Clinical Trial Results:
A 50-Week Open-Label, Flexible-Dose Trial of Asenapine Extension Treatment to P06107 in Pediatric Subjects with Acute Manic or Mixed Episodes Associated With Bipolar I Disorder
Summary
|
|
EudraCT number |
2010-022648-19 |
Trial protocol |
Outside EU/EEA |
Global end of trial date |
05 Sep 2014
|
Results information
|
|
Results version number |
v2(current) |
This version publication date |
29 Sep 2016
|
First version publication date |
11 Mar 2015
|
Other versions |
v1 |
Version creation reason |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
|
|||
Trial identification
|
|||
Sponsor protocol code |
P05898
|
||
Additional study identifiers
|
|||
ISRCTN number |
- | ||
US NCT number |
NCT01349907 | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
|
|||
Sponsor organisation name |
Merck Sharp & Dohme Corp.
|
||
Sponsor organisation address |
2000 Galloping Hill Road, Kenilworth, NJ, United States, 07033
|
||
Public contact |
Clinical Trials Disclosure, Merck Sharp & Dohme Corp., ClinicalTrialsDisclosure@merck.com
|
||
Scientific contact |
Clinical Trials Disclosure, Merck Sharp & Dohme Corp., ClinicalTrialsDisclosure@merck.com
|
||
Paediatric regulatory details
|
|||
Is trial part of an agreed paediatric investigation plan (PIP) |
Yes
|
||
EMA paediatric investigation plan number(s) |
EMEA-000228-PIP01-08 | ||
Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
|
||
Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
Yes
|
||
Results analysis stage
|
|||
Analysis stage |
Final
|
||
Date of interim/final analysis |
05 Sep 2014
|
||
Is this the analysis of the primary completion data? |
Yes
|
||
Primary completion date |
05 Sep 2014
|
||
Global end of trial reached? |
Yes
|
||
Global end of trial date |
05 Sep 2014
|
||
Was the trial ended prematurely? |
No
|
||
General information about the trial
|
|||
Main objective of the trial |
This study will investigate the safety and tolerability of a flexible dosing regimen of asenapine for the long term treatment of manic or mixed episodes associated with bipolar I disorder in children and adolescents who completed the 3-week treatment base trial P06107 (NCT01244815).
|
||
Protection of trial subjects |
This study was conducted in conformance with Good Clinical practice standards and applicable country and/or local statutes and regulations regarding ethical committee review, informed consent, and the protection of human subjects participating in biomedical research. The following additional measures defined for this individual study were in place for the protection of trial subjects: For participants whose symptoms worsen or are not adequately controlled on assigned treatment, rescue medication may be administered during the trial in the following circumstances. For the control of agitation, anxiety, insomnia, restlessness, or akathisia and extrapyramidal symptoms (EPS) some benzodiazepines (i.e. lorazepam up to 4 mg/day or an equivalent dose of short-acting benzodiazepines) and EPS medications (i.e. anticholinergics) are allowed. Benadryl (dipenhydramine) and beta blockers are also permitted, provided that they are not taken within 8 hours of efficacy assessments.
|
||
Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
16 Jun 2011
|
||
Long term follow-up planned |
No
|
||
Independent data monitoring committee (IDMC) involvement? |
Yes
|
||
Population of trial subjects
|
|||
Number of subjects enrolled per country |
|||
Country: Number of subjects enrolled |
United States: 303
|
||
Country: Number of subjects enrolled |
Russian Federation: 19
|
||
Worldwide total number of subjects |
322
|
||
EEA total number of subjects |
0
|
||
Number of subjects enrolled per age group |
|||
In utero |
0
|
||
Preterm newborn - gestational age < 37 wk |
0
|
||
Newborns (0-27 days) |
0
|
||
Infants and toddlers (28 days-23 months) |
0
|
||
Children (2-11 years) |
53
|
||
Adolescents (12-17 years) |
268
|
||
Adults (18-64 years) |
1
|
||
From 65 to 84 years |
0
|
||
85 years and over |
0
|
|
|||||||||||||||||||||||||||||||
Recruitment
|
|||||||||||||||||||||||||||||||
Recruitment details |
- | ||||||||||||||||||||||||||||||
Pre-assignment
|
|||||||||||||||||||||||||||||||
Screening details |
