Back to resultsA Study To Evaluate The Safety, Tolerability And Pharmacokinetics of HS-10345 In Treatment-Resistant Depression
Primary Purpose
Treatment Resistant Depressive Disorder
Status
Completed
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
HS-10345 84mg
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Treatment Resistant Depressive Disorder focused on measuring Treatment resistant depressive disorder, Intranasal, HS-10345
Eligibility Criteria
Inclusion Criteria:
- Each subject must sign an informed consent form (ICF) indicating that he or she understands the purpose of and procedures required for the study and are willing to participate in the study.
- Participant must meet Diagnostic and Statistical Manual of Mental Disorders -5 Edition -Text Revised (DSM-5) diagnostic criteria for Major Depressive Disorder (MDD), without psychotic features, based upon clinical assessment, and confirmed by the Mini International Neuropsychiatric Interview (MINI).
- Participant must have had an inadequate response to at least 1 antidepressants in the current episode of depression assessed by the antidepressant treatment response questionnaire (ATRQ), and was taking another oral antidepressant 2 weeks before entering the screening period which will be assessed "non-response" by Montgomery Asberg Depression Rating Scale (MADRS) during the screening period, defined as MADRS total score reduced ≤25%.
- Comfortable with self-administration of intranasal medication and able to follow instructions provided.
- A woman of childbearing potential must have a negative serum (β-human chorionic gonadotropin [β-hCG]) at Screening and a negative urine pregnancy test prior to Period 1 randomization on Day 1.
Exclusion Criteria:
- Subject has a current DSM-5 diagnosis of psychotic disorder, MDD with psychosis, bipolar, obsessive compulsive disorder (OCD), intellectual disability, Autism spectrum Disorder, borderline personality disorder, antisocial personality disorder, histrionic personality disorder, and narcissistic personality disorder.
- Subject has suicidal ideation with intent to act within the past 6 months based on the Columbia-Suicide Severity Rating Scale (C-SSRS), or has a history of suicidal behavior within the past year as assessed on the C-SSRS.
- Subject has uncontrolled hypertension (SBP > 140 mmHg or DBP > 90 mmHg) despite diet, exercise or a stable dose of a permitted anti-hypertensive treatment at Screening or Day 1 prior to Period 1 randomization; or any past history of hypertensive crisis.
- Subject had a history of severe pulmonary insufficiency or SpO2<93% at screening time or prior to dosing.
- Anatomical or medical conditions that may impede delivery or absorption of study medication.
- Subject is a woman who is pregnant, breast-feeding, or planning to become pregnant while enrolled in this study or within 12 weeks after the last dose of study drug.
- Hepatitis B surface antigen (HBsAg), hepatitis C antibody (HCVAb), syphilis antibody and human immunodeficiency virus (HIV) antibody tests positive.
- Subject has had major surgery, (e.g., requiring general anesthesia) within 12 weeks before screening, or has surgery planned during the time the subject is expected to participate in the study.
Sites / Locations
- Beijing Anding Hospital, Capital Medical University
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
HS-10345 84mg
Placebo
Arm Description
Participants will self-administer intranasal HS-10345 84mg on Days 1, 4, 8, and 11 during the double-blind phase
Participants will be self-administered on Days 1, 4, 8, and 11 during the double-blind phase
Outcomes
Primary Outcome Measures
Number of participants with adverse events (AEs) and Serious Adverse Events (SAEs)
Participants during hospitalization will be closely observed to assure maximal safety and to collect occurrence of all adverse event. To follow-up on the 7th day after discharge, all participants will return to the hospital for information regarding their health condition. All adverse events will be collected with special attention to occurrence of psychotomimetic and dissociative effects after study drug administration.
Change from Baseline (Day -1) in Columbia-Suicide Severity Rating Scale (C-SSRS) Total Score at Day 15 in the Double-Blind Treatment Phase
This scale is intended to be used by individuals who have received training in its administration. The questions contained in the Columbia-Suicide Severity Rating Scale are suggested probes. Ultimately, the determination of the presence of suicidal ideation or behavior depends on the judgment of the individual administering the scale. A negative change in score indicates improvement.
