Schizophrenia
Conditions
Keywords
Schizophrenia, Digital Therapeutic, CBT, smartphone app, mental disorder, psychosis, acute psychotic reaction, chronic psychosis, failure to recognize what is real, false beliefs, unclear thinking,, confused thinking, auditory hallucinations, paranoia, reduced social engagement, reduced emotional expression
Brief summary
The purpose of the study was to determine in patients currently being administered antipsychotic pharmacotherapy whether PEAR-004 could further reduce symptoms of schizophrenia as measured by the Positive and Negative Syndrome Scale (PANSS). The overall rationale for the study was to assess the first prescription digital therapeutic (PDT) in schizophrenia using a form of proven psychosocial intervention, cognitive behavioral therapy (CBT), to supplement standard of care with antipsychotic medications.
Detailed description
This was a randomized, sham-controlled, rater-blinded, parallel group trial. Overall, 112 subjects were randomized 1:1 in to the following groups: * Group A: Clinician-directed pharmacotherapy + PEAR-004 * Group B: Clinician-directed pharmacotherapy + sham app An up to 28-day screening period included standard screening assessments as defined in the assessment schedule. Eligible subjects were randomized on Day 1 into one of the treatment groups. Subjects in both groups continued to receive their clinician-directed standard-of-care treatment for schizophrenia, including pharmacotherapy. Subjects in Group A used PEAR 004 and subjects in Group B used a sham for a period of 12 weeks. Subjects returned to the clinic for outpatient visits at Week 4 (day 29), Week 8 (day 57), and Week 12 (day 85). At each visit, standard assessments were performed according to the assessment schedule, including PANSS, ISST-Plus, CGI, BMQ, MAP-SR, WHOQOL-BREF, BDI-II, ISI, and adverse events (AEs). A final follow-up visit was performed at Week 16 (day 115),
Interventions
DEVICEPEAR-004
PEAR-004 (an investigational digital therapeutic) or sham (control) was downloaded to the subject's phone and then the assigned application was unlocked using a prescription code provided by Pear Therapeutics. As this was a digital therapeutic device study, dose or mode of administration is not applicable.
DEVICESham
PEAR-004 (an investigational digital therapeutic) or sham (control) was downloaded to the subject's phone and then the assigned application was unlocked using a prescription code provided by Pear Therapeutics. As this was a digital therapeutic device study, dose or mode of administration is not applicable.
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Signed informed consent must be obtained prior to participation in the study. * Healthy male and female subjects 18 to 65 years of age, inclusive, and in good health as determined by medical history, physical examination, and vital signs at screening * SCID-based DSM-5 diagnosis of schizophrenia and a total PANSS score \> 60 * Proficient in English at 5th grade reading level or higher, in the judgement of the investigator * Capable of using a mobile device (compatible with PEAR-004) and using common applications, in the judgement of the investigator Key
Exclusion criteria
* Major change in primary antipsychotic medication in the prior 4 weeks before screening (e.g., switching to a new agent or a dose adjustment within two weeks of randomization) * Planning to move out of the geographic area within 3 months * Unable to use English to participate in the consent process, the interventions or assessments * Inability to comply with study procedures, due to severe medical conditions or otherwise * Meet DSM-5 diagnosis for a current episode of major depression, mania, or hypomania in the past month * Meet DSM-5 diagnosis for a current moderate or severe alcohol or cannabis use disorder in the past 2 months * Meet DSM-5 diagnosis for a current substance use disorder (other than alcohol or cannabis) in the past 2 months * Considered high risk for suicidal behavior based on ISST-Plus score at screening, or in the judgement of the investigator * Previously participated in a clinical study involving PEAR-004