Participants were chosen from children and adolescents with a manic or mixed episode associated with bipolar I disorder who completed the 3-week efficacy and safety base trial P06107. | ||||||||||||||||||||||||||||||
Period 1
|
|||||||||||||||||||||||||||||||
Period 1 title |
Overall trial (overall period)
|
||||||||||||||||||||||||||||||
Is this the baseline period? |
Yes | ||||||||||||||||||||||||||||||
Allocation method |
Non-randomised - controlled
|
||||||||||||||||||||||||||||||
Blinding used |
Not blinded | ||||||||||||||||||||||||||||||
Arms
|
|||||||||||||||||||||||||||||||
Are arms mutually exclusive |
Yes
|
||||||||||||||||||||||||||||||
Arm title
|
Placebo/Asenapine | ||||||||||||||||||||||||||||||
Arm description |
Participants treated with placebo in base trial P06107 were first treated with open-label flavored asenapine 2.5 mg twice per day (BID), then up-titrated to 5 mg BID at Day 4, then up-titrated to 10 mg BID at Day 7. After Day 7, flexible dosing of asenapine was continued for up to 50 weeks. | ||||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||||
Investigational medicinal product name |
Rescue medication
|
||||||||||||||||||||||||||||||
Investigational medicinal product code |
|||||||||||||||||||||||||||||||
Other name |
|||||||||||||||||||||||||||||||
Pharmaceutical forms |
Tablet
|
||||||||||||||||||||||||||||||
Routes of administration |
Oral use
|
||||||||||||||||||||||||||||||
Dosage and administration details |
For participants whose symptoms worsen or are not adequately controlled on assigned treatment, rescue medication may be administered during the trial in the following circumstances. For the control of agitation, anxiety, insomnia, restlessness, or akathisia and extrapyramidal symptoms (EPS) some benzodiazepines (i.e. lorazepam up to 4 mg/day or an equivalent dose of short-acting benzodiazepines) and EPS medications (i.e. anticholinergics) are allowed. Benadryl (dipenhydramine) and beta blockers are also permitted, provided that they are not taken within 8 hours of efficacy assessments.
|
||||||||||||||||||||||||||||||
Investigational medicinal product name |
Asenapine
|
||||||||||||||||||||||||||||||
Investigational medicinal product code |
|||||||||||||||||||||||||||||||
Other name |
|||||||||||||||||||||||||||||||
Pharmaceutical forms |
Sublingual tablet
|
||||||||||||||||||||||||||||||
Routes of administration |
Oral use
|
||||||||||||||||||||||||||||||
Dosage and administration details |
One flavored asenapine sublingual tablet BID (either 2.5, 5 or 10 mg) starting at 2.5 mg on Day 1 for three consecutive days. Normally on Day 4, the dose will increase to 5 mg BID beginning with the evening dose. Normally on Day 7, the dose will increase to 10 mg BID beginning with the evening dose. The dose may be up-titrated earlier than Days 4 and 7 at the investigator's discretion. Beginning on Day 8 (or after at least 1 day on 10 mg asenapine BID) dosing will be flexible (2.5, 5, or 10 mg BID) until up to Week 50.
|
||||||||||||||||||||||||||||||
Arm title
|
Asenapine/Asenapine | ||||||||||||||||||||||||||||||
Arm description |
Participants treated with asenapine in base trial P06107 were first treated with open-label flavored asenapine 2.5 mg BID, then up-titrated to 5 mg BID at Day 4, then up-titrated to 10 mg BID at Day 7. After Day 7, flexible dosing of asenapine was continued for up to 50 weeks. | ||||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||||
Investigational medicinal product name |
Asenapine
|
||||||||||||||||||||||||||||||
Investigational medicinal product code |
|||||||||||||||||||||||||||||||
Other name |
|||||||||||||||||||||||||||||||
Pharmaceutical forms |
Sublingual tablet
|
||||||||||||||||||||||||||||||
Routes of administration |
Oral use
|
||||||||||||||||||||||||||||||
Dosage and administration details |
One flavored asenapine sublingual tablet BID (either 2.5, 5 or 10 mg) starting at 2.5 mg on Day 1 for three consecutive days. Normally on Day 4, the dose will increase to 5 mg BID beginning with the evening dose. Normally on Day 7, the dose will increase to 10 mg BID beginning with the evening dose. The dose may be up-titrated earlier than Days 4 and 7 at the investigator's discretion. Beginning on Day 8 (or after at least 1 day on 10 mg asenapine BID) dosing will be flexible (2.5, 5, or 10 mg BID) until up to Week 50.
