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A Study of Cariprazine in the Prevention of Relapse of Symptoms in Participants With Schizophrenia

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ClinicalTrials.gov Identifier: NCT01412060
Recruitment Status : Completed
First Posted : August 8, 2011
Results First Posted : July 6, 2018
Last Update Posted : July 6, 2018
Sponsor:
Collaborator:
Gedeon Richter Ltd.
Information provided by (Responsible Party):
Forest Laboratories

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Prevention
Condition Schizophrenia
Interventions Drug: Placebo
Drug: Cariprazine
Enrollment 765
Recruitment Details  
Pre-assignment Details A total of 765 participants were enrolled and received cariprazine in Run-in Phase; 751 of these, had at least 1 postbaseline Positive and Negative Syndrome Scale (PANSS) evaluation and 364 entered Stabilization Phase. Only 200 participants who completed Open-label phase, received either placebo (n=99) or cariprazine (n=101) in Double-Blind Phase.
Arm/Group Title Cariprazine - Open-label Phase Placebo - Double-blind Treatment Phase Cariprazine - Double-blind Treatment Phase
Hide Arm/Group Description Participants received 3, 6, or 9 mg cariprazine orally once a day for 6 weeks; the dose could be modified during this time. The cariprazine dose was fixed at 3, 6, or 9 mg for the last 14 weeks of this 20 week Open-label Phase. Participants received placebo orally once a day for 26 to 72 weeks. Participants received 3, 6, or 9 mg cariprazine orally once a day for 26 to 72 weeks.
Period Title: Open-label Run-in Period (RIP)
Started 765 0 0
Completed 418 0 0
Not Completed 347 0 0
Reason Not Completed
Adverse Event             86             0             0
Insufficient Therapeutic Response             66             0             0
Protocol Violation             27             0             0
Withdrawal of Consent             117             0             0
Lost to Follow-up             32             0             0
Other Miscellaneous Reasons             19             0             0
Period Title: Period Between RIP and SP
Started 418 0 0
Completed 364 0 0
Not Completed 54 0 0
Reason Not Completed
Adverse Event             4             0             0
Insufficient Therapeutic Response             19             0             0
Protocol Violation             2             0             0
Withdrawal of Consent             1             0             0
Lost to Follow-up             5             0             0
Other Miscellaneous Reasons             23             0             0
Period Title: Open-label Stabilization Period (SP)
Started 364 0 0
Completed 264 0 0
Not Completed 100 0 0
Reason Not Completed
Adverse Event             9             0             0
Insufficient Therapeutic Response             9             0             0
Protocol Violation             14             0             0
Withdrawal of Consent             40             0             0
Lost to Follow-up             9             0             0
Other Miscellaneous Reasons             19             0             0
Period Title: Period Between SP and DBP
Started 264 0 0
Completed 200 0 0
Not Completed 64 0 0
Reason Not Completed
Protocol Violation             2             0             0
Withdrawal of Consent             2             0             0
Lost to Follow-up             1             0             0
Did Not Met Criteria to Enter Next Phase             4             0             0
Other Miscellaneous Reasons             55             0             0
Period Title: Double-blind Treatment Phase (DBP)
Started 0 99 101
Completed 0 16 18
Not Completed 0 83 83
Reason Not Completed
Adverse Event             0             5             6
Protocol Violation             0             4             5
Withdrawal of Consent             0             10             15
Lost to Follow-up             0             6             5
Other Miscellaneous Reasons             0             11             27
Relapse             0             47             25
Arm/Group Title Cariprazine - Open-label Phase
Hide Arm/Group Description Participants received 3, 6, or 9 mg cariprazine orally once a day for 6 weeks; the dose could be modified during this time. The cariprazine dose was fixed at 3, 6, or 9 mg for the last 14 weeks of this 20 week Open-label Phase.
Overall Number of Baseline Participants 765
Hide Baseline Analysis Population Description
Run-in Phase safety population: All participants who received at least 1 dose of open-label cariprazine during the Run-in Phase of the study.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 765 participants
38.4  (10.4)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 765 participants
Female
221
  28.9%
Male
544
  71.1%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 765 participants
Hispanic or Latino
37
   4.8%
Not Hispanic or Latino
728
  95.2%
Unknown or Not Reported
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 765 participants
American Indian or Alaska Native
0
   0.0%
Asian
149
  19.5%
Native Hawaiian or Other Pacific Islander
1
   0.1%
Black or African American
313
  40.9%
White
299
  39.1%
More than one race
3
   0.4%
Unknown or Not Reported
0
   0.0%
Weight  
Mean (Standard Deviation)
Unit of measure:  Kg
Number Analyzed 765 participants
78.07  (20.10)
Height  
Mean (Standard Deviation)
Unit of measure:  Cm
Number Analyzed 765 participants
170.98  (9.95)
Body Mass Index (BMI)  
Mean (Standard Deviation)
Unit of measure:  Kg/m^2
Number Analyzed 765 participants
26.50  (5.63)
Waist circumference  
Mean (Standard Deviation)
Unit of measure:  Cm
Number Analyzed 765 participants
90.39  (15.34)
1.Primary Outcome
Title Time From Baseline to the First Symptom Relapse During the Double-blind Phase
Hide Description

