Major Depressive Disorder
Conditions
Brief summary
This study compares the effectiveness of 2 digital therapeutics in adult participants diagnosed with major depressive disorder (MDD) who are on antidepressant therapy (ADT) monotherapy for the treatment of depression.
Detailed description
This is a pivotal, 13-week, multi-center, randomized, controlled trial to evaluate the effectiveness and safety of two digital therapeutics in adult participants diagnosed with MDD who are on antidepressant therapy (ADT) monotherapy for the treatment of depression. The trial consists of a 3-week screening period, a 6-week treatment period, and a 4-week extension. Trial visits will be conducted remotely either by video visit or telephone. The screening visit may be performed in person at the discretion of the investigator. Eligible participants will be randomized to 1 of 2 digital therapeutics within a mobile application that will reside on the participant's personal iPhone or smartphone. The trial population will include male and female participants between 22 and 64 years of age with a primary diagnosis of major depressive disorder (MDD) who are on an ADT for the treatment of depression. This trial will analyze data gathered from approximately 360 participants in the United States. An interim analysis will be conducted when a targeted sample of the first 180 participants has completed week 6 or discontinued the trial prior to week 6.
Interventions
DEVICECT-152 - Digital Therapeutic
CT-152 mobile app was used by the participants as per the schedule specified in the respective arm.
DEVICESham
Sham mobile app was used by the participants as per the schedule specified in the respective arm.
Sponsors
Click Therapeutics, Inc.
Otsuka Pharmaceutical Development & Commercialization, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
22 Years to 64 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Participants with a current primary diagnosis of MDD. * Participants with a Hamilton Rating Scale for Depression, 17-item (HAM-D17) score ≥ 18 * Participants who are receiving treatment with an adequate dose and duration of an ADT and who are willing to maintain that same treatment regimen for the duration of this trial. * Participants who are the only users of an iPhone or an Android smartphone, and agree to download and use the digital mobile application as required by the protocol. Key
Exclusion criteria
* Participants with an inadequate response to \> 1 adequate trial of ADT for the current episode. * Participants who are receiving or have received psychotherapy within 90 days prior to screening. * Participants who are currently using a computer, web, or smartphone software-based application for mental health or depression. * Participants with a history of schizophrenia, schizoaffective disorder, other psychotic disorder, or Bipolar I/II disorder, or current posttraumatic stress disorder, panic disorder, obsessive-compulsive disorder, or personality disorder * General Anxiety Disorder/social anxiety can be present as long as they are not the main disorder requiring treatment.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to Week 6 in the MADRS Total Score | Baseline (Day 1) to Week 6 | The MADRS is used to assess depressive symptom severity. It consists of 10 items (apparent sadness, reported sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts and suicidal thoughts), each rated from 0 to 6 with zero being the best rating and 6 being the worst rating. The MADRS total score is the sum of ratings for all 10 items. The total score ranges from 0 to 60. A higher score on the MADRS represents a more severe level of depression. A negative change from baseline indicates improvement. Least square (LS) mean was estimated using Mixed Model Repeated Measures (MMRM) method. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to Week 6 in the GAD-7 Total Score | Baseline (Day 1) to Week 6 | The GAD-7 is self-reported questionnaire designed to assess anxiety in participants. The scale contains 7 items (anxiety symptoms) and each item was rated by the participants from 0 (not at all) to 3 (nearly every day) based on how much they were bothered by each symptom. The total score ranges from 0 to 21. A higher score on the GAD-7 represents greater anxiety symptomatology. A negative change from baseline indicates improvement. LS mean was estimated using MMRM method. |
Other
| Measure | Time frame | Description |
|---|---|---|
| MADRS Response Rate at Weeks 2, 4, and 6 | Baseline (Day 1), Weeks 2, 4 and 6 | The MADRS is used to assess depressive symptom severity. It consists of 10 items (apparent sadness, reported sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts and suicidal thoughts), each rated from 0 to 6 with zero being the best rating and 6 being the worst rating. The MADRS total score is the sum of ratings for all 10 items. The total score ranges from 0 to 60. A higher score on the MADRS represents a more severe level of depression. MADRS Response Rate was defined as the percentage of participants who achieved a reduction in the MADRS total score by 50% or more from baseline. |
| Change From Baseline to Weeks 2, 4 and 6 in the Clinical Global Impression - Severity of Illness (CGI-S) Score | Baseline (Day 1) to Weeks 2, 4 and 6 | The CGI-S is a standardized, clinician-administered global rating scale that measures disease severity on a 7-point Likert scale To perform this assessment, the investigator (or designee) answered the following question: Considering your total clinical experience with this particular population, how mentally ill (as related to agitation) is the participant at this time? Response choices are 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; and 7 = among the most extremely ill subjects. The score 0 (not assessed) will be set to missing. LS mean was estimated using MMRM method. |
| Change From Baseline to Week 6 in the World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0) Total Score | Baseline (Day 1) to Week 6 | The WHODAS 2.0 is a 36-item self-assessment scale to measure a participant's function and disability across 6 domains of life: cognition (understanding & communicating), mobility (moving & getting around), self-care (hygiene, dressing, eating, staying alone), getting along (interacting with others), life activities (domestic responsibilities, leisure, work & school), & participation (community & society). Each item is rated from 0 (none) to 4 (extreme or cannot do). The total score of the 36 items is converted into a metric ranging from 0 (no-disability) to 100 (full- disability) by dividing the total score by the maximum possible value of the total score, which is 144 for 36 items and multiplying by 100. LS Mean was estimated using ANCOVA method. |
| Change From Baseline to Weeks 2 and 4 in the MADRS Total Score | Baseline (Day 1) to Weeks 2 and 4 | The MADRS is used to assess depressive symptom severity. It consists of 10 items (apparent sadness, reported sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts and suicidal thoughts), each rated from 0 to 6 with zero being the best rating and 6 being the worst rating. The MADRS total score is the sum of ratings for all 10 items. The total score ranges from 0 to 60. A higher score on the MADRS represents a more severe level of depression. A negative change from baseline indicates improvement. LS mean was estimated using MMRM method. |
| MADRS Partial Response at Weeks 2, 4 and 6 | Baseline (Day 1), Weeks 2, 4 and 6 | The MADRS is used to assess depressive symptom severity. It consists of 10 items (apparent sadness, reported sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts and suicidal thoughts), each rated from 0 to 6 with zero being the best rating and 6 being the worst rating. The MADRS total score is the sum of ratings for all 10 items. The total score ranges from 0 to 60. A higher score on the MADRS represents a more severe level of depression. MADRS partial response was defined as the percentage of participants who achieved a reduction in the MADRS total score by 30% or more and less than 50% from baseline. |
| MADRS Response Rate at Weeks 8 and 10 | Baseline (Day 1), Weeks 8 and 10 | The MADRS is used to assess depressive symptom severity. It consists of 10 items (apparent sadness, reported sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts and suicidal thoughts), each rated from 0 to 6 with zero being the best rating and 6 being the worst rating. The MADRS total score is the sum of ratings for all 10 items. The total score ranges from 0 to 60. A higher score on the MADRS represents a more severe level of depression. MADRS Response Rate (full or partial) was defined as the percentage of participants who achieved a reduction in the MADRS total score by 30% or more from baseline. |
| Change From Screening to Weeks 4 and 6 in the PHQ-9 Total Score. | Screening to Weeks 4 and 6 | The PHQ-9 is a standardized, self-administered rating scale that assesses the severity of depressive symptoms. The scale consists of 9 items, representing the 9 criteria upon which the diagnosis of DSM-IV depressive disorders is based. Each item is rated from 0 (not at all) to 3 (nearly every day). The total score ranges from 0 to 27. A higher score on the PHQ-9 represents a higher severity of depressive symptoms. LS mean was estimated using MMRM method. |
| Change From Baseline to Weeks 2 and 4 in the GAD-7 Total Score | Baseline (Day 1) to Weeks 2 and 4 | The GAD-7 is self-reported questionnaire designed to assess anxiety in participants. The scale contains 7 items (anxiety symptoms) and each item was rated by the participants from 0 (not at all) to 3 (nearly every day) based on how much they were bothered by each symptom. The total score ranges from 0 to 21. A higher score on the GAD-7 represents greater anxiety symptomatology. A negative change from baseline indicates improvement. LS mean was estimated using MMRM method. |
Countries
United States
Participant flow
Recruitment details
Participants were enrolled at 37 investigative sites in the United States from 25 February 2021 to 26 October 2022.
Pre-assignment details
Participants with major depressive disorder were enrolled and randomized in a 1:1 ratio to 1 of the 2 digital mobile applications (CT-152 or sham) on Day 1.
Participants by arm
| Arm | Count |
|---|---|
| Digital Therapeutic A - CT-152 Participants received digital treatment session by using the CT-152 mobile app from Day 1 up to Week 6 of the treatment period. Each treatment session consisted of EFMT exercises and a psychotherapy lesson. From Week 7 up to Week 10 participants continued using the CT-152 app with optional psychotherapy lesson but did not receive any new EFMT exercises during this period. Participants continued receiving brief SMS messages during Weeks 7 to 10 as a reminder of the previously completed CT-152 treatment courses. | 194 |
| Digital Therapeutic B - Sham Participants received digital treatment session by using a sham mobile app from Day 1 up to Week 6 of the treatment period. Each treatment session consisted of a SMT exercise only. From Week 7 up to Week 10 participants continued using the sham app but did not receive any new SMT exercises during this period. Participants continued receiving brief SMS messages during Weeks 7 to 10 as a reminder of the previously completed sham treatment courses. | 192 |
| Total | 386 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lack of Efficacy | 0 | 1 |
| Overall Study | Lost to Follow-up | 11 | 8 |
| Overall Study | Non-Compliance With Study Treatment | 3 | 3 |
| Overall Study | Protocol Deviation | 6 | 6 |
| Overall Study | Reason Not Specified | 0 | 1 |
| Overall Study | Technical Problem | 0 | 1 |
| Overall Study | Withdrawal by Subject | 9 | 8 |
Baseline characteristics
| Characteristic | Digital Therapeutic B - Sham | Total | Digital Therapeutic A - CT-152 |
|---|---|---|---|
| Age, Continuous | 42.2 years STANDARD_DEVIATION 12.1 | 42.6 years STANDARD_DEVIATION 12.1 | 43.0 years STANDARD_DEVIATION 12.1 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 16 Participants | 36 Participants | 20 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 174 Participants | 347 Participants | 173 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants | 3 Participants | 1 Participants |
| Generalized Anxiety Disorder-7 (GAD-7) Total Score | 9.7 score on a scale STANDARD_DEVIATION 4.8 | 9.6 score on a scale STANDARD_DEVIATION 4.7 | 9.5 score on a scale STANDARD_DEVIATION 4.5 |
| MADRS Total Score | 28.4 score on a scale STANDARD_DEVIATION 6 | 28.4 score on a scale STANDARD_DEVIATION 6 | 28.4 score on a scale STANDARD_DEVIATION 6 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 1 Participants | 6 Participants | 5 Participants |
| Race/Ethnicity, Customized Asian | 4 Participants | 9 Participants | 5 Participants |
| Race/Ethnicity, Customized Black or African American | 25 Participants | 61 Participants | 36 Participants |
| Race/Ethnicity, Customized Other | 2 Participants | 9 Participants | 7 Participants |
| Race/Ethnicity, Customized White | 160 Participants | 301 Participants | 141 Participants |
| Sex: Female, Male Female | 167 Participants | 332 Participants | 165 Participants |
| Sex: Female, Male Male | 25 Participants | 54 Participants | 29 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 187 | 0 / 186 |
| other Total, other adverse events | 3 / 187 | 10 / 186 |
| serious Total, serious adverse events | 1 / 187 | 0 / 186 |
Outcome results
Primary
Change From Baseline to Week 6 in the MADRS Total Score
The MADRS is used to assess depressive symptom severity. It consists of 10 items (apparent sadness, reported sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts and suicidal thoughts), each rated from 0 to 6 with zero being the best rating and 6 being the worst rating. The MADRS total score is the sum of ratings for all 10 items. The total score ranges from 0 to 60. A higher score on the MADRS represents a more severe level of depression. A negative change from baseline indicates improvement. Least square (LS) mean was estimated using Mixed Model Repeated Measures (MMRM) method.
Time frame: Baseline (Day 1) to Week 6
Population: FAS included all randomized participants who received at least 1 occurrence of either CT-152 or sham use and had baseline and at least 1 postbaseline assessment of MADRS total score. Overall number of participants analyzed is the number of participants with data available for analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Digital Therapeutic A - CT-152 | Change From Baseline to Week 6 in the MADRS Total Score | -9.03 score on a scale | Standard Error 0.73 |
| Digital Therapeutic B - Sham | Change From Baseline to Week 6 in the MADRS Total Score | -7.25 score on a scale | Standard Error 0.73 |
p-value: 0.056895% CI: [-3.6, 0.05]MMRM
Secondary
Change From Baseline to Week 6 in the GAD-7 Total Score
The GAD-7 is self-reported questionnaire designed to assess anxiety in participants. The scale contains 7 items (anxiety symptoms) and each item was rated by the participants from 0 (not at all) to 3 (nearly every day) based on how much they were bothered by each symptom. The total score ranges from 0 to 21. A higher score on the GAD-7 represents greater anxiety symptomatology. A negative change from baseline indicates improvement. LS mean was estimated using MMRM method.
Time frame: Baseline (Day 1) to Week 6
Population: FAS included all randomized participants who received at least 1 occurrence of either CT-152 or sham use and had baseline and at least 1 postbaseline assessment of MADRS total score. Overall number of participants analyzed is the number of participants with data available for analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Digital Therapeutic A - CT-152 | Change From Baseline to Week 6 in the GAD-7 Total Score | -3.41 score on a scale | Standard Error 0.34 |
| Digital Therapeutic B - Sham | Change From Baseline to Week 6 in the GAD-7 Total Score | -2.64 score on a scale | Standard Error 0.34 |
p-value: 0.070595% CI: [-1.61, 0.07]MMRM
Other Pre-specified
Change From Baseline to Week 6 in the World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0) Total Score
The WHODAS 2.0 is a 36-item self-assessment scale to measure a participant's function and disability across 6 domains of life: cognition (understanding & communicating), mobility (moving & getting around), self-care (hygiene, dressing, eating, staying alone), getting along (interacting with others), life activities (domestic responsibilities, leisure, work & school), & participation (community & society). Each item is rated from 0 (none) to 4 (extreme or cannot do). The total score of the 36 items is converted into a metric ranging from 0 (no-disability) to 100 (full- disability) by dividing the total score by the maximum possible value of the total score, which is 144 for 36 items and multiplying by 100. LS Mean was estimated using ANCOVA method.
Time frame: Baseline (Day 1) to Week 6
Population: FAS included all randomized participants who received at least 1 occurrence of either CT-152 or sham use and had baseline and at least 1 postbaseline assessment of MADRS total score. Overall number of participants analyzed is the number of participants with data available for analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Digital Therapeutic A - CT-152 | Change From Baseline to Week 6 in the World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0) Total Score | -5.58 score on a scale | Standard Error 1.15 |
| Digital Therapeutic B - Sham | Change From Baseline to Week 6 in the World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0) Total Score | -4.56 score on a scale | Standard Error 1.18 |
p-value: 0.446395% CI: [-3.66, 1.61]ANCOVA
Other Pre-specified
Change From Baseline to Weeks 2, 4 and 6 in the Clinical Global Impression - Severity of Illness (CGI-S) Score
The CGI-S is a standardized, clinician-administered global rating scale that measures disease severity on a 7-point Likert scale To perform this assessment, the investigator (or designee) answered the following question: Considering your total clinical experience with this particular population, how mentally ill (as related to agitation) is the participant at this time? Response choices are 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; and 7 = among the most extremely ill subjects. The score 0 (not assessed) will be set to missing. LS mean was estimated using MMRM method.
Time frame: Baseline (Day 1) to Weeks 2, 4 and 6
Population: FAS included all randomized participants who received at least 1 occurrence of either CT-152 or sham use and had baseline and at least 1 postbaseline assessment of MADRS total score. Overall number of participants analyzed is the number of participants with data available for analysis. Number analyzed is the number of participants with data available for analysis at the specified timepoints.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Digital Therapeutic A - CT-152 | Change From Baseline to Weeks 2, 4 and 6 in the Clinical Global Impression - Severity of Illness (CGI-S) Score | Week 4 | -0.84 score on a scale | Standard Error 0.07 |
| Digital Therapeutic A - CT-152 | Change From Baseline to Weeks 2, 4 and 6 in the Clinical Global Impression - Severity of Illness (CGI-S) Score | Week 2 | -0.54 score on a scale | Standard Error 0.06 |
| Digital Therapeutic A - CT-152 | Change From Baseline to Weeks 2, 4 and 6 in the Clinical Global Impression - Severity of Illness (CGI-S) Score | Week 6 | -1.06 score on a scale | Standard Error 0.08 |
| Digital Therapeutic B - Sham | Change From Baseline to Weeks 2, 4 and 6 in the Clinical Global Impression - Severity of Illness (CGI-S) Score | Week 2 | -0.34 score on a scale | Standard Error 0.06 |
| Digital Therapeutic B - Sham | Change From Baseline to Weeks 2, 4 and 6 in the Clinical Global Impression - Severity of Illness (CGI-S) Score | Week 4 | -0.52 score on a scale | Standard Error 0.07 |
| Digital Therapeutic B - Sham | Change From Baseline to Weeks 2, 4 and 6 in the Clinical Global Impression - Severity of Illness (CGI-S) Score | Week 6 | -0.80 score on a scale | Standard Error 0.08 |
Comparison: Week 2p-value: 0.003995% CI: [-0.32, -0.06]MMRM
Comparison: Week 4p-value: 0.000395% CI: [-0.5, -0.15]MMRM
Comparison: Week 6p-value: 0.009895% CI: [-0.46, -0.06]MMRM
Other Pre-specified
Change From Baseline to Weeks 2 and 4 in the GAD-7 Total Score
The GAD-7 is self-reported questionnaire designed to assess anxiety in participants. The scale contains 7 items (anxiety symptoms) and each item was rated by the participants from 0 (not at all) to 3 (nearly every day) based on how much they were bothered by each symptom. The total score ranges from 0 to 21. A higher score on the GAD-7 represents greater anxiety symptomatology. A negative change from baseline indicates improvement. LS mean was estimated using MMRM method.
Time frame: Baseline (Day 1) to Weeks 2 and 4
Population: FAS included all randomized participants who received at least 1 occurrence of either CT-152 or sham use and had baseline and at least 1 postbaseline assessment of MADRS total score. Overall number of participants analyzed is the number of participants with data available for analysis. Number analyzed is the number of participants with data available for analysis at the specified timepoints.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Digital Therapeutic A - CT-152 | Change From Baseline to Weeks 2 and 4 in the GAD-7 Total Score | Week 2 | -1.22 score on a scale | Standard Error 0.3 |
| Digital Therapeutic A - CT-152 | Change From Baseline to Weeks 2 and 4 in the GAD-7 Total Score | Week 4 | -2.22 score on a scale | Standard Error 0.33 |
| Digital Therapeutic B - Sham | Change From Baseline to Weeks 2 and 4 in the GAD-7 Total Score | Week 2 | -0.88 score on a scale | Standard Error 0.3 |
| Digital Therapeutic B - Sham | Change From Baseline to Weeks 2 and 4 in the GAD-7 Total Score | Week 4 | -1.93 score on a scale | Standard Error 0.33 |
Comparison: Week 2p-value: 0.354995% CI: [-1.06, 0.38]MMRM
Comparison: Week 4p-value: 0.494895% CI: [-1.09, 0.53]MMRM
Other Pre-specified
Change From Baseline to Weeks 2 and 4 in the MADRS Total Score
The MADRS is used to assess depressive symptom severity. It consists of 10 items (apparent sadness, reported sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts and suicidal thoughts), each rated from 0 to 6 with zero being the best rating and 6 being the worst rating. The MADRS total score is the sum of ratings for all 10 items. The total score ranges from 0 to 60. A higher score on the MADRS represents a more severe level of depression. A negative change from baseline indicates improvement. LS mean was estimated using MMRM method.
Time frame: Baseline (Day 1) to Weeks 2 and 4
Population: FAS included all randomized participants who received at least 1 occurrence of either CT-152 or sham use and had baseline and at least 1 postbaseline assessment of MADRS total score. Overall number of participants analyzed is the number of participants with data available for analysis. Number analyzed is the number of participants with data available for analysis at the specified timepoints.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Digital Therapeutic A - CT-152 | Change From Baseline to Weeks 2 and 4 in the MADRS Total Score | Week 2 | -3.85 score on a scale | Standard Error 0.58 |
| Digital Therapeutic A - CT-152 | Change From Baseline to Weeks 2 and 4 in the MADRS Total Score | Week 4 | -6.62 score on a scale | Standard Error 0.67 |
| Digital Therapeutic B - Sham | Change From Baseline to Weeks 2 and 4 in the MADRS Total Score | Week 2 | -3.23 score on a scale | Standard Error 0.59 |
| Digital Therapeutic B - Sham | Change From Baseline to Weeks 2 and 4 in the MADRS Total Score | Week 4 | -5.16 score on a scale | Standard Error 0.67 |
Comparison: Week 2p-value: 0.368795% CI: [-1.99, 0.74]MMRM
Comparison: Week 4p-value: 0.082895% CI: [-3.1, 0.19]MMRM
Other Pre-specified
Change From Screening to Weeks 4 and 6 in the PHQ-9 Total Score.
The PHQ-9 is a standardized, self-administered rating scale that assesses the severity of depressive symptoms. The scale consists of 9 items, representing the 9 criteria upon which the diagnosis of DSM-IV depressive disorders is based. Each item is rated from 0 (not at all) to 3 (nearly every day). The total score ranges from 0 to 27. A higher score on the PHQ-9 represents a higher severity of depressive symptoms. LS mean was estimated using MMRM method.
Time frame: Screening to Weeks 4 and 6
Population: FAS included all randomized participants who received at least 1 occurrence of either CT-152 or sham use and had baseline and at least 1 postbaseline assessment of MADRS total score. Overall number of participants analyzed is the number of participants with data available for analysis. Number analyzed is the number of participants with data available for analysis at the specified timepoints.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Digital Therapeutic A - CT-152 | Change From Screening to Weeks 4 and 6 in the PHQ-9 Total Score. | Week 6 | -6.68 score on a scale | Standard Error 0.45 |
| Digital Therapeutic A - CT-152 | Change From Screening to Weeks 4 and 6 in the PHQ-9 Total Score. | Week 4 | -5.14 score on a scale | Standard Error 0.43 |
| Digital Therapeutic B - Sham | Change From Screening to Weeks 4 and 6 in the PHQ-9 Total Score. | Week 4 | -3.85 score on a scale | Standard Error 0.45 |
| Digital Therapeutic B - Sham | Change From Screening to Weeks 4 and 6 in the PHQ-9 Total Score. | Week 6 | -5.10 score on a scale | Standard Error 0.46 |
Comparison: Week 4p-value: 0.010295% CI: [-2.28, -0.31]MMRM
Comparison: Week 6p-value: 0.002995% CI: [-2.62, -0.54]MMRM
Other Pre-specified
MADRS Partial Response at Weeks 2, 4 and 6
The MADRS is used to assess depressive symptom severity. It consists of 10 items (apparent sadness, reported sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts and suicidal thoughts), each rated from 0 to 6 with zero being the best rating and 6 being the worst rating. The MADRS total score is the sum of ratings for all 10 items. The total score ranges from 0 to 60. A higher score on the MADRS represents a more severe level of depression. MADRS partial response was defined as the percentage of participants who achieved a reduction in the MADRS total score by 30% or more and less than 50% from baseline.
Time frame: Baseline (Day 1), Weeks 2, 4 and 6
Population: FAS included all randomized participants who received at least 1 occurrence of either CT-152 or sham use and had baseline and at least 1 postbaseline assessment of MADRS total score. Overall number of participants analyzed is the number of participants with data available for analysis. Number analyzed is the number of participants with data available for analysis at the specified timepoints.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Digital Therapeutic A - CT-152 | MADRS Partial Response at Weeks 2, 4 and 6 | Week 6 | 19.89 percentage of participants |
| Digital Therapeutic A - CT-152 | MADRS Partial Response at Weeks 2, 4 and 6 | Week 2 | 13.14 percentage of participants |
| Digital Therapeutic A - CT-152 | MADRS Partial Response at Weeks 2, 4 and 6 | Week 4 | 19.32 percentage of participants |
| Digital Therapeutic B - Sham | MADRS Partial Response at Weeks 2, 4 and 6 | Week 4 | 16.48 percentage of participants |
| Digital Therapeutic B - Sham | MADRS Partial Response at Weeks 2, 4 and 6 | Week 6 | 17.05 percentage of participants |
| Digital Therapeutic B - Sham | MADRS Partial Response at Weeks 2, 4 and 6 | Week 2 | 11.11 percentage of participants |
Comparison: Week 2p-value: 0.575795% CI: [0.65, 2.16]Cochran-Mantel-Haenszel
Comparison: Week 4p-value: 0.510295% CI: [0.75, 1.78]Cochran-Mantel-Haenszel
Comparison: Week 6p-value: 0.534295% CI: [0.74, 1.79]Cochran-Mantel-Haenszel
Other Pre-specified
MADRS Response Rate at Weeks 2, 4, and 6
The MADRS is used to assess depressive symptom severity. It consists of 10 items (apparent sadness, reported sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts and suicidal thoughts), each rated from 0 to 6 with zero being the best rating and 6 being the worst rating. The MADRS total score is the sum of ratings for all 10 items. The total score ranges from 0 to 60. A higher score on the MADRS represents a more severe level of depression. MADRS Response Rate was defined as the percentage of participants who achieved a reduction in the MADRS total score by 50% or more from baseline.
Time frame: Baseline (Day 1), Weeks 2, 4 and 6
Population: FAS included all randomized participants who received at least 1 occurrence of either CT-152 or sham use and had baseline and at least 1 postbaseline assessment of MADRS total score. Overall number of participants analyzed is the number of participants with data available for analysis. Number analyzed is the number of participants with data available for analysis at the specified timepoints.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Digital Therapeutic A - CT-152 | MADRS Response Rate at Weeks 2, 4, and 6 | Week 6 | 28.41 percentage of participants |
| Digital Therapeutic A - CT-152 | MADRS Response Rate at Weeks 2, 4, and 6 | Week 2 | 10.86 percentage of participants |
| Digital Therapeutic A - CT-152 | MADRS Response Rate at Weeks 2, 4, and 6 | Week 4 | 18.18 percentage of participants |
| Digital Therapeutic B - Sham | MADRS Response Rate at Weeks 2, 4, and 6 | Week 4 | 13.64 percentage of participants |
| Digital Therapeutic B - Sham | MADRS Response Rate at Weeks 2, 4, and 6 | Week 6 | 20.45 percentage of participants |
| Digital Therapeutic B - Sham | MADRS Response Rate at Weeks 2, 4, and 6 | Week 2 | 5.85 percentage of participants |
Comparison: Week 2p-value: 0.14295% CI: [0.84, 3.34]Cochran-Mantel-Haenszel
Comparison: Week 4p-value: 0.293995% CI: [0.79, 2.16]Cochran-Mantel-Haenszel
Comparison: Week 6p-value: 0.088495% CI: [0.96, 1.99]Cochran-Mantel-Haenszel
Other Pre-specified
MADRS Response Rate at Weeks 8 and 10
The MADRS is used to assess depressive symptom severity. It consists of 10 items (apparent sadness, reported sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts and suicidal thoughts), each rated from 0 to 6 with zero being the best rating and 6 being the worst rating. The MADRS total score is the sum of ratings for all 10 items. The total score ranges from 0 to 60. A higher score on the MADRS represents a more severe level of depression. MADRS Response Rate (full or partial) was defined as the percentage of participants who achieved a reduction in the MADRS total score by 30% or more from baseline.
Time frame: Baseline (Day 1), Weeks 8 and 10
Population: FAS included all randomized participants who received at least 1 occurrence of either CT-152 or sham use and had baseline and at least 1 postbaseline assessment of MADRS total score. Overall number of participants analyzed is the number of participants with data available for analysis. Number analyzed is the number of participants with data available for analysis at the specified timepoints.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Digital Therapeutic A - CT-152 | MADRS Response Rate at Weeks 8 and 10 | Week 8 | 54.88 percentage of participants |
| Digital Therapeutic A - CT-152 | MADRS Response Rate at Weeks 8 and 10 | Week 10 | 60.71 percentage of participants |
| Digital Therapeutic B - Sham | MADRS Response Rate at Weeks 8 and 10 | Week 8 | 54.84 percentage of participants |
| Digital Therapeutic B - Sham | MADRS Response Rate at Weeks 8 and 10 | Week 10 | 57.50 percentage of participants |
Comparison: Week 895% CI: [0.82, 1.22]
Comparison: Week 1095% CI: [0.88, 1.25]