|
||||||||||||||||||||||||||||||
Investigational medicinal product name |
Rescue medication
|
||||||||||||||||||||||||||||||
Investigational medicinal product code |
|||||||||||||||||||||||||||||||
Other name |
|||||||||||||||||||||||||||||||
Pharmaceutical forms |
Tablet
|
||||||||||||||||||||||||||||||
Routes of administration |
Oral use
|
||||||||||||||||||||||||||||||
Dosage and administration details |
For participants whose symptoms worsen or are not adequately controlled on assigned treatment, rescue medication may be administered during the trial in the following circumstances. For the control of agitation, anxiety, insomnia, restlessness, or akathisia and extrapyramidal symptoms (EPS) some benzodiazepines (i.e. lorazepam up to 4 mg/day or an equivalent dose of short-acting benzodiazepines) and EPS medications (i.e. anticholinergics) are allowed. Benadryl (dipenhydramine) and beta blockers are also permitted, provided that they are not taken within 8 hours of efficacy assessments.
|
||||||||||||||||||||||||||||||
|
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Baseline characteristics reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo/Asenapine
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Participants treated with placebo in base trial P06107 were first treated with open-label flavored asenapine 2.5 mg twice per day (BID), then up-titrated to 5 mg BID at Day 4, then up-titrated to 10 mg BID at Day 7. After Day 7, flexible dosing of asenapine was continued for up to 50 weeks. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Asenapine/Asenapine
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Participants treated with asenapine in base trial P06107 were first treated with open-label flavored asenapine 2.5 mg BID, then up-titrated to 5 mg BID at Day 4, then up-titrated to 10 mg BID at Day 7. After Day 7, flexible dosing of asenapine was continued for up to 50 weeks. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|||
End points reporting groups
|
|||
Reporting group title |
Placebo/Asenapine
|
||
Reporting group description |
Participants treated with placebo in base trial P06107 were first treated with open-label flavored asenapine 2.5 mg twice per day (BID), then up-titrated to 5 mg BID at Day 4, then up-titrated to 10 mg BID at Day 7. After Day 7, flexible dosing of asenapine was continued for up to 50 weeks. | ||
Reporting group title |
Asenapine/Asenapine
|
||
Reporting group description |
Participants treated with asenapine in base trial P06107 were first treated with open-label flavored asenapine 2.5 mg BID, then up-titrated to 5 mg BID at Day 4, then up-titrated to 10 mg BID at Day 7. After Day 7, flexible dosing of asenapine was continued for up to 50 weeks. |
|
|||||||||||||
End point title |
Number of participants who experienced clinical or laboratory adverse events [1] | ||||||||||||
End point description |
A clinical or laboratory adverse event is any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to this medicinal product. Participants analyzed received at least one dose of trial medication, and were 17 years old or younger. One treated participant from the Placebo/Asenapine group, who was 18 years old, was excluded from this analysis.
|
||||||||||||
End point type |
Primary
|
||||||||||||
End point timeframe |
Day 1 of treatment to 30 days after the last dose of study drug (up to approximately 54 weeks)
|
||||||||||||
Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical analysis was planned or performed for this primary endpoint; or for any other endpoint in this study. |
|||||||||||||
|
|||||||||||||
Notes [2] - One participant who was 18 years old was excluded from this analysis. |
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Change from baseline in Young Mania Rating Scale (Y-MRS) total score at Day 182 | ||||||||||||
End point description |
The Y-MRS assesses the severity of manic episodes by assigning a severity rating to each of 11 items (Elevated mood, Increased motor activity-energy, Sexual interest, Sleep, Irritability, Speech, Language-thought disorder, Thought content, Disruptive-aggressive behavior, Appearance, Insight). Seven of the 11 items are rated on a scale of 0-4, and 4 of the items are rated on a scale of 0-8. The Y-MRS total score, observed cases (OC), the assessment closest to the scheduled assessment day within the allowed window, is the sum of the ratings for the 11 individual items, and can range from 0-60, with higher scores indicating greater severity of symptoms. Improvement in symptoms is represented by change from baseline values that are negative. The Full Analysis Set (FAS) is analyzed consisting of participants 17 years old or younger, who have taken at least one dose of trial medication, and have a baseline and at least one post-baseline Y-MRS assessment.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline and Day 182
|
||||||||||||
|
|||||||||||||
Notes [3] - Full Analysis Set (FAS) [4] - FAS |
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Change from baseline in Y-MRS total score at Day 350 | ||||||||||||
End point description |
The Y-MRS assesses the severity of manic episodes by assigning a severity rating to each of 11 items (Elevated mood, Increased motor activity-energy, Sexual interest, Sleep, Irritability, Speech, Language-thought disorder, Thought content, Disruptive-aggressive behavior, Appearance, Insight). Seven of the 11 items are rated on a scale of 0-4, and 4 of the items are rated on a scale of 0-8. The Y-MRS total score, OC, is the sum of the ratings for the 11 individual items, and can range from 0-60, with higher scores indicating greater severity of symptoms. Improvement in symptoms is represented by change from baseline values that are negative. The FAS is analyzed consisting of participants 17 years old or younger, who have taken at least one dose of trial medication, and have a baseline and at least one post-baseline Y-MRS assessment.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline and Day 350
