Clinical Trial Results:
A Phase 2a Randomized, Double-blind, Placebo-controlled, Parallel-group, Multi-center Study Investigating the Efficacy, Safety, and Tolerability of JNJ-42165279 in Subjects with Major Depressive Disorder and Anxious Distress
Summary
|
|
EudraCT number |
2015-002007-29 |
Trial protocol |
ES GB |
Global end of trial date |
04 Feb 2019
|
Results information
|
|
Results version number |
v1(current) |
This version publication date |
19 Feb 2020
|
First version publication date |
19 Feb 2020
|
Other versions |
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 |
42165279MDD2001
|
||
Additional study identifiers
|
|||
ISRCTN number |
- | ||
US NCT number |
NCT02498392 | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
|
|||
Sponsor organisation name |
Janssen Research & Development, LLC
|
||
Sponsor organisation address |
920 Route 202, South Raritan, United States,
|
||
Public contact |
Clinical Registry Group, Janssen Research & Development, LLC, ClinicalTrialsEU@its.jnj.com
|
||
Scientific contact |
Clinical Registry Group, Janssen Research & Development, LLC, ClinicalTrialsEU@its.jnj.com
|
||
Paediatric regulatory details
|
|||
Is trial part of an agreed paediatric investigation plan (PIP) |
No
|
||
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? |
No
|
||
Results analysis stage
|
|||
Analysis stage |
Final
|
||
Date of interim/final analysis |
04 Feb 2019
|
||
Is this the analysis of the primary completion data? |
No
|
||
Global end of trial reached? |
Yes
|
||
Global end of trial date |
04 Feb 2019
|
||
Was the trial ended prematurely? |
No
|
||
General information about the trial
|
|||
Main objective of the trial |
The primary objective of this study was to evaluate the efficacy in terms of reduction of symptoms of depression and anxiety, as assessed by the change from baseline on a 17-item Hamilton Depression Rating Scale (HDRS17), and overall safety and tolerability of treatment with adjunctive JNJ-42165279 compared to placebo in subjects with major depressive disorder (MDD) with anxiety symptoms who had inadequate response to treatment with a selective serotonin reuptake inhibitor (SSRI) or serotonergic/noradrenergic reuptake inhibitor (SNRI).
|
||
Protection of trial subjects |
This study was conducted in accordance with the ethical principles that have their origin in the Declaration of Helsinki and that are consistent with Good Clinical Practices and applicable regulatory requirements. Physical examination, neurological examination, vital signs, body weight, body temperature, clinical laboratory assessments, 12-lead electrocardiogram (ECG), urine drug screen, alcohol screening test, pregnancy testing, Columbia Suicide Severity Rating Scale (C-SSRS) assessments and evaluation of adverse events (AEs) and concomitant medications were performed during the study to monitor subject's safety.
|
||
Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
08 Oct 2015
|
||
Long term follow-up planned |
No
|
||
Independent data monitoring committee (IDMC) involvement? |
No
|
||
Population of trial subjects
|
|||
Number of subjects enrolled per country |
|||
Country: Number of subjects enrolled |
Spain: 6
|
||
Country: Number of subjects enrolled |
United Kingdom: 35
|
||
Country: Number of subjects enrolled |
Moldova, Republic of: 18
|
||
Country: Number of subjects enrolled |
Russian Federation: 44
|
||
Country: Number of subjects enrolled |
Ukraine: 39
|
||
Country: Number of subjects enrolled |
United States: 18
|
||
Worldwide total number of subjects |
160
|
||
EEA total number of subjects |
41
|
||
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) |
0
|
||
Adolescents (12-17 years) |
0
|
||
Adults (18-64 years) |
160
|
||
From 65 to 84 years |
0
|
||
85 years and over |
0
|
|
||||||||||||||||||||||||||||
Recruitment
|
||||||||||||||||||||||||||||
Recruitment details |
