A Phase I Study of NS-079 in Healthy Participants

A Phase I, Double-blind, Placebo-controlled Study to Evaluate Safety, Pharmacokinetics, and Pharmacodynamics of NS-079 in Healthy Participants

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:

• Is NS-079 safe and tolerable in heathy participants under tested dosing regimen?
• What is the pharmacokinectic profile of NS-079 in healthy participants under tested dosing regimen and the effect of paroxetine? Researchers will compare NS-079 to a placebo to see the safety and tolerability when use NS-079.

Study Overview

• Status: Not yet recruiting
• Conditions: Healthy Adult Participants
• Intervention / Treatment: Drug: NS-136 tablet; Drug: Placebo; Drug: Paroxetine

• Study Type: Interventional
• Enrollment (Estimated): 78
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Jin Lili, MS; Phone Number: +86 13918207440; Email: lili.jin@neushen.com

Study Locations

• China
  • Sichuan
    • Chengdu, Sichuan, China, 610000
      • Chengdu Xinhua Hospital
      • Contact: Study Director; Phone Number: 86-02860212019; Email: yongxlan@126.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria

1. Healthy males or females aged 18-55 years (inclusive), with a body mass index (BMI) between 18.00 and 32.00 kg/m2(inclusive) at screening.
2. Not participated in any other clinical trials and received an investigational drug or device within the past 30 days or 5 half-lives prior to screening, whichever is longer.
3. Women of non-childbearing potential (WONCBP) (as defined in Appendix 1); women of childbearing potential (WOCBP) who are abstinent from heterosexual intercourse as a preferred and usual lifestyle choice, or who agree to use highly effective contraception (as defined in Appendix 1) in combination with a condom from the time of signing the informed consent form until at least 90 days after the last dose of investigational product, agree to refrain from ova donation during this period, and return a negative pregnancy test at screening and baseline (Day -1).
4. Surgically sterile males (with verbal confirmation of the absence of sperm in the ejaculate); males who are abstinent from heterosexual intercourse as a preferred and usual lifestyle choice, or who agree to use highly effective contraception with a female partner (as defined in Appendix 1) in combination with a condom from the time of signing the informed consent form until at least 90 days after the last dose of investigational product, and agree to refrain from sperm donation during this period.
5. In good health, determined by the investigator/delegate on the basis of medical history, physical examinations, vital signs, electrocardiograms (ECGs), clinical laboratory tests (hematology, coagulation, urinalysis, blood biochemistry). Repeated examination is allowed once per timepoint at the investigator/delegate's discretion.
6. Full understanding of the purpose, nature, procedures of the study, and the potential adverse reactions. Participant voluntarily participates and signs the informed consent form before any study procedures begin.
7. Agree to provide a biological sample (blood or saliva/buccal swab, per site capability) for Cytochrome P450 2D6 (CYP2D6) pharmacogenetic genotyping during the screening period, and the genotyping results must be available prior to randomization and dosing.
8. Participants must be confirmed CYP2D6 Normal Metabolizers (NM) or Intermediate Metabolizers (IM) based on pharmacogenetic genotyping. For Part 3 [DDI] participants only: Must have a confirmed CYP2D6 NM status based on pharmacogenetic genotyping.

Exclusion Criteria

1. 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.
2. Known hypersensitivity to or severe intolerance of paroxetine or any SSRI (including serotonin syndrome or discontinuation syndrome) (for Part 3 [DDI] only).
3. 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.
4. 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.
5. 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.
6. 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.
7. 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).
8. 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.
9. 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.
10. 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.
11. 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.