|
||||||||||||
|
|||||||||||||
Notes [5] - FAS at Day 350 [6] - FAS at Day 350 |
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Percentage of participants who were Y-MRS total score remitters (Y-MRS =<12) at Day 182 | ||||||||||||
End point description |
The Y-MRS is an 11-item clinician-rated instrument for assessing the severity of manic episodes. The Y-MRS total score, OC for each participant is the sum of the ratings for the 11 individual items, and can range from 0-60, with higher scores indicating greater severity of symptoms. A remitter is a participant with a Y-MRS total score of 12 or lower. The FAS is analyzed consisting of participants 17 years old or younger, who have taken at least one dose of trial medication, and have a baseline and at least one post-baseline Y-MRS assessment.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Day 182
|
||||||||||||
|
|||||||||||||
Notes [7] - FAS at Day 182 [8] - FAS at Day 182 |
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Percentage of participants who were Y-MRS total score responders at Day 182 | ||||||||||||
End point description |
The Y-MRS is an 11-item clinician-rated instrument for assessing the severity of manic episodes.The Y-MRS total score, OC for each participant is the sum of the ratings for the 11 individual items, and can range from 0-60, with higher scores indicating greater severity of symptoms. A Y-MRS responder experiences a 50% or more decrease from baseline in Y-MRS total score. The FAS is analyzed consisting of participants 17 years old or younger, who have taken at least one dose of trial medication, and have a baseline and at least one post-baseline Y-MRS assessment.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Day 182
|
||||||||||||
|
|||||||||||||
Notes [9] - FAS at Day 182 [10] - FAS at Day 182 |
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Percentage of participants who were Y-MRS total score remitters (Y-MRS =<12) at Day 350 | ||||||||||||
End point description |
The Y-MRS is an 11-item clinician-rated instrument for assessing the severity of manic episodes. The Y-MRS total score, OC for each participant is the sum of the ratings for the 11 individual items, and can range from 0-60, with higher scores indicating greater severity of symptoms. A remitter is a participant with a Y-MRS total score of 12 or lower. The FAS is analyzed consisting of participants 17 years old or younger, who have taken at least one dose of trial medication, and have a baseline and at least one post-baseline Y-MRS assessment.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Day 350
|
||||||||||||
|
|||||||||||||
Notes [11] - FAS at Day 350 [12] - FAS at Day 350 |
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Percentage of participants who were Y-MRS total score responders at Day 350 | ||||||||||||
End point description |
The Y-MRS is an 11-item clinician-rated instrument for assessing the severity of manic episodes.The Y-MRS total score, OC for each participant is the sum of the ratings for the 11 individual items, and can range from 0-60, with higher scores indicating greater severity of symptoms. A Y-MRS responder experiences a 50% or more decrease from baseline in Y-MRS total score. The FAS is analyzed consisting of participants 17 years old or younger, who have taken at least one dose of trial medication, and have a baseline and at least one post-baseline Y-MRS assessment.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Day 350
|
||||||||||||
|
|||||||||||||
Notes [13] - FAS at Day 350 [14] - FAS at Day 350 |
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Time to first total Y-MRS 50% response | ||||||||||||
End point description |
The Y-MRS is an 11-item clinician-rated instrument for assessing the severity of manic episodes. The Y-MRS total score, OC for each participant is the sum of the ratings for the 11 individual items, ranging from 0-60, with higher scores indicating more severe symptoms. The time to 50% response is the number of days on treatment to achieve a 50% decrease from baseline in Y-MRS total score. The FAS is analyzed consisting of participants 17 years old or younger, who have taken at least one dose of trial medication, and have a baseline and at least one post-baseline Y-MRS assessment.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Up to Week 50
|
||||||||||||
|
|||||||||||||
Notes [15] - FAS population [16] - FAS population |
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Time to failure to maintain response in Y-MRS total score | ||||||||||||
End point description |
The Y-MRS is an 11-item clinician-rated instrument for assessing the severity of manic episodes. The Y-MRS total score, OC for each participant is the sum of the ratings for the 11 individual items, ranging from 0-60, with higher scores indicating more severe symptoms. The time to failure is the number of days from first achieving a 50% or more decrease from baseline in Y-MRS total score to the first subsequent day of a less than 50% decrease from baseline in Y-MRS total score. The FAS is analyzed consisting of participants 17 years old or younger, who have taken at least one dose of trial medication, and have a baseline and at least one post-baseline Y-MRS assessment. Results were shown as "0" because either time to failure or the 95% Confidence Interval (CI) were unable to be determined even after 362 days of follow-up (NA). For the Asenapine/Asenapine arm: Median - NA, 95% CI - 268.0 to NA. For the Placebo/Asenapine arm: Median -194.0, 95% CI - 78.0 to NA.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Up to Week 50
