Treatment Resistant Depressive DisorderPhase 1NCT05196971
A Study To Evaluate The Safety, Tolerability And Pharmacokinetics of HS-10345 In Treatment-Resistant Depression
A Phase 1 study testing HS-10345 84mg in people with Treatment Resistant Depressive Disorder, run by Jiangsu Hansoh Pharmaceutical Co., Ltd. at 1 site in China.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 to 64 years
- Conditions the study is for
- Treatment Resistant Depressive Disorder
- What is being tested?
- HS-10345 84mg
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 12 participants
- Where
- 1 siteChina
- Study dates
- 28 Oct 2021to 31 Oct 2022
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 64 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
China1 site
Beijing Anding Hospital, Capital Medical University
Beijing, Beijing Municipality
About this study
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
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).
Read the 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.
- Conditions
- Treatment Resistant Depressive Disorder
- Being tested
- HS-10345 84mg, Placebo
- Keywords
- Treatment resistant depressive disorder, Intranasal, HS-10345
- Medical subject headings
- Depressive Disorder, Treatment-Resistant
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
HS-10345 84mgDrug
Also called HS-10345
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
PlaceboDrug
Also called HS-10345 Placebo
6 sprays of placebo self-administered as an intranasal formulation for 4 days (Days 1, 4, 8, 11) during the double-blind phase
| Study group | Role | What they receive |
|---|---|---|
| HS-10345 84mg | Experimental | Participants will self-administer intranasal HS-10345 84mg on Days 1, 4, 8, and 11 during the double-blind phase Receives: Drug: HS-10345 84mg |
| Placebo | Placebo comparator | Participants will be self-administered on Days 1, 4, 8, and 11 during the double-blind phase Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: up to 7 weeks
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.
Measured: up to 15 days
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.
Measured: up to 2 hours
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.
Measured: up to 2 hours
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.
Measured: up to 15 days
Secondary outcomes (6)
Cmax - maximum HS-10345 plasma concentration
The maximum concentration of the HS-10345 in plasma after drug administration, obtained directly from the measured concentrations.
Measured: up to 72 hours after each study drug administration
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.
Measured: up to 24 hours after each 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.
Measured: up to 72 hours after each study drug administration
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
Measured: up to 72 hours after each study drug administration
T1/2 - plasma elimination half-life for HS-10345
T1/2 will be calculated as 0.693/Kel
Measured: up to 72 hours after each study drug administration
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
Measured: up to 15 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Jan 2022
- Study start28 Oct 2021
- Primary completion30 Apr 2022
- Study completion31 Oct 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Treatment Resistant Depressive DisorderStudies of the same condition, open and under way.
- More trials run by Jiangsu Hansoh Pharmaceutical Co., Ltd.The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- Jiangsu Hansoh Pharmaceutical Co., Ltd.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Gang Wang, Principal investigator, Beijing Anding Hospital, Capital Medical University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05196971
- Sponsor's protocol ID
- HS-10345-102
- Status last verified
- Feb 2023
- First submitted
- 9 Jan 2022
- Last updated
- 9 Mar 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 Mar 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT05196971
- Acronym / sponsor ID
- HS-10345-102
- Conditions
- Treatment Resistant Depressive Disorder
- Keywords
- Treatment resistant depressive disorder, Intranasal, HS-10345
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- Jiangsu Hansoh Pharmaceutical Co., Ltd.Industry (pharma, biotech, devices)
- Study start
- 28 Oct 2021 (actual)
- Primary completion
- 30 Apr 2022 (actual)
- Study completion
- 31 Oct 2022 (actual)
- First posted
- 19 Jan 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| HS-10345 84mg | Experimental | Drug: HS-10345 84mgParticipants will self-administer intranasal HS-10345 84mg on Days 1, 4, 8, and 11 during the double-blind phase |
| Placebo | Placebo comparator | Drug: PlaceboParticipants will be self-administered on Days 1, 4, 8, and 11 during the double-blind phase |
Who may qualify
- Ages
- 18 to 64 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (8 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| HS-10345 84mgAlso: HS-103456 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 | Drug | HS-10345 84mg |
| PlaceboAlso: HS-10345 Placebo6 sprays of placebo self-administered as an intranasal formulation for 4 days (Days 1, 4, 8, 11) during the double-blind phase | Drug | Placebo |
Primary outcome
Number of participants with adverse events (AEs) and Serious Adverse Events (SAEs)
Time frame: up to 7 weeks
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
Time frame: up to 15 days
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
Time frame: up to 2 hours
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
Time frame: up to 2 hours
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
Time frame: up to 15 days
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.
6 secondary outcomes
Cmax - maximum HS-10345 plasma concentration
Time frame: up to 72 hours after each study drug administration
AUC (0-24) - area under the HS-10345 plasma concentration-time curve from time 0 to 24 hours after study drug administration
Time frame: up to 24 hours after each study drug administration
Tmax - time to reach maximum HS-10345 plasma concentration
Time frame: up to 72 hours after each study drug administration
AUC (0-inf) - area under the HS-10345 plasma concentration-time curve from time 0 to infinity time
Time frame: up to 72 hours after each study drug administration
T1/2 - plasma elimination half-life for HS-10345
Time frame: up to 72 hours after each study drug administration
Change from Baseline (Day -1) in Montgomery Asberg Depression Rating Scale (MADRS) Total Score at Day 2/8/15- Analysis of Covariance (ANCOVA) Analysis
Time frame: up to 15 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Mar 2023.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Gang Wang principal investigator
Beijing Anding Hospital, Capital Medical University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing HS-10345 84mg in people with Treatment Resistant Depressive Disorder, run by Jiangsu Hansoh Pharmaceutical Co., Ltd. at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 Mar 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of participants with adverse events (AEs) and Serious Adverse Events (SAEs) (time frame: up to 7 weeks). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Mar 2023.