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Trial record 28 of 49 for:    "Depressive Disorder" [DISEASE] AND Behavioral | ( Map: Belgium )

A Long-term, Safety and Efficacy Study of Intranasal Esketamine in Treatment-resistant Depression (SUSTAIN-2)

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ClinicalTrials.gov Identifier: NCT02497287
Recruitment Status : Completed
First Posted : July 14, 2015
Results First Posted : April 29, 2019
Last Update Posted : May 21, 2019
Sponsor:
Information provided by (Responsible Party):
Janssen Research & Development, LLC

Tracking Information
First Submitted Date  ICMJE May 18, 2015
First Posted Date  ICMJE July 14, 2015
Results First Submitted Date  ICMJE April 3, 2019
Results First Posted Date  ICMJE April 29, 2019
Last Update Posted Date May 21, 2019
Actual Study Start Date  ICMJE September 30, 2015
Actual Primary Completion Date October 28, 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 3, 2019)
  • Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) [ Time Frame: Up to End of Follow up Phase (Week 56) ]
    An adverse event is any untoward medical occurrence in a clinical study participants who administered a medicinal (investigational or non-investigational) product and does not necessarily have a causal relationship with the treatment. A TEAE defined as an event that was new in onset or increased in severity following treatment initiation.
  • Percentage of Participants With Cystitis, Urinary Tract Infections, Renal and Urinary Tract Symptoms, Renal and Urinary Disorders [ Time Frame: Up to End of Follow up Phase (Week 56) ]
    Percentage of participants with cystitis, urinary tract infections, renal and urinary tract symptoms, renal and urinary disorders were evaluated. Cystitis and urinary tract infections are selected MedDRA preferred terms, "renal and urinary tract symptoms" refers to any preferred term (PT) in the group of selected PTs; and "renal and urinary disorders" refers to a MedDRA System Organ Class (SOC).
  • Change From Baseline in Cognitive Test Battery: Detection Test (DET) Score [ Time Frame: Baseline (IND) up to the Endpoint (last post-baseline assessment value during 52 weeks of Optimization/Maintenance [OP/MA] Phase) ]
    This battery is a series of computerized cognition tests (detection, identification, one card learning, one back and groton maze learning) designed to measure reaction time, visual learning and memory, and executive function/sequencing. The DET is a measure of psychomotor function and uses a well-validated simple reaction time. In this outcome measure, speed of performance of participants (calculated as mean of the logarithmic base 10 transformed reaction times) for correct responses was reported. Total score ranges from 2 to 3.3 log 10 milliseconds (msec). Lower score indicates better performance. Higher change from baseline indicates better performance.
  • Change From Baseline in Cognitive Test Battery: Identification Test (IDN) Score [ Time Frame: Baseline (IND) up to the Endpoint (last post-baseline assessment value during 52 weeks of OP/MA Phase) ]
    This battery is a series of computerized cognition tests (detection, identification, one card learning, one back and groton maze learning) designed to measure reaction time, visual learning and memory, and executive function/sequencing. IDN test is a measure of visual attention (choice reaction time) and scored for speed of response (mean of the log10 transformed reaction times for correct responses). Total score ranges from 2 to 3.3 log 10 msec. Lower score indicates better performance. Higher change from baseline indicates better performance.
  • Change From Baseline in Cognitive Test Battery: One Card Learning Test (OCL) Score [ Time Frame: Baseline (IND) up to the Endpoint (last post-baseline assessment value during 52 weeks of OP/MA Phase) ]
    This battery is a series of computerized cognition tests (detection, identification, one card learning, one back and groton maze learning) designed to measure reaction time, visual learning and memory, and executive function/sequencing. OCL test is a measure of visual episodic memory and visual recall test scored using arcsine transformation of the percentage of correct responses (CR). The range for OCL is 0 to 100 percent (%) accuracy; presented as an arcsin transformation, the range is 0 to 1.57. Higher score indicates better performance. Higher change from baseline indicates better performance.
  • Change From Baseline in Cognitive Test Battery: One Back Test (ONB) Score [ Time Frame: Baseline (IND) up to the Endpoint (last post-baseline assessment value during 52 weeks of OP/MA Phase) ]
    The ONB is a measure of working memory and scored for speed of correct response (mean of the log10-transformed reaction times for correct responses). Total score ranges from 2 to 3.54 log10 msec. Lower score indicates better performance. Higher change from baseline indicates better performance.
  • Change From Baseline in Cognitive Test Battery: Groton Maze Learning Test (GMLT) Score [ Time Frame: Baseline (IND) up to the Endpoint (last post-baseline assessment value during 52 weeks of OP/MA Phase) ]
    This battery is a series of computerized cognition tests (detection, identification, one card learning, one back and groton maze learning) designed to measure reaction time, visual learning and memory, and executive function/sequencing. GMLT measures executive function; maze/sequencing test, scored for total number of errors. Total score ranges from 0 to 999 number of errors. Lower score indicates better performance. Higher change from baseline indicates better performance.
  • Change From Baseline in Hopkins Verbal Learning Test-Revised (HVLT-R) Score: Total Recall [ Time Frame: Baseline (IND) up to the Endpoint (last post-baseline assessment value during 52 weeks of OP/MA Phase) ]
    Hopkins Verbal Learning Test (HVLT) measures performance in verbal memory, learning, and long-term recall in which a list of words is read up to three times. Approximately 20-25 minutes later, a delayed recall trial and a recognition trial are completed. The delayed recall requires free recall of any words remembered. The recognition trial is composed of 24 words, including the 12 target words and 12 false-positives. When scoring the HVLT, the three learning trials are combined to calculate a total recall score (0-36); the delayed recall trial creates the delayed recall score (0 -12); the retention (%) score (0-100%) is calculated by dividing the delayed recall trial by the higher of learning trial 2 or 3; and the recognition discrimination index is comprised by subtracting the total number of false positives from the total number of true positives. A higher score = higher cognition.