|
||||||||||||
|
|||||||||||||
Notes [17] - Y-MRS 50% responders in base trial P06107, who were also FAS population in P05898 [18] - Y-MRS 50% responders in base trial P06107, who were also FAS population in P05898 |
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Change from baseline in Clinical Global Impression Scale for assessing overall Bipolar Illness (CGI-BP overall) at Day 182 | ||||||||||||
End point description |
The CGI-BP overall OC is a single value score for assessing overall bipolar illness, recorded on a 7-point scale ranging from 1 for normal/not ill, to 7 for very severely ill. An improvement in symptoms is represented by change from baseline values that are negative. The FAS is analyzed consisting of participants 17 years old or younger, who have taken at least one dose of trial medication, and have a baseline and at least one post-baseline Y-MRS assessment.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline and Day 182
|
||||||||||||
|
|||||||||||||
Notes [19] - FAS at Day 182 [20] - FAS at Day 182 |
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Change from baseline in Clinical Global Impression Scale for assessing overall Bipolar Illness (CGI-BP overall) at Day 350 | ||||||||||||
End point description |
The CGI-BP overall OC is a single value score for assessing overall bipolar illness, recorded on a 7-point scale ranging from 1 for normal/not ill, to 7 for very severely ill. An improvement in symptoms is represented by change from baseline values that are negative. The FAS is analyzed consisting of participants 17 years old or younger, who have taken at least one dose of trial medication, and have a baseline and at least one post-baseline Y-MRS assessment.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline and Day 350
|
||||||||||||
|
|||||||||||||
Notes [21] - FAS at Day 350 [22] - FAS at Day 350 |
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Change from baseline in Clinical Global Impression Scale for assessing depression (CGI-BP depression) at Day 182 | ||||||||||||
End point description |
The CGI-BP depression OC is a single value score for assessing depression, recorded on a 7-point scale ranging from 1 for normal/not ill, to 7 for very severely ill. An improvement in symptoms is represented by change from baseline values that are negative. The FAS is analyzed consisting of participants 17 years old or younger, who have taken at least one dose of trial medication, and have a baseline and at least one post-baseline Y-MRS assessment.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline and Day 182
|
||||||||||||
|
|||||||||||||
Notes [23] - FAS at Day 182 [24] - FAS at Day 182 |
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Change from baseline in Clinical Global Impression Scale for assessing depression (CGI-BP depression) at Day 350 | ||||||||||||
End point description |
The CGI-BP depression OC is a single value score for assessing depression, recorded on a 7-point scale ranging from 1 for normal/not ill, to 7 for very severely ill. An improvement in symptoms is represented by change from baseline values that are negative. The FAS is analyzed consisting of participants 17 years old or younger, who have taken at least one dose of trial medication, and have a baseline and at least one post-baseline Y-MRS assessment.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline and Day 350
|
||||||||||||
|
|||||||||||||
Notes [25] - FAS at day 350 [26] - FAS at Day 350 |
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Change from baseline in Clinical Global Impression Scale for assessing mania (CGI-BP mania) at Day 182 | ||||||||||||
End point description |
The CGI-BP mania OC is a single value score for assessing mania, recorded on a 7-point scale ranging from 1 for normal/not ill, to 7 for very severely ill. An improvement in symptoms is represented by change from baseline values that are negative. The FAS is analyzed consisting of participants 17 years old or younger, who have taken at least one dose of trial medication, and have a baseline and at least one post-baseline Y-MRS assessment.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline and Day 182
|
||||||||||||
|
|||||||||||||
Notes [27] - FAS at Day 182 [28] - FAS at Day 182 |
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Change from baseline in Clinical Global Impression Scale for assessing mania (CGI-BP mania) at Day 350 | ||||||||||||
End point description |
The CGI-BP mania OC is a single value score for assessing mania, recorded on a 7-point scale ranging from 1 for normal/not ill, to 7 for very severely ill. An improvement in symptoms is represented by change from baseline values that are negative. The FAS is analyzed consisting of participants 17 years old or younger, who have taken at least one dose of trial medication, and have a baseline and at least one post-baseline Y-MRS assessment.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline and Day 350
|
||||||||||||
|
|||||||||||||
Notes [29] - FAS at Day 350 [30] - FAS at Day 350 |
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Change from baseline in Children's Depression Rating Scale, Revised (CDRS-R) total score at Day 182 | ||||||||||||
