Clinical Trial Evaluating the Efficacy, Safety, and Toler... | NCT03593213 | Trialant
NCT03593213
Sponsor
AbbVie
Status
Terminated
Last Update Posted
Apr 11, 2022Actual
Enrollment
587Actual
Phase
Phase 3
Conditions
Schizophrenia
Interventions
Cariprazine
Placebo
Countries
United States
Bulgaria
Malaysia
Poland
Puerto Rico
Romania
Serbia
South Korea
Taiwan
Thailand
Ukraine
Protocol Section
Identification Module
NCT ID
NCT03593213
Obsolete or Duplicate NCT IDs
NCT04519099
Organization Study
RGH-MD-24
Secondary IDs
ID
Type
Description
Link
2017-000818-34
EudraCT Number
Brief Title
Clinical Trial Evaluating the Efficacy, Safety, and Tolerability of Cariprazine in a Dose-Reduction Paradigm in the Prevention of Relapse in Participants With Schizophrenia
Official Title
A Double-Blind, Placebo-Controlled, Randomized Withdrawal, Multicenter Clinical Trial Evaluating the Efficacy, Safety, and Tolerability of Cariprazine in a Dose-Reduction Paradigm in the Prevention of Relapse in Patients With Schizophrenia
Acronym
Not provided
Organization
AbbVieINDUSTRY
Status Module
Record Verification Date
Apr 2022
Overall Recruitment Status or Expanded Access Status
Terminated
Last Known Status
Not provided
Delayed Posting
Not provided
Why Stopped
FDA Released Allergan from this post marketing requirement
Expanded Access Info
No
Start Date
Jul 30, 2018Actual
Primary Completion Date
Feb 11, 2021Actual
Completion Date
Feb 11, 2021Actual
First Submitted Date
Jul 10, 2018
First Submission Date that Met QC Criteria
Jul 10, 2018
First Posted Date
Jul 20, 2018Actual
Results Waived
Not provided
Results First Submitted Date
Feb 10, 2022
Results First Submitted that Met QC Criteria
Feb 10, 2022
Results First Posted Date
Mar 8, 2022Actual
Certification/Extension (aka Delayed Results) First Submitted Date
Not provided
Certification/Extension First Submitted that Passed QC Review
Not provided
Certification/Extension First Posted Date
Not provided
Last Update Submitted Date
Apr 7, 2022
Last Update Posted Date
Apr 11, 2022Actual
Sponsor/Collaborators Module
Responsible Party, by Official Title
Sponsor
Lead Sponsor
AbbVieINDUSTRY
Collaborators
Not provided
Oversight Module
Has Data Monitoring Committee (DMC)
No
Is FDA Regulated Drug
Yes
Is FDA Regulated Device
No
Is Unapproved Device
Not provided
Pediatric Postmarket Surveillance of a Device Product
Not provided
Product Exported from US
Not provided
FDAAA801 Violation
Not provided
Description Module
Brief Summary
To evaluate the efficacy and safety of cariprazine at a target dose of 4.5 milligram per day (mg/d) compared with placebo in prevention of relapse in patients with schizophrenia
To evaluate the efficacy and safety of cariprazine at a target dose of 3.0 mg/d compared with placebo in prevention of relapse in patients with schizophrenia who were initially stabilized on a target dose of 4.5 mg/d
Cariprazine 1.5 mg capsules orally once daily at Week 1, titrated to 3.0 mg capsules orally once daily at Week 2 and then titrated to 4.5 mg orally once daily from Week 3 through Week 18 in the Open-label Treatment Period.
Drug: Cariprazine
Placebo (Double-blind Treatment Period)
Placebo Comparator
Cariprazine placebo-matching capsules orally once daily from Week 19 through Week 44 in Double-blind Treatment Period.
Time to First Relapse During Double-blind Treatment Period
Time to Relapse is the number of days from randomization to first relapse.
