A Double-Blind, Randomized, Placebo-Controlled, Parallel-Group, Fixed-Dose, Phase 2 Study Evaluating the Safety and Efficacy of Cariprazine as an Adjunctive Therapy to Antidepressant Therapies (ADTs), in the Treatment of Subjects With Generalized Anxiety Disorder (GAD) Who Have Had an Inadequate Response to ADT Alone
试验速览
- 阶段
- 2 期
- 状态
- 撤回
- 发起方
- 试验地点
- 36
- 主要终点
- Change from Baseline in the Hamilton Anxiety Scale (HAM-A) Total Score
研究概览
简要总结
Generalized anxiety disorder (GAD) is usually treated with antidepressant therapy (ADT); however, sometimes ADTs alone are not enough to adequately treat GAD. The purpose of this study is to assess adverse events and the change in disease activity with cariprazine when added to ADTs compared with placebo in adult participants with GAD who have had an inadequate response to 1 or more prior ADTs alone.
Cariprazine is an approved drug being developed for the treatment of GAD. The participants are placed into 1 of 4 groups, called treatment arms. Each group receives a different treatment. There is a 1 in 4 chance that participants will be assigned to placebo. Around 1072 participants age 18-65 with GAD and an inadequate response to ADT alone will be enrolled in the study in the United States.
After a 2-week screening period, participants will receive daily oral capsules of cariprazine of varying doses or placebo for 6 weeks, followed by a 4-week safety follow-up period for a total study duration of 10 weeks.
There may be higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the study at a hospital or clinic. The effect of the treatment will be checked by medical assessments, blood tests, checking for side effects and completing questionnaires.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participants with generalized anxiety disorder (GAD).
- •Taking one of the FDA-approved antidepressant therapies (ADTs) for the treatment of GAD (i.e., escitalopram, paroxetine, duloxetine, and venlafaxine XR).
- •Continuing to exhibit anxiety symptoms (Hamilton Anxiety Scale [HAM-A] total score >= 22) at Visit 1 (Screening) and Visit 2 (Baseline, Week 0) despite being on an adequate dose and duration (at least 6 weeks of continuous use, with a minimum of 3 of 6 weeks above the minimum labeled dose for GAD).
- •Documentation of inadequate response to at least 1 ADT must be confirmed on the GAD-Antidepressant Treatment Response Questionnaire (GAD-ATRQ).
- •Must have a minimum score of 22 on the rater-administrated HAM-A and a minimum score of 4 on the rater-administered Clinical Global Impression of Severity Scale (CGI-S), at both Visit 1 (Screening) and Visit 2 (Baseline, Week 0).
- •A score of less than 12 on the rater-administered Hamilton Depression Rating Scale-17-item (HAMD-17) at Visit 1 (Screening) and Visit 2 (Baseline, Week 0).
- •Laboratory values must meet the criteria specified in the protocol within the screening period prior to the first dose of study drug.
排除标准
- •Psychiatric comorbidities, risk of suicide, self-injury, and/or harm to others; any current Diagnostic and Statistical Manual of Mental Disorders - 5th edition (DSM-5) psychiatric diagnosis other than generalized anxiety disorder (GAD) (other than specific phobias) or history of alcohol or any other substance-related disorders within the 6 months before Visit 1 (Screening).
- •Pregnancy, current breastfeeding status, plans to become pregnant or to donate eggs during the study or for approximately 30 days after the last dose of investigational product (female participants).
- •History of an allergic reaction, hypersensitivity, or intolerance to constituents of cariprazine (and its excipients) and/or other products of the same class or to any of the protocol-approved rescue medications.
- •Any clinically relevant or significant electrocardiogram (ECG) abnormalities, including ECG with QT interval corrected for heart rate (QTc) using Fridericia's formula (QTcF) >450 msec (males) or >470 msec (females).
- •History of seizure disorder, with the exception of febrile seizure, stroke, significant head injury, tumor of the central nervous system, or any other condition that predisposes to seizure.
- •Specific medical conditions precluding study drug use and/or study participation, such as history of neuroleptic malignant syndrome; cataracts or retinal detachment; allergic reactions/hypersensitivity to cariprazine and/or protocol-approved rescue medications; pregnancy per above; cardiovascular disease; seizure history; and any other disease that is clinically unstable or would make the participant an unsuitable candidate to participate in the study, based on the investigator's judgment.
研究组 & 干预措施
Cariprazine 0.75 mg/day + Antidepressant Therapy
Antidepressant (paroxetine, escitalopram, venlafaxine XR, or duloxetine) + cariprazine 0.75 mg/day oral, once daily for 6 weeks
干预措施: Cariprazine 0.75 mg/day (Drug)
Cariprazine 1.5 mg/day + Antidepressant Therapy
Antidepressant (paroxetine, escitalopram, venlafaxine XR, or duloxetine) + cariprazine 1.5 mg/day oral, once daily for 6 weeks
干预措施: Cariprazine 1.5 mg/day (Drug)
Cariprazine 3.0 mg/day + Antidepressant Therapy
Antidepressant (paroxetine, escitalopram, venlafaxine XR, or duloxetine) + cariprazine 1.5 mg/day oral for 2 weeks followed by cariprazine 3.0 mg/day oral, once daily for 4 weeks.
干预措施: Cariprazine 3.0 mg/day (Drug)
Placebo + Antidepressant Therapy
Antidepressant (paroxetine, escitalopram, venlafaxine XR, or duloxetine) + oral placebo, once daily for 6 weeks
干预措施: Placebo (Other)
结局指标
主要结局
Change from Baseline in the Hamilton Anxiety Scale (HAM-A) Total Score
时间窗: Week 6
The HAM-A is a 14-item, clinician-reported measure used to quantify and categorize the participant's anxiety over the past week. Items are rated on a 5-point Likert rating scale. The HAM-A total score ranges from 0 to 56, with higher scores indicating greater anxiety severity.
次要结局
- Change from Baseline in Hamilton Depression Rating Scale-17 item, via Structured Interview Guide for the Hamilton Depression Scale (HAMD-17) Total Score(Week 6)
- Change from Baseline in SDS: Anxiety Total Score(Week 6)
- Change from Baseline in Clinical Global Impression of Severity Scale (CGI-S)(Week 6)
- Percentage of Participants in Remission(Week 6)
- Percentage of Participants with HAM-A Response(Week 6)
- Percentage of Participants with CGI-I Responder Status of "Much Better" or "Very Much Better"(Week 6)
- Percentage of Participants with Patient Global Impression of Change Scale (PGI-C) Responder Status of "Much Better" or "Very Much Better"(Week 6)
- Change from Baseline in Patient Global Impression of Severity Scale (PGI-S)(Week 6)