A Study to Evaluate Efficacy and Safety of Toludesvenlafaxine Hydrochloride Sustained-release Tablets in Generalized Anxiety Disorder.

Study Overview
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Brief Summary
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The study aims to evaluate the efficacy and safety of Toludesvenlafaxine Hydrochloride Sustained-release Tablets compared to placebo in adults participants with generalized anxiety disorder over a period of 8 weeks.

Detailed Description
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The study consists of two periods: screening period (2 weeks) and double-blind treatment period (8 weeks). After the screening period, generalized anxiety disorder patients who satisfies the inclusion criteria are randomly assigned in the 1:1:1 ratio to receive either placebo or Toludesvenlafaxine Hydrochloride Sustained-release Tablets at two dose levels (80 ,160 mg/day) for 8 weeks. Participants are evaluated at screening, baseline visits and double-blind period.

Official Title
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A Multicenter, Randomized, Double-blind, Placebo-controlled Phase Ⅲ Study to Evaluate the Efficacy and Safety of Toludesvenlafaxine Hydrochloride Sustained-release Tablets in Participants With Generalized Anxiety Disorder.

Conditions
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Generalized Anxiety Disorder

Intervention / Treatment
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* Drug: Toludesvenlafaxine Hydrochloride Sustained-release Tablet 80mg
* Drug: Toludesvenlafaxine Hydrochloride Sustained-release Tablet 160mg
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female aged 18 to 65 years subjects; Meet the Diagnostic and Statistical Manual of Manual Disorders, fifth Edition(DSM-5) criteria for Generalized Anxiety Disorder; Have a Hamilton Anxiety(HAMA) Rating Scale total score ≥21 points at screening and baseline; Have a Hamilton Anxiety(HAMA) Rating Scale score ≥2 points on both item 1(anxious mood) and item 2(tension) at screening and baseline; Have a clinical Global Impression -severity illness (CGI-S) score≥4 points at screening and baseline. Exclusion Criteria: Meet the diagnostic criteria for other psychotic disorders(defined by DSM-5, except for GAD), including major depression disorder within 6 months prior to screening , presence or history of Schizophrenia Spectrum and Other Psychotic Disorders, Bipolar and Related Disorders, Obsessive-Compulsive and related Disorders, post-traumatic stress disorder, anorexia nervosa or bulimia and personality disorder; Meet the diagnostic criteria for substance or alcohol abuse (defined by DSM-5, except for nicotine or caffeine) within 6 months prior to screening; Have anxious symtoms secondary to other physical illnesses or mental illnesses and anxious induced by psychoactive substance; Withdrawal psychotropic drugs within 5 half-lives (at least 2 weeks for monoamine oxidase inhibitors, at least 1 month for fluoxetine, and at least 2 weeks for benzodiazepines or barbiturates) prior to randomization; Have received psychosurgery or physical therapy for psychiatric illness (such as transcranial magnetic stimulation) within 3 months prior to screening; Have received systematic psychotherapy or other non-drug therapies for psychiatric disorders (such as acupuncture or light therapy) within 6 weeks prior to screening; Concomitant with serious and unstable illness, including cardiovascular, hepatic, renal, hematological, endocrine illness, malignant tumors and other physical illness; Have a history of seizures (except for seizures caused by febrile convulsions in childhood); Have a history of gastrointestinal disease or surgery known to interfere with investigation product absorption or excretion; Known or suspected allergic or severe reaction to investigation product or inactive ingredients; or allergic to venlafaxine or desvenlafaxine; or allergic constitution (defined as allergic to two or more drugs or food) and unfit to participate judged by investigator;

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Toludesvenlafaxine Hydrochloride Sustained-release Tablets 80 mg group<br>orally once a day | Drug: Toludesvenlafaxine Hydrochloride Sustained-release Tablet 80mg<br>* orally once a day<br>|
| Experimental: Toludesvenlafaxine Hydrochloride Sustained-release Tablets 160 mg group<br>orally once a day | Drug: Toludesvenlafaxine Hydrochloride Sustained-release Tablet 160mg<br>* orally once a day<br>|
| Sham Comparator: Placebo<br>orally once a day | Drug: placebo<br>* orally once a day<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in the Hamilton Anxiety(HAMA) Rating Scale total score at endpoint | The HAMA Scale consist of 14 items that include psychic, somatic, and behavioral symptoms associated with anxiety. Each items is rated on a 5-point scale of 0(not present) to 4(very severe) so that scores may range from 0 to 56, with high scores indicating greater illness severity. | from baseline to week 8 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in the Hamilton Anxiety(HAMA) Rating Scale psychic factor score (Items 1 6 and Item 14) at endpoint | The psychic factor score is the sum of items 1-6 and items 14(including items such as anxious mood, tension, fear, insomnia, and behavioral symptoms).Each items is rated on a 5-point scale of 0(not present) to 4(very severe) so that scores may range from 0 to 28, with high scores indicating greater illness severity. | from baseline to week 8 | 
| Change from baseline in the Hamilton Anxiety(HAMA) Rating Scale somatic factor score (Items 7 13) at endpoint | The somatic factor score is the sum of items 7-13(including items such as cardiovascular, respiratory, and gastrointestinal symptoms).Each items is rated on a 5-point scale of 0(not present) to 4(very severe) so that scores may range from 0 to 28, with high scores indicating greater illness severity. | from baseline to week 8 | 
| Change from baseline in the Hamilton Anxiety(HAMA) Rating Scale item 1（Anxious mood）Score at endpoint | The item is rated on a 5-point scale of 0(not present) to 4(very severe) so that score may range from 0 to 4, with high scores indicating greater illness severity. | from baseline to week 8 | 
| Change from baseline in the Hamilton Anxiety(HAMA) Rating Scale item 2（Tension）Score at endpoint | The item is rated on a 5-point scale of 0(not present) to 4(very severe) so that score may range from 0 to 4, with high scores indicating greater illness severity. | from baseline to week 8 | 
| Percentage of participants with response at endpoint | Response was defined as a≥50% reduction from baseline to endpoint in the HAMA total score. | from baseline to week 8 | 
| Percentage of participants with remission at endpoint | Remission was defined as a HAMA total score ≤7 points at endpoint | from baseline to week 8 | 
| Clinical Global Impression Scale - improvement (CGI-I) score at endpoint | The CGI-I scale measures the participant's improvement (or worsening) as assessed by the investigator relative to Baseline on a 7-point scale: 1, very much improved; 2, much improved; 3, minimally improved; 4, no change; 5, minimally worse; 6, much worse; or 7, very much worse. | from baseline to week 8 | 
| Change from baseline in Clinical Global Impression Scale - severity (CGI-S) score at endpoint | The CGI-S scale is a 7-point scale to rate the severity of the patient's illness. Patient is assessed on severity of mental illness on the following scale: 1, normal, not at all ill; 2, borderline mentally ill; 3, mildly ill; 4, moderately ill; 5, markedly ill; 6, severely ill; or 7, extremely ill. | from baseline to week 8 | 
| Change from baseline in the Sheehan Disability Scale(SDS) score at endpoint | The SDS scale consists of 3 items evaluating impairment in work/school， social life/leisure activities, and family life/home responsibilities. Each item is scored on a scale of 0(unimpaired) to 10(highly impaired). | from baseline to week 8 | 
| Change from baseline in the Pittsburgh Sleep Quality Index (PSQI) score at endpoint | The scale consists of 3 items evaluating impairment in work/school， social life/leisure activities, and family life/home responsibilities. Each item is scored on a scale of 0(unimpaired) to 10(highly impaired). | from baseline to week 8 | 
| Incidence and severity of adverse effects (AEs) |  | from baseline to week 8 | 
| Change from baseline in the Columbia Suicide severity Rating Scale (C-SSRS) score at endpoint | The C-SSRS captured the occurrence, severity, and frequency of suicide-related thoughts and behaviors. Suicidal ideation: a yes answer to any 1 of 5 suicidal ideation questions: wish to be dead, and 4 different categories of active suicidal ideation. Suicidal behavior: a yes answer to any 1 of 5 suicidal behavior questions: preparatory acts or behavior, aborted attempt, interrupted attempt, actual attempt, and completed suicide. | from baseline to week 8 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Toludesvenlafaxine Hydrochloride Sustained-release Tablet, generalized anxiety disorder, efficacy, safety