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Lurasidone Pediatric Bipolar Study (Illuminate)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02046369
Recruitment Status : Completed
First Posted : January 27, 2014
Results First Posted : December 20, 2017
Last Update Posted : December 20, 2017
Sponsor:
Information provided by (Responsible Party):
Sunovion

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Bipolar I Depression
Interventions Drug: Lurasidone
Drug: Placebo
Enrollment 350
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Luradisone Placebo
Hide Arm/Group Description

Luradisone 20- 80 mg administered once daily

Lurasidone: Lurasidone flexibly dosed 20-80 mg once daily

Placebo administered once daily

Placebo: Placebo Comparator once daily

Period Title: Overall Study
Started 176 174
Completed 162 156
Not Completed 14 18
Reason Not Completed
Adverse Event             3             3
Lack of Efficacy             3             3
Lost to Follow-up             3             3
Protocol Violation             1             2
Withdrawal by Subject             3             6
never received study drug             0             1
non compliance             1             0
Arm/Group Title Luradisone Placebo Total
Hide Arm/Group Description

Luradisone 20- 80 mg administered once daily

Lurasidone: Lurasidone flexibly dosed 20-80 mg once daily

Placebo administered once daily

Placebo: Placebo Comparator once daily

Total of all reporting groups
Overall Number of Baseline Participants 175 172 347
Hide Baseline Analysis Population Description
Baseline analysis was done on the safety population, which has 347 subjects
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 175 participants 172 participants 347 participants
<=18 years
175
 100.0%
172
 100.0%
347
 100.0%
Between 18 and 65 years
0
   0.0%
0
   0.0%
0
   0.0%
>=65 years
0
   0.0%
0
   0.0%
0
   0.0%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 175 participants 172 participants 347 participants
14.2  (2.18) 14.3  (2.01) 14.2  (2.11)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 175 participants 172 participants 347 participants
Female
87
  49.7%
83
  48.3%
170
  49.0%
Male
88
  50.3%
89
  51.7%
177
  51.0%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 175 participants 172 participants 347 participants
Hispanic or Latino
0
   0.0%
0
   0.0%
0
   0.0%
Not Hispanic or Latino
175
 100.0%
172
 100.0%
347
 100.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 175 participants 172 participants 347 participants
American Indian or Alaska Native
2
   1.1%
0
   0.0%
2
   0.6%
Asian
7
   4.0%
4
   2.3%
11
   3.2%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
16
   9.1%
20
  11.6%
36
  10.4%
White
135
  77.1%
125
  72.7%
260
  74.9%
More than one race
15
   8.6%
23
  13.4%
38
  11.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 175 participants 172 participants 347 participants
Colombia 7 7 14
South Korea 4 3 7
Hungary 5 5 10
United States 75 75 150
Philippines 2 0 2
Ukraine 33 33 66
Poland 2 3 5
Mexico 16 17 33
Bulgaria 9 8 17
France 1 0 1
Russia 21 21 42
Psychiatric History  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 175 participants 172 participants 347 participants
12.44  (2.790) 12.17  (2.680) 12.30  (2.735)
Bipolar I disorder history   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 175 participants 172 participants 347 participants
Without rapid cycling (0-3 cycles past 12 months 149 147 296
Without rapid cycling(4-7 cycles past 12 months 26 24 50
With 8 or more cycles within past 12 months 0 1 1
[1]
Measure Description: the number of participants with the number of cycles in the past 12 months is measured.
1.Primary Outcome
Title Change in the Children's Depression Rating Scale, Revised (CDRS-R) Total Score as Compared to Placebo From Double-Blind Baseline to Week 6 (Day 43) Baseline
Hide Description

CDRS-R total score: changes from baseline over time - mixed model for repeated measures. LS Mean and SE for change from baseline are based on Mixed Model for Repeated Measures.

The CDRS-R total score ranges from 17-113. In general, higher values of CDRS-R total score represent greater severity of illness.

The primary efficacy endpoint will be assessed between the placebo and treatment group.

