder (including schizophrenia, schizoaffective disorder, or bipolar disorder) in a first-degree relative.
Clinically significant (as judged by the investigator/delegate) current or past suicidality based on the Columbia-Suicide Severity Rating Scale (C-SSRS), or psychiatric history indicating current suicidal ideation, or a history of active suicidal ideation or suicide attempts.
Underwent major surgery within the past 6 months prior to the first dose (such as coronary artery bypass grafting, hepatectomy, gynecological surgery, etc.)
Occurrence of acute neurological, digestive, respiratory, cardiovascular, endocrine, hematological, or other systemic diseases that may affect the absorption, distribution, metabolism, excretion, and safety evaluation of the investigational product within 3 months prior to screening judged by investigator/delegate.
Donation of blood or experienced blood loss ≥400 mL within the 3 months prior to the first dose; difficulties in venous blood collection; planned blood donation during the study or within 30 days after the study.
Use of any prescription or non-prescription medications, including over-the-counter (OTC) medications within 14 days or 5 elimination half-lives (whichever is longer) prior to the first dose; use of any herbal products or nutritional/dietary supplements within 21 days prior to the first dose, except paracetamol (≤2 g per day); and use of any central nervous system acting drugs (including monoamine oxidase inhibitors [MAOIs], SSRIs), serotonergic supplements (e.g., St. John's Wort, 5-hydroxytryptophan [5-HTP], L-tryptophan), or strong/moderate CYP2D6 inhibitor (e.g., bupropion, fluoxetine, paroxetine (prior use prohibited; protocol-directed administration as CYP2D6 index inhibitor in Part 3 [DDI] only), quinidine, terbinafine, duloxetine, cinacalcet) within 30 days or 5 elimination half-lives (whichever is longer) prior to the first dose. For Part 3 [DDI] only: Unwillingness or inability to abstain from NSAIDs (e.g., ibuprofen, naproxen, diclofenac) or aspirin throughout the paroxetine dosing and washout period; paracetamol (≤2 g/day) is the only permitted analgesic during this period.
Receipt of vaccines within the 4 weeks prior to the first dose of the investigational product.
Other factors deemed unsuitable for participation in the trial by the investigator/delegate.
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Jin Lili, MS | Contact | +86 13918207440 | lili.jin@neushen.com |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Chengdu Xinhua Hospital | Chengdu | Sichuan | 610000 | China |
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| ID | Term |
|---|---|
| D017374 | Paroxetine |
| ID | Term |
|---|---|
| D010880 | Piperidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
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NS-079 MAD Dose 2 |
|
| NS-079 Arm 8 | Experimental | NS-079 MAD Dose 3 |
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| Placebo Arm 9 | Placebo Comparator | NS-079 SAD Dose 1 PBO |
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| Placebo Arm 10 | Placebo Comparator | NS-079 SAD Dose 2 PBO |
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| Placebo Arm 11 | Placebo Comparator | NS-079 SAD Dose 3 PBO |
|
| Placebo Arm 12 | Placebo Comparator | NS-079 SAD Dose 4 PBO |
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| Placebo Arm 13 | Placebo Comparator | NS-079 SAD Dose 5 PBO |
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| Placebo Arm 14 | Placebo Comparator | NS-079 MAD Dose 1 PBO |
|
| Placebo Arm 15 | Placebo Comparator | NS-079 MAD Dose 2 PBO |
|
| Placebo Arm 16 | Placebo Comparator | NS-079 MAD Dose 3 PBO |
|
| NS-079 Arm 17 | Experimental | NS-079 DDI dose 1 |
|
| NS-136 tablet | Drug | Investigational product NS-079 |
|
| Paroxetine | Drug | DDI study treatment drug |
|
Tmax
| for SAD, day 1-4; for MAD, day 1-14, for DDI, day1-30 |
| Main pharmacokinetic parameters | t1/2 | for SAD, day 1-4; for MAD, day 1-14, for DDI, day1-30 |
| Main pharmacokinetic parameters | CL/F | for SAD, day 1-4; for MAD, day 1-14, for DDI, day1-30 |
| Main pharmacokinetic parameters | Vd/F | for SAD, day 1-4; for MAD, day 1-14, for DDI, day1-30 |
| Main pharmacokinetic parameters | Cmin,ss | for MAD, day 1-14 |
| Main pharmacokinetic parameters | Tmax,ss | for MAD, day 1-14 |
| Main pharmacokinetic parameters | Cavg,ss | for MAD, day 1-14 |
| Main pharmacokinetic parameters | AUCss,0-tau | for MAD, day 1-14 |
| Main pharmacokinetic parameters | AUCss,0-∞ | for MAD, day 1-14 |
| Main pharmacokinetic parameters | CLss/F | for MAD, day 1-14 |
| Main pharmacokinetic parameters | accumulation factor (Rac) | for MAD, day 1-14 |
| Main pharmacokinetic parameters | DF | for MAD, day 1-14 |
| Main urine pharmacokinetic parameters | Ae% | For SAD, Day 1-4; for DDI, day 1-30 |
| Main urine pharmacokinetic parameters | CLr | For SAD, Day 1-4; for DDI, day 1-30 |
| Main urine pharmacokinetic parameters | ER | For SAD, Day 1-4; for DDI, day 1-30 |