- | |||||||||||||||||||||||||||
Pre-assignment
|
||||||||||||||||||||||||||||
Screening details |
A total of 160 subjects were enrolled into the lead-in period, and 153 were randomized into the double-blind (DB) treatment period and received at least 1 dose of double-blind study agent. Of the 153 subjects, 137 completed study. | |||||||||||||||||||||||||||
Period 1
|
||||||||||||||||||||||||||||
Period 1 title |
Double-blind (DB) Lead-in Period
|
|||||||||||||||||||||||||||
Is this the baseline period? |
No | |||||||||||||||||||||||||||
Allocation method |
Non-randomised - controlled
|
|||||||||||||||||||||||||||
Blinding used |
Double blind | |||||||||||||||||||||||||||
Roles blinded |
Subject, Investigator | |||||||||||||||||||||||||||
Arms
|
||||||||||||||||||||||||||||
Arm title
|
Placebo | |||||||||||||||||||||||||||
Arm description |
Lead-in Period: All subjects received matching placebo tablets orally once daily (qd). At the end of the lead-in period, response status of the subjects was assessed according to the double-blind response criteria based on reduction in Hamilton Depression Rating Scale (HDRS17) relative to lead-in baseline. Double-blind treatment period: Following initial placebo lead-in period, subjects self-administered adjunctive matching placebo tablets orally qd for 6 weeks. Withdrawal period: Subjects who completed the double-blind treatment period prior to Week 11 were treated with placebo for the remaining time of the treatment phase of the study, which varied depending on the duration of the placebo lead-in for the specific subject. | |||||||||||||||||||||||||||
Arm type |
Placebo | |||||||||||||||||||||||||||
Investigational medicinal product name |
Placebo
|
|||||||||||||||||||||||||||
Investigational medicinal product code |
||||||||||||||||||||||||||||
Other name |
||||||||||||||||||||||||||||
Pharmaceutical forms |
Tablet
|
|||||||||||||||||||||||||||
Routes of administration |
Oral use
|
|||||||||||||||||||||||||||
Dosage and administration details |
Matching placebo was administered orally.
|
|||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||
Period 2
|
||||||||||||||||||||||||||||
Period 2 title |
DB Treatment(6 week) + Withdrawal Period
|
|||||||||||||||||||||||||||
Is this the baseline period? |
Yes [1] | |||||||||||||||||||||||||||
Allocation method |
Randomised - controlled
|
|||||||||||||||||||||||||||
Blinding used |
Double blind | |||||||||||||||||||||||||||
Roles blinded |
Subject, Investigator | |||||||||||||||||||||||||||
Arms
|
||||||||||||||||||||||||||||
Are arms mutually exclusive |
Yes
|
|||||||||||||||||||||||||||
Arm title
|
Placebo | |||||||||||||||||||||||||||
Arm description |
Lead-in Period: All subjects received matching placebo tablets orally once daily (qd). At the end of the lead-in period, response status of the subjects was assessed according to the double-blind response criteria based on reduction in HDRS17 relative to lead-in baseline. Double-blind treatment period: Following initial placebo lead-in period, subjects self-administered adjunctive matching placebo tablets orally qd for 6 weeks. Withdrawal period: Subjects who completed the double-blind treatment period prior to Week 11 were treated with placebo for the remaining time of the treatment phase of the study, which varied depending on the duration of the placebo lead-in for the specific subject. | |||||||||||||||||||||||||||
Arm type |
Placebo | |||||||||||||||||||||||||||
Investigational medicinal product name |
Placebo
|
|||||||||||||||||||||||||||
Investigational medicinal product code |
||||||||||||||||||||||||||||
Other name |
||||||||||||||||||||||||||||
Pharmaceutical forms |
Tablet
|
|||||||||||||||||||||||||||
Routes of administration |
Oral use
|
|||||||||||||||||||||||||||
Dosage and administration details |
Matching placebo was administered orally.
|
|||||||||||||||||||||||||||
Arm title
|
JNJ-42165279 25 mg | |||||||||||||||||||||||||||
Arm description |
Double-blind treatment period: Following the initial placebo lead-in period, the subjects self-administered JNJ-42165279 25 mg tablets orally once daily for 6 weeks. | |||||||||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||||||||
Investigational medicinal product name |
JNJ-42165279
|
|||||||||||||||||||||||||||
Investigational medicinal product code |
||||||||||||||||||||||||||||
Other name |
||||||||||||||||||||||||||||
Pharmaceutical forms |
Tablet
|
|||||||||||||||||||||||||||
Routes of administration |
Oral use
|
|||||||||||||||||||||||||||
Dosage and administration details |
JNJ-42165279 was administered orally at a dose of 25 mg tablet once daily for 6 weeks.
|
|||||||||||||||||||||||||||
Notes [1] - Period 1 is not the baseline period. It is expected that period 1 will be the baseline period. Justification: Baseline data was reported for safety analysis set for DB treatment period which was less than all enrolled analysis set. |
||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||
Notes [2] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same. Justification: The baseline period shows the disposition of safety analysis set. |
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Baseline characteristics reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Lead-in Period: All subjects received matching placebo tablets orally once daily (qd). At the end of the lead-in period, response status of the subjects was assessed according to the double-blind response criteria based on reduction in HDRS17 relative to lead-in baseline. Double-blind treatment period: Following initial placebo lead-in period, subjects self-administered adjunctive matching placebo tablets orally qd for 6 weeks. Withdrawal period: Subjects who completed the double-blind treatment period prior to Week 11 were treated with placebo for the remaining time of the treatment phase of the study, which varied depending on the duration of the placebo lead-in for the specific subject. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
JNJ-42165279 25 mg
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Double-blind treatment period: Following the initial placebo lead-in period, the subjects self-administered JNJ-42165279 25 mg tablets orally once daily for 6 weeks. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|||
End points reporting groups
|
|||
Reporting group title |
Placebo
|
||
Reporting group description |
Lead-in Period: All subjects received matching placebo tablets orally once daily (qd). At the end of the lead-in period, response status of the subjects was assessed according to the double-blind response criteria based on reduction in Hamilton Depression Rating Scale (HDRS17) relative to lead-in baseline. Double-blind treatment period: Following initial placebo lead-in period, subjects self-administered adjunctive matching placebo tablets orally qd for 6 weeks. Withdrawal period: Subjects who completed the double-blind treatment period prior to Week 11 were treated with placebo for the remaining time of the treatment phase of the study, which varied depending on the duration of the placebo lead-in for the specific subject. | ||
Reporting group title |
Placebo
|
||
Reporting group description |
Lead-in Period: All subjects received matching placebo tablets orally once daily (qd). At the end of the lead-in period, response status of the subjects was assessed according to the double-blind response criteria based on reduction in HDRS17 relative to lead-in baseline. Double-blind treatment period: Following initial placebo lead-in period, subjects self-administered adjunctive matching placebo tablets orally qd for 6 weeks. Withdrawal period: Subjects who completed the double-blind treatment period prior to Week 11 were treated with placebo for the remaining time of the treatment phase of the study, which varied depending on the duration of the placebo lead-in for the specific subject. | ||
Reporting group title |
JNJ-42165279 25 mg
|
||
Reporting group description |
Double-blind treatment period: Following the initial placebo lead-in period, the subjects self-administered JNJ-42165279 25 mg tablets orally once daily for 6 weeks. |
|
|||||||||||||
End point title |
Double-blind Treatment Period: Change from Baseline in Hamilton Depression Rating Scale (HDRS17) Total Score at Week 6 (eITT Population) | ||||||||||||
End point description |
HDRS-17 is clinician-administered rating scale designed to assess severity of symptoms in subjects diagnosed with depression. Each of 17 items is rated by clinician on either 3-point (0-2) or 5-point (0-4) scale with rating of 0:absent, 1:doubtful to mild, 2:mild to moderate, 3:moderate to severe, and 4:very severe. A total score (0 to 52) was calculated by adding scores of all 17 items. For each item as well as total score, higher score represents more severe condition. The enriched intention-to-treat (eITT) analysis set included all enrolled subjects who were randomized into double-blind treatment period, who were lead-in placebo non-responder, who received at least one dose of double-blind study medication (either placebo or JNJ-42165279) and had at least one post-baseline HDRS17 assessment in double-blind treatment period. Here 'N' (number of subjects analyzed) signifies number of subjects who were evaluable for this endpoint.
|
||||||||||||
End point type |
Primary
|
||||||||||||
End point timeframe |
Baseline and Week 6
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Statistical Analysis 1 | ||||||||||||
Statistical analysis description |
Here 'MMRM' refers to Mixed-effects Model Using Repeated Measures.
|
||||||||||||
Comparison groups |
Placebo v JNJ-42165279 25 mg
|
||||||||||||
Number of subjects included in analysis |
94
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
P-value |
= 0.416 | ||||||||||||
Method |
MMRM | ||||||||||||
Parameter type |
Difference of Least Square (LS) Means | ||||||||||||
Point estimate |
-0.2
|
||||||||||||
Confidence interval |
|||||||||||||
level |
60% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-1.1 | ||||||||||||
upper limit |
0.66 | ||||||||||||
Variability estimate |
Standard error of the mean
|
||||||||||||
Dispersion value |
1.04
|
|
|||||||||||||
End point title |
Double-blind Treatment Period: Change from Baseline in Hamilton Depression Rating Scale (HDRS17) Total Score at Week 6 (fITT Population) | ||||||||||||
End point description |
HDRS17 is a clinician-administered rating scale designed to assess severity of symptoms in subjects diagnosed with depression. Each of the 17 items is rated by clinician on either a 3-point (0 to 2) or a 5-point (0 to 4) scale which used a rating of 0:absent, 1:doubtful to mild, 2:mild to moderate, 3:moderate to severe, and 4:very severe. HDRS17 total score is calculated as sum of 17 item scores and ranges from 0 to 52. For each item as well as the total score, higher scores indicate greater severity of depression. The full intent-to-treat (fITT) analysis set included both placebo responders and placebo non-responders. Here 'N' (number of subjects analyzed) signifies number of subjects who were evaluable for this endpoint.
|
||||||||||||
End point type |
Primary
|
||||||||||||
End point timeframe |
Baseline and Week 6
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Statistical Analysis 1 | ||||||||||||
Statistical analysis description |
Here 'MMRM' refers to Mixed-effects Model Using Repeated Measures.
|
||||||||||||
Comparison groups |
Placebo v JNJ-42165279 25 mg
|
||||||||||||
Number of subjects included in analysis |
141
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
P-value |
= 0.647 [1] | ||||||||||||
Method |
MMRM | ||||||||||||
Parameter type |
Difference of Least Square (LS) Means | ||||||||||||
Point estimate |
0.3
|
||||||||||||
Confidence interval |
|||||||||||||
level |
60% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-0.41 | ||||||||||||
upper limit |
1.07 | ||||||||||||
Variability estimate |
Standard error of the mean
|
||||||||||||
Dispersion value |
0.88
|
||||||||||||
Notes [1] - 1-sided |
|
|||||||||||||
End point title |
Double-blind Treatment Period: Change from Baseline in Hamilton Anxiety Rating Subscale (HAM-A6) Score at Week 6 (eITT Population) | ||||||||||||
End point description |
The HAM-A6 is a 6-item subscale derived from the original Hamilton Anxiety scale (HAM-A) which consists of 5 psychic anxiety symptoms (anxious mood, psychic tension, fears, intellectual disturbances, and anxious behavior observed at the interview), as well as one somatic item (muscular tension). The HAM-A6 score ranges from 0 to 24; higher scores indicate greater severity of symptoms. The HAM-A6 score is calculated by summing the 6 item scores. The eITT analysis set included all enrolled subjects who were randomized into double-blind treatment period, who were lead-in placebo non-responder, who received at least one dose of double-blind study medication (either placebo or JNJ-42165279) and had at least one post-baseline HDRS17 assessment in the double-blind treatment period. Here 'N' (number of subjects analyzed) signifies number of subjects who were evaluable for this endpoint.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline and Week 6
|
||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Double-blind Treatment Period: Change from Baseline in Hamilton Depression Rating Subscale (HAM-D6) Score at Week 6 (eITT Population) | ||||||||||||
End point description |
HAM-D6 is a 6-item subscale derived from HDRS17 and consists of depressed mood, guilt feelings, work and interests, psychomotor retardation, psychic anxiety, and somatics symptoms (tiredness and pains), rated on a 5-point scale, where 0 = not present, and 1-4 represent increasingly severe symptoms. One item (that is, somatic symptoms) is rated on only a 3-point scale, ranging from 0-2. The HAM-D6 is calculated from summing the 6 items and the score ranges from 0 (normal) to 22 (severe), with higher scores indicating greater severity of core symptoms. The eITT analysis set included all enrolled subjects who were randomized into double-blind treatment period, who were lead-in placebo non-responder, who received at least one dose of double-blind study medication (either placebo or JNJ-42165279) and had at least one post-baseline HDRS17 assessment in double-blind treatment period. Here 'N' (number of subjects analyzed) signifies number of subjects who were evaluable for this endpoint.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline and Week 6
|
||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Double-blind Treatment Period: Change from Baseline in Structured Interview Guide of the Hamilton Anxiety Scale (SIGH-A) Total Score at Week 6 (eITT Population) | ||||||||||||
End point description |
The SIGH-A scale consists of 14 items with a score of 0 to 4, where 0=absent, 1=mild, 2=moderate, 3=severe, 4=incapacitating. The SIGH-A total score is calculated by summing the 14 item scores, and ranges from 0 to 56. For each individual item score and total score, higher scores indicate greater severity. The eITT analysis set included all enrolled subjects who were randomized into double-blind treatment period, who were lead-in placebo non-responder, who received at least one dose of double-blind study medication (either placebo or JNJ-42165279) and had at least one post-baseline HDRS17 assessment in the double-blind treatment period. Here 'N' (number of subjects analyzed) signifies number of subjects who were evaluable for this endpoint.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline and Week 6
|
||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Double-blind Treatment Period: Change from Baseline in the HDRS17 Anxiety/Somatization Factor Total Score at Week 6 (eITT Population) | ||||||||||||
End point description |
HDRS17 anxiety/somatization factor is derived from HDRS including 6 items: psychic anxiety, somatic anxiety, gastrointestinal somatic symptoms, general somatic symptoms, hypochondriasis, and insight. Each of 6 items is rated by clinician on either a 3-point (0 to 2) or a 5-point (0 to 4) scale with rating of 0:absent, 1:doubtful to mild, 2:mild to moderate, 3:moderate to severe, and 4:very severe and is calculated as sum of 6 item scores ranging from 0 to 18, with higher scores indicating greater severity of symptoms for each item as well as total score. The eITT analysis set included all enrolled subjects who were randomized into DB treatment period, who were lead-in placebo non-responder, who received at least one dose of double-blind study medication (either placebo or JNJ-42165279) and had at least one post-baseline HDRS17 assessment in double-blind treatment period. Here 'N' (number of subjects analyzed) signifies number of subjects who were evaluable for this endpoint.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline and Week 6
|
||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Double-blind Treatment Period: Percentage of Subjects With Greater than or Equal to (>=) 30 Percent (%) Improvement on the HDRS-17 Total Score at Week 6 (eITT Population) | ||||||||||||
End point description |
Percentage of subjects who had >=30% improvement on HDRS17 total score at Week 6 was reported. HDRS-17 is clinician-administered rating scale designed to assess severity of symptoms in subjects diagnosed with depression. Each of 17 items is rated by clinician on either 3-point (0-2) or 5-point (0-4) scale with rating of 0:absent, 1:doubtful to mild, 2:mild to moderate, 3:moderate to severe, and 4:very severe. A total score (0 to 52) was calculated by adding scores of all 17 items. For each item as well as total score, higher score represents more severe condition. eITT analysis set included all enrolled subjects who were randomized into DB treatment period,who were lead-in placebo non-responder, who received at least one dose of double-blind study medication (either placebo or JNJ-42165279) and had at least one post-baseline HDRS17 assessment in double-blind treatment period. Here 'N' (number of subjects analyzed) signifies number of subjects who were evaluable for this endpoint.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Week 6
|
||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Double-blind Treatment Period: Percentage of Subjects With >= 50% Improvement on the HDRS-17 Total Score at Week 6 (eITT Population) | ||||||||||||
End point description |
Percentage of subjects who had >=50% improvement on HDRS17 total score at Week 6 was reported. HDRS-17 is clinician-administered rating scale designed to assess severity of symptoms in subjects diagnosed with depression. Each of 17 items is rated by clinician on either 3-point (0-2) or 5-point (0-4) scale with rating of 0:absent, 1:doubtful to mild, 2:mild to moderate, 3:moderate to severe, and 4:very severe. A total score (0 to 52) was calculated by adding scores of all 17 items. For each item as well as total score, higher score represents more severe condition. eITT analysis set included all enrolled subjects who were randomized into DB treatment period,who were lead-in placebo non-responder, who received at least one dose of double-blind study medication (either placebo or JNJ-42165279) and had at least one post-baseline HDRS-17 assessment in DB treatment period. Here 'N' (number of subjects analyzed) signifies number of subjects who were evaluable for this endpoint.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Week 6
|
||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Double-blind Treatment Period: Percentage of Subjects With Remission as Assessed by HDRS-17 Total Score at Week 6 (eITT Population) | ||||||||||||
End point description |
Percentage of subjects with HDRS-17 total score less than or equal to 7 were considered as remitters. HDRS-17 is clinician-administered rating scale designed to assess severity of symptoms in subjects with depression. Each of 17 items is rated by clinician on either 3-point(0-2) or 5-point(0-4) scale with rating of 0:absent,1:doubtful to mild,2:mild to moderate,3:moderate to severe, and 4:very severe. A total score (0 to 52) was calculated by adding scores of all 17 items. For each item as well as total score, higher score represents more severe condition. eITT analysis set included all enrolled subjects who were randomized into double-blind treatment period,who were lead-in placebo non-responder,who received at least one dose of double-blind study medication (either placebo or JNJ-42165279) and had at least one post-baseline HDRS17 assessment in double-blind treatment period. Here 'N' (number of subjects analyzed) signifies number of subjects who were evaluable for this endpoint.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Week 6
|
||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Double-blind Treatment Period: Percentage of Subjects With >= 30% Improvement on SIGH-A Total Score at Week 6 (eITT Population) | ||||||||||||
End point description |
The percentage of subjects who had >= 30% improvement on SIGH-A total score at Week 6 was reported. The SIGH-A scale consists of 14 items with a score of 0 to 4, where 0=absent, 1=mild, 2=moderate, 3=severe, 4=incapacitating. The SIGH-A total score is calculated by summing the 14 item scores, and ranges from 0 to 56. For each individual item score and total score, higher scores indicate greater severity. The eITT analysis set included all enrolled subjects who were randomized into double-blind treatment period, who were lead-in placebo non-responder, who received at least one dose of double-blind study medication (either placebo or JNJ-42165279) and had at least one post-baseline HDRS17 assessment in the double-blind treatment period. Here 'N' (number of subjects analyzed) signifies number of subjects who were evaluable for this endpoint.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Week 6
|
||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Double-blind Treatment Period: Percentage of Subjects With >= 50% Improvement on SIGH-A Total Score at Week 6 (eITT Population) | ||||||||||||
End point description |
The percentage of subjects who had >= 50% improvement on SIGH-A total score at Week 6 was reported. The SIGH-A scale consists of 14 items with a score of 0 to 4, where 0=absent, 1=mild, 2=moderate, 3=severe, 4=incapacitating. The SIGH-A total score is calculated by summing the 14 item scores, and ranges from 0 to 56. For each individual item score and total score, higher scores indicate greater severity. The eITT analysis set included all enrolled subjects who were randomized into double-blind treatment period, who were lead-in placebo non-responder, who received at least one dose of double-blind study medication (either placebo or JNJ-42165279) and had at least one post-baseline HDRS17 assessment in the double-blind treatment period. Here 'N' (number of subjects analyzed) signifies number of subjects who were evaluable for this endpoint.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Week 6
|
||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Double-blind Treatment Period: Percentage of Subjects With a Clinical Global Impression Improvement (CGI-I) Score of Very Much Improved or Much Improved at Week 6 (eITT Population) | ||||||||||||
End point description |