Time Frame baseline, Week 6
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT population includes all randomized subjects who received at least one dose of study medication and had at least one post-baseline assessment in any efficacy variable
Arm/Group Title Luradisone Placebo
Hide Arm/Group Description:

Luradisone 20- 80 mg administered once daily

Lurasidone: Lurasidone flexibly dosed 20-80 mg once daily

Placebo administered once daily

Placebo: Placebo Comparator once daily

Overall Number of Participants Analyzed 173 170
Least Squares Mean (Standard Deviation)
Unit of Measure: units on a scale
baseline 59.2  (8.24) 58.6  (8.26)
week 6 -21.0  (1.06) -15.3  (1.08)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Luradisone, Placebo
Comments A mean difference in change from Baseline in CDRS-R total score of 5.0 units was assumed for the lurasidone 20-80 mg/day arm over the placebo arm, and a common standard deviation of 14.2 units (effect size=0.35), a sample size of 145 subjects per treatment arm was calculated to yield a power of 85%. With an expected attrition rate of 15%, approximately 170 subjects per treatment arm (340 in total) were to be randomized in a 1:1 ratio .
Type of Statistical Test Superiority
Comments The primary efficacy endpoint (the change from baseline in CDRS-R total score at Week 6)will be analyzed using a likelihood-based mixed model for repeated measures (MMRM).The response (dependent) variable is the change from baseline in CDRS-R total score assessed weekly (Weeks 1 to 6).The MMRM model includes fixed effects terms for treatment, visit (as a categorical variable), pooled country, age stratum (stratification factor, CDRS-R total score at baseline, and treatment-by-visit interaction.
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method LS mean differnece (SE)
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean differnce (SE)
Estimated Value -5.7
Confidence Interval (2-Sided) 95%
-8.4 to -3.0
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.39
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Change From Baseline in Pediatric Anxiety Rating Scale (PARS) Score as Compared to Placebo.
Hide Description PARS score: changes from baseline over time - mixed model for repeated measures-LS Mean and SE for change from baseline are based on Mixed Model for Repeated Measures.The PARS is a clinician-rated instrument for assessing over time the severity of anxiety symptoms associated with common DSM-IV anxiety disorders in children ages 6‑17 years. The PARS is administered separately to the subject and to the caregiver. The instrument has 2 sections. The first section includes a 50-item symptom checklist, which the clinician rates as present or absent during the past week. The second section is comprised of 7 severity impairment items reflecting the severity/impairment of all symptoms endorsed in Section 1 of the PARS (during the past week). Each question is answered on a 0-5 Likert scale (0 for none, and 1-5 for minimal to extreme) with alternative responses of 8=Not Applicable and 9=Does Not Know. The PAR total score over all 7 questions ranges in value from 0 to 35.
Time Frame baseline and week 6
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT population included all randomized subjects who received at least one dose of study medication and had at least one post-baseline assessment in any efficacy variable
Arm/Group Title Luradisone Placebo
Hide Arm/Group Description:

Luradisone 20- 80 mg administered once daily

Lurasidone: Lurasidone flexibly dosed 20-80 mg once daily

Placebo administered once daily

Placebo: Placebo Comparator once daily

Overall Number of Participants Analyzed 173 170
Least Squares Mean (Standard Deviation)
Unit of Measure: units on a scale
baseline 10.9  (7.72) 11.5  (7.60)
week 6 -3.4  (0.44) -2.3  (0.45)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Luradisone, Placebo
Comments LS mean difference, and the associated 95% CI and p-value for change from baseline are based on Mixed Model for Repeated Measures (MMRM).
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0385
Comments [Not Specified]
Method LS mean differnece (SE)
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean differnce (SE)
Estimated Value -1.1
Confidence Interval (2-Sided) 95%
-2.2 to -0.1
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.54
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Change From Baseline in Pediatric Quality of Life Enjoyment and Satisfaction Questionnaire (PQ-LES-Q) Score as Compared to Placebo.
Hide Description

PQ-LES-Q percentage maximum possible score: changes from baseline over time - mixed model for repeated measures

LS Mean and SE for change from baseline are based on Mixed Model for Repeated Measures

Time Frame baseline
Hide Outcome Measure Data
Hide Analysis Population Description
the ITT population included all randomized subjects who received at least one dose of study medication and had at least one post-baseline assessment on any efficacy variable
Arm/Group Title Luradisone Placebo
Hide Arm/Group Description:

