Clinical trial NCT05196971: 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
Overall status: COMPLETED
Phase: PHASE1
Conditions: Treatment Resistant Depressive Disorder
Keywords: Treatment resistant depressive disorder
Intranasal
HS-10345
Lead sponsor: Jiangsu Hansoh Pharmaceutical Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2022-01-19
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Maximum age (years): 64
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

1. 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.
2. 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).
3. 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%.
4. Comfortable with self-administration of intranasal medication and able to follow instructions provided.
5. 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:

1. 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.
2. 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.
3. 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.
4. Subject had a history of severe pulmonary insufficiency or SpO2\<93% at screening time or prior to dosing.
5. Anatomical or medical conditions that may impede delivery or absorption of study medication.
6. 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.
7. Hepatitis B surface antigen (HBsAg), hepatitis C antibody (HCVAb), syphilis antibody and human immunodeficiency virus (HIV) antibody tests positive.
8. 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.

Primary outcomes:
measure: Number of participants with adverse events (AEs) and Serious Adverse Events (SAEs)
timeFrame: up to 7 weeks
measure: Change from Baseline (Day -1) in Columbia-Suicide Severity Rating Scale (C-SSRS) Total Score at Day 15 in the Double-Blind Treatment Phase
timeFrame: up to 15 days
measure: 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
timeFrame: up to 2 hours
measure: 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
timeFrame: up to 2 hours
measure: 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
timeFrame: up to 15 days
Secondary outcomes:
measure: Cmax - maximum HS-10345 plasma concentration
timeFrame: up to 72 hours after each study drug administration
measure: AUC (0-24) - area under the HS-10345 plasma concentration-time curve from time 0 to 24 hours after study drug administration
timeFrame: up to 24 hours after each study drug administration
measure: Tmax - time to reach maximum HS-10345 plasma concentration
timeFrame: up to 72 hours after each study drug administration
measure: AUC (0-inf) - area under the HS-10345 plasma concentration-time curve from time 0 to infinity time
timeFrame: up to 72 hours after each study drug administration
measure: T1/2 - plasma elimination half-life for HS-10345
timeFrame: up to 72 hours after each study drug administration
measure: Change from Baseline (Day -1) in Montgomery Asberg Depression Rating Scale (MADRS) Total Score at Day 2/8/15- Analysis of Covariance (ANCOVA) Analysis
timeFrame: up to 15 days
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Anding Hospital, Capital Medical University
state: Beijing
Study officials:
affiliation: Beijing Anding Hospital, Capital Medical University
name: Gang Wang
role: PRINCIPAL_INVESTIGATOR
References: