A Study to Evaluate the Efficacy, Safety, and Pharmacokinetic Characteristics of (R)-Ketamine Hydrochloride Nasal Spray in Patients With Depression and Acute Suicidal Ideation or Behavior

A Randomized, Double-blind, Placebo-controlled Phase Il Study to Evaluate the Efficacy, Safety, and Pharmacokinetic Characteristics of (R)-Ketamine Hydrochloride Nasal Spray in Patients With Depression and Acute Suicidal Ideation or Behavior

The purpose of this study is to learn about:

• To evaluate the efficacy of PRT-042 nasal spray for the Rapid Reduction of the depressive symptoms in adults with major depressive disorder (MDD) with acute suicidal ideation or behavior
• To evaluate the safety and pharmacokinetic (PK) characteristics after multiple dose of PRT-042 nasal spray in adults with major depressive disorder (MDD) with acute suicidal ideation or behavior

Study Overview

• Status: Recruiting
• Conditions: Major Depressive Disorder (MDD
• Intervention / Treatment: Drug: Low Dose PRT042 nasal spray; Drug: median Dose PRT042 nasal spray; Drug: high dose PRT042 nasal spray; Drug: placebo

• Study Type: Interventional
• Enrollment (Estimated): 98
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: ke yao; Phone Number: 86-028-85170738; Email: ke.yao@btyy.com

Study Locations

• China
  • Beijing, China
    • Recruiting
    • Beijing HuiLongGuan Hospital
    • Contact: Fude Yang
  • Beijing, China
    • Recruiting
    • Beijing Anding Hospital Capital Medical University
    • Contact: Wei Wang
  • Chengdu, China
    • Recruiting
    • The Fourth People's Hospital of Chengdu
    • Contact: Feiyan Wang
  • Hangzhou, China
    • Recruiting
    • Hangzhou Seventh People's Hospital
    • Contact: Tao Li
    • Contact: Zhonglin Tan
  • Hefei, China
    • Recruiting
    • The Fourth Affiliated Hospital of Anhui Medical University
    • Contact: Huanzhong Liu
  • Ningbo, China
    • Recruiting
    • The Affiliated Kangning Hospital of Ningbo University
    • Contact: Yongming Xu
  • Suzhou, China
    • Recruiting
    • Suzhou Guangji Hospital
    • Contact: Yansong Liu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Participant must meet Diagnostic and Statistical Manual of Mental Disorders (5th edition) (DSM-5) diagnostic criteria for Major Depressive Disorder (MDD), without psychotic features, based upon clinical assessment and confirmed by the Mini International Psychiatric Interview (MINI) .
2. Participants must have current suicidal ideation with intent, confirmed by a "Yes" response to Question B3 [Think (even momentarily) about harming or of hurting or of injuring yourself: with at least some intent or awareness that you might die as a result; or think about suicide (ie, about killing yourself)?] and Question B10 [Intend to act on thoughts of killing yourself?] obtained from the MINI.
3. Participant has a Montgomery Asberg Depression Rating Scale (MADRS) total score of greater than (≥) 28 and the score for item 10"suicide ideation" of greater than (≥) 3 predose on Day 1

Exclusion Criteria:

1. Participant has a current DSM-5 diagnosis of bipolar (or related disorders), antisocial personality disorder, or obsessive compulsive disorder.
2. Participant has a current clinical diagnosis of autism, dementia, or intellectual disability.
3. Participant has a current or prior DSM-5 diagnosis of a psychotic disorder, or MDD with psychotic features .
4. Participant meets the DSM-5 severity criteria for moderate or severe substance or alcohol use disorder, within the 6 months before screening
5. Participant has a current or prior diagnosis of a reatment resistant depression
6. Any nasal conditions or diseases that, in the investigator's judgment, may significantly affect the administration or absorption of a nasal product.
7. Participant has a history of malignancy within 5 years before screening
8. Pregnant or breastfeeding women, or those with a positive pregnancy test result during screening.
9. Previous participation in another clinical trial and receiving the investigational drug within 3 months prior to dosing.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: placebo	Drug: placebo; two times a week, for 4 weeks
Experimental: Low Dose PRT042 nasal spray	Drug: Low Dose PRT042 nasal spray; two times a week, for 4 weeks
Experimental: median Dose PRT042 nasal spray	Drug: median Dose PRT042 nasal spray; two times a week, for 4 weeks
Experimental: high Dose PRT042 nasal spray	Drug: high dose PRT042 nasal spray; two times a week, for 4 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Montgomery Asberg Depression Rating Scale (MADRS) Total Score at 24 Hours After the First Dose (Day 2)	The MADRS is a clinician-rated scale designed to measure depression severity and detects changes due to antidepressant treatment. The test consists of 10 items, each of which is scored from 0 (item not present or normal) to 6 (severe or continuous presence of the symptoms), for a total score of 60. Higher scores represent a more severe condition.	Baseline (Day 1, predose) and 24 hours first post dose (Day 2)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Montgomery Asberg Depression Rating Scale Total Score During Double-blind Phase	The MADRS is a clinician-rated scale designed to measure depression severity and detects changes due to antidepressant treatment. The test consists of 10 items, each of which is scored from 0 (item not present or normal) to 6 (severe or continuous presence of the symptoms), for a total score of 60. Higher scores represent a more severe condition.	Days 1 (4 hours postdose), 4, 8, 11, 15, 18, 22 and Day 25
Number of Participants who Achieved Response （≥50% decrease from baseline MADRS total score）Through the Double-blind Phase		Days 1 (4 hours postdose),2, 4, 8, 11, 15, 18, 22 and Day 25
Number of Participants Who Achieved Remission (MADRS Total Score Less Than or Equal to [<=] 12) Through the Double-blind Phase		Days 1 (4 hours postdose), 2, 4, 8, 11, 15, 18, 22 and Day 25
5. Change From Baseline in Clinical Global Impression- Severity of Suicidality-Revised (CGI-SS-R) During Double-blind Phase	CGI-SS-R was derived from the Clinical Global Impression Severity Scale (CGI-S), a global rating scale that gives an overall measure of the severity of a participants illness. The CGI-SS-R rating is scored on a 7-point scale from 0 (normal, not at all suicidal) to 6 (among the most extremely suicidal participants). A higher score indicates a more severe condition and a reduction in score indicates improvement (that is, lower severity of suicidality).	Days 1 (4 hours postdose), 2, 4, 8, 11, 15, 18, 22 and Day 25
Number of Participants Who Achieved Resolution of Suicidality (CGI-SS-R Score of 0 or 1) Through Double-blind Phase		up to Day 25
Change From Baseline in Clinical Global Impression of Imminent Suicide Risk (CGI-SR-I) Scale Total Score During Double-blind Phase	The CGI-SR-I is a scale summarizing the clinician's best assessment of the likelihood that the participant will attempt suicide in the next 7 days. The CGI-SR-I rating is scored on a 7-point scale: where' 0 (no imminent suicide risk); 1 (minimal imminent suicide risk), 2 (mild imminent suicide risk), 3 (moderate imminent suicide risk), 4 (marked imminent suicide risk), 5 (severely imminent suicide risk), 6 (extreme imminent suicide risk). Higher score indicates a more severe condition. Negative change in score indicates improvement.	Days 1 (4 hours postdose), 2, 4, 8, 11, 15, 18, 22 and Day 25
8. Change From Baseline in Beck Hopelessness Scale (BHS) Total Score During Double-blind Phase	BHS is a self-reported measure to assess one's level of negative expectations or pessimism regarding future. It consists of 20 true-false items that examine respondent's attitude over past week by either endorsing a pessimistic statement or denying an optimistic statement; 9 are keyed false and 11 are keyed true. For every statement, each response was assigned score of 0 or 1. Total BHS score is sum of item responses, ranged from 0-20, where higher score represented higher level of hopelessness.	Baseline, Days 8 ,15 and 25
Change From Baseline in Beck Scale for Suicide Ideation -Chinese Version (BSI-CV) Total Score During Double-blind Phase	BSI-CV is a self-reported measure with 19 items, scored on a 3-point scale (0 to 2). The final score ranges from 0 to 38, with higher scores indicating a greater likelihood of suicide.	Baseline, Days 8 ,15 and 25
Number of Participants With Treatment Emergent Adverse Events (TEAEs)、Vital Signs Abnormalities、Abnormal Electrocardiogram (ECG) Values et al: DB Treatment Phase		up to Day 25
Area Under the Plasma Concentration-Time Curve From Time Zero to Infinite Time (AUC [0-infinity])		up to Day 25
Maximum Plasma Concentration [Cmax]		up to Day 25
plasma elimination half-life [T1/2]		up to Day 25

Collaborators and Investigators

• Sponsor: Sichuan Purity Pharmaceutical Technology Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): May 27, 2025
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): June 1, 2026

Study Registration Dates

• First Submitted: September 1, 2025
• First Submitted That Met QC Criteria: September 18, 2025
• First Posted (Actual): September 26, 2025

Study Record Updates

• Last Update Posted (Actual): January 22, 2026
• Last Update Submitted That Met QC Criteria: January 19, 2026
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Mood Disorders; Depressive Disorder; Depressive Disorder, Major
• Other Study ID Numbers: PRT042-II-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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