End point description |
The CDRS-R is a 17-item clinician-rated instrument for assessing the presence and severity of depressive symptoms in children. Fourteen of the 17 items are rated on a scale of 1-7, and 3 of the items are rated on a scale of 1-5, with higher scores indicating greater severity of symptoms. The CDRS-R total score, OC for each participant is the sum of the ratings for the 17 individual items, and can range from 17-113, with higher scores indicating greater severity of symptoms. Iimprovement in symptoms is represented by change from baseline values that are negative. The FAS is analyzed consisting of participants 17 years old or younger, who have taken at least one dose of trial medication, and have a baseline and at least one post-baseline Y-MRS assessment.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline and Day 182
|
||||||||||||
|
|||||||||||||
Notes [31] - FAS at Day 182 [32] - FAS at Day 182 |
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Change from baseline in Children's Depression Rating Scale, Revised (CDRS-R) total score at Day 350 | ||||||||||||
End point description |
The CDRS-R is a 17-item clinician-rated instrument for assessing the presence and severity of depressive symptoms in children. Fourteen of the 17 items are rated on a scale of 1-7, and 3 of the items are rated on a scale of 1-5, with higher scores indicating greater severity of symptoms. The CDRS-R total score, OC for each participant is the sum of the ratings for the 17 individual items, and can range from 17-113, with higher scores indicating greater severity of symptoms. Iimprovement in symptoms is represented by change from baseline values that are negative. The FAS is analyzed consisting of participants 17 years old or younger, who have taken at least one dose of trial medication, and have a baseline and at least one post-baseline Y-MRS assessment.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline and Day 350
|
||||||||||||
|
|||||||||||||
Notes [33] - FAS at Day 350 [34] - FAS at Day 350 |
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Percentage of CDRS-R responders at Day 182 | ||||||||||||
End point description |
The CDRS-R is a 17-item clinician-rated instrument for assessing the presence and severity of depressive symptoms in children. The CDRS-R total score, OC for each participant is the sum of the ratings for the 17 individual items, and can range from 17-113, with higher scores indicating greater severity of symptoms. A CDRS-R responder experiences a 50% or more decrease from baseline in CDRS-R total score. The FAS is analyzed consisting of participants 17 years old or younger, who have taken at least one dose of trial medication, and have a baseline and at least one post-baseline Y-MRS assessment.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Day 182
|
||||||||||||
|
|||||||||||||
Notes [35] - FAS at Day 182 [36] - FAS at Day 182 |
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Percentage of CDRS-R responders at Day 350 | ||||||||||||
End point description |
The CDRS-R is a 17-item clinician-rated instrument for assessing the presence and severity of depressive symptoms in children. The CDRS-R total score, OC for each participant is the sum of the ratings for the 17 individual items, and can range from 17-113, with higher scores indicating greater severity of symptoms. A CDRS-R responder experiences a 50% or more decrease from baseline in CDRS-R total score. The FAS is analyzed consisting of participants 17 years old or younger, who have taken at least one dose of trial medication, and have a baseline and at least one post-baseline Y-MRS assessment.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Day 350
|
||||||||||||
|
|||||||||||||
Notes [37] - FAS at Day 350 [38] - FAS at Day 350 |
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Percentage of participants with emergent depression based on CDRS-R at Day 182 | ||||||||||||
End point description |
The CDRS-R is a 17-item clinician-rated instrument for assessing the presence and severity of depressive symptoms in children. The CDRS-R total score, OC for each participant is the sum of the ratings for the 17 individual items, and can range from 17-113, with higher scores indicating greater severity of symptoms. Participants with a CDRS-R score of 40 or greater (whose baseline CDRS-R less than 40) are defined as exhibiting emergent depression which is a strong indicator of the presence or potential for a major depressive disorder. The FAS is analyzed consisting of participants 17 years old or younger, who have taken at least one dose of trial medication, and have a baseline and at least one post-baseline Y-MRS assessment.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Day 182
|
||||||||||||
|
|||||||||||||
Notes [39] - FAS at Day 182 [40] - FAS at Day 182 |
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Percentage of participants with emergent depression based on CDRS-R at Day 350 | ||||||||||||
End point description |
The CDRS-R is a 17-item clinician-rated instrument for assessing the presence and severity of depressive symptoms in children. The CDRS-R total score, OC for each participant is the sum of the ratings for the 17 individual items, and can range from 17-113, with higher scores indicating greater severity of symptoms. Participants with a CDRS-R score of 40 or greater (whose baseline CDRS-R less than 40) are defined as exhibiting emergent depression which is a strong indicator of the presence or potential for a major depressive disorder. The FAS is analyzed consisting of participants 17 years old or younger, who have taken at least one dose of trial medication, and have a baseline and at least one post-baseline Y-MRS assessment.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Day 350