The percentage of subjects with a CGI-I score of very much improved or much improved at Week 6 was reported. CGI-I is a 7-point scale that required the clinician to assess how much the subject’s illness had improved or worsened relative to a baseline state at the beginning of the intervention. The CGI-I is rated as: 1=very much improved; 2=much improved; 3=minimally improved; 4=no change; 5=minimally worse; 6=much worse; 7=very much worse. For each individual item score and total score, higher scores indicate greater severity. The eITT analysis set included all enrolled subjects who were randomized into double-blind treatment period, who were lead-in placebo non-responder, who received at least one dose of double-blind study medication (either placebo or JNJ-42165279) and had at least one post-baseline HDRS17 assessment in the double-blind treatment period. Here 'N' (number of subjects analyzed) signifies number of subjects who were evaluable for this endpoint.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Week 6
|
||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
||||||||||||||||||||||||||||||||||||||||||||||
Adverse events information
|
||||||||||||||||||||||||||||||||||||||||||||||
Timeframe for reporting adverse events |
Up to 6 weeks
|
|||||||||||||||||||||||||||||||||||||||||||||
Assessment type |
Non-systematic | |||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
|
||||||||||||||||||||||||||||||||||||||||||||||
Dictionary name |
MedDRA | |||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
21.1
|
|||||||||||||||||||||||||||||||||||||||||||||
Reporting groups
|
||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo
|
|||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Lead-in Period: All subjects received matching placebo tablets orally once daily (qd). At the end of the lead-in period, response status of the subjects was assessed according to the double-blind response criteria based on reduction in HDRS17 relative to lead-in baseline. Double-blind treatment period: Following initial placebo lead-in period, subjects self-administered adjunctive matching placebo tablets orally qd for 6 weeks. Withdrawal period: Subjects who completed the double-blind treatment period prior to Week 11 were treated with placebo for the remaining time of the treatment phase of the study, which varied depending on the duration of the placebo lead-in for the specific subject. | |||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
JNJ-42165279 25mg
|
|||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Double-blind treatment period: Following the Lead-in Period, the subjects self-administered JNJ-42165279 25 milligrams (mg) tablets orally once daily for 6 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 |
||
31 Aug 2015 |
The overall reason for Amendment INT-1 was to clarify the updated procedure performed by an independent central rater and to address the US Food and Drug Administration (FDA) comments. |
||
03 Jul 2017 |
The overall reason for Amendment INT-2 was to update the information on toxicology, to increase the number of subjects participating in the study from 140 to 143, to replace 3 subjects who had to stop early when the study was put on hold, to add neurological examinations to confirm the safety of participation in the study and treatment with JNJ 42165279, to make change in allowed medication and control of drug intake. |
||
25 Aug 2017 |
The overall reason for Amendment INT-4 was based on a regulatory decision, to allow women of childbearing potential to participate in this study under conditions of pregnancy testing and the use of high-quality contraception, and additionally, to add the optional use of a diary or electronic device to document the intake of study medication. |
||
24 Oct 2017 |
The overall reason for Amendment INT-5 was based on regulator’s request to exclude subjects with abnormal high liver function analytes from the study, to add an exclusion criterion for breast feeding women; on request of investigators: to add Venlafaxine (immediate release) to the list of allowed antidepressant drugs, on request of investigators: to add instructions on the use of PRN (as needed) non-benzodiazepine sleep aids, and additionally, to add specific instructions of the calculation of corrected QT (QTc) interval to determine stopping or exclusion criteria. |
||
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. | |||
The relationship of plasma anandamide and trough drug concentrations observed suggest that few subjects had substantial recovery of fatty acid amide hydrolase activity between doses. Higher doses or exposures could have resulted in greater effects. |