Relapse is defined as any 1 of the following:
Increase in Positive and Negative Syndrome Scale(PANSS) by ≥30% for participants who had total score of ≥50 at randomization or ≥10-point increased score with total score <50 at randomization [PANSS=30 questions where 1=absence of symptoms to 7=extremely severe symptom;total score=30 to 210;higher score more severe symptoms]
Increase in Clinical Global Impression-Severity (CGI-S) score by 2 or more points [1=normal to 7=among most extremely ill]
Score of >4 on 1 or more of 7 PANSS items:P1-delusions,P2-conceptual disorganization,P3-hallucinatory behavior,P6-suspiciousness,P7-hostility,G8-uncooperativeness,G14-poor impulse control
Deliberate self-injury
Initiation of treatment with mood stabilizer,antidepressant,antipsychotics or benzodiazepine that exceeds specified allowance
Psychiatric hospitalization
Exacerbation of psychiatric illness
Randomization (Week 18) to End of Treatment (Week 44)
Secondary Outcomes
Not provided
Other Outcomes
Not provided
Eligibility Module
Eligibility Criteria
Inclusion Criteria:
Diagnosis of schizophrenia for a minimum of 1 year before Visit 1 (Screening).
Ability to follow study instructions, complete study assessment tools with minimal assistance and no alteration to the assessment tools, and likely to complete all required visits.
Participant meets Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria for schizophrenia as determined by Structured Clinical Interview for DSM-5 (SCID-5).
Positive and Negative Syndrome Scale (PANSS) total score >= 70 and <= 120 at Visit 1 and Visit 2 (Day 1).
Rating of at least 4 (moderate) on at least 2 of the following 4 PANSS positive symptoms; P1: delusions; P2: conceptual disorganization; P3: hallucinatory behaviour; P6: suspiciousness/persecution at Visit 1 and Visit 2.
Exclusion Criteria:
Currently meeting DSM-5 criteria for any of the following:
Schizoaffective disorder, schizophreniform disorder, and other psychotic disorders
Bipolar I and II disorder
Autism spectrum disorder, intellectual development disorder, delirium, major/minor neurocognitive disorder
History of meeting DSM-5 criteria for substance-related disorders (excluding caffeine-related and tobacco-related disorders) within the prior 3 months before Visit 1.
Prior participation in any clinical trials involving experimental or investigational drugs within 6 months before Visit 1 or planned during the study.
Female Participants who are pregnant, planning to become pregnant during the course of the study, or are currently lactating.
Accepts Healthy Volunteers
No
Sex
All
Sex/Gender Based
Not provided
Sex/Gender Description
Not provided
Minimum Age
18 Years
Maximum Age
64 Years
Standard Ages
Adult
Study Population
Not provided
Sampling Method
Not provided
Contacts/Locations Module
Central Contacts
Not provided
Overall Officials
Not provided
Locations
Facility
Status
City
State
ZIP
Country
Contacts
Pillar Clinical Research
Bentonville
Arkansas
72712
United States
Woodland International Research Group
References Module
No data available
No data is available for this block.
IPD Sharing Statement Module
Plan to Share IPD
Yes
Description
AbbVie is committed to responsible data sharing regarding the clinical trials we sponsor. This includes access to anonymized, individual and trial-level data (analysis data sets), as well as other information (e.g., protocols and clinical study reports), as long as the trials are not part of an ongoing or planned regulatory submission. This includes requests for clinical trial data for unlicensed products and indications.
Types
Study Protocol
Statistical Analysis Plan (SAP)
Clinical Study Report (CSR)
Time Frame
For details on when studies are available for sharing, please refer to the link below.
Access Criteria
Access to this clinical trial data can be requested by any qualified researchers who engage in rigorous, independent scientific research, and will be provided following review and approval of a research proposal and Statistical Analysis Plan (SAP) and execution of a Data Use Agreement (DUA). For more information on the process, or to submit a request, visit the following link.
Cariprazine 1.5 mg capsules orally once daily at Week 1, titrated to 3.0 mg capsules orally once daily at Week 2 and then titrated to 4.5 mg orally once daily from Week 3 through Week 18 in the Open-label Treatment Period.
Cariprazine 4.5 mg capsules orally once daily from Week 19 through Week 44 in Double-blind Treatment Period.
BG003
Total
Total of all reporting groups
Denominators
Units
Counts
Participants
BG00053
BG00149
BG00254
BG003156
Baseline Measures
Title
Description
Population Description
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Denominator Units Selected
Denominators
Classes
Age, Continuous
Mean
Standard Deviation
years
Title
Denominators
Categories
Title
Measurements
BG00041.7± 10.94
BG00140.6± 10.84
BG00242.7± 11.08
BG003
Sex: Female, Male
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Female
BG00014
BG00117
BG002
Race (NIH/OMB)
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
American Indian or Alaska Native
BG0001
BG0010
BG002
Race/Ethnicity, Customized
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Hispanic
BG00010
BG00112
BG002
Type
Title
Description
Population Description
Reporting Status
Anticipated Posting Date
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Time Frame
Units Analyzed
Denominator Units Selected
Arm/Group Information
Denominators
Classes
Analyses
Primary
Time to First Relapse During Double-blind Treatment Period
Time to Relapse is the number of days from randomization to first relapse.
Relapse is defined as any 1 of the following:
Increase in Positive and Negative Syndrome Scale(PANSS) by ≥30% for participants who had total score of ≥50 at randomization or ≥10-point increased score with total score <50 at randomization [PANSS=30 questions where 1=absence of symptoms to 7=extremely severe symptom;total score=30 to 210;higher score more severe symptoms]
Increase in Clinical Global Impression-Severity (CGI-S) score by 2 or more points [1=normal to 7=among most extremely ill]
Score of >4 on 1 or more of 7 PANSS items:P1-delusions,P2-conceptual disorganization,P3-hallucinatory behavior,P6-suspiciousness,P7-hostility,G8-uncooperativeness,G14-poor impulse control
Deliberate self-injury
Initiation of treatment with mood stabilizer,antidepressant,antipsychotics or benzodiazepine that exceeds specified allowance
Psychiatric hospitalization
Exacerbation of psychiatric illness
The Double-blind Intent-to Treat (DB ITT) population included all participants in the DB safety population who had at least 1 post-randomization assessment of the PANSS or CGI-S scores during the DB treatment period of the study.
Posted
Median
95% Confidence Interval
days
Randomization (Week 18) to End of Treatment (Week 44)
ID
Title
Description
OG000
Placebo (Double-blind Treatment Period)
Cariprazine placebo-matching capsules orally once daily from Week 19 through Week 44 in Double-blind Treatment Period.
Cariprazine 4.5 mg capsules orally once daily from Week 19 through Week 44 in Double-blind Treatment Period.
Units
Counts
Participants
OG00053
OG00149
OG00253
Title
Denominators
Categories
Title
Measurements
OG000NA(183.0 to NA)The median, and upper limit of 95% confidence interval (CI) was not estimable due to low number of participants with event.
OG001NA(184.0 to NA)The median, and upper limit of 95% CI was not estimable due to low number of participants with event.
OG002
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Log Rank
=0.1576
The significance level was 0.05 using the log rank test.
Hazard Ratio (HR)
0.56
2-Sided
95
0.25
1.29
Hazard ratio (cariprazine 3.0 or 4.5 mg/day vs. placebo) was based on Cox proportional hazards regression model, with treatment group as an explanatory variable.
Superiority
Time Frame
First dose to last dose + 30 days in the Open-label Treatment Period (Up to 23 weeks); First dose to last dose + 30 days in the Double-blind Treatment Period (Up to 35 weeks)
Description
All-cause mortality included all participants. Open-label (OL) Safety Population (OLTP) included all participants in the screened population who took at least 1 dose of OL cariprazine during the OLTP of the study. DB safety population included all participants in the randomized population who took at least 1 dose of DB IP.
Cariprazine 1.5 mg capsules orally once daily at Week 1, titrated to 3.0 mg capsules orally once daily at Week 2 and then titrated to 4.5 mg orally once daily from Week 3 through Week 18 in the Open-label Treatment Period.
Safety Follow-up Period following treatment with Cariprazine 4.5 mg/day in the Open-label Treatment Period for participants who did not continue to the Double-blind Treatment Period.
0
273
7
273
0
273
EG002
Placebo (Double-blind Treatment Period)
Cariprazine placebo-matching capsules orally once daily from Week 19 through Week 44 in Double-blind Treatment Period.
Safety Follow-up Period following treatment with Cariprazine 4.5 mg/day in the Double-blind Treatment Period.
0
56
2
54
0
54
Serious Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Abdominal pain
Gastrointestinal disorders
MedDRA (24.0)
Systematic Assessment
EG0001 affected587 at risk
EG0010 affected273 at risk
EG0020 affected53 at risk
EG0030 affected49 at risk
EG0040 affected54 at risk
EG0050 affected53 at risk
EG0060 affected49 at risk
EG0070 affected54 at risk
Gastritis
Gastrointestinal disorders
MedDRA (24.0)
Systematic Assessment
EG0001 affected587 at risk
EG0010 affected273 at risk
EG0020 affected53 at risk
EG003
Hand fracture
Injury, poisoning and procedural complications
MedDRA (24.0)
Systematic Assessment
EG0001 affected587 at risk
EG0010 affected273 at risk
EG0020 affected53 at risk
EG003
Road traffic accident
Injury, poisoning and procedural complications
MedDRA (24.0)
Systematic Assessment
EG0001 affected587 at risk
EG0010 affected273 at risk
EG0020 affected53 at risk
EG003
Rheumatoid arthritis
Musculoskeletal and connective tissue disorders
MedDRA (24.0)
Systematic Assessment
EG0001 affected587 at risk
EG0010 affected273 at risk
EG0020 affected53 at risk
EG003
Seizure
Nervous system disorders
MedDRA (24.0)
Systematic Assessment
EG0001 affected587 at risk
EG0010 affected273 at risk
EG0020 affected53 at risk
EG003
Schizophrenia
Psychiatric disorders
MedDRA (24.0)
Systematic Assessment
EG0004 affected587 at risk
EG0012 affected273 at risk
EG0024 affected53 at risk
EG003
Delusion
Psychiatric disorders
MedDRA (24.0)
Systematic Assessment
EG0002 affected587 at risk
EG0010 affected273 at risk
EG0020 affected53 at risk
EG003
Paranoia
Psychiatric disorders
MedDRA (24.0)
Systematic Assessment
EG0002 affected587 at risk
EG0010 affected273 at risk
EG0020 affected53 at risk
EG003
Psychotic disorder
Psychiatric disorders
MedDRA (24.0)
Systematic Assessment
EG0002 affected587 at risk
EG0011 affected273 at risk
EG0020 affected53 at risk
EG003
Agitation
Psychiatric disorders
MedDRA (24.0)
Systematic Assessment
EG0001 affected587 at risk
EG0010 affected273 at risk
EG0020 affected53 at risk
EG003
Hallucination, tactile
Psychiatric disorders
MedDRA (24.0)
Systematic Assessment
EG0001 affected587 at risk
EG0010 affected273 at risk
EG0020 affected53 at risk
EG003
Homicidal ideation
Psychiatric disorders
MedDRA (24.0)
Systematic Assessment
EG0001 affected587 at risk
EG0010 affected273 at risk
EG0020 affected53 at risk
EG003
Mental disorder
Psychiatric disorders
MedDRA (24.0)
Systematic Assessment
EG0001 affected587 at risk
EG0010 affected273 at risk
EG0020 affected53 at risk
EG003
Suicidal ideation
Psychiatric disorders
MedDRA (24.0)
Systematic Assessment
EG0001 affected587 at risk
EG0011 affected273 at risk
EG0020 affected53 at risk
EG003
Suicide attempt
Psychiatric disorders
MedDRA (24.0)
Systematic Assessment
EG0001 affected587 at risk
EG0011 affected273 at risk
EG0020 affected53 at risk
EG003
Homicide
Social circumstances
MedDRA (24.0)
Systematic Assessment
EG0001 affected587 at risk
EG0010 affected273 at risk
EG0020 affected53 at risk
EG003
Miscarriage of partner
Social circumstances
MedDRA (24.0)
Systematic Assessment
EG0001 affected587 at risk
EG0010 affected273 at risk
EG0020 affected53 at risk
EG003
Social stay hospitalisation
Social circumstances
MedDRA (24.0)
Systematic Assessment
EG0001 affected587 at risk
EG0010 affected273 at risk
EG0020 affected53 at risk
EG003
Cataract subcapsular
Eye disorders
MedDRA (24.0)
Systematic Assessment
EG0000 affected587 at risk
EG0010 affected273 at risk
EG0021 affected53 at risk
EG003
Retinal detachment
Eye disorders
MedDRA (24.0)
Systematic Assessment
EG0000 affected587 at risk
EG0010 affected273 at risk
EG0021 affected53 at risk
EG003
Food poisoning
Gastrointestinal disorders
MedDRA (24.0)
Systematic Assessment
EG0000 affected587 at risk
EG0011 affected273 at risk
EG0020 affected53 at risk
EG003
Abscess limb
Infections and infestations
MedDRA (24.0)
Systematic Assessment
EG0000 affected587 at risk
EG0011 affected273 at risk
EG0020 affected53 at risk
EG003
Abortion spontaneous
Pregnancy, puerperium and perinatal conditions
MedDRA (24.0)
Systematic Assessment
The number of participants at risk is based on the female population.