12. History or presence of the following conditions:

    1. . Clinically significant (as judged by the investigator/delegate) neurological or psychiatric disorders, defined as any of the following: history of epilepsy or any seizure disorder (excluding childhood febrile seizures); history of dementia or any clinically diagnosed cognitive disorder; clinically significant migraine, defined as: history of migraine with aura; chronic migraine (≥4 migraine days/month on average over the past 6 months); or use of prophylactic migraine medication or triptans within 30 days prior to first dose; any current or lifetime clinical diagnosis of schizophrenia spectrum or other psychotic disorder, bipolar I or II disorder, or borderline personality disorder; clinically significant depression, defined as: any current or lifetime clinical diagnosis of major depressive disorder or other depressive disorder; any history of pharmacological treatment for depression; any current clinical diagnosis of anxiety disorder or any history of pharmacological treatment for anxiety within 1 year prior to screening; or any history of psychiatric hospitalization. Neurological and psychiatric history will be assessed at Screening through clinical interview by the investigator/delegate, supplemented by review of available medical records.
    2. . Clinically significant (as judged by the investigator/delegate) cardiovascular disorders, including history of prolonged QTc interval (defined as QTcF >450 ms for males or >470 ms for females, or any clinically significant ECG abnormality); or chronic cardiovascular diseases (specifically including history of cardiac valvulopathy or pulmonary hypertension or hypertension); or current hypertension (resting systolic blood pressure > 140 mmHg or diastolic blood pressure >90 mmHg). Blood pressure assessment can be repeated at the discretion of the investigator/delegate.
    3. . Clinically significant (as judged by the investigator/delegate) systemic diseases or conditions, including immunodeficiency or immunosuppressive disorders; malignant neoplastic diseases; or clinically significant endocrine, respiratory, hematologic (including coagulation), or digestive system diseases that may interfere with the safety of the participant or the interpretation of study results.
    4. . Any of the following laboratory or medical history findings: AST or ALT >2 × ULN, or known or suspected Gilbert's Syndrome; eGFR <60 ml/min/1.73m2; History of cholecystectomy.
13. Family history of a psychotic disorder (including schizophrenia, schizoaffective disorder, or bipolar disorder) in a first-degree relative.
14. 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.
15. Underwent major surgery within the past 6 months prior to the first dose (such as coronary artery bypass grafting, hepatectomy, gynecological surgery, etc.)
16. 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.
17. 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.
18. 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.
19. Receipt of vaccines within the 4 weeks prior to the first dose of the investigational product.
20. Other factors deemed unsuitable for participation in the trial by the investigator/delegate.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Triple

Number of Arms

17

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: NS-079 Arm 1; NS-079 SAD Dose 1	Drug: NS-136 tablet; Investigational product NS-079
Experimental: NS-079 Arm 2; NS-079 SAD Dose 2	Drug: NS-136 tablet; Investigational product NS-079
Experimental: NS-079 Arm 3; NS-079 SAD Dose 3	Drug: NS-136 tablet; Investigational product NS-079
Experimental: NS-079 Arm 4; NS-079 SAD Dose 4	Drug: NS-136 tablet; Investigational product NS-079
Experimental: NS-079 Arm 5; NS-079 SAD Dose 5	Drug: NS-136 tablet; Investigational product NS-079
Experimental: NS-079 Arm 6; NS-079 MAD Dose 1	Drug: NS-136 tablet; Investigational product NS-079
Experimental: NS-079 Arm 7; NS-079 MAD Dose 2	Drug: NS-136 tablet; Investigational product NS-079
Experimental: NS-079 Arm 8; NS-079 MAD Dose 3	Drug: NS-136 tablet; Investigational product NS-079
Placebo Comparator: Placebo Arm 9; NS-079 SAD Dose 1 PBO	Drug: Placebo; NS-079 matching placebo
Placebo Comparator: Placebo Arm 10; NS-079 SAD Dose 2 PBO	Drug: Placebo; NS-079 matching placebo
Placebo Comparator: Placebo Arm 11; NS-079 SAD Dose 3 PBO	Drug: Placebo; NS-079 matching placebo
Placebo Comparator: Placebo Arm 12; NS-079 SAD Dose 4 PBO	Drug: Placebo; NS-079 matching placebo
Placebo Comparator: Placebo Arm 13; NS-079 SAD Dose 5 PBO	Drug: Placebo; NS-079 matching placebo
Placebo Comparator: Placebo Arm 14; NS-079 MAD Dose 1 PBO	Drug: Placebo; NS-079 matching placebo
Placebo Comparator: Placebo Arm 15; NS-079 MAD Dose 2 PBO	Drug: Placebo; NS-079 matching placebo
Placebo Comparator: Placebo Arm 16; NS-079 MAD Dose 3 PBO	Drug: Placebo; NS-079 matching placebo
Experimental: NS-079 Arm 17; NS-079 DDI dose 1	Drug: NS-136 tablet; Investigational product NS-079; Drug: Paroxetine; DDI study treatment drug

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: NeuShen Therapeutics

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): May 1, 2027

Study Registration Dates

• First Submitted: June 16, 2026
• First Submitted That Met QC Criteria: June 22, 2026
• First Posted (Actual): June 25, 2026

Study Record Updates

• Last Update Posted (Actual): June 25, 2026
• Last Update Submitted That Met QC Criteria: June 22, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: 5-HT2A receptor
• Additional Relevant MeSH Terms: Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Piperidines; Paroxetine
• Other Study ID Numbers: NS079HV101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No