CClinicalTrials.gg
CompletedNCT01058096Updated Apr 17, 2017Results posted

Safety and Efficacy of Cariprazine for Mania

A Phase 3 interventional study of Cariprazine and Placebo in Bipolar Disorder and Mania, sponsored by Forest Laboratories. Completed at 28 sites in 2 countries. Open to participants aged 18 Years to 65 Years. Per ClinicalTrials.gov, last updated 2017-04-17.

Sponsored by Forest Laboratories · Phase 3, Interventional, and Treatment

Phase
Phase 3
Study type
Interventional
Enrollment
323
Allocation
Randomized
Ages
18 Years to 65 Years
Sex
All
01

Study summary

The objective of this study is to evaluate the efficacy, safety, and tolerability of cariprazine monotherapy versus placebo for the treatment of acute manic or mixed episodes associated with bipolar I disorder.

02

Conditions studied

  • Bipolar Disorder
  • Mania

Keywords

  • Acute Mania
  • Bipolar I Disorder
03

Who can participate

Ages eligible
18 Years to 65 Years
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • Patients who have provided informed consent prior to any study specific procedures
  • Patients currently meeting the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) criteria for bipolar I disorder, as confirmed by the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (SCID) manic or mixed type with or without psychotic symptoms
  • Voluntarily hospitalized for current manic episode
  • Patients with normal physical examination, laboratory, vital signs,and/ or electrocardiogram (ECG)

Exclusion criteria

Exclusion Criteria:

  • Patients with a DSM-IV-TR diagnosis of an axis I disorder other than bipolar I disorder that was the primary focus of treatment within the previous six months
04

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Triple (Participant, Investigator, Outcomes assessor)
Enrollment
323 participants (actual)

Study arms

  • Experimental
    Cariprazine

    Cariprazine 3 mg - 12 mg capsules oral administration, once per day for 3 weeks.

    Drug: Cariprazine

  • Placebo comparator
    Placebo

    Placebo dose-matching cariprazine capsules oral administration, once per day for 3 weeks.

    Drug: Placebo

Interventions

  • DrugCariprazine

    Patients who meet eligibility criteria will be administered a once daily oral dose of cariprazine.

  • DrugPlacebo

    Patients who meet eligibility criteria will be administered a once daily oral dose of placebo.

05

What researchers measure

Primary outcomes

  1. Change From Baseline in the Young Mania Rating Scale (YMRS) Total Score at Week 3

    The YMRS is an 11-item scale that assesses manic symptoms based on the participant's perception of his or her condition over the previous 48 hours, as well as the physician's clinical observations during the interview. The 11-items are elevated mood, increased motor activity-energy, sexual interest, sleep, irritability, rate and amount of speech, language-thought disorder, content, disruptive-aggressive behavior, appearance, and insight. The severity of the abnormality for 7-items are rated on a 5-point scale (0-4) and 4-items on a 9-point scale (0-8). The individual scores are summed for a total possible score of 0 (best) to 60 (worst). A negative change from Baseline indicates improvement. Analysis was a mixed model for repeated measurements (MMRM) observed cases (OC), with treatment group, pooled study center, visit, treatment group-by-visit interaction as factors, baseline value and baseline-by-visit interaction as covariates and an unstructured covariance matrix.

    Time frame: Baseline, Week 3

Secondary outcomes

  1. Change From Baseline in Clinical Global Impression-Severity (CGI-S) Total Score at Week 3

    The CGI-S measures the investigator's assessment of overall severity of the participant's illness compared with the severity of illness in other patients the physician has observed using a 7-point scale (1=Normal, not ill at all to 7=Among the most extremely ill participants). A negative change from Baseline indicates improvement. Analysis was based on a MMRM using the observed cases (OC) data, with treatment group, pooled study center, visit, treatment group-by-visit interaction as factors, baseline value and baseline-by-visit interaction as covariates and an unstructured covariance matrix.

    Time frame: Baseline, Week 3

06

Results

Posted Apr 17, 2017
Limitations and caveats
All participants from 1 investigative site are excluded due to GCP violations.

