Clinical trial NCT05937867: A Phase II Study of HS-10353 in Participants With Postpartum Depression
Official title: A Randomized, Double-blinded, Placebo-controlled，Phase II Clinical Study to Evaluate the Efficacy and Safety of HS-10353 in Participants With Postpartum Depression
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Postpartum Depression
Lead sponsor: Jiangsu Hansoh Pharmaceutical Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2023-07-10
Enrollment: 96
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The primary purpose of this study is to determine if treatment with HS-10353 reduces depressive symptoms in participants with postpartum depression (PPD) compared to placebo as assessed by the change from baseline in the 17-item Hamilton Rating Scale for Depression (HAM-D17) total score at Day 15. And the secondary purpose of this study is to evaluate the safety and tolerability of HS-10353 compared to placebo as assessed by the incidence of adverse events, clinical laboratory evaluations, electrocardiogram (ECG) parameters, the Columbia Suicide Severity Rating Scale (C-SSRS), and the 20-item Physician Withdrawal Checklist (PWC-20).


Eligibility criteria: Inclusion Criteria:

* Female subjects aged 18 to 45 years (including cut-off)
* Based on the investigator's clinical evaluation, subjects met the Diagnostic and Statistical Manual of Mental Disorders 5th Edition (DSM-5) criteria for recurrent depressive disorder (MDD) or single episode MDD without psychotic symptoms, and the onset of this depression occurred between 28 weeks of gestation and 4 weeks postpartum
* ≤12 months post partum
* Hamilton Depression Scale (HAM-D17) total score ≥26
* Subjects who are not taking antidepressants for a current episode, or who have taken an oral antidepressant (SSRIs or SNRIs limited, including citalopram, Escitalopram, paroxetine, sertraline, venlafaxine, norvenlafaxine, duloxetine, Minapram) for at least 30 days at a pre-screening stable dose (allowing for a reduction of the drug within 1 week prior to screening),Or who had used any antidepressant before screening but had stopped taking it for at least five drug half-lives
* Agree to discontinue the use of other new antidepressants, antipsychotics, mood stabilizers, and benzodiazepine sedatives and hypnotics during administration
* According to the investigators, the subjects were generally in good physical condition, and no clinically significant abnormalities were found in physical examination, vital signs, 12-lead electrocardiogram (ECG), and laboratory tests (blood routine, blood biochemistry, coagulation function, urine routine, etc.) during screening
* Urine beta-human chorionic gonadotropin (beta-hCG) negative
* Agree to abstain from sex or other effective contraceptive methods for 30 days from screening until the last dose, and no egg donation plan is planned during this period
* If you have stopped breastfeeding, you must agree to stop breastfeeding before the first dose, and at least 7 days after the last dose.Able to communicate well with researchers, willing and able to comply with the lifestyle restrictions specified in the protocol, and cooperate with the completion of the experiment
* Subjects should fully understand the study content and process, as well as possible adverse reactions, and voluntarily sign an informed consent form (ICF).

Exclusion Criteria:

* Accompanied by psychotic symptoms
* In addition to depression, current history and previous history met the diagnostic criteria for other psychiatric disorders in the DSM-5 and were judged by the investigators to have potential implications for clinical studies
* Meet the diagnostic criteria for treatment-resistant depressive disorder
* Homicidal ideation/intent was present, or based on the Columbia Suicide Severity Assessment Scale (C-SSRS), the subject had a history of suicidal intent/self-harm behavior during the current depressive episode
* Atypical antipsychotics, mood stabilizers (e.g., olanzapine, risperidone, quetiapine, aripiprazole, iprazole, Ziprasidone, calilrazine, sodium valproate, lithium carbonate) were used during the current depressive episode.
* History of modified electrical tics (MECT), transcranial magnetic stimulation (TMS), or prior treatment with vagus nerve stimulation (VNS) or deep brain stimulation (DBS) within 1 month prior to screening
* Present or previous history of disease or dysfunction affecting clinical trials, including but not limited to nervous system, cardiovascular system, urinary system, digestive system, respiratory system, skeletal musculoskeletal system, metabolic endocrine system, skin disease, blood system disease, immune disease and tumor, clinically significant chronic disease or poor disease control,The researchers assessed that they were not fit to participate in this study
* The presence of any surgical condition or condition that may significantly affect the absorption, distribution, metabolism and excretion of the drug, or that may pose a hazard to the subjects participating in the trial;Such as gastrointestinal surgery history (gastrectomy, gastrostomy, enterectomy, etc.), urinary tract obstruction or dysuria, gastroenteritis, gastrointestinal ulcer, gastrointestinal bleeding history, etc
* Previous history of seizures (except convulsions caused by febrile convulsions in children)
* History of severe allergies
* A history of drug abuse or benzodiazepine dependence within the last 1 year
* A history of alcohol abuse in the last 6 months (i.e. drinking more than 14 standard units per week, 1 unit =360ml beer or 45ml spirits with 40% alcohol or 150ml wine)
* Participate in any clinical study within 30 days prior to screening
* Take CYP3A4, CYP2C9, or CYP2C19 suppressants (e.g. Clarithromycin, itraconazole, ketoconazole, voriconazole, fluvoxamine, fluconazole, fluoxetine, ticlopidine) for 14 days prior to first dosing (or 5 half-lives, whichever is longer) and throughout the study period.Or grapefruit/grapefruit juice, grapefruit/grapefruit, Seville orange or products rich in such substances
* CYP inducers such as rifampin, carbmazepine, Ritonavir, enzalutamide, efavirenan, nevirapine, phenytoin, phenobarbital, or St. John's Wort were taken within 14 days prior to first administration (or 5 half-lives, whichever is longer) and throughout the study period
* 12-lead electrocardiogram and other test indicators abnormal and clinically significant, such as: Friericia corrected QT interval (QTcF= QT/RR0.33), absolute value \> 470ms
* Hepatitis B surface antigen (HBsAg), hepatitis C antibody (HCV-Ab), human immunodeficiency virus antibody (HIV-Ab), syphilis seroresponse (TRUST) positive
* Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \> 1.5 times upper limit of normal (ULN), serum creatinine (Cr) \> 1.5 times ULN
* Poor compliance or other problems, the researcher considered it inappropriate to participate in the study

Primary outcomes:
measure: Change from baseline in the HAM-D17 total score at day 15
timeFrame: Baseline, Day 15
Secondary outcomes:
measure: Change From Baseline in the HAM-D Total Score at Days 3, 8, 21 and 28
timeFrame: Baseline, Day 3, Day 8, Day 21, Day 28
measure: Percentage of Participants With HAM-D17 Response
timeFrame: Baseline, Day 3, Day 8, Day 15, Day 21, Day 28
measure: Percentage of Participants With HAM-D17 Remission
timeFrame: Baseline, Day 3, Day 8, Day 15, Day 21, Day 28
measure: Change From Baseline in the Clinical Global Impressions - Severity Scale (CGI-S) Total Score
timeFrame: Baseline, Day 3, Day 8, Day 15, Day 21, Day 28
measure: Percentage of Participants With Clinical Global Impression - Improvement (CGI-I) Response
timeFrame: Baseline, Day 3, Day 8, Day 15, Day 21, Day 28
measure: Change From Baseline in Montgomery and Åsberg Depression Rating Scale (MADRS) Total Score
timeFrame: Baseline, Day 3, Day 8, Day 15, Day 21, Day 28
measure: Change From Baseline in Self-Reported Measures of Depressive Symptoms, as Assessed by the Edinburgh Postnatal Depression Scale (EPDS) Total Score
timeFrame: Baseline, Day 3, Day 8, Day 15, Day 21, Day 28
measure: Change From Baseline in Self-Reported Measures of Depressive Symptoms, as Assessed by the 9-item Patient Health Questionnaire (PHQ-9) Score
timeFrame: Baseline, Day 3, Day 8, Day 15, Day 21, Day 28
measure: Change From Baseline in Hamilton Anxiety Rating Scale (HAM-A) Total Score
timeFrame: Baseline, Day 3, Day 8, Day 15, Day 21, Day 28
measure: Change From Baseline in (PWC-20) Total Score
timeFrame: Baseline, Day 15, Day 21
measure: Number of Participants With adverse events (AEs), serious adverse events (SAEs), and adverse events leading to withdrawal from the trial, and association with the investigational drug
timeFrame: Up to Day 28
measure: Number of Participants With Potentially Clinically Significant Vital Sign Measurements
timeFrame: Up to Day 28
measure: Number of Participants With Potentially Clinically Significant Laboratory Evaluations
timeFrame: Up to Day 28
Other outcomes:
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