Change from Baseline (Day -1) in The Clinician Administered Dissociative States Scale (CADSS) Total Score at 40 minutes and 2 hours after dosing in the Double-Blind Treatment Phase- ANCOVA Analysis on Ranks
This scale is intended to be used to assess the dissociative states of participants. It contains 23 objective items, every item ranges from 0 to 4. A negative change in score indicates improvement.
Change From pre-dosing in Modified Observer's Assessment of Alertness and Sedation (MOAA/S) Total Score at 20 minutes、40 minutes and 2 hours after dosing in the Double-Blind Treatment Phase- ANCOVA Analysis on Ranks
The Modified Observer's Assessment of Alertness and Sedation (MOAA/S) scale is frequently used in sedation-related drug and device studies to assess a subject's level of sedation. It ranges from 0 to 5, with a score of 5 defined as awake or minimally sedated, and a score of 0 defined as general anesthesia. This scale is intended to be used by individuals who have received training in its administration. A positive change in score indicates improvement.
Change from Baseline (Day -1) in Physician Withdrawal Checklist (PWC-20) Total Score at Day 15 in the Double-Blind Treatment Phase and Day 21 in the Follow-Up Phase- ANCOVA Analysis on Ranks
The PWC-20 was developed to detect any potential BZ-like treatment discontinuation (withdrawal) symptoms caused by experimental anxiolytics of the non-SSRI type. A negative change in score indicates improvement.
Secondary Outcome Measures
Cmax - maximum HS-10345 plasma concentration
The maximum concentration of the HS-10345 in plasma after drug administration, obtained directly from the measured concentrations.
AUC (0-24) - area under the HS-10345 plasma concentration-time curve from time 0 to 24 hours after study drug administration
The AUC (0-24) is a measure of total plasma exposure to the drug from time point zero to 24 hours after study drug administration.
Tmax - time to reach maximum HS-10345 plasma concentration
The Tmax is time to reach the maximum plasma concentration (Cmax), obtained directly from the actual sampling times.
AUC (0-inf) - area under the HS-10345 plasma concentration-time curve from time 0 to infinity time
The AUC(0-inf) is a measure of total plasma exposure to the drug from time point zero extrapolated to infinity
T1/2 - plasma elimination half-life for HS-10345
T1/2 will be calculated as 0.693/Kel
Change from Baseline (Day -1) in Montgomery Asberg Depression Rating Scale (MADRS) Total Score at Day 2/8/15- Analysis of Covariance (ANCOVA) Analysis
MADRS is clinician-rated scale designed to measure depression severity, and to detect changes due to antidepressant treatment. Scale consists of 10 items (apparent sadness, reported sadness, inner tension, sleep, appetite, concentration, lassitude, interest level, pessimistic thoughts, and suicidal thoughts), each of which is scored from 0 (item is not present or is normal) to 6 (severe or continuous presence of symptoms), summed for a total possible score of 0 to 60. Higher scores represent more severe condition. A negative change in score indicates improvement
Full Information
NCT ID
NCT05196971
First Posted
January 9, 2022
Last Updated
March 7, 2023
Sponsor
Jiangsu Hansoh Pharmaceutical Co., Ltd.
1. Study Identification
Unique Protocol Identification Number
NCT05196971
Brief Title
A Study To Evaluate The Safety, Tolerability And Pharmacokinetics of HS-10345 In Treatment-Resistant Depression
Official Title
A Phase Ib，Randomized, Double-Blind, Placebo-Controlled Study Evaluating The Safety, Tolerability And Pharmacokinetics of HS-10345 In Chinese Adult Subjects With Treatment Resistant Depression
Study Type
Interventional
2. Study Status
Record Verification Date
February 2023
Overall Recruitment Status
Completed
Study Start Date
October 28, 2021 (Actual)
Primary Completion Date
April 30, 2022 (Actual)
Study Completion Date
October 31, 2022 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Jiangsu Hansoh Pharmaceutical Co., Ltd.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
The purpose of this study is to assess the safety, tolerability and pharmacokinetics of intranasal HS-10345 (84mg) compared with placebo in participants with treatment-resistant depression (TRD).
Detailed Description
This will be a randomized, double-blind, placebo-controlled, multicenter study. Approximately 24 male and female adult participants diagnosed with TRD will participant in this study. There will be 4 study phases: a 4-week screening phase, a 1-day baseline phase, a double-blind treatment phase (Day 1 to Day 15), and a 1-week post-treatment (follow-up) phase. Firstly, 12 patients will be assigned to intranasal placebo or HS-10345 of 84mg. Extra 12 patients may be enrolled depending on the pharmacokinetics analysis of 84mg. Safety assessments will be performed throughout the study. The maximum study duration for a participant will be 7 weeks.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Treatment Resistant Depressive Disorder
Keywords
Treatment resistant depressive disorder, Intranasal, HS-10345
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
12 (Actual)
8. Arms, Groups, and Interventions
Arm Title
HS-10345 84mg
Arm Type
Experimental
Arm Description
Participants will self-administer intranasal HS-10345 84mg on Days 1, 4, 8, and 11 during the double-blind phase
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Participants will be self-administered on Days 1, 4, 8, and 11 during the double-blind phase
Intervention Type
Drug
Intervention Name(s)
HS-10345 84mg
Other Intervention Name(s)
HS-10345
Intervention Description
6 sprays of HS-10345 84 mg self-administered as an intranasal formulation for 4 days (Days 1, 4, 8, 11) during the double-blind phase
Intervention Type
Drug
Intervention Name(s)
Placebo
Other Intervention Name(s)
HS-10345 Placebo
Intervention Description
6 sprays of placebo self-administered as an intranasal formulation for 4 days (Days 1, 4, 8, 11) during the double-blind phase
Primary Outcome Measure Information:
Title
Number of participants with adverse events (AEs) and Serious Adverse Events (SAEs)
Description
Participants during hospitalization will be closely observed to assure maximal safety and to collect occurrence of all adverse event. To follow-up on the 7th day after discharge, all participants will return to the hospital for information regarding their health condition. All adverse events will be collected with special attention to occurrence of psychotomimetic and dissociative effects after study drug administration.
Time Frame
up to 7 weeks
Title
Change from Baseline (Day -1) in Columbia-Suicide Severity Rating Scale (C-SSRS) Total Score at Day 15 in the Double-Blind Treatment Phase
Description
This scale is intended to be used by individuals who have received training in its administration. The questions contained in the Columbia-Suicide Severity Rating Scale are suggested probes. Ultimately, the determination of the presence of suicidal ideation or behavior depends on the judgment of the individual administering the scale. A negative change in score indicates improvement.
Time Frame
up to 15 days
Title
Change from Baseline (Day -1) in The Clinician Administered Dissociative States Scale (CADSS) Total Score at 40 minutes and 2 hours after dosing in the Double-Blind Treatment Phase- ANCOVA Analysis on Ranks
Description
This scale is intended to be used to assess the dissociative states of participants. It contains 23 objective items, every item ranges from 0 to 4. A negative change in score indicates improvement.
Time Frame
up to 2 hours
Title
Change From pre-dosing in Modified Observer's Assessment of Alertness and Sedation (MOAA/S) Total Score at 20 minutes、40 minutes and 2 hours after dosing in the Double-Blind Treatment Phase- ANCOVA Analysis on Ranks
Description
The Modified Observer's Assessment of Alertness and Sedation (MOAA/S) scale is frequently used in sedation-related drug and device studies to assess a subject's level of sedation. It ranges from 0 to 5, with a score of 5 defined as awake or minimally sedated, and a score of 0 defined as general anesthesia. This scale is intended to be used by individuals who have received training in its administration. A positive change in score indicates improvement.
Time Frame
up to 2 hours
Title
Change from Baseline (Day -1) in Physician Withdrawal Checklist (PWC-20) Total Score at Day 15 in the Double-Blind Treatment Phase and Day 21 in the Follow-Up Phase- ANCOVA Analysis on Ranks
Description
The PWC-20 was developed to detect any potential BZ-like treatment discontinuation (withdrawal) symptoms caused by experimental anxiolytics of the non-SSRI type. A negative change in score indicates improvement.
Time Frame
up to 15 days
Secondary Outcome Measure Information:
Title
Cmax - maximum HS-10345 plasma concentration
Description
The maximum concentration of the HS-10345 in plasma after drug administration, obtained directly from the measured concentrations.
Time Frame
up to 72 hours after each study drug administration
Title
AUC (0-24) - area under the HS-10345 plasma concentration-time curve from time 0 to 24 hours after study drug administration
Description
The AUC (0-24) is a measure of total plasma exposure to the drug from time point zero to 24 hours after study drug administration.