|
||||||||||||
|
|||||||||||||
Notes [41] - FAS at Day 350 [42] - FAS at Day 350 |
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Change from baseline in Children's Global Assessment Scale (CGAS) at Day 182 | ||||||||||||
End point description |
CGAS is a scale with a possible range of 1 to 100, measuring psychological, social, and school functioning in children. Minimum scores, OC range from 1-10, representing the need for constant supervision (worse result) to maximum scores of 91-100, representing superior functioning (better result). An improvement in function is represented by a change from baseline value that is positive. The FAS is analyzed consisting of participants 17 years old or younger, who have taken at least one dose of trial medication, and have a baseline and at least one post-baseline Y-MRS assessment.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline and Day 182
|
||||||||||||
|
|||||||||||||
Notes [43] - FAS at Day 182 [44] - FAS at Day 182 |
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Change from baseline in Children's Global Assessment Scale (CGAS) at Day 350 | ||||||||||||
End point description |
CGAS is a scale with a possible range of 1 to 100, measuring psychological, social, and school functioning in children. Minimum scores, OC range from 1-10, representing the need for constant supervision (worse result) to maximum scores of 91-100, representing superior functioning ( better result). An improvement in function is represented by a change from baseline value that is positive. The FAS is analyzed consisting of participants 17 years old or younger, who have taken at least one dose of trial medication, and have a baseline and at least one post-baseline Y-MRS assessment.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline and Day 350
|
||||||||||||
|
|||||||||||||
Notes [45] - FAS at Day 350 [46] - FAS at Day 350 |
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Percentage of participants with a CGAS score of equal or greater than 70 at Day 350 | ||||||||||||
End point description |
CGAS is a scale with a possible range of 1 to 100, measuring psychological, social, and school functioning in children. Minimum scores, OC range from 1-10, representing the need for constant supervision (worse result) to maximum scores of 91-100, representing superior functioning (better result). The percentage of participants with a score of 70 or greater, represent those with normal or superior social functioning. The FAS is analyzed consisting of participants 17 years old or younger, who have taken at least one dose of trial medication, and have a baseline and at least one post-baseline Y-MRS assessment.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Day 350
|
||||||||||||
|
|||||||||||||
Notes [47] - FAS at Day 350 [48] - FAS at Day 350 |
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Percentage of participants with a CGAS score of equal or greater than 70 at Day 182 | ||||||||||||
End point description |
CGAS is a scale with a possible range of 1 to 100, measuring psychological, social, and school functioning in children. Minimum scores, OC range from 1-10, representing the need for constant supervision (worse result) to maximum scores of 91-100, representing superior functioning (better result). The percentage of participants with a score of 70 or greater, represent those with normal to superior social functioning. The FAS is analyzed consisting of participants 17 years old or younger, who have taken at least one dose of trial medication, and have a baseline and at least one post-baseline Y-MRS assessment.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Day 182
|
||||||||||||
|
|||||||||||||
Notes [49] - FAS at Day 182 [50] - FAS at Day 182 |
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Change from baseline in Pediatric Quality of Life Enjoyment and Satisfaction Questionnaires (PQ-LES-Q) total score at Day 182 | ||||||||||||
End point description |
PQ-LES-Q is a questionnaire to assess quality of life enjoyment and satisfaction in children and adolescents. The participant rates 15 items reflecting quality of life from the previous week on a scale of 1=very poor to 5=very good. Items 1-14 assess specific areas (e.g., health, mood or feelings); item 15 is a global assessment of overall quality of life. The PQ-LES-Q total score for each participant, OC is the sum of the rating assigned to each of the first 14 items, and ranges from 14 to 70, with a higher score indicating better quality of life. An improvement in quality of life is represented by change from baseline values that are positive. The FAS is analyzed consisting of participants 17 years old or younger, who have taken at least one dose of trial medication, and have a baseline and at least one post-baseline Y-MRS assessment.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline and Day 182
|
||||||||||||
|
|||||||||||||
Notes [51] - FAS at Day 182 [52] - FAS at Day 182 |
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Change from baseline in PQ-LES-Q total score at Day 350 | ||||||||||||
End point description |