  • Change From Baseline in Hopkins Verbal Learning Test-Revised (HVLT-R) Score: Delayed Recall [ Time Frame: Baseline (IND) up to the Endpoint (last post-baseline assessment value during 52 weeks of OP/MA Phase) ]
    HVLT measures performance in verbal memory, learning, and long-term recall in which a list of words is read up to three times. Approximately 20-25 minutes later, a delayed recall trial and a recognition trial are completed. The delayed recall requires free recall of any words remembered. The recognition trial is composed of 24 words, including the 12 target words and 12 false-positives. When scoring the HVLT, the three learning trials are combined to calculate a total recall score (0-36); the delayed recall trial creates the delayed recall score (0 -12); the retention (%) score (0-100%) is calculated by dividing the delayed recall trial by the higher of learning trial 2 or 3; and the recognition discrimination index is comprised by subtracting the total number of false positives from the total number of true positives. A higher score = higher cognition.
  • Change From Baseline in Hopkins Verbal Learning Test-Revised (HVLT-R) Score: Number of Words Recalled [ Time Frame: Baseline (IND) up to the Endpoint (last post-baseline assessment value during 52 weeks of OP/MA Phase) ]
    HVLT measures performance in verbal memory, learning, and long-term recall in which a list of words is read up to three times. Approximately 20-25 minutes later, a delayed recall trial and a recognition trial are completed. The delayed recall requires free recall of any words remembered. The recognition trial is composed of 24 words, including the 12 target words and 12 false-positives. When scoring the HVLT, the three learning trials are combined to calculate a total recall score (0-36); the delayed recall trial creates the delayed recall score (0 -12); the retention (%) score (0-100%) is calculated by dividing the delayed recall trial by the higher of learning trial 2 or 3; and the recognition discrimination index is comprised by subtracting the total number of false positives from the total number of true positives. A higher score = higher cognition.
  • Change From Baseline in Hopkins Verbal Learning Test-Revised (HVLT-R) Score: Recognition Discrimination Index [ Time Frame: Baseline (IND) up to the Endpoint (last post-baseline assessment value during 52 weeks of OP/MA phase) ]
    HVLT measures performance in verbal memory, learning, and long-term recall in which a list of words is read up to three times. Approximately 20-25 minutes later, a delayed recall trial and a recognition trial are completed. The delayed recall requires free recall of any words remembered. The recognition trial is composed of 24 words, including the 12 target words and 12 false-positives. When scoring the HVLT, the three learning trials are combined to calculate a total recall score (0-36); the delayed recall trial creates the delayed recall score (0 -12); the retention (%) score (0-100%) is calculated by dividing the delayed recall trial by the higher of learning trial 2 or 3; and the recognition discrimination index is comprised by subtracting the total number of false positives from the total number of true positives. A higher score = higher cognition.
Original Primary Outcome Measures  ICMJE
 (submitted: July 10, 2015)
  • Change from baseline in Bladder Pain/ Interstitial Cystitis Symptom Score (BPIC-SS) score greater than (>)18 over time [ Time Frame: Baseline (Day 1) up to end of Follow Up phase (Week 56) ]
    Bladder Pain/ Interstitial Cystitis Symptom Score (BPIC-SS), is a scale to monitor for symptoms of cystitis, bladder pain, and interstitial cystitis.
  • Change from baseline in Cogstate computerized cognitive battery domains and Hopkins Verbal Learning Test-Revised (HVLT-R) [ Time Frame: Baseline (Day 1) up to end of Follow Up phase (Week 56) ]
    The cognitive battery will provide assessment of multiple cognitive domains, including attention, visual learning and memory, and executive function. The HVLT-R is a measure of verbal learning and memory.
  • Incidence of withdrawal symptoms assessed by Physician Withdrawal Checklist (PWC-20) [ Time Frame: Week 52 (end of optimization/maintenance phase) or Week 54 (week 2 of Follow Up phase) or Week 56 (week 4 of Follow Up phase) ]
    The PWC-20 is a 20-item questionnaire to assess potential development of discontinuation symptoms after stopping of study drug.
Change History Complete list of historical versions of study NCT02497287 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: April 3, 2019)
  • Change From Baseline to Endpoint in Montgomery Asberg Depression Rating Scale (MADRS) Total Score During Induction (IND) Phase [ Time Frame: Baseline (IND) up to the Endpoint (last post-baseline assessment value during 4 weeks of IND phase) ]
    MADRS measures depression severity, detects changes due to AD treatment. It consists 10 items (evaluate apparent sadness, reported sadness, inner tension, sleep, appetite, concentration, lassitude, interest level, pessimistic thoughts, suicidal thoughts), scored from 0 (item not present or normal) to 6 (severe or continuous presence of the symptoms), summed for a total possible score of 0 to 60. Higher scores indicate more severe condition. Negative change in score indicates improvement. Missing data was imputed using last observation carried forward (LOCF) method, last post baseline observation during the phase was carried forward as the "Endpoint".
  • Change From Baseline to Endpoint in MADRS Total Score During Optimization/Maintenance (OP/MA) Phase [ Time Frame: Baseline (OP/MA) up to the Endpoint (last post-baseline assessment value during 52 weeks of OP/MA Phase) ]
    MADRS measure depression severity, detects changes due to AD treatment. It evaluates 10 items: apparent sadness, reported sadness, inner tension, sleep, appetite, concentration, lassitude, interest level, pessimistic thoughts, suicidal thoughts, each of which is scored from 0 (item is not present or is normal) to 6 (severe or continuous presence of the symptoms), summed for a total possible score of 0 to 60. Higher scores represent a more severe condition. Negative change in score indicates improvement. Missing data was imputed using LOCF method and the last post baseline observation during the phase was carried forward as the "Endpoint".
  • Change From Baseline to Endpoint in Patient Health Questionnaire - 9 (PHQ-9) Total Score During IND Phase [ Time Frame: Baseline (IND) up to the Endpoint (last post-baseline assessment value during 4 weeks of IND phase) ]
    PHQ-9 is a 9-item, self-reporting scale assessing depressive symptoms. Each item was rated on a 4-point scale (0 = Not at all, 1 = Several Days, 2 = More than half the days, and 3 = Nearly every day), with a total score range of 0-27. A higher score indicates greater severity of depression. Severity of PHQ-9 categorized as follows: none-minimal (0-4), mild (5-9), moderate (10-14), moderately severe (15-19), severe (20-27). The recall period is 2 weeks. Negative change in score indicates improvement. Missing data was imputed using LOCF method and the last post baseline observation during the phase was carried forward as the "Endpoint".
  • Change From Baseline to Endpoint in PHQ-9 Total Score During OP/MA Phase [ Time Frame: Baseline (OP/MA) up to the Endpoint (last post-baseline assessment value during 52 weeks of OP/MA phase) ]
    PHQ-9 is a 9-item, self-reporting scale assessing depressive symptoms. Each item was rated on a 4-point scale (0 = Not at all, 1 = Several Days, 2 = More than half the days, and 3 = Nearly every day), with a total score range of 0-27. A higher score indicates greater severity of depression. severity of PHQ-9 categorized as follows: none-minimal (0-4), mild (5-9), moderate (10-14), moderately severe (15-19), severe (20-27). The recall period is 2 weeks. Negative change in score indicates improvement. Missing data was imputed using LOCF method and the last post baseline observation during the phase was carried forward as the "Endpoint".
  • Change From Baseline to Endpoint in Clinical Global Impression of Severity (CGI-S) Scale Score During IND Phase [ Time Frame: Baseline (IND) up to the Endpoint (last post-baseline assessment value during 4 weeks of IND phase) ]
    CGI-S measures severity of participant's illness that include knowledge of participant's history, psychosocial circumstances, symptoms, behavior, impact of symptoms on participant's ability to function. CGI-S evaluates severity of psychopathology on a scale range from 0 - 7, where 0=not assessed; 1=normal (not at all ill); 2=borderline mentally ill; 3=mildly ill; 4=moderately ill; 5=markedly ill; 6=severely ill; 7=among the most extremely ill patients. Negative change in score indicates improvement. Missing data was imputed using LOCF method and the last post baseline observation during the phase was carried forward as "Endpoint".
  • Change From Baseline to Endpoint in CGI-S Scale Score During OP/MA Phase [ Time Frame: Baseline (OP/MA) up to the Endpoint (last post-baseline assessment value during 52 weeks of OP/MA phase) ]
    The CGI-S measures the severity of the participant's illness that include knowledge of the participant's history, psychosocial circumstances, symptoms, behavior, and the impact of the symptoms on the participant's ability to function. The CGI-S evaluates the severity of psychopathology on a scale of 0 to 7, where 0=not assessed; 1=normal (not at all ill); 2=borderline mentally ill; 3=mildly ill; 4=moderately ill; 5=markedly ill; 6=severely ill; 7=among the most extremely ill patients. Negative change in score indicates improvement. Missing data was imputed using LOCF method and the last post baseline observation during the phase was carried forward as the "Endpoint".
  • Change From Baseline to Endpoint in Generalized Anxiety Disorder (GAD-7) Total Score During IND Phase [ Time Frame: Baseline (IND) up to the Endpoint (last post-baseline assessment value during 4 weeks of IND phase) ]
    GAD-7 is brief, validated 7-item self-reported assessment of overall anxiety. Participant's responded to each item using a 4 point scale with response categories: 0=not at all, 1=several days, 2=more than half the days, and 3=nearly every day. Item responses are summed to yield total score ranges from 0 to 21, higher scores indicate more anxiety. Negative change in score indicates improvement. Severity of GAD-7 is categorized as: None (0-4), Mild (5-9), Moderate (10-14), Severe (15 -21). Missing data was imputed using LOCF method, last post baseline observation during the phase was carried forward as "Endpoint".
  • Change From Baseline to Endpoint in GAD-7 Total Score During OP/MA Phase [ Time Frame: Baseline (OP/MA) up to the Endpoint (last post-baseline assessment value during 52 weeks of OP/MA phase) ]
    GAD-7 is brief and validated 7-item self-reported assessment of overall anxiety. Participants respond to each item using a 4 point scale with response categories: 0=not at all, 1=several days, 2=more than half the days, and 3=nearly every day. Item responses are summed to yield a total score ranges from 0 to 21, higher scores indicate more anxiety. Negative change in score indicates improvement. Severity of the GAD-7 is categorized as follows: None (0-4), Mild (5-9), Moderate (10-14), Severe (15 -21). Missing data was imputed using LOCF method and the last post baseline observation during the phase was carried forward as the "Endpoint".
  • Change From Baseline to Endpoint in European Quality of Life (EuroQol) 5-Dimension, 5-Level (EQ 5D-5L) During IND Phase: Sum Score [ Time Frame: Baseline (IND) up to the Endpoint (last post-baseline assessment value during 4 weeks of IND phase) ]
    EQ-5D-5L consists of EQ-5D-5L descriptive system and EQ visual analogue scale (EQ VAS). EQ-5D-5L descriptive system comprises of 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each has 5 levels of perceived problems (1-no problem, 2-slight problems, 3-moderate problems, 4-severe problems, 5-extreme problems). Participant selects answer for each of 5 dimensions considering response that best matches his/her health "today". Responses were used to generate a Health Status Index (HSI). HSI ranges from -0.148 to 0.949 and is anchored at 0 (health state value equal to dead) and 1 (full health). EQ VAS self-rating records the respondent's own assessment of his/her overall health status at time of completion, on a scale of 0 (worst health you can imagine) to 100 (best health you can imagine). Sum score ranges from 0 to 100 where, sum score = (sum of the scores from the 5 dimensions minus 5) *5. Higher score indicates worst health state.
  • Change From Baseline to Endpoint in EQ-5D-5L Score During IND Phase: EQ-VAS [ Time Frame: Baseline (IND) up to the Endpoint (last post-baseline assessment value during 4 weeks of IND phase) ]
    EQ-5D-5L consists of EQ-5D-5L descriptive system and EQ VAS. EQ VAS self-rating records the respondent's own assessment of his/her overall health status at time of completion, on a scale of 0 (worst health you can imagine) to 100 (best health you can imagine).
  • Change From Baseline to Endpoint in EQ-5D-5L Scale Score During IND Phase: Health Status Index [ Time Frame: Baseline (IND) up to the Endpoint (last post-baseline assessment value during 4 weeks of IND phase) ]
    EQ-5D-5L consists of EQ-5D-5L descriptive system and EQ VAS. EQ-5D-5L descriptive system comprises of 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each has 5 levels of perceived problems (1-no problem, 2-slight problems, 3-moderate problems, 4-severe problems, 5-extreme problems). Participant selects answer for each of 5 dimensions considering response that best matches his/her health "today". Responses were used to generate a HSI. HSI ranges from -0.148 to 0.949 and is anchored at 0 (health state value equal to dead) and 1 (full health).
  • Change From Baseline to Endpoint in European Quality of Life (EuroQol) 5-Dimension, 5-Level (EQ 5D-5L) During OP/MA Phase: Sum Score [ Time Frame: Baseline (OP/MA) up to the Endpoint (last post-baseline assessment value during 52 weeks of OP/MA phase) ]
    EQ-5D-5L consists of EQ-5D-5L descriptive system and EQ VAS. EQ-5D-5L descriptive system comprises of 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each has 5 levels of perceived problems (1-no problem, 2-slight problems, 3-moderate problems, 4-severe problems, 5-extreme problems). Participant selects answer for each of 5 dimensions considering response that best matches his/her health "today". Responses were used to generate a Health Status Index (HSI). HSI ranges from -0.148 to 0.949 and is anchored at 0 (health state value equal to dead) and 1 (full health). EQ VAS self-rating records the respondent's own assessment of his/her overall health status at time of completion, on a scale of 0 (worst health you can imagine) to 100 (best health you can imagine). Sum score ranges from 0 to 100 where, sum score = (sum of the scores from the 5 dimensions minus 5) *5. Higher score indicates worst health state.
  • Change From Baseline to Endpoint in EQ-5D-5L Score During OP/MA Phase: EQ-VAS [ Time Frame: Baseline (OP/MA) up to the Endpoint (last post-baseline assessment value during 52 weeks of OP/MA phase) ]
    EQ-5D-5L consists of EQ-5D-5L descriptive system and EQ VAS. EQ VAS self-rating records the respondent's own assessment of his/her overall health status at time of completion, on a scale of 0 (worst health you can imagine) to 100 (best health you can imagine).
  • Change From Baseline to Endpoint in EQ-5D-5L Scale Score During OP/MA Phase: Health Status Index [ Time Frame: Baseline (OP/MA) up to the Endpoint (last post-baseline assessment value during 52 weeks of OP/MA phase) ]
    EQ-5D-5L consists of EQ-5D-5L descriptive system and EQ VAS. EQ-5D-5L descriptive system comprises of 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each has 5 levels of perceived problems (1-no problem, 2-slight problems, 3-moderate problems, 4-severe problems, 5-extreme problems). Participant selects answer for each of 5 dimensions considering response that best matches his/her health "today". Responses were used to generate a HSI. HSI ranges from -0.148 to 0.949 and is anchored at 0 (health state value equal to dead) and 1 (full health).
  • Change From Baseline in Sheehan Disability Scale (SDS) Total Score During IND Phase [ Time Frame: Baseline (IND) up to the Endpoint (last post-baseline assessment value during 4 weeks of IND Phase) ]
    SDS was a 5 item questionnaire used for assessment of functional impairment and associated disability. The first three items assess disruption of (1) work/school, (2) social life, (3) family life/home responsibilities using a 0 to 10 rating scale. Score for the first three items are summed to create a total score of 0 to 30, higher score indicates greater impairment and a negative change in score indicates improvement. Missing data was imputed using LOCF method and the last post baseline observation during the phase was carried forward as the "Endpoint".
  • Change From Baseline in Sheehan Disability Scale Total Score During OP/MA Phase [ Time Frame: Baseline (OP/MA) up to the Endpoint (last post-baseline assessment value during 52 weeks of OP/MA phase) ]
    SDS was a participant-reported outcome measure and was a 5 item questionnaire used for assessment of functional impairment and associated disability. The first three items assess disruption of (1) work/school, (2) social life, and (3) family life/home responsibilities using a 0 to 10 rating scale. The score for the first three items are summed to create a total score of 0 to 30 where a higher score indicates greater impairment and a negative change in score indicates improvement. Missing data was imputed using LOCF method and the last post baseline observation during the phase was carried forward as the "Endpoint".