Time Frame
up to 24 hours after each study drug administration
Title
Tmax - time to reach maximum HS-10345 plasma concentration
Description
The Tmax is time to reach the maximum plasma concentration (Cmax), obtained directly from the actual sampling times.
Time Frame
up to 72 hours after each study drug administration
Title
AUC (0-inf) - area under the HS-10345 plasma concentration-time curve from time 0 to infinity time
Description
The AUC(0-inf) is a measure of total plasma exposure to the drug from time point zero extrapolated to infinity
Time Frame
up to 72 hours after each study drug administration
Title
T1/2 - plasma elimination half-life for HS-10345
Description
T1/2 will be calculated as 0.693/Kel
Time Frame
up to 72 hours after each study drug administration
Title
Change from Baseline (Day -1) in Montgomery Asberg Depression Rating Scale (MADRS) Total Score at Day 2/8/15- Analysis of Covariance (ANCOVA) Analysis
Description
MADRS is clinician-rated scale designed to measure depression severity, and to detect changes due to antidepressant treatment. Scale consists of 10 items (apparent sadness, reported sadness, inner tension, sleep, appetite, concentration, lassitude, interest level, pessimistic thoughts, and suicidal thoughts), each of which is scored from 0 (item is not present or is normal) to 6 (severe or continuous presence of symptoms), summed for a total possible score of 0 to 60. Higher scores represent more severe condition. A negative change in score indicates improvement
Time Frame
up to 15 days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
64 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Each subject must sign an informed consent form (ICF) indicating that he or she understands the purpose of and procedures required for the study and are willing to participate in the study.
Participant must meet Diagnostic and Statistical Manual of Mental Disorders -5 Edition -Text Revised (DSM-5) diagnostic criteria for Major Depressive Disorder (MDD), without psychotic features, based upon clinical assessment, and confirmed by the Mini International Neuropsychiatric Interview (MINI).
Participant must have had an inadequate response to at least 1 antidepressants in the current episode of depression assessed by the antidepressant treatment response questionnaire (ATRQ), and was taking another oral antidepressant 2 weeks before entering the screening period which will be assessed "non-response" by Montgomery Asberg Depression Rating Scale (MADRS) during the screening period, defined as MADRS total score reduced ≤25%.
Comfortable with self-administration of intranasal medication and able to follow instructions provided.
A woman of childbearing potential must have a negative serum (β-human chorionic gonadotropin [β-hCG]) at Screening and a negative urine pregnancy test prior to Period 1 randomization on Day 1.
Exclusion Criteria:
Subject has a current DSM-5 diagnosis of psychotic disorder, MDD with psychosis, bipolar, obsessive compulsive disorder (OCD), intellectual disability, Autism spectrum Disorder, borderline personality disorder, antisocial personality disorder, histrionic personality disorder, and narcissistic personality disorder.
Subject has suicidal ideation with intent to act within the past 6 months based on the Columbia-Suicide Severity Rating Scale (C-SSRS), or has a history of suicidal behavior within the past year as assessed on the C-SSRS.
Subject has uncontrolled hypertension (SBP > 140 mmHg or DBP > 90 mmHg) despite diet, exercise or a stable dose of a permitted anti-hypertensive treatment at Screening or Day 1 prior to Period 1 randomization; or any past history of hypertensive crisis.
Subject had a history of severe pulmonary insufficiency or SpO2<93% at screening time or prior to dosing.
Anatomical or medical conditions that may impede delivery or absorption of study medication.
Subject is a woman who is pregnant, breast-feeding, or planning to become pregnant while enrolled in this study or within 12 weeks after the last dose of study drug.
Hepatitis B surface antigen (HBsAg), hepatitis C antibody (HCVAb), syphilis antibody and human immunodeficiency virus (HIV) antibody tests positive.
Subject has had major surgery, (e.g., requiring general anesthesia) within 12 weeks before screening, or has surgery planned during the time the subject is expected to participate in the study.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Gang Wang
Organizational Affiliation
Beijing Anding Hospital, Capital Medical University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Beijing Anding Hospital, Capital Medical University
City
Beijing
State/Province
Beijing
Country
China
12. IPD Sharing Statement
Learn more about this trial
A Study To Evaluate The Safety, Tolerability And Pharmacokinetics of HS-10345 In Treatment-Resistant Depression
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