PQ-LES-Q is a questionnaire to assess quality of life enjoyment and satisfaction in children and adolescents. The participant rates 15 items reflecting quality of life from the previous week on a scale of 1=very poor to 5=very good. Items 1-14 assess specific areas (e.g., health, mood or feelings); item 15 is a global assessment of overall quality of life. The PQ-LES-Q total score for each participant, OC is the sum of the rating assigned to each of the first 14 items, and ranges from 14 to 70, with a higher score indicating better quality of life. An improvement in quality of life is represented by change from baseline values that are positive. The FAS is analyzed consisting of participants 17 years old or younger, who have taken at least one dose of trial medication, and have a baseline and at least one post-baseline Y-MRS assessment.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline and Day 350
|
||||||||||||
|
|||||||||||||
Notes [53] - FAS at Day 350 [54] - FAS at Day 350 |
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Change from baseline in PQ-LES-Q overall score at Day 182 | ||||||||||||
End point description |
PQ-LES-Q is a questionnaire to assess quality of life enjoyment and satisfaction in children and adolescents. The participant rates 15 items reflecting quality of life from the previous week. Item 15, the PQ-LES-Q overall score, OC is a global assessment of overall quality of life, and ranges from 1 to 5, with a higher score indicating better quality of life. An improvement in quality of life is represented by change from baseline values that are positive. The FAS is analyzed consisting of participants 17 years old or younger, who have taken at least one dose of trial medication, and have a baseline and at least one post-baseline Y-MRS assessment.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline and Day 182
|
||||||||||||
|
|||||||||||||
Notes [55] - FAS at Day 182 [56] - FAS at Day 182 |
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Change from baseline in PQ-LES-Q overall score at Day 350 | ||||||||||||
End point description |
PQ-LES-Q is a questionnaire to assess quality of life enjoyment and satisfaction in children and adolescents. The participant rates 15 items reflecting quality of life from the previous week. Item 15, the PQ-LES-Q overall score, OC is a global assessment of overall quality of life, and ranges from 1 to 5, with a higher score indicating better quality of life. An improvement in quality of life is represented by change from baseline values that are positive. The FAS is analyzed consisting of participants 17 years old or younger, who have taken at least one dose of trial medication, and have a baseline and at least one post-baseline Y-MRS assessment.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline and Day 350
|
||||||||||||
|
|||||||||||||
Notes [57] - FAS at Day 350 [58] - FAS at Day 350 |
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Adverse events information
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Timeframe for reporting adverse events |
30 days after the last dose of study drug (up to approximately 54 weeks)
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Adverse event reporting additional description |
All enrolled and treated participants
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
17.1
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Asenapine/Asenapine
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Participants treated with asenapine in base trial P06107 were first treated with open-label flavored asenapine 2.5 mg twice per day (BID), then up-titrated to 5 mg BID at day 4, then up-titrated to 10 mg BID at day 7. After day 7, flexible dosing of asenapine was continued for up to 50 weeks. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo/Asenapine
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Participants treated with placebo in base trial P06107 were first treated with open-label flavored asenapine 2.5 mg twice per day (BID), then up-titrated to 5 mg BID at day 4, then up-titrated to 10 mg BID at day 7. After day 7, flexible dosing of asenapine was continued for up to 50 weeks. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|||
Substantial protocol amendments (globally) |
|||
Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
||
04 May 2011 |
Amendment 1: Raised the lower age limit to greater than or equal to 12 years of age, and allowed participants who turned 18 years of age during acute trial (P06107) to continue into extension trial (P05898). |
||
02 Dec 2011 |
Amendment 2: Addition of new investigators, and revised information for one investigator |
||
12 Jan 2012 |
Amendment 3: Inclusion of 10 and 11 year olds; revision of options for conducting visits; updated text on non-sexually active females; updating of allowed rescue therapy; updated to clarify safety follow-up visit; added drug hypersensitivity reactions as a closely monitored event; updated monitoring of liver enzymes; clarified definition of "clinically important at any time"; updated reference section. |
||
28 Jun 2012 |
Amendment 4:Extended length of trial to 50 weeks of treatment; added Cognition Battery and laboratory tests at Days 182 and 350; updated sponsor in title page; updated text for monitoring participants; updated footnote for date of informed consent; added text to clarify visit windows; deleted subgroup analysis; deleted efficacy parameter "sustained Y-MRS remitter". |
||
15 May 2013 |
Amendment 5: Added clarification about growth analysis for Russia; added subgroup analysis by geographic region; provided guidance for interim analysis, and interim CSR |
||
Interruptions (globally) |
|||
Were there any global interruptions to the trial? No | |||
Limitations and caveats |
|||
Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
None reported |