A Study To Assess Adverse Events and Change in Disease Activity With Oral Cariprazine When Added to Antidepressant Therapies (ADTs) Compared to Placebo in Adult Participants With Generalized Anxiety Disorder (GAD) Who Have Had an Inadequate Response to ADTs Alone

Generalized Anxiety Disorder Clinical Trial

— CAR aGAD Ph 2  

Official title:

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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT04965272
• Other study ID #: M21-209
• Status: Withdrawn
• Phase: Phase 2
• Start date: August 18, 2021
• Est. completion date: August 24, 2021

Study information

• Verified date: April 2022
• Source: AbbVie
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: August 24, 2021
• Est. primary completion date: August 24, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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.

Related Conditions & MeSH terms

• Anxiety Disorders
• Disease
• Generalized Anxiety Disorder

Intervention

Drug:
• Cariprazine 0.75 mg/day
Oral Capsule
• Cariprazine 1.5 mg/day
Oral Capsule
• Cariprazine 3.0 mg/day
Oral Capsule

Other:
• Placebo
Oral Capsule

Locations

Country	Name	City	State
United States	Austin Clinical Trial Partners /ID# 229727	Austin	Texas
United States	Boston Clinical Trials /ID# 231003	Boston	Massachusetts
United States	Integrative Clinical Trials /ID# 230955	Brooklyn	New York
United States	SPRI Clinical Trails /ID# 230957	Brooklyn	New York
United States	Center for Emotional Fitness /ID# 230450	Cherry Hill	New Jersey
United States	Great Lakes Clinical Trials /ID# 231296	Chicago	Illinois
United States	Axiom Research /ID# 230728	Colton	California
United States	Ohio State Harding Hospital /ID# 231302	Columbus	Ohio
United States	ATP Clinical Research, Inc /ID# 230445	Costa Mesa	California
United States	ProScience Research Group /ID# 231520	Culver City	California
United States	FutureSearch Trials of Dallas, LP /ID# 230535	Dallas	Texas
United States	WR-PRI, LLC - Encino /ID# 230434	Encino	California
United States	Carolina Institute for Clinical Research - Fayetteville /ID# 230961	Fayetteville	North Carolina
United States	Galiz Research - Palmetto Medical Plaza /ID# 230446	Hialeah	Florida
United States	Earle Research /ID# 230969	Houston	Texas
United States	Synergy San Diego /ID# 231006	Lemon Grove	California
United States	Alivation Research /ID# 230449	Lincoln	Nebraska
United States	Preferred Research Partners /ID# 232286	Little Rock	Arkansas
United States	Pharmacology Research Institute - Wake LLC /ID# 230722	Los Alamitos	California
United States	Hassman Research Institute Marlton /ID# 233252	Marlton	New Jersey
United States	Clinical Neuroscience Solutions - Memphis /ID# 230734	Memphis	Tennessee
United States	Research Strategies of Memphis /ID# 230443	Memphis	Tennessee
United States	ActivMed Practices and Research, LLC. /ID# 230441	Methuen	Massachusetts
United States	Baber Research Group /ID# 230447	Naperville	Illinois
United States	Clinilabs, Inc. /ID# 230958	New York	New York
United States	Fieve Clinical Research, Inc. /ID# 230452	New York	New York
United States	Manhattan Behavioral Medicine PLLC /ID# 229713	New York	New York
United States	Pharmacology Research Inst /ID# 230869	Newport Beach	California
United States	Sooner Clinical Research /ID# 229731	Oklahoma City	Oklahoma
United States	Anderson Clinical Research /ID# 230440	Redlands	California
United States	California Neuroscience Research Medical Group, Inc. /ID# 230453	Sherman Oaks	California
United States	Viking Clinical Research /ID# 230379	Temecula	California
United States	Pacific Clinical Research Management Group /ID# 229725	Upland	California
United States	CincyScience /ID# 229719	West Chester	Ohio
United States	Grayline Research Center /ID# 230455	Wichita Falls	Texas
United States	Woodstock Research Center /ID# 231005	Woodstock	Vermont

Sponsors (1)

Lead Sponsor	Collaborator
AbbVie

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change from Baseline in the Hamilton Anxiety Scale (HAM-A) Total Score	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.	Week 6
Secondary	Change from Baseline in Clinical Global Impression of Severity Scale (CGI-S)	The CGI-S is a single, clinician-reported item that measures the clinician's impression of a subject's current anxiety severity considering their total clinical experience with the patient population. The measure uses a 5-point Likert rating scale, with higher scores indicating greater anxiety severity.	Week 6
Secondary	Percentage of Participants in Remission	Remission is defined as HAM-A total score <=7, Clinical Global Impression of Improvement Scale (CGI-I) = 1, and Sheehan Disability Scale: Anxiety (SDS: Anxiety) total score <= 5	Week 6
Secondary	Percentage of Participants with HAM-A Response	HAM-A response is defined as >= 50% reduction from baseline in HAM-A total score	Week 6
Secondary	Percentage of Participants with CGI-I Responder Status of "Much Better" or "Very Much Better"	The CGI-I is a single, clinician reported item that measures the clinician's impression of how much a participant's anxiety has changed since starting the study medication compared to the participant's condition at baseline. The measure uses a 7-point Likert rating scale with responses ranging from "very much better" (1) to "very much worse" (7).	Week 6
Secondary	Percentage of Participants with Patient Global Impression of Change Scale (PGI-C) Responder Status of "Much Better" or "Very Much Better"	The PGI-C is a single, patient-reported item that assesses the participant's perceived overall change in their anxiety since they started taking the study medication. The measure uses a 7-point Likert rating scale with responses ranging from "very much better" (1) to "very much worse" (7).	Week 6
Secondary	Change from Baseline in Patient Global Impression of Severity Scale (PGI-S)	The PGI-S is a single, patient-reported item that assesses the participant's perceived level of anxiety over the past 7 days. The measure uses a 5-point Likert rating scale with responses ranging from "none" (1) to "very severe" (5), with higher scores indicating greater anxiety severity.	Week 6
Secondary	Change from Baseline in SDS: Anxiety Total Score	The SDS: Anxiety is a 5-item, patient-reported measure used to assess functional impairment in the domains of work/school, social life, and family life on a 10-point numeric rating scale with verbal anchors. The 3 items assessing work/school, social life, and home life or family responsibilities impairment are summed into a single dimensional measure of global functional impairment, with scores ranging from 0 (unimpaired) to 30 (highly impaired). Higher scores indicate greater impairment.	Week 6
Secondary	Change from Baseline in Hamilton Depression Rating Scale-17 item, via Structured Interview Guide for the Hamilton Depression Scale (HAMD-17) Total Score	The HAMD-17 is a 17-item, clinician-reported measure used to quantify and categorize the participant's depression over the past week. The HAMD-17 total score ranges from 0 to 52 with higher scores indicating greater depression severity.	Week 6

External Links

•   This clinical study may be evaluating a usage that is not currently FDA approved. Please see US Prescribing Information for approved uses.