The purpose of this study is to evaluate the efficacy and safety and tolerability of JNJ-42165279 in participants with major depressive disorder (MDD) with anxiety symptoms who have had inadequate response to treatment with a selective serotonin reuptake inhibitor (SSRI) or serotonergic/noradrenergic reuptake inhibitor (SNRI).
This is a multicenter, double-blind (neither physician nor participant knows the treatment that the participant receives), placebo-controlled, randomized, parallel-group study in participants with Major Depressive Disorder (MDD) with Anxious Distress. Participants who had treatment initiated with a SSRI/SNRI allowed by the protocol will be evaluated at the investigation site. The site assessment will be reviewed and validated by an independent central rater. The review will include the clinical history of MDD, SSRI/SNRI treatment of adequate dose and duration for the current episode of depression, and current symptom severity on the Hamilton Depression Rating Scale (HDRS17). Enrolled participants will be maintained on SSRI/SNRI treatment throughout the study to determine whether additional treatment with JNJ-4216579 can reduce the symptoms of MDD with anxious distress.The study will consist of 3 phases: a Screening Phase of up to 4 weeks, an 11-week double-blind Treatment Phase, and a 3-week post-treatment (follow up) Phase. The double-blind treatment Phase of the trial will consist of 3 periods. The first period is a placebo lead-in of double-blind duration, after which participants will enter the treatment period when they will be randomly assigned to JNJ-42165279 or continuation on placebo for 6 weeks. Participants who successfully complete the treatment period prior to the end of Week 11, will be treated with placebo for the remaining time of the double-blind phase of the study, which will vary depending on the duration of the placebo lead-in for the specific participant. The total study duration for each participant will be approximately 18 weeks. Efficacy and safety of JNJ-42165279 will be evaluated. Participants' safety will be monitored throughout the study.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
161
JNJ-42165279 will be administered orally at a dose of 25 milligrams (mg) tablet once daily for 6 weeks.
Matching Placebo will be administered orally.
Unnamed facility
Costa Mesa, California, United States
Unnamed facility
Double-blind Treatment Period: Change From Baseline in Hamilton Depression Rating Scale (HDRS17) Total Score at Week 6 (eITT Population)
HDRS17 is clinician-administered rating scale designed to assess severity of symptoms in participants 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.
Time frame: Baseline and Week 6
Double-blind Treatment Period: Change From Baseline in HDRS17 Total Score at Week 6 (fITT Population)
HDRS17 is a clinician-administered rating scale designed to assess severity of symptoms in participants 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.
Time frame: Baseline and Week 6
Double-blind Treatment Period: Change From Baseline in Hamilton Anxiety Rating Subscale (HAM-A6) Score at Week 6 (eITT Population)
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). Each of the 6 items is rated by the clinician on a 5-point scale ranging from 0 (not present) to 4 (maximum degree). The HAM-A6 score was calculated by summing the 6 item scores, and ranges from 0 to 24. Higher scores indicated greater severity of symptoms.
Time frame: Baseline and Week 6
Double-blind Treatment Period: Change From Baseline in HAM-A6 Score at Week 6 (fITT Population)
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Oceanside, California, United States
Unnamed facility
Miami, Florida, United States
Unnamed facility
Natick, Massachusetts, United States
Unnamed facility
Cedarhurst, New York, United States
Unnamed facility
Raleigh, North Carolina, United States
Unnamed facility
Allentown, Pennsylvania, United States
Unnamed facility
Salt Lake City, Utah, United States
Unnamed facility
Chisinau, Moldova
Unnamed facility
Orenburg, Russia
...and 22 more locations
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). Each of the 6 items is rated by the clinician on a 5-point scale ranging from 0 (not present) to 4 (maximum degree). The HAM-A6 score was calculated by summing the 6 item scores, and ranges from 0 to 24. Higher scores indicated greater severity of symptoms.
Time frame: Baseline and Week 6
Double-blind Treatment Period: Change From Baseline in Hamilton Depression Rating Subscale (HAM-D6) Score at Week 6 (eITT Population)
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 pain), rated on a 5-point scale, where 0 = not present, and 1-4 represent increasingly severe symptoms. Each of these items is rated by the clinician on either a 3-point (0 to 2) or a 5-point scale (0 to 4). The point scale used a rating of 0 (absent), 1 (doubtful to mild), 2 (mild to moderate), 3 (moderate to severe), and 4 (very severe). General somatic is scored 0 to 2 and all others are scored 0 to 4. 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.
Time frame: Baseline and Week 6
Double-blind Treatment Period: Change From Baseline in HAM-D6 Score at Week 6 (fITT Population)
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 somatic symptoms (tiredness and pain), rated on a 5-point scale, where 0 = not present, and 1-4 represent increasingly severe symptoms. Each of these items is rated by the clinician on either a 3-point (0 to 2) or a 5-point scale (0 to 4). The point scale used a rating of 0 (absent), 1 (doubtful to mild), 2 (mild to moderate), 3 (moderate to severe), and 4 (very severe). General somatic is scored 0 to 2 and all others are scored 0 to 4. 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.
Time frame: Baseline and Week 6
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)
The SIGH-A was included as a means to determine the frequency and severity of signs and symptoms of anxiety; and determine both their influence on treatment and their responsiveness to treatment. 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.
Time frame: Baseline and Week 6
Double-blind Treatment Period: Change From Baseline in SIGH-A Total Score at Week 6 (fITT Population
The SIGH-A was included as a means to determine the frequency and severity of signs and symptoms of anxiety; and determine both their influence on treatment and their responsiveness to treatment. 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.
Time frame: Baseline and Week 6
Double-blind Treatment Period: Change From Baseline in the HDRS17 Anxiety/Somatization Factor Total Score at Week 6 (eITT Population)
The HDRS17 anxiety/somatization factor derived from Cleary and Guy's factor analysis of the HDRS17 scale, includes six items from the original 17-item version: 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.
Time frame: Baseline and Week 6
Double-blind Treatment Period: Change From Baseline in the HDRS17 Anxiety/Somatization Factor Total Score at Week 6 (fITT Population)
The HDRS17 anxiety/somatization factor derived from Cleary and Guy's factor analysis of the HDRS17 scale, includes six items from the original 17-item version: 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.
Time frame: Baseline and Week 6
Double-blind Treatment Period: Percentage of Participants With Greater Than or Equal to (>=) 30 Percent (%) Improvement on the HDRS17 Total Score at Week 6 (eITT Population)
Percentage of participants who had \>=30% improvement (responders) on HDRS17 total score at Week 6 were reported. HDRS17 is clinician-administered rating scale designed to assess severity of symptoms in participants 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.
Time frame: Week 6
Double-blind Treatment Period: Percentage of Participants With >= 30 % Improvement on the HDRS17 Total Score at Week 6 (fITT Population)
Percentage of participants who had \>=30% improvement (responders) on HDRS17 total score at Week 6 was reported. HDRS17 is clinician-administered rating scale designed to assess severity of symptoms in participants 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.
Time frame: Week 6
Double-blind Treatment Period: Percentage of Participants With >= 50% Improvement in the HDRS17 Total Score at Week 6 (eITT Population)
Percentage of participants who had \>=50% improvement (responders) in HDRS17 total score at Week 6 were reported. HDRS17 is clinician-administered rating scale designed to assess severity of symptoms in participants 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.
Time frame: Week 6
Double-blind Treatment Period: Percentage of Participants With >= 50% Improvement in the HDRS17 Total Score at Week 6 (fITT Population)
Percentage of participants who had \>=50% improvement (responders) in HDRS17 total score at Week 6 were reported. HDRS17 is clinician-administered rating scale designed to assess severity of symptoms in participants 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.
Time frame: Week 6
Double-blind Treatment Period: Percentage of Participants With >= 30% Improvement on SIGH-A Total Score at Week 6 (eITT Population)
The SIGH-A was included as a means to determine the frequency and severity of signs and symptoms of anxiety and determine both their influence on treatment and their responsiveness to treatment. The percentage of participants who had \>= 30% improvement (responders) 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.
Time frame: Week 6
Double-blind Treatment Period: Percentage of Participants With >= 30% Improvement on SIGH-A Total Score at Week 6 (fITT Population)
The SIGH-A was included as a means to determine the frequency and severity of signs and symptoms of anxiety and determine both their influence on treatment and their responsiveness to treatment. The percentage of participants who had \>= 30% improvement (responders) 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.
Time frame: Week 6
Double-blind Treatment Period: Percentage of Participants With >= 50% Improvement on SIGH-A Total Score at Week 6 (eITT Population)
The SIGH-A was included as a means to determine the frequency and severity of signs and symptoms of anxiety and determine both their influence on treatment and their responsiveness to treatment. The percentage of participants who had \>= 50% improvement (responders) 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.
Time frame: Week 6
Double-blind Treatment Period: Percentage of Participants With >= 50% Improvement on SIGH-A Total Score at Week 6 (fITT Population)
The SIGH-A was included as a means to determine the frequency and severity of signs and symptoms of anxiety and determine both their influence on treatment and their responsiveness to treatment. The percentage of participants who had \>= 50% improvement (responders) 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.
Time frame: Week 6
Double-blind Treatment Period: Percentage of Participants With Remission as Assessed by HDRS17 Total Score Less Than or Equal to (<=) 7 at Week 6 (eITT Population)
Percentage of participants with HDRS17 total score \<= 7 were considered as remitters. HDRS17 is clinician-administered rating scale designed to assess severity of symptoms in participants 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.
Time frame: Week 6
Double-blind Treatment Period: Percentage of Participants With Remission as Assessed by HDRS17 Total Score <= 7 at Week 6 (fITT Population)
Percentage of participants with HDRS17 total score \<= 7 were considered as remitters. HDRS17 is clinician-administered rating scale designed to assess severity of symptoms in participants 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.
Time frame: Week 6
Double-blind Treatment Period: Percentage of Participants With a Clinical Global Impression Improvement (CGI-I) Score of Very Much Improved or Much Improved at Week 6 (eITT Population)
The percentage of participants 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 participant'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.
Time frame: Week 6
Double-blind Treatment Period: Percentage of Participants With a Clinical Global Impression Improvement (CGI-I) Score of Very Much Improved or Much Improved at Week 6 (fITT Population)
The percentage of participants 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 participant'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.
Time frame: Week 6
Maximum Plasma Concentration (Cmax) of JNJ-42165279
Cmax is defined as maximum plasma concentration of JNJ-42165279. The data was pooled across visits at different timepoints to calculate Cmax.
Time frame: Pre-dose, 2 to 4 hours post-dose on Days 14, 35, 63, and 77
Area Under the Plasma Concentration-time Curve From Zero to Dosing Intervals (AUC[0-tau]) of JNJ-42165279
AUC(0-tau) is defined as area under the plasma concentration-time curve from 0 to t hours post dosing (time t is the dosing interval). The data was pooled across visits at different timepoints to calculate AUC(0-tau).
Time frame: Pre-dose, 2 to 4 hours post-dose on Days 14, 35, 63, and 77
Time to Reach the Maximum Plasma Concentration (Tmax) of JNJ-42165279
Tmax is defined as time to reach the maximum plasma concentration of JNJ-42165279. The data was pooled across visits at different timepoints to calculate Tmax.
Time frame: Pre-dose, 2 to 4 hours post-dose on Days 14, 35, 63, and 77