Luradisone 20- 80 mg administered once daily

Lurasidone: Lurasidone flexibly dosed 20-80 mg once daily

Placebo administered once daily

Placebo: Placebo Comparator once daily

Overall Number of Participants Analyzed 173 169
Least Squares Mean (Standard Deviation)
Unit of Measure: units on a scale
baseline 49.6  (15.49) 49.7  (17.31)
week 6 11.8  (1.10) 7.9  (1.13)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Luradisone, Placebo
Comments LS mean difference, and the associated 95% CI and p-value for change from baseline are based on Mixed Model for Repeated Measures (MMRM).
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0044
Comments [Not Specified]
Method LS mean differnece (SE)
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean differnce (SE)
Estimated Value 3.9
Confidence Interval (2-Sided) 95%
1.2 to 6.5
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.35
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Change From Baseline in Clinician-rated Children’s Global Assessment Scale (CGAS) Score as Compared to Placebo.
Hide Description CGAS Score: changes from baseline over time - mixed model for repeated measures. LS Mean and SE for change from baseline are based on Mixed Model for Repeated Measures. LS Mean and SE for change from baseline are based on Mixed Model for Repeated Measures
Time Frame baseline and week 6
Hide Outcome Measure Data
Hide Analysis Population Description
the ITT population included all randomized subjects who received at least one dose of study medication and had at least one post-baseline assessment in any efficacy variable
Arm/Group Title Luradisone Placebo
Hide Arm/Group Description:

Luradisone 20- 80 mg administered once daily

Lurasidone: Lurasidone flexibly dosed 20-80 mg once daily

Placebo administered once daily

Placebo: Placebo Comparator once daily

Overall Number of Participants Analyzed 173 170
Least Squares Mean (Standard Deviation)
Unit of Measure: units on a scale
baseline 48.8  (8.73) 49.5  (6.99)
week 6 14.0  (0.96) 9.3  (0.99)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Luradisone, Placebo
Comments LS mean difference, and the associated 95% CI and p-value for change from baseline are based on Mixed Model for Repeated Measures (MMRM).
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method LS mean differnece (SE)
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean differnce (SE)
Estimated Value 4.7
Confidence Interval (2-Sided) 95%
2.4 to 7.0
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.19
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Change From Baseline in Attention-Deficit/Hyperactivity Disorder Rating Scale (ADHD-RS) Score as Compared to Placebo.
Hide Description ADHD-RS total score: changes from baseline over time -ANCOVA-LS Mean and SE for change from baseline are based on ANCOVA. The Pediatric Quality of Life Enjoyment and Satisfaction Questionnaire (PQ-LES-Q is a 15-item self-report measure of the degree of enjoyment and satisfaction in various areas of daily living, based on the content of the Short From of the Q-LES-Q. Each item is rated on a 5-point scale, ranging from 1 (very poor) to 5 (very good). The first 14 items are the same as the General Activities section of the regular Q-LES-Q form and are used to compute the raw score. The PQ-LES-Q-SF percentage maximum possible score is calculated as follows:% Max = 100 × (Raw Score – Minimum Score) / (Maximum Score – Minimum Score),where the Minimum Score equals 14 and the Maximum Score equals 70, and the % maximum possible score can range from 0% to 100%. Higher scores indicate better quality of life.
Time Frame baseline and week 6
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT population included all randomized subjects who received at least one dose of study medication and had at least one post-baseline assessment in any efficacy variable
Arm/Group Title Luradisone Placebo
Hide Arm/Group Description:

Luradisone 20- 80 mg administered once daily

Lurasidone: Lurasidone flexibly dosed 20-80 mg once daily

Placebo administered once daily

Placebo: Placebo Comparator once daily

Overall Number of Participants Analyzed 173 167
Least Squares Mean (Standard Deviation)
Unit of Measure: units on a scale
baseline 11.8  (10.85) 12.3  (11.62)
week 6 -2.6  (7.26) -2.0  (7.61)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Luradisone, Placebo
Comments LS mean difference, and the associated 95% CI and p-value for change from baseline are based on Mixed Model for Repeated Measures (MMRM).
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3715
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean differnce (SE)
Estimated Value -0.7
Confidence Interval (2-Sided) 95%
-2.2 to 0.8
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.77
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Change From Baseline in Clinical Global Impressions-Bipolar-Severity (CGI-BP-S) Depression Score
Hide Description Change from baseline in Clinical Global Impressions-Bipolar-Severity (CGI-BP-S) depression score changes from baseline over time - mixed model for repeated measures. LS Mean and SE for change from baseline are based on Mixed Model for Repeated Measures.The CGI-BP-S is a three-question clinician-rated assessment of the subject’s current illness state (depression, mania, and overall) using a 7-point scale (1(normal, not ill) to 7 (very severely ill)) for each question, where a higher score is associated with greater illness severity.
Time Frame baseline and week 6
Hide Outcome Measure Data
Hide Analysis Population Description
the ITT population included all randomized subjects who received at least one dose of study medication and had at least one post-baseline assessment in any efficacy variable
Arm/Group Title Luradisone Placebo
Hide Arm/Group Description:

Luradisone 20- 80 mg administered once daily

Lurasidone: Lurasidone flexibly dosed 20-80 mg once daily

Placebo administered once daily

Placebo: Placebo Comparator once daily

Overall Number of Participants Analyzed 173 170
Least Squares Mean (Standard Deviation)
Unit of Measure: units on a scale
baseline 4.6  (0.65) 4.5  (0.57)
week 6 -1.49  (0.085) -1.05  (0.087)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Luradisone, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments LS mean difference, and the associated 95% CI and p-value for change from baseline are based on Mixed Model for Repeated Measures (MMRM).
Method LS mean differnece (SE)
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean differnce (SE)
Estimated Value -0.44
Confidence Interval (2-Sided) 95%
-0.66 to -0.22
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.112
Estimation Comments [Not Specified]
Time Frame Through study completion. Treatment emergent adverse event (TEAE) is defined as an AE with a start date on or after the date of first does through 7 days after study drug discontinuation (14 days for serious adverse events and deaths) for subjects who complete the double blind study but do not enter the extension study or early discontinue during the double blind study), or through the last study day of the double blind period for subjects continuing into the extension study
Adverse Event Reporting Description number of participants at risk is equal to the number of patients in the safety population (172 in placebo and 175 in lurasidone)
 
Arm/Group Title Luradisone Placebo
Hide Arm/Group Description

Luradisone 20- 80 mg administered once daily

Lurasidone: Lurasidone flexibly dosed 20-80 mg once daily

Placebo administered once daily

Placebo: Placebo Comparator once daily

All-Cause Mortality
Luradisone Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Luradisone Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   2/175 (1.14%)      4/172 (2.33%)    
Injury, poisoning and procedural complications     
humerus fracture  1  1/175 (0.57%)  1 0/172 (0.00%)  0
Pregnancy, puerperium and perinatal conditions     
abortion spontaneous  1  0/175 (0.00%)  0 1/172 (0.58%)  1
Psychiatric disorders     
Bipolar I disorder  1  1/175 (0.57%)  1 1/172 (0.58%)  1
depression  1  0/175 (0.00%)  0 1/172 (0.58%)  1
psychotic disorder  1  0/175 (0.00%)  0 1/172 (0.58%)  1
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (16.0)
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Luradisone Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   112/175 (64.00%)      75/172 (43.60%)    
Gastrointestinal disorders     
nausea  1  28/175 (16.00%)  35 10/172 (5.81%)  13
vomiting  1  11/175 (6.29%)  15 6/172 (3.49%)  8
Infections and infestations     
nasopharyngitis  1  7/175 (4.00%)  7 10/172 (5.81%)  10
Investigations     
weight increased  1  12/175 (6.86%)  12 3/172 (1.74%)  3
Nervous system disorders     
headache  1  25/175 (14.29%)  30 26/172 (15.12%)  38
somnolence  1  16/175 (9.14%)  20 8/172 (4.65%)  9
dizziness  1  10/175 (5.71%)  12 8/172 (4.65%)  8
Psychiatric disorders     
insomnia  1  9/175 (5.14%)  9 4/172 (2.33%)  4
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (16.0)
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.
In the event the Study is part of a multi-center study, the first publication of the results of the Study shall be made in conjunction with the results of other participating study sites as a multi-center publication; provided however, if a multi-center publication is not forthcoming within twenty-four (24) months following completion of the Study at all sites, Institution and Investigator shall be free to publish.
Results Point of Contact
Name/Title: CNS Medical Director
Organization: Sunovion Pharmaceuticals Inc.
Phone: 1-866-503-6351
Responsible Party: Sunovion
ClinicalTrials.gov Identifier: NCT02046369     History of Changes
Other Study ID Numbers: D1050326
2013-004903-37 ( EudraCT Number )
First Submitted: January 23, 2014
First Posted: January 27, 2014
Results First Submitted: September 13, 2017
Results First Posted: December 20, 2017
Last Update Posted: December 20, 2017