  • Percentage of Participants With Response as Assessed by MADRS Total Score During IND Phase [ Time Frame: Days 8, 15, 22 and Endpoint (last post-baseline assessment during 4 weeks of IND phase) ]
    Response is defined as greater than or equal to (>=) 50 % reduction from baseline in the MADRS total score. MADRS measures depression severity, detects changes due to AD treatment. It consists 10 items (evaluate apparent sadness, reported sadness, inner tension, sleep, appetite, concentration, lassitude, interest level, pessimistic thoughts, suicidal thoughts), scored from 0 (item not present or normal) to 6 (severe or continuous presence of the symptoms), summed for a total possible score of 0 to 60. Higher scores indicate more severe condition. Negative change in score indicates improvement. Missing data was imputed using LOCF method and the last post baseline observation during the phase was carried forward as the "Endpoint".
  • Percentage of Participants With Response as Assessed by PHQ-9 Total Score During IND Phase [ Time Frame: Day 15 and Endpoint (last post-baseline assessment value during 4 Week IND phase) ]
    Response is defined as >= 50 % reduction from baseline (IND phase) in PHQ-9 total score. PHQ-9 is a 9-item, self-reporting scale assessing depressive symptoms. Each item was rated on a 4-point scale (0 = Not at all, 1 = Several Days, 2 = More than half the days, and 3 = Nearly every day), with a total score range of 0-27. The scores are summed for a total score ranging from 0-27. A higher score indicates greater severity of depression. Severity of PHQ-9 categorized as follows: none-minimal (0-4), mild (5-9), moderate (10-14), moderately severe (15-19), severe (20-27). The recall period is 2 weeks. Negative change in score indicates improvement. Missing data was imputed using LOCF method and the last post baseline observation during the phase was carried forward as the "Endpoint".
  • Percentage of Participants With Remission as Assessed by MADRS Total Score During IND Phase [ Time Frame: Days 8, 15, 22 and Endpoint (last post-baseline assessment value during 4 weeks of IND Phase) ]
    Remission is defined as MADRS total score less than or equal to (<=) 12. MADRS measures depression severity, detects changes due to AD treatment. It consists 10 items (evaluate apparent sadness, reported sadness, inner tension, sleep, appetite, concentration, lassitude, interest level, pessimistic thoughts, suicidal thoughts), scored from 0 (item not present or normal) to 6 (severe or continuous presence of the symptoms), summed for a total possible score of 0 to 60. Higher scores indicate more severe condition. Negative change in score indicates improvement. Missing data was imputed using LOCF method and the last post baseline observation during the phase was carried forward as the "Endpoint".
  • Percentage of Participants With Remission as Assessed by PHQ-9 Total Score During IND Phase [ Time Frame: Day 15 and Endpoint (last post-baseline assessment value during 4 weeks of IND phase) ]
    Remission is defined as PHQ-9 total score <= 4. PHQ-9 is a 9-item, self-reporting scale assessing depressive symptoms. Each item was rated on a 4-point scale (0 = Not at all, 1 = Several Days, 2 = More than half the days, and 3 = Nearly every day), with a total score range of 0-27. The scores are summed for a total score ranging from 0-27. A higher score indicates greater severity of depression. severity of PHQ-9 categorized as follows: none-minimal (0-4), mild (5-9), moderate (10-14), moderately severe (15-19), severe (20-27). The recall period is 2 weeks. Negative change in score indicates improvement. Missing data was imputed using LOCF method and the last post baseline observation during the phase was carried forward as the "Endpoint".
  • Percentage of Participants With an Increase Score From Predose at Any Time in Clinician-Administered Dissociative States Scale (CADSS) Total Score During IND Phase [ Time Frame: Predose, up to 1.5 hours postdose (up to end of IND phase [Week 4]) ]
    The CADSS used to measure present-state dissociative symptoms, and to assess treatment-emergent dissociative symptoms. It comprises 23 subjective items divided into 3 components: depersonalization (with score range from 0 to 28), derealization (with score range from 0 to 52), and amnesia (with score range from 0 to 8). Participants responses are coded on a 5-point scale (0 = "Not at all", 1 = "Mild", 2 = "Moderate", 3 = 'Severe" and 4 = "Extreme"). The total score is sum of the 23 items and range from 0 to 92, where 0 (best) and 92 (worst). A higher score indicates a more severe condition.
  • Percentage of Participants With an Increase Score From Predose at Any Time in CADSS Total Score During OP/MA Phase [ Time Frame: Predose, up to 1.5 hours postdose (up to end of OP/MA phase [Week 52]) ]
    The CADSS used to measure present-state dissociative symptoms, and to assess treatment-emergent dissociative symptoms. It comprises 23 subjective items divided into 3 components: depersonalization (with score range from 0 to 28), derealization (with score range from 0 to 52), and amnesia (with score range from 0 to 8). Participants responses are coded on a 5-point scale (0 = "Not at all", 1 = "Mild", 2 = "Moderate", 3 = 'Severe" and 4 = "Extreme"). The total score is sum of the 23 items and range from 0 to 92, where 0 (best) and 92 (worst). A higher score indicates a more severe condition.
  • Percentage of Participants With Treatment-Emergent Acute Hypertension (Systolic and Diastolic) During IND and OP/MA Phases [ Time Frame: Up to End of OP/MA phase (Week 52) ]
    Percentage of participants with treatment-emergent acute hypertension (Systolic Blood Pressure >=180 millimeters of mercury [mm Hg] or Diastolic Blood Pressure >= 110 mm Hg) during IND and OP/MA Phases were evaluated.
Original Secondary Outcome Measures  ICMJE
 (submitted: July 10, 2015)
  • Number of participants with Treatment-Emergent Adverse Events (TEAEs) [ Time Frame: Day 1 post dose through end of Follow Up Phase (Week 56) ]
  • Change from baseline in Heart Rate [ Time Frame: Baseline of each dosing session (predose) up to the last post-dose measurement (40 minutes, 1 and 1.5 hours) from the start of Induction Phase to End of Optimization/Maintenance Phase (week 52) ]
    Change from baseline (predose) in heart rate will be assessed.
  • Change from Baseline in systolic and diastolic blood pressure [ Time Frame: Baseline of each dosing session (predose) up to the last post-dose measurement (40 minutes, 1 and 1.5 hours) from the start of Induction Phase to End of Optimization/Maintenance Phase (week 52) ]
    Change From Baseline (predose) in systolic and diastolic blood pressure will be assessed.
  • Change from Baseline in Respiratory rate [ Time Frame: Baseline of each dosing session (predose) up to the last post-dose measurement (40 minutes, 1 and 1.5 hours) from the start of Induction Phase to End of Optimization/Maintenance Phase (week 52) ]
    Change from Baseline in Respiratory rate (predose) will be assessed.
  • Change from Baseline in blood oxygen saturation [ Time Frame: Baseline of each dosing session (predose),up to the last post dose measurement (1.5 hours or longer) from the start of Induction Phase to End of Optimization/Maintenance Phase (week 52) ]
    Change From Baseline in Blood oxygen saturation (predose) will be assessed.
  • Change from Baseline in Modified Observer's Assessment of Alertness/Sedation (MOAAS) scale score [ Time Frame: Baseline of each dosing session (predose),up to the last post dose measurement (1.5 hours or longer) from the start of Induction Phase to End of Optimization/Maintenance Phase (week 52) ]
    Effects on alertness and sedation are measured using Modified Observer's Assessment of Alertness/Sedation (MOAAS) scale.
  • Change from Baseline in Brief Psychiatric Rating Scale Total Score [ Time Frame: Baseline of each dosing session (predose),up to the last post dose measurement (1.5 hours) from the start of Induction Phase to End of Optimization/Maintenance Phase (week 52) ]
    Potential psychosis-like effects are measured using Brief Psychiatric Rating Scale, positive-symptom subscale (BPRS+).
  • Change from Baseline in Clinician-Administered Dissociative States Scale (CADSS) total score [ Time Frame: Baseline of each dosing session (predose) , up to the last post-dose measurement (1.5 hours) from the start of Induction Phase to End of Optimization/Maintenance Phase (week 52) ]
    Dissociative symptoms are assessed using CADSS.
  • Change from Baseline in Columbia Suicide Severity Rating Scale (CSSRS) Score [ Time Frame: Baseline (Day 1) up to the End of Optimization/Maintenance Phase (week 52) ]
    Potential effects on suicidal ideation/behavior are evaluated with Columbia Suicide Severity Rating Scale (CSSRS).
  • Change from Baseline in Nasal Tolerability [ Time Frame: Baseline of each dosing session (predose) to 1-hour post-dose from the start of Induction Phase to End of Optimization/Maintenance Phase (week 52) ]
    Nasal tolerability will be assessed by a Nasal Tolerability Questionnaire.
  • Change from Baseline in Montgomery Asberg Depression Rating Scale (MADRS) Total Score [ Time Frame: Baseline up to End of Induction Phase (Day 28) and end of Optimization/Maintenance Phase (Week 52) ]
    The MADRS is a clinician-rated scale designed to measure depression severity and detects changes due to antidepressant treatment.
  • Change from Baseline in Clinical Global Impression-Severity (CGI-S) score [ Time Frame: Baseline up to End of Optimization/Maintenance Phase (Week 52) ]
    The CGI-S evaluates the severity of psychopathology on a scale of 0 to 7.
  • Change from Baseline in Subject-reported Depressive Symptoms Using the Patient Health Questionnaire - 9 (PHQ-9) Total Score [ Time Frame: Baseline up to End of Optimization/Maintenance Phase (Week 52) ]
    The PHQ-9 is a 9-item scale used to assess depressive symptoms. The responses for each item are summed to provide a total score (range of 0 to 27) with higher scores indicating greater severity of depressive symptoms.
  • Change from Baseline in Subject-reported Generalized Anxiety Disorder (GAD-7) Score [ Time Frame: Baseline up to End of Optimization/Maintenance Phase (Week 52) ]
    The GAD-7 is a brief and validated measure of overall anxiety.
  • Change from Baseline in Subject-Reported Health-related Quality of Life and Health Status as Assessed by EuroQol-5 Dimension-5 Level (EQ-5D-5L) [ Time Frame: Baseline up to End of Optimization/Maintenance Phase (Week 52) ]
    The EQ-5D-5L is a standardized instrument for use as a measure of health outcome. It consists of the EQ-5D-5L descriptive system and the EQ visual analogue scale (EQ-VAS). The EQ-5D-5L descriptive system comprises the following 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. The EQ-VAS self-rating records the respondent's own assessment of his or her overall health status at the time of completion, on a scale of 0 to 100.
  • Change from Baseline in Subject-reported Functioning and Associated Disability as Assessed by the Sheehan Disability Scale (SDS) Total Score [ Time Frame: Baseline up to End of Optimization/Maintenance Phase (Week 52) ]
    The SDS is a subject-reported outcome measure and is a 5-item questionnaire which has been widely used and accepted for assessment of functional impairment and associated disability.
  • Percentage of participants with Response [ Time Frame: Baseline (Day 1) of Induction Phase up to End of Optimization/Maintenance Phase (Week 52 ) ]
    Percentage of participants with greater than or equal to (>=) 50% reduction from baseline (induction phase) in the MADRS total score and PHQ 9 total score will be reported.
  • Percentage of participants with Remission [ Time Frame: Baseline (Day 1) of Induction Phase up to End of Optimization/Maintenance Phase (Week 52 ) ]
    Percentage of participants with MADRS total score less than or equal to (<=) 12 will be reported.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures
 (submitted: July 10, 2015)
  • Change from baseline in hematology, biochemistry and urinalysis parameters [ Time Frame: Baseline to Follow up (week 56) ]
    Safety parameters
  • Change from Baseline in Electrocardiogram (ECG) intervals [ Time Frame: Baseline of each dosing session (predose) up to the last post-dose measurement (1 hour) from the start of Induction Phase to End of Optimization/Maintenance Phase (week 52) ]
    Safety parameters
  • Number of participants with suicidal ideations with some intent to act based on Columbia Suicide Severity Rating Scale (CSSRS) [ Time Frame: Baseline (Day 1) up to End of Optimization/Maintenance Phase (week 52) ]
    Potential effects on suicidal ideation/behavior are evaluated with Columbia Suicide Severity Rating Scale (CSSRS).
 
Descriptive Information
Brief Title  ICMJE A Long-term, Safety and Efficacy Study of Intranasal Esketamine in Treatment-resistant Depression
Official Title  ICMJE An Open-label, Long-term, Safety and Efficacy Study of Intranasal Esketamine in Treatment-resistant Depression
Brief Summary The purpose of this open-label, multicenter study is to assess the long term safety and efficacy of intranasal esketamine plus an oral antidepressant in participants with treatment-resistant depression (TRD).
Detailed Description This is an open-label (the researchers and participants know the treatment the participant is receiving), multicenter (more than 1 study site), long-term safety and efficacy study of intranasal esketamine plus an oral antidepressant in participants with treatment-resistant depression (TRD). Participants will enter the study either directly (direct-entry participants) or after completing the Double-Blind Induction Phase of ESKETINTRD3005 (transferred-entry participants). The study consists of 4 phases: Screening Phase (4 weeks), Open-Label Induction Phase (4 weeks), Open-Label Optimization/Maintenance phase (48 weeks), and Follow up Phase (4 weeks). Transferred entry non-responders in the ESKETINTRD3005 may enter study at the Open-Label Induction Phase and responders in the ESKETINTRD3005 may enter Optimization/Maintenance phase. In the Open-Label Induction Phase, participants will self-administer flexibly-dosed intranasal esketamine (participants who are less than (<) 65 years old self-administer 56 mg or 84 mg dose, participants who are greater than or equal to (>=) 65 years old self-administer 28 mg, 56 mg or 84 mg dose) twice weekly for 4 weeks. The starting dose for all participants >= 65 years old will be 28 mg. In addition, each direct-entry participants will be assigned to receive 1 of 4 selected oral antidepressant medications (escitalopram or sertraline or duloxetine or venlafaxine extended release [XR]), initiated on Day 1 of the open-label induction phase and continued through the duration of the study. Transferred-entry participants will continue their same antidepressant from ESKETINTRD3005 through the duration of this study. Participants who are responders at the end of the Open-Label Induction phase and transferred-entry responder participants (from study ESKETINTRD3005) will enter the Optimization/Maintenance Phase where intranasal esketamine treatment sessions will be reduced from that in the induction phase (twice weekly) to weekly for the first 4 weeks of this phase, and then individualized to either once weekly or once every other week based on the severity of depressive symptoms. Participants' safety and depressive symptoms will be assessed and monitored throughout the study.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Treatment-resistant Depression
Intervention  ICMJE
  • Drug: Esketamine (Intranasal Spray)
    Open-Label Induction Phase: Participants will self-administer esketamine intranasally twice per week for 4 weeks as a flexible dose regimen (56 mg or 84 mg for those < 65 years; 28 mg, 56 mg or 84 mg for those >= 65 years). Participants >= 65 years old will start at a dose of 28 mg on Day 1. Optimization/Maintenance Phase: Participants will self-administer esketamine intranasally (56 mg or 84 mg for those < 65 years; 28 mg, 56 mg or 84 mg for those >= 65 years) once weekly then individualized to either once weekly or once every other week based on the severity of depressive symptoms. Transferred-entry responder participants from ESKETINTRD3005 >= 65 years old will start at a dose of 28 mg in Week 5.
  • Drug: Duloxetine (Oral Antidepressant)
    Duloxetine could be selected as the oral antidepressant medication by the investigator based on review of Massachusetts General Hospital - Antidepressant Treatment Response Questionnaire (MGH-ATRQ) and relevant prior antidepressant medication information. The minimum therapeutic dose is 60 milligram per day (mg/day).
  • Drug: Escitalopram (Oral Antidepressant)
    Escitalopram could be selected as the oral antidepressant medication by the investigator based on review of MGH-ATRQ and relevant prior antidepressant medication information. The minimum therapeutic dose is 10 mg/day. Participants >= 65 years of age will be titrated up to 20 mg/day, but can lower the dose to 10 mg/day for tolerability.
  • Drug: Sertraline (Oral Antidepressant)
    Sertraline could be selected as the oral antidepressant medication by the investigator based on review of MGH-ATRQ and relevant prior antidepressant medication information. Sertraline will be titrated up to a dose of 150 mg/day, but if not tolerated the dose can be reduced to the minimum therapeutic dose of 50 mg/day.
  • Drug: Venlafaxine Extended Release (XR) (Oral Antidepressant)
    Venlafaxine Extended Release could be selected as the oral antidepressant medication by the investigator based on review of MGH-ATRQ and relevant prior antidepressant medication information. Venlafaxine Extended Release will be titrated for participants < 65 years of age up to a dose of 225 mg/day, but if not tolerated the dose can be reduced to the minimum therapeutic dose of 150 mg/day. For participants >= 65, it can be titrated up to a dose of 150 mg/day, but if not tolerated the dose can be reduced to the minimum therapeutic dose of 75 mg/day.
Study Arms  ICMJE Experimental: Intranasal Esketamine plus oral antidepressant
Open-Label Induction Phase: Participants will self-administer esketamine intranasally twice per week for 4 weeks as a flexible dose regimen (56 mg or 84 mg). Participants greater than or equal to (>=) 65 will start at a dose of 28 mg on Day 1. Direct-entry participants will initiate a new, open-label oral antidepressant (duloxetine, escitalopram, sertraline, or venlafaxine extended release [XR]) on Day 1; transferred-entry participants will continue the same oral antidepressant from ESKETINTRD3005. Optimization/Maintenance Phase: Participants will self-administer esketamine (56mg or 84mg for those < 65 years; 28 mg, 56 mg or 84 mg for those >= 65 years) intranasally once per week for 4 weeks; transferred entry responder subjects from ESKETINTRD3005 will start at a dose of 28 mg in the first week. All participants will continue their same oral antidepressant during this phase.
Interventions:
  • Drug: Esketamine (Intranasal Spray)
  • Drug: Duloxetine (Oral Antidepressant)
  • Drug: Escitalopram (Oral Antidepressant)
  • Drug: Sertraline (Oral Antidepressant)
  • Drug: Venlafaxine Extended Release (XR) (Oral Antidepressant)
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: April 3, 2019)
802
Original Estimated Enrollment  ICMJE
 (submitted: July 10, 2015)
877
Actual Study Completion Date  ICMJE October 28, 2017
Actual Primary Completion Date October 28, 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

A). For Direct-Entry Participants

  • At the time of signing the informed consent form (ICF), participant must be a man or woman ≥18 (or older if the minimum legal age of consent in the country in which the study is taking place is greater than [>]18)
  • At the start of the screening phase, participant must meet the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) diagnostic criteria for single-episode major depressive disorder (MDD) (if single-episode MDD, the duration must be greater than or equal to [>=] 2 years) or recurrent MDD, without psychotic features, based upon clinical assessment and confirmed by the Mini-International Neuropsychiatric Interview (MINI)
  • At screening, participant must have a MADRS total score of >=22
  • At the start of the screening phase, participants must have had nonresponse to >=2 oral antidepressant treatments in the current episode of depression, as assessed using the the MGHATRQ and confirmed by documented records (example medical/pharmacy/prescription records or a letter from treating a physician, etc,) B). For Transferred-entry Participants
  • All participants who completed the double-blind induction phase of ESKETINTRD3005 study, regardless of their response status, will be eligible to participate in this study, if they meet the study specific eligibility criteria

Exclusion Criteria:

A). For Direct-Entry Participants

  • Participant's depressive symptoms have previously not responded to: Esketamine or ketamine in the current major depressive episode per clinical judgment or All of the 4 oral antidepressant treatment options available in the respective country for the open-label induction phase (that is, duloxetine, escitalopram, sertraline, and venlafaxine XR) in the current major depressive episode (based on Massachusetts General Hospital - Antidepressant Treatment Response Questionnaire [ MGH-ATRQ])
  • Participant has a current or prior DSM-5 diagnosis of a psychotic disorder or MDD with psychotic features, bipolar or related disorders (confirmed by the MINI), obsessive compulsive disorder (current only), intellectual disability (DSM-5 diagnostic codes 317, 318.0, 318.1, 318.2, 315.8, and 319), autism spectrum disorder, borderline personality disorder, antisocial personality disorder, histrionic personality disorder, or narcissistic personality disorder
  • Participant has homicidal ideation/intent, per the investigator's clinical judgment, or has suicidal ideation with some intent to act within 6 months prior to the start of the screening phase, per the investigator's clinical judgment or based on the Columbia Suicide Severity Rating Scale (C-SSRS)
  • Participants with history of moderate or severe substance or alcohol use disorder according to DSM-5 criteria
  • Participants who has a Mini Mental State Examination (MMSE) <25; Has neurodegenerative disorder (example, Alzheimer's disease, vascular dementia, Parkinson's disease), or evidence of mild cognitive impairment (MCI) B). Transferred-Entry Participants
  • Participant has taken any prohibited therapies that would not permit dosing on Day 1
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Belgium,   Argentina,   Australia,   Austria,   Brazil,   Bulgaria,   Finland,   France,   Germany,   Korea, Republic of,   Lithuania,   Malaysia,   Mexico,   Poland,   South Africa,   Spain,   Sweden,   Taiwan,   Turkey,   United Kingdom,   United States
Removed Location Countries Romania
 
Administrative Information
NCT Number  ICMJE NCT02497287
Other Study ID Numbers  ICMJE CR107148
ESKETINTRD3004 ( Other Identifier: Janssen Research & Development, LLC )
2014-004587-38 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Janssen Research & Development, LLC
Study Sponsor  ICMJE Janssen Research & Development, LLC
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Janssen Research & Development, LLC Clinical Trial Janssen Research & Development, LLC
PRS Account Janssen Research & Development, LLC
Verification Date May 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP