Clinical trial NCT04965272: 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
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
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: Generalized Anxiety Disorder
Keywords: Generalized Anxiety Disorder (GAD)
Cariprazine
Vraylar
Depression
Antidepressant therapy
Lead sponsor: AbbVie
Sponsor class: INDUSTRY
First posted: 2021-07-16
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Change from Baseline in the Hamilton Anxiety Scale (HAM-A) Total Score
timeFrame: Week 6
Secondary outcomes:
measure: Change from Baseline in Clinical Global Impression of Severity Scale (CGI-S)
timeFrame: Week 6
measure: Percentage of Participants in Remission
timeFrame: Week 6
measure: Percentage of Participants with HAM-A Response
timeFrame: Week 6
measure: Percentage of Participants with CGI-I Responder Status of "Much Better" or "Very Much Better"
timeFrame: Week 6
measure: Percentage of Participants with Patient Global Impression of Change Scale (PGI-C) Responder Status of "Much Better" or "Very Much Better"
timeFrame: Week 6
measure: Change from Baseline in Patient Global Impression of Severity Scale (PGI-S)
timeFrame: Week 6
measure: Change from Baseline in SDS: Anxiety Total Score
timeFrame: Week 6
measure: Change from Baseline in Hamilton Depression Rating Scale-17 item, via Structured Interview Guide for the Hamilton Depression Scale (HAMD-17) Total Score
timeFrame: Week 6
Other outcomes:
Locations:
city: Little Rock
country: United States
facility: Preferred Research Partners /ID# 232286
state: Arkansas
city: Colton
country: United States
facility: Axiom Research /ID# 230728
state: California
city: Costa Mesa
country: United States
facility: ATP Clinical Research, Inc /ID# 230445
state: California
city: Culver City
country: United States
facility: ProScience Research Group /ID# 231520
state: California
city: Encino
country: United States
facility: WR-PRI, LLC - Encino /ID# 230434
state: California
city: Lemon Grove
country: United States
facility: Synergy San Diego /ID# 231006
state: California
city: Los Alamitos
country: United States
facility: Pharmacology Research Institute - Wake LLC /ID# 230722
state: California
city: Newport Beach
country: United States
facility: Pharmacology Research Inst /ID# 230869
state: California
city: Redlands
country: United States
facility: Anderson Clinical Research /ID# 230440
state: California
city: Sherman Oaks
country: United States
facility: California Neuroscience Research Medical Group, Inc. /ID# 230453
state: California
city: Temecula
country: United States
facility: Viking Clinical Research /ID# 230379
state: California
city: Upland
country: United States
facility: Pacific Clinical Research Management Group /ID# 229725
state: California
city: Hialeah
country: United States
facility: Galiz Research - Palmetto Medical Plaza /ID# 230446
state: Florida
city: Chicago
country: United States
facility: Great Lakes Clinical Trials /ID# 231296
state: Illinois
city: Naperville
country: United States
facility: Baber Research Group /ID# 230447
state: Illinois
city: Boston
country: United States
facility: Boston Clinical Trials /ID# 231003
state: Massachusetts
city: Methuen
country: United States
facility: ActivMed Practices and Research, LLC. /ID# 230441
state: Massachusetts
city: Lincoln
country: United States
facility: Alivation Research /ID# 230449
state: Nebraska
city: Cherry Hill
country: United States
facility: Center for Emotional Fitness /ID# 230450
state: New Jersey
city: Marlton
country: United States
facility: Hassman Research Institute Marlton /ID# 233252
state: New Jersey
city: Brooklyn
country: United States
facility: Integrative Clinical Trials /ID# 230955
state: New York
city: Brooklyn
country: United States
facility: SPRI Clinical Trails /ID# 230957
state: New York
city: New York
country: United States
facility: Fieve Clinical Research, Inc. /ID# 230452
state: New York
city: New York
country: United States
facility: Clinilabs, Inc. /ID# 230958
state: New York
city: New York
country: United States
facility: Manhattan Behavioral Medicine PLLC /ID# 229713
state: New York
city: Fayetteville
country: United States
facility: Carolina Institute for Clinical Research - Fayetteville /ID# 230961
state: North Carolina
city: Columbus
country: United States
facility: Ohio State Harding Hospital /ID# 231302
state: Ohio
city: West Chester
country: United States
facility: CincyScience /ID# 229719
state: Ohio
city: Oklahoma City
country: United States
facility: Sooner Clinical Research /ID# 229731
state: Oklahoma
city: Memphis
country: United States
facility: Research Strategies of Memphis /ID# 230443
state: Tennessee
city: Memphis
country: United States
facility: Clinical Neuroscience Solutions - Memphis /ID# 230734
state: Tennessee
city: Austin
country: United States
facility: Austin Clinical Trial Partners /ID# 229727
state: Texas
city: Dallas
country: United States
facility: FutureSearch Trials of Dallas, LP /ID# 230535
state: Texas
city: Houston
country: United States
facility: Earle Research /ID# 230969
state: Texas
city: Wichita Falls
country: United States
facility: Grayline Research Center /ID# 230455
state: Texas
city: Woodstock
country: United States
facility: Woodstock Research Center /ID# 231005
state: Vermont
Study officials:
affiliation: Allergan
name: ALLERGAN INC.
role: STUDY_DIRECTOR
References: