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

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.

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.

Study Overview

• Status: Recruiting
• Conditions: Generalized Anxiety Disorder
• Intervention / Treatment: Drug: Toludesvenlafaxine Hydrochloride Sustained-release Tablet 80mg; Drug: Toludesvenlafaxine Hydrochloride Sustained-release Tablet 160mg; Drug: placebo

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 555
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Zhang Hongyan; Phone Number: 13601237138; Email: hongyanzhang@bjmu.edu.cn

Study Locations

• China
  • Beijing, China
    • Recruiting
    • Peking University Sixth Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Male or female aged 18 to 65 years subjects;
2. Meet the Diagnostic and Statistical Manual of Manual Disorders, fifth Edition(DSM-5) criteria for Generalized Anxiety Disorder;
3. Have a Hamilton Anxiety(HAMA) Rating Scale total score ≥21 points at screening and baseline;
4. Have a Hamilton Anxiety(HAMA) Rating Scale score ≥2 points on both item 1(anxious mood) and item 2(tension) at screening and baseline;
5. Have a clinical Global Impression -severity illness (CGI-S) score≥4 points at screening and baseline.

Exclusion Criteria:

1. 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;
2. Meet the diagnostic criteria for substance or alcohol abuse (defined by DSM-5, except for nicotine or caffeine) within 6 months prior to screening;
3. Have anxious symtoms secondary to other physical illnesses or mental illnesses and anxious induced by psychoactive substance;
4. 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;
5. Have received psychosurgery or physical therapy for psychiatric illness (such as transcranial magnetic stimulation) within 3 months prior to screening;
6. Have received systematic psychotherapy or other non-drug therapies for psychiatric disorders (such as acupuncture or light therapy) within 6 weeks prior to screening;
7. Concomitant with serious and unstable illness, including cardiovascular, hepatic, renal, hematological, endocrine illness, malignant tumors and other physical illness;
8. Have a history of seizures (except for seizures caused by febrile convulsions in childhood);
9. Have a history of gastrointestinal disease or surgery known to interfere with investigation product absorption or excretion;
10. 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;

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

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

What is the study measuring?

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
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
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

Collaborators and Investigators

• Sponsor: Luye Pharma Group Ltd.
• Investigators: Principal Investigator: Zhang Hongyan, Peking University Sixth Hospital

Study record dates

Study Major Dates

• Study Start (Actual): July 12, 2023
• Primary Completion (Estimated): April 30, 2026
• Study Completion (Estimated): April 30, 2026

Study Registration Dates

• First Submitted: July 24, 2023
• First Submitted That Met QC Criteria: July 24, 2023
• First Posted (Actual): August 1, 2023

Study Record Updates

• Last Update Posted (Actual): March 15, 2024
• Last Update Submitted That Met QC Criteria: March 12, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: safety; efficacy; generalized anxiety disorder; Toludesvenlafaxine Hydrochloride Sustained-release Tablet
• Additional Relevant MeSH Terms: Mental Disorders; Anxiety Disorders
• Other Study ID Numbers: LY03005/CT-CHN-307

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No