Participant flow

Double-blind Treatment Phase
Participant flow — Double-blind Treatment Phase
MilestonePlaceboCariprazine
Started154158
Completed106108
Not completed4850
Withdrew: Adverse event1115
Withdrew: Insufficient therapeutic response167
Withdrew: Protocol violation21
Withdrew: Withdrawal of consent1726
Withdrew: Lost to follow-up01
Withdrew: Other unspecified20
Safety Follow-up
Participant flow — Safety Follow-up
MilestonePlaceboCariprazine
Started133134
Completed129130
Not completed44

Outcome measures

PrimaryChange From Baseline in the Young Mania Rating Scale (YMRS) Total Score at Week 3

The YMRS is an 11-item scale that assesses manic symptoms based on the participant's perception of his or her condition over the previous 48 hours, as well as the physician's clinical observations during the interview. The 11-items are elevated mood, increased motor activity-energy, sexual interest, sleep, irritability, rate and amount of speech, language-thought disorder, content, disruptive-aggressive behavior, appearance, and insight. The severity of the abnormality for 7-items are rated on a 5-point scale (0-4) and 4-items on a 9-point scale (0-8). The individual scores are summed for a total possible score of 0 (best) to 60 (worst). A negative change from Baseline indicates improvement. Analysis was a mixed model for repeated measurements (MMRM) observed cases (OC), with treatment group, pooled study center, visit, treatment group-by-visit interaction as factors, baseline value and baseline-by-visit interaction as covariates and an unstructured covariance matrix.

Time frame:
Baseline, Week 3
Reported as:
Least squares mean · score on a scale
Change From Baseline in the Young Mania Rating Scale (YMRS) Total Score at Week 3
score on a scalePlaceboCariprazine
Change From Baseline in the Young Mania Rating Scale (YMRS) Total Score at Week 3-15.3 ± 0.9-19.6 ± 0.9
Statistical analysis
  • Placebo vs Cariprazine · Mixed Models Analysis · p = 0.0004 · Least squares mean difference: -4.3 · 95% CI -6.7 to -1.9cariprazine - placebo
SecondaryChange From Baseline in Clinical Global Impression-Severity (CGI-S) Total Score at Week 3

The CGI-S measures the investigator's assessment of overall severity of the participant's illness compared with the severity of illness in other patients the physician has observed using a 7-point scale (1=Normal, not ill at all to 7=Among the most extremely ill participants). A negative change from Baseline indicates improvement. Analysis was based on a MMRM using the observed cases (OC) data, with treatment group, pooled study center, visit, treatment group-by-visit interaction as factors, baseline value and baseline-by-visit interaction as covariates and an unstructured covariance matrix.

Time frame:
Baseline, Week 3
Reported as:
Least squares mean · score on a scale
Change From Baseline in Clinical Global Impression-Severity (CGI-S) Total Score at Week 3
score on a scalePlaceboCariprazine
Change From Baseline in Clinical Global Impression-Severity (CGI-S) Total Score at Week 3-1.3 ± 0.1-1.6 ± 0.1
Statistical analysis
  • Placebo vs Cariprazine · MMRM analysis · p = 0.0027 · Least squares mean difference: -0.4 · 95% CI -0.7 to -0.1cariprazine - placebo

Adverse events

Collected over First dose of study drug to 30 days past last dose (Up to 51 days). Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Placebo—5/154 (3.2%)69/154 (44.8%)
Cariprazine—6/158 (3.8%)110/158 (69.6%)
Most frequent serious events
Most frequent serious events
EventPlaceboCariprazine
ManiaPsychiatric disorders1/1543/158
Hepatitis EInfections and infestations1/1540/158
Social stay hospitalisationSocial circumstances1/1540/158
Bipolar disorderPsychiatric disorders1/1540/158
Non-cardiac chest painGeneral disorders1/1540/158
AkathisiaNervous system disorders0/1541/158
ConvulsionNervous system disorders0/1541/158
Suicidal ideationPsychiatric disorders0/1541/158
Most frequent other events
Showing 10 of 15
Most frequent other events
EventPlaceboCariprazine
AkathisiaNervous system disorders8/15435/158
Extrapyramidal DisorderNervous system disorders3/15424/158
TremorNervous system disorders9/15419/158
HeadacheNervous system disorders16/15418/158
DyspepsiaGastrointestinal disorders7/15417/158
NauseaGastrointestinal disorders10/15416/158
VomitingGastrointestinal disorders7/15416/158
ConstipationGastrointestinal disorders10/15414/158
DizzinessNervous system disorders6/15414/158
DiarrhoeaGastrointestinal disorders6/15411/158

Baseline characteristics

Safety Population included all randomized participants who took at least 1 dose of double-blind investigational product.

Age, Continuous
Age, Continuous(years)PlaceboCariprazineTotal
Mean36.7 ± 11.835.8 ± 11.436.3 ± 11.5
Sex: Female, Male
Sex: Female, Male(Participants)PlaceboCariprazineTotal
Female5953112
Male95105200
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)PlaceboCariprazineTotal
Hispanic or Latino5510
Not Hispanic or Latino149153302
Unknown or Not Reported000
Race/Ethnicity, Customized
Race/Ethnicity, Customized(Participants)PlaceboCariprazineTotal
White333366
Black/African American293362
Asian8891179
American Indian or Alaska Native303
Other112
Weight
Weight(kilogram (kg))PlaceboCariprazineTotal
Mean71.86 ± 20.2769.55 ± 20.0670.69 ± 20.17
Height
Height(centimeter (cm))PlaceboCariprazineTotal
Mean166.39 ± 10.64165.21 ± 10.68165.79 ± 10.66
Body Mass Index (BMI)
Body Mass Index (BMI)(kg/meter(m)^2)PlaceboCariprazineTotal
Mean25.73 ± 5.9825.24 ± 5.9825.48 ± 5.98
07

Study locations

28 sites
  • Forest Investigative Site 004
    Long Beach, California 90813, United States
  • Forest Investigative Site 005
    Riverside, California 92506, United States
  • Forest Investigative Site 007
    San Diego, California 92123, United States
  • Forest Investigative Site 009
    Chicago, Illinois 60640, United States
  • Forest Investigative Site 006
    Lake Charles, Louisiana 70601, United States
  • Forest Investigative Site 001
    Flowood, Mississippi 39232, United States
  • Forest Investigative Site 003
    Creve Couer, Missouri 63141, United States
  • Forest Investigative Site 008
    Cleveland, Ohio 44109, United States
  • Forest Investigative Site 010
    Oklahoma City, Oklahoma 73116, United States
  • Forest Investigative Site 002
    Houston, Texas 77008, United States
  • Forest Investigative Site 106
    Vijayawada, Andhra Pradesh 520002, India
  • Forest Investigative Site 112
    Vizag, Andhra Pradesh 530017, India
  • Forest Investigator Site 108
    Varanasi, Durgakund 221005, India
  • Forest Investigative Site 103
    Ahmedabad, Gujarat 380013, India
  • Forest Investigative Site 120
    Ahmedabad, Gujarat 380015, India
  • Forest Investigative Site 105
    Bangalore, Karnataka 560010, India
  • Forest Investigative Site 107
    Bangalore, Karnataka 560027, India
  • Forest Investigative Site 118
    Mangalore, Karnataka 575001, India
  • Forest Investigative Site 113
    Mangalore, Karnataka 575018, India
  • Forest Investigative Site 115
    Manipal, Karnataka 576104, India
  • Forest Investigative Site 114
    Mysore, Karnataka 570004, India
  • Forest Investigative Site 101
    Aurangabad, Maharashtra 431005, India
  • Forest Investigative Site 110
    Nasik, Maharashtra 422101, India
  • Forest Investigative Site 111
    Pune, Maharashtra 411004, India
  • Forest Investigative Site 104
    Pune, Maharashtra 411030, India
  • Forest Investigative Site 121
    Chennai, Tamilnadu 600003, India
  • Forest Investigative Site 109
    Kanpur, Uttar Pradesh 200005, India
  • Forest Investigative Site 119
    Lucknow, Uttar Pradesh 226006, India
08

References and documents

Publications

  • McIntyre RS, Masand PS, Earley W, Patel M. Cariprazine for the treatment of bipolar mania with mixed features: A post hoc pooled analysis of 3 trials. J Affect Disord. 2019 Oct 1;257:600-606. doi: 10.1016/j.jad.2019.07.020. Epub 2019 Jul 5. PubMed 31344528 ↗
  • Earley W, Durgam S, Lu K, Ruth A, Nemeth G, Laszlovszky I, Yatham LN. Clinically relevant response and remission outcomes in cariprazine-treated patients with bipolar I disorder. J Affect Disord. 2018 Jan 15;226:239-244. doi: 10.1016/j.jad.2017.09.040. Epub 2017 Sep 25. PubMed 29017067 ↗
09

Registry details

Key details

Study ID
NCT01058096
Lead sponsor
Forest Laboratories
Collaborators
Gedeon Richter Ltd.
Responsible party
Sponsor
First posted
Jan 28, 2010
Start date
Feb 2010
Primary completion
Jul 2011
Completion
Jul 2011
Results posted
Apr 17, 2017
Last update
Apr 17, 2017

Study contacts

Elizabeth Diaz, MD
study director · Forest Laboratories

Oversight

Data monitoring committee
No
View the source record on ClinicalTrials.gov ↗

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