Relapse was defined as meeting ≥1 of the following criteria:1-Hospitalization due to worsening of condition;2-increase in Positive and Negative Syndrome Scale(PANSS) total score by ≥30% for participants,scored ≥50 or a ≥10-point increase for participants,scored <50 at randomization;3-increase in Clinical Global Impressions-Severity(CGI-S) score by ≥2 points at Week 20;4-deliberate self-injury or aggressive behaviour;5-suicidal/homicidal ideation judged clinically significant by Investigator;6-score of >4 on 1 or more of following PANSS items:P1,P2,P3,P6,P7,G8 or G14. Second assessment not performed based on Investigator discretion.

PANSS is 30-item rating scale. Each item scored on 7-point scale. Total score ranges from 30 to 210. Lower score indicates fewer schizophrenic symptoms. CGI-S is 7-point scale,measures severity of participant’s illness in comparison with others with same diagnosis. Lower score indicates less severe illness. 25th percentile for time to relapse was reported.

Time Frame Up to 34 Weeks and Bi-Weekly thereafter until Week 92
Hide Outcome Measure Data
Hide Analysis Population Description
Double-blind intent-to-treat population: All participants who received at least 1 dose of double-blind investigational product and who had at least 1 post-randomization assessment of PANSS or CGI-S during the Double-blind Treatment Phase.
Arm/Group Title Placebo Cariprazine
Hide Arm/Group Description:
Participants received placebo orally once a day for 26 to 72 weeks. Placebo: Placebo was supplied in capsules.
Participants received 3, 6, or 9 mg cariprazine orally once a day for 26 to 72 weeks. Cariprazine: Cariprazine was supplied in capsules.
Overall Number of Participants Analyzed 99 101
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Days
92
(44 to 151)
224 [1] 
(99 to NA)
[1]
The upper limit of the confidence interval could not be calculated due to insufficient number of events.
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Cariprazine
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0010
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.45
Confidence Interval (2-Sided) 95%
0.28 to 0.73
Estimation Comments Hazard ratio (cariprazine 3-9 mg vs placebo) is based on Cox proportional hazards regression model, with treatment group as an explanatory variable.
Time Frame First dose until 30 days after last dose of investigational product [Open-Label (Up to 184 days) and Double-Blind (Up to 536 days)]
Adverse Event Reporting Description

Run-in Phase Safety Population: All randomized participants who received at least 1 dose of investigational product and who had at least 1 post-randomization assessment of PANSS or CGI-S during the open-label phase (OLP) of the study.

Double-blind Safety Population: All participants in the Randomized Population who took at least 1 dose of double-blind investigational product.

Adverse events data was reported in periods as per the treatment received.