EG0000 affected188 at risk
EG0011 affected95 at risk
EG0020 affected14 at risk
EG003
Other Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Headache
Nervous system disorders
MedDRA (24.0)
Systematic Assessment
EG00038 affected587 at risk
EG0010 affected273 at risk
EG0020 affected53 at risk
EG0030 affected49 at risk
EG0040 affected54 at risk
EG0050 affected53 at risk
EG0060 affected49 at risk
EG0070 affected54 at risk
Insomnia
Psychiatric disorders
MedDRA (24.0)
Systematic Assessment
EG00050 affected587 at risk
EG0010 affected273 at risk
EG0020 affected53 at risk
EG003
Cataract nuclear
Eye disorders
MedDRA (24.0)
Systematic Assessment
EG0000 affected587 at risk
EG0010 affected273 at risk
EG0022 affected53 at risk
EG003
Diarrhoea
Gastrointestinal disorders
MedDRA (24.0)
Systematic Assessment
EG0000 affected587 at risk
EG0010 affected273 at risk
EG0023 affected53 at risk
EG003
Ovarian cyst
Reproductive system and breast disorders
MedDRA (24.0)
Systematic Assessment
Number of participants at risk is based on the female population.
EG0000 affected188 at risk
EG0010 affected95 at risk
EG0020 affected14 at risk
EG003
Certain Agreements
Are all PI(s) employees of the sponsor?
No
Restriction Type
OTHER
Results Disclosure Restriction on PI(s)?
Yes
Other Details
AbbVie requests that any investigator or institution that plans on presenting/publishing results disclosure, provide written notification of their request 60 days prior to their presentation/publication. AbbVie requests that no presentation/publication will be instituted until 12 months after a study is completed, or after the first presentation/publication whichever occurs first. A delay may be proposed of a presentation/publication if AbbVie needs to secure patent or proprietary protection.
Schizophrenia Spectrum and Other Psychotic Disorders
D001523
Mental Disorders
Browse Leaves
Not provided
Browse Branches
Not provided
ID
Term
C533287
cariprazine
Ancestor Terms
Not provided
Browse Leaves
Not provided
Browse Branches
Not provided
54 subjects
8 subjects
Adverse Event
FG0000 subjects
FG0012 subjects
FG0020 subjects
FG0034 subjects
Withdrawal by Subject
FG0000 subjects
FG0014 subjects
FG0022 subjects
FG0033 subjects
Lost to Follow-up
FG0000 subjects
FG0015 subjects
FG0024 subjects
FG0031 subjects
Pregnancy
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0031 subjects
Protocol Deviation
FG0000 subjects
FG0013 subjects
FG0022 subjects
FG0035 subjects
Non-compliance with Study Drug
FG0000 subjects
FG0011 subjects
FG0022 subjects
FG0030 subjects
Study Terminated by Sponsor
FG0000 subjects
FG0019 subjects
FG00211 subjects
FG00313 subjects
Reason not Specified
FG0000 subjects
FG0011 subjects
FG0023 subjects
FG0030 subjects
41.7
± 10.92
22
BG00353
Male
BG00039
BG00132
BG00232
BG003103
1
BG0032
Asian
BG0000
BG0010
BG0022
BG0032
Native Hawaiian or Other Pacific Islander
BG0000
BG0010
BG0020
BG0030
Black or African American
BG00034
BG00138
BG00239
BG003111
White
BG00017
BG00111
BG00211
BG00339
More than one race
BG0001
BG0010
BG0021
BG0032
Unknown or Not Reported
BG0000
BG0010
BG0020
BG0030
10
BG00332
Non-Hispanic
BG00043
BG00137
BG00244
BG003124
NA
(NA to NA)
The median, lower and upper limit of 95% CI was not estimable due to low number of participants with event.
OG000
OG002
Log Rank
=0.2066
The significance level was 0.05 using the log rank test.
Hazard Ratio (HR)
0.61
2-Sided
95
0.26
1.45
Hazard ratio (cariprazine 3.0 or 4.5 mg/day vs. placebo) was based on Cox proportional hazards regression model, with treatment group as an explanatory variable.