An Efficacy, Safety and Tolerability Study of JNJ-42165279 in Participants With Major Depressive Disorder With Anxious Distress

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

Population: The enriched intent-to-treat (eITT) analysis set included all enrolled participants 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 participants analyzed) signifies number of participants who were evaluable for this outcome measure.

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

Population: The full intent-to-treat (fITT) analysis set included both placebo responders and placebo non-responders and defined as all enrolled participants who were randomized into the double-blind treatment period, who received at least one dose of double-blind study medication and had at least one post-baseline HDRS17 assessment during the double-blind treatment period. Here 'N' (number of participants analyzed) signifies number of participants who were evaluable for this outcome measure.

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

Population: The Pharmacokinetic analysis set included all participants who received at least 1 dose of JNJ-42165279 and with measurable JNJ-42165279 concentrations in plasma. Here n (number analyzed) is defined as number of participants analyzed for specified category.

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

Population: The Full ITT (fITT) Analysis Set is defined as all enrolled participants who were randomized into the double-blind treatment period, who received at least one dose of double-blind study medication and have at least one post-baseline HDRS17 assessment during the double-blind treatment period. Here 'N' (number of participants analyzed) signifies number of participants who were evaluable for this outcome measure.

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

Population: The fITT Analysis Set is defined as all enrolled participants who were randomized into the double-blind treatment period, who received at least one dose of double-blind study medication and have at least one post-baseline HDRS17 assessment during the double-blind treatment period. Here 'N' (number of participants analyzed) signifies number of participants who were evaluable for this outcome measure.

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

Population: The eITT analysis set included all enrolled participants 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 participants analyzed) signifies number of participants who were evaluable for this outcome measure.

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

Population: The eITT analysis set included all enrolled participants 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 participants analyzed) signifies number of participants who were evaluable for this outcome measure.

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

Population: The fITT Analysis Set is defined as all enrolled participants who were randomized into the double-blind treatment period, who received at least one dose of double-blind study medication and have at least one post-baseline HDRS17 assessment during the double-blind treatment period. Here 'N' (number of participants analyzed) signifies number of participants who were evaluable for this outcome measure.

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

Population: The eITT analysis set included all enrolled participants 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 participants analyzed) signifies number of participants who were evaluable for this outcome measure.

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

Population: The eITT analysis set included all enrolled participants 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 participants analyzed) signifies number of participants who were evaluable for this outcome measure.

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

Population: The fITT Analysis Set is defined as all enrolled participants who were randomized into the double-blind treatment period, who received at least one dose of double-blind study medication and have at least one post-baseline HDRS17 assessment during the double-blind treatment period. Here 'N' (number of participants analyzed) signifies number of participants who were evaluable for this outcome measure

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

Population: The eITT analysis set included all enrolled participants 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 participants analyzed) signifies number of participants who were evaluable for this outcome measure.

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

Population: The fITT Analysis Set is defined as all enrolled participants who were randomized into the double-blind treatment period, who received at least one dose of double-blind study medication and have at least one post-baseline HDRS17 assessment during the double-blind treatment period. Here 'N' (number of participants analyzed) signifies number of participants who were evaluable for this outcome measure.

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

Population: The fITT Analysis Set is defined as all enrolled participants who were randomized into the double-blind treatment period, who received at least one dose of double-blind study medication and have at least one post-baseline HDRS17 assessment during the double-blind treatment period. Here 'N' (number of participants analyzed) signifies number of participants who were evaluable for this outcome measure.

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

Population: The eITT analysis set included all enrolled participants 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 DB treatment period. Here 'N' (number of participants analyzed) signifies number of participants who were evaluable for this outcome measure.

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

Population: The fITT Analysis Set is defined as all enrolled participants who were randomized into the double-blind treatment period, who received at least one dose of double-blind study medication and have at least one post-baseline HDRS17 assessment during the double-blind treatment period. Here 'N' (number of participants analyzed) signifies number of participants who were evaluable for this outcome measure.

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

Population: The eITT analysis set included all enrolled participants 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 participants analyzed) signifies number of participants who were evaluable for this outcome measure.

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

Population: The fITT Analysis Set is defined as all enrolled participants who were randomized into the double-blind treatment period, who received at least one dose of double-blind study medication and have at least one post-baseline HDRS17 assessment during the double-blind treatment period. Here 'N' (number of participants analyzed) signifies number of participants who were evaluable for this outcome measure.

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

Population: The eITT analysis set included all enrolled participants 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 participants analyzed) signifies number of participants who were evaluable for this outcome measure.

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

Population: The fITT Analysis Set is defined as all enrolled participants who were randomized into the double-blind treatment period, who received at least one dose of double-blind study medication and have at least one post-baseline HDRS17 assessment during the double-blind treatment period. Here 'N' (number of participants analyzed) signifies number of participants who were evaluable for this outcome measure.

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

Population: The eITT analysis set included all enrolled participants 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 participants analyzed) signifies number of participants who were evaluable for this outcome measure.

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

Population: The fITT Analysis Set is defined as all enrolled participants who were randomized into the double-blind treatment period, who received at least one dose of double-blind study medication and have at least one post-baseline HDRS17 assessment during the double-blind treatment period. Here 'N' (number of participants analyzed) signifies number of participants who were evaluable for this outcome measure.

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

Population: The eITT analysis set included all enrolled participants 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 participants analyzed) signifies number of participants who were evaluable for this outcome measure.

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

Population: The Pharmacokinetic analysis set included all participants who received at least 1 dose of JNJ-42165279 and with measurable JNJ-42165279 concentrations in plasma. Here n (number analyzed) is defined as number of participants analyzed for specified categories.

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

Population: The Pharmacokinetic analysis set included all participants who received at least 1 dose of JNJ-42165279 and with measurable JNJ-42165279 concentrations in plasma. Sparse samples was collected between 2 hours and 4 hours. It was not possible to accurately determine Tmax as Cmax is expected to be around 1 hour post-dose.