 
Arm/Group Title Cariprazine - Open-label Phase Placebo - Double-blind Treatment Phase Cariprazine - Double-blind Treatment Phase Open-label - Safety Follow-up Phase Placebo - Safety Follow-up Phase Cariprazine - Safety Follow-up Phase
Hide Arm/Group Description Participants received 3, 6, or 9 mg cariprazine orally once a day for 6 weeks; the dose could be modified during this time. The cariprazine dose was fixed at 3, 6, or 9 mg for the last 14 weeks of this 20 week Open-label Phase. Participants received placebo orally once a day for 26 to 72 weeks. Participants received 3, 6, or 9 mg cariprazine orally once a day for 26 to 72 weeks. Participants received no treatment during the 4 weeks Safety Follow-up Phase. Participants received no treatment during the 4 weeks Safety Follow-up Phase. Participants received no treatment during the 4 weeks Safety Follow-up Phase.
All-Cause Mortality
Cariprazine - Open-label Phase Placebo - Double-blind Treatment Phase Cariprazine - Double-blind Treatment Phase Open-label - Safety Follow-up Phase Placebo - Safety Follow-up Phase Cariprazine - Safety Follow-up Phase
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/765 (0.00%)   0/99 (0.00%)   0/101 (0.00%)   0/765 (0.00%)   0/99 (0.00%)   0/101 (0.00%) 
Show Serious Adverse Events Hide Serious Adverse Events
Cariprazine - Open-label Phase Placebo - Double-blind Treatment Phase Cariprazine - Double-blind Treatment Phase Open-label - Safety Follow-up Phase Placebo - Safety Follow-up Phase Cariprazine - Safety Follow-up Phase
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   50/765 (6.54%)   14/99 (14.14%)   14/101 (13.86%)   6/765 (0.78%)   2/99 (2.02%)   0/101 (0.00%) 
Cardiac disorders             
Atrial fibrillation  1  0/765 (0.00%)  1/99 (1.01%)  0/101 (0.00%)  0/765 (0.00%)  0/99 (0.00%)  0/101 (0.00%) 
Sinus tachycardia  1  0/765 (0.00%)  1/99 (1.01%)  0/101 (0.00%)  0/765 (0.00%)  0/99 (0.00%)  0/101 (0.00%) 
Tachycardia paroxysmal  1  0/765 (0.00%)  1/99 (1.01%)  0/101 (0.00%)  0/765 (0.00%)  0/99 (0.00%)  0/101 (0.00%) 
Ear and labyrinth disorders             
Middle ear effusion  1  0/765 (0.00%)  1/99 (1.01%)  0/101 (0.00%)  0/765 (0.00%)  0/99 (0.00%)  0/101 (0.00%) 
Gastrointestinal disorders             
Haematemesis  1  1/765 (0.13%)  0/99 (0.00%)  0/101 (0.00%)  0/765 (0.00%)  0/99 (0.00%)  0/101 (0.00%) 
General disorders             
Pyrexia  1  1/765 (0.13%)  0/99 (0.00%)  0/101 (0.00%)  0/765 (0.00%)  0/99 (0.00%)  0/101 (0.00%) 
Drug ineffective  1  0/765 (0.00%)  0/99 (0.00%)  1/101 (0.99%)  0/765 (0.00%)  0/99 (0.00%)  0/101 (0.00%) 
Hepatobiliary disorders             
Cholecystitis acute  1  0/765 (0.00%)  1/99 (1.01%)  0/101 (0.00%)  0/765 (0.00%)  0/99 (0.00%)  0/101 (0.00%) 
Immune system disorders             
Hypersensitivity  1  0/765 (0.00%)  0/99 (0.00%)  1/101 (0.99%)  0/765 (0.00%)  0/99 (0.00%)  0/101 (0.00%) 
Infections and infestations             
Pneumonia  1  1/765 (0.13%)  0/99 (0.00%)  1/101 (0.99%)  0/765 (0.00%)  0/99 (0.00%)  0/101 (0.00%) 
Otitis media acute  1  0/765 (0.00%)  1/99 (1.01%)  0/101 (0.00%)  0/765 (0.00%)  0/99 (0.00%)  0/101 (0.00%) 
Injury, poisoning and procedural complications             
Foreign body  1  1/765 (0.13%)  0/99 (0.00%)  0/101 (0.00%)  0/765 (0.00%)  0/99 (0.00%)  0/101 (0.00%) 
Overdose  1  1/765 (0.13%)  0/99 (0.00%)  0/101 (0.00%)  0/765 (0.00%)  0/99 (0.00%)  0/101 (0.00%) 
Ankle fracture  1  0/765 (0.00%)  0/99 (0.00%)  1/101 (0.99%)  0/765 (0.00%)  0/99 (0.00%)  0/101 (0.00%) 
Fall  1  0/765 (0.00%)  0/99 (0.00%)  1/101 (0.99%)  0/765 (0.00%)  0/99 (0.00%)  0/101 (0.00%) 
Multiple injuries  1  0/765 (0.00%)  0/99 (0.00%)  1/101 (0.99%)  0/765 (0.00%)  0/99 (0.00%)  0/101 (0.00%) 
Road traffic accident  1  0/765 (0.00%)  0/99 (0.00%)  1/101 (0.99%)  0/765 (0.00%)  0/99 (0.00%)  0/101 (0.00%) 
Investigations             
Psychiatric evaluation  1  1/765 (0.13%)  0/99 (0.00%)  0/101 (0.00%)  0/765 (0.00%)  0/99 (0.00%)  0/101 (0.00%) 
Musculoskeletal and connective tissue disorders             
Intervertebral disc protrusion  1  1/765 (0.13%)  0/99 (0.00%)  0/101 (0.00%)  0/765 (0.00%)  0/99 (0.00%)  0/101 (0.00%) 
Rhabdomyolysis  1  1/765 (0.13%)  0/99 (0.00%)  0/101 (0.00%)  0/765 (0.00%)  0/99 (0.00%)  0/101 (0.00%) 
Pain in extremity  1  0/765 (0.00%)  0/99 (0.00%)  1/101 (0.99%)  0/765 (0.00%)  0/99 (0.00%)  0/101 (0.00%) 
Nervous system disorders             
Convulsion  1  1/765 (0.13%)  0/99 (0.00%)  0/101 (0.00%)  1/765 (0.13%)  0/99 (0.00%)  0/101 (0.00%) 
Extrapyramidal disorder  1  1/765 (0.13%)  0/99 (0.00%)  0/101 (0.00%)  0/765 (0.00%)  0/99 (0.00%)  0/101 (0.00%) 
Generalised tonic-clonic seizure  1  0/765 (0.00%)  1/99 (1.01%)  0/101 (0.00%)  0/765 (0.00%)  0/99 (0.00%)  0/101 (0.00%) 
Ischaemic stroke  1  0/765 (0.00%)  1/99 (1.01%)  0/101 (0.00%)  0/765 (0.00%)  0/99 (0.00%)  0/101 (0.00%) 
Psychiatric disorders             
Schizophrenia  1  19/765 (2.48%)  7/99 (7.07%)  5/101 (4.95%)  3/765 (0.39%)  0/99 (0.00%)  0/101 (0.00%) 
Psychotic disorder  1  10/765 (1.31%)  2/99 (2.02%)  2/101 (1.98%)  3/765 (0.39%)  1/99 (1.01%)  0/101 (0.00%) 
Suicidal ideation  1  5/765 (0.65%)  0/99 (0.00%)  0/101 (0.00%)  0/765 (0.00%)  0/99 (0.00%)  0/101 (0.00%) 
Schizophrenia, paranoid type  1  3/765 (0.39%)  0/99 (0.00%)  2/101 (1.98%)  0/765 (0.00%)  0/99 (0.00%)  0/101 (0.00%) 
Drug abuse  1  1/765 (0.13%)  0/99 (0.00%)  0/101 (0.00%)  0/765 (0.00%)  0/99 (0.00%)  0/101 (0.00%) 
Insomnia  1  1/765 (0.13%)  0/99 (0.00%)  0/101 (0.00%)  0/765 (0.00%)  0/99 (0.00%)  0/101 (0.00%) 
Psychotic behaviour  1  1/765 (0.13%)  0/99 (0.00%)  0/101 (0.00%)  0/765 (0.00%)  0/99 (0.00%)  0/101 (0.00%) 
Restlessness  1  1/765 (0.13%)  0/99 (0.00%)  0/101 (0.00%)  0/765 (0.00%)  0/99 (0.00%)  0/101 (0.00%) 
Suicide attempt  1  1/765 (0.13%)  0/99 (0.00%)  0/101 (0.00%)  0/765 (0.00%)  0/99 (0.00%)  0/101 (0.00%) 
Respiratory, thoracic and mediastinal disorders             
Chronic obstructive pulmonary disease  1  0/765 (0.00%)  0/99 (0.00%)  0/101 (0.00%)  0/765 (0.00%)  1/99 (1.01%)  0/101 (0.00%) 
Social circumstances             
Social stay hospitalisation  1  2/765 (0.26%)  0/99 (0.00%)  0/101 (0.00%)  0/765 (0.00%)  0/99 (0.00%)  0/101 (0.00%) 
Victim of crime  1  1/765 (0.13%)  0/99 (0.00%)  0/101 (0.00%)  0/765 (0.00%)  0/99 (0.00%)  0/101 (0.00%) 
Surgical and medical procedures             
Intentional product misuse  1  1/765 (0.13%)  0/99 (0.00%)  0/101 (0.00%)  0/765 (0.00%)  0/99 (0.00%)  0/101 (0.00%) 
1
Term from vocabulary, MedDRA (17.1)
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Cariprazine - Open-label Phase Placebo - Double-blind Treatment Phase Cariprazine - Double-blind Treatment Phase Open-label - Safety Follow-up Phase Placebo - Safety Follow-up Phase Cariprazine - Safety Follow-up Phase
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   425/765 (55.56%)   28/99 (28.28%)   35/101 (34.65%)   0/765 (0.00%)   0/99 (0.00%)   0/101 (0.00%) 
Gastrointestinal disorders             
Constipation  1  39/765 (5.10%)  0/99 (0.00%)  0/101 (0.00%)  0/765 (0.00%)  0/99 (0.00%)  0/101 (0.00%) 
Dyspepsia  1  46/765 (6.01%)  0/99 (0.00%)  0/101 (0.00%)  0/765 (0.00%)  0/99 (0.00%)  0/101 (0.00%) 
Nausea  1  48/765 (6.27%)  0/99 (0.00%)  0/101 (0.00%)  0/765 (0.00%)  0/99 (0.00%)  0/101 (0.00%) 
Diarrhoea  1  0/765 (0.00%)  5/99 (5.05%)  4/101 (3.96%)  0/765 (0.00%)  0/99 (0.00%)  0/101 (0.00%) 
Infections and infestations             
Nasopharyngitis  1  0/765 (0.00%)  5/99 (5.05%)  8/101 (7.92%)  0/765 (0.00%)  0/99 (0.00%)  0/101 (0.00%) 
Investigations             
Weight increased  1  49/765 (6.41%)  0/99 (0.00%)  0/101 (0.00%)  0/765 (0.00%)  0/99 (0.00%)  0/101 (0.00%) 
Nervous system disorders             
Akathisia  1  148/765 (19.35%)  0/99 (0.00%)  0/101 (0.00%)  0/765 (0.00%)  0/99 (0.00%)  0/101 (0.00%) 
Extrapyramidal disorder  1  55/765 (7.19%)  3/99 (3.03%)  6/101 (5.94%)  0/765 (0.00%)  0/99 (0.00%)  0/101 (0.00%) 
Headache  1  92/765 (12.03%)  7/99 (7.07%)  8/101 (7.92%)  0/765 (0.00%)  0/99 (0.00%)  0/101 (0.00%) 
Tremor  1  0/765 (0.00%)  0/99 (0.00%)  8/101 (7.92%)  0/765 (0.00%)  0/99 (0.00%)  0/101 (0.00%) 
Psychiatric disorders             
Anxiety  1  39/765 (5.10%)  0/99 (0.00%)  0/101 (0.00%)  0/765 (0.00%)  0/99 (0.00%)  0/101 (0.00%) 
Insomnia  1  110/765 (14.38%)  8/99 (8.08%)  8/101 (7.92%)  0/765 (0.00%)  0/99 (0.00%)  0/101 (0.00%) 
Restlessness  1  70/765 (9.15%)  0/99 (0.00%)  0/101 (0.00%)  0/765 (0.00%)  0/99 (0.00%)  0/101 (0.00%) 
Schizophrenia  1  0/765 (0.00%)  6/99 (6.06%)  4/101 (3.96%)  0/765 (0.00%)  0/99 (0.00%)  0/101 (0.00%) 
1
Term from vocabulary, MedDRA (17.1)
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
All data generated in this study will be the property of Forest Research Institute, Inc. An integrated clinical and statistical report will be prepared at the completion of the study. Publication of the results by the Investigator will be subject to mutual agreement between the Investigator and Forest Research Institute, Inc.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Therapeutic Area Head
Organization: Allergan
Phone: 714-246-4500
EMail: clinicaltrials@allergan.com
Layout table for additonal information
Responsible Party: Forest Laboratories
ClinicalTrials.gov Identifier: NCT01412060     History of Changes
Other Study ID Numbers: RGH-MD-06
2011-002048-29 ( EudraCT Number )
First Submitted: August 4, 2011
First Posted: August 8, 2011
Results First Submitted: June 5, 2018
Results First Posted: July 6, 2018
Last Update Posted: July 6, 2018