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Total Positive and Negative Syndrome Scale (PANSS) Score | Baseline, Day 29, Day 57, Day 85 | The Positive and Negative Syndrome Scale (PANSS) is a well validated, standardized method of evaluating and monitoring psychotic symptoms. The PANSS assesses: positive (hallucinations, delusions, thought disorder), negative (blunted affect, abstract thinking and general symptomatology. The positive and negative subscale each consist of 7 items rated from 1(absent) - 7(extreme) with a minimum score = 7, maximum score = 49. The general subscale consists of 16 items with a minimum score = 16, maximum score = 112. A Total PANSS score (positive+ negative + general scores) has a minimum of 30 and maximum of 210. Higher scores represent more severity in symptoms. |
| Percent of Dropout | Day 115 | Dropout rate to evaluate retention to assigned study treatment |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in the Negative PANSS Score | Baseline, Day 29, Day 57, Day 85 | The PANSS includes 3 scales and 30 items: 7 items that make up the Positive Scale (eg, delusions, conceptual disorganization, hallucinatory behavior); 7 items that make up the Negative Scale (eg, blunted affect, emotional withdrawal, poor rapport, passive/apathetic social withdrawal); and 16 items that make up the General Psychopathology Scale (eg, somatic concern, anxiety, guilt feelings, mannerisms and posturing, motor retardation, uncooperativeness, disorientation, poor impulse control, preoccupation). Individual items are scored with values ranging from 1 to 7. Total Negative and Positive Subscale scores each range from 7 to 49; higher score indicates greater severity. |
| Change From Baseline in the Motivation and Pleasure Self-report (MAP-SR) Score | Baseline, Day 29, Day 57, Day 85 | The MAP-SR is a 15-item self-report measure that provides a total score index of current motivation/pleasure negative symptoms. Responses are given on a 5-point scale where 0 = no pleasure or motivation and 4 = extreme pleasure or motivation. Total scores range from 0 to 60 and higher scores indicate greater motivation and pleasure during everyday activities. |
| Change From Baseline in the World Health Organization Quality of Life (WHOQOL-BREF) Scale | Baseline, Day 29, Day 57, Day 85 | The WHOQOL-BREF is a 26-item, self-report questionnaire and short version of WHOQOL-100, consisting of 4 domains: physical health (7 items) (Domain 1), psychological health (6 items) (Domian 2), social relationships (3 items) (Domain 3), and environmental health (8 items) (Domain 4); it also contains QOL and general health items. Domain scores are scaled in a positive direction (i.e. higher scores denote higher quality of life). The mean score of items within each domain is used to calculate the domain score. Each individual item of the WHOQOL-BREF is scored from 1=not at all to 5=completely on a response scale, which is stipulated as a 5-point ordinal scale. The scores are then transformed linearly to a scale of 0 (the worse quality of life) to 100 (the worse quality of life). |
| Change From Baseline in the Beck Depression Inventory, Second Ed. (BDI-II) Total Score | Baseline, Day 29, Day 57, Day 85 | Beck Depression Inventory (BDI) is a 21-items self reported inventory with a scale evaluating depressive symptoms and the changes in BDI after treatment compared to baseline. The range of scores is 0 to 63, with higher scores indicating greater severity of depression. |
| Percentage Change From Baseline in Total PANSS Score (Within Assigned Treatment Group) | Baseline, Day 29, Day 57, Day 85 | The Positive and Negative Syndrome Scale (PANSS) is a well validated, standardized method of evaluating and monitoring psychotic symptoms. The PANSS assesses: positive (hallucinations, delusions, thought disorder), negative (blunted affect, abstract thinking and general symptomatology. The positive and negative subscale each consist of 7 items rated from 1(absent) - 7(extreme) with a minimum score = 7, maximum score = 49. The general subscale consists of 16 items with a minimum score = 16, maximum score = 112. A Total PANSS score (positive+ negative + general scores) has a minimum of 30 and maximum of 210. Higher scores represent more severity in symptoms. |
| Change From Baseline in the Positive PANSS Score | Baseline, Day 29, Day 57, Day 85 | The PANSS includes 3 scales and 30 items: 7 items that make up the Positive Scale (eg, delusions, conceptual disorganization, hallucinatory behavior); 7 items that make up the Negative Scale (eg, blunted affect, emotional withdrawal, poor rapport, passive/apathetic social withdrawal); and 16 items that make up the General Psychopathology Scale (eg, somatic concern, anxiety, guilt feelings, mannerisms and posturing, motor retardation, uncooperativeness, disorientation, poor impulse control, preoccupation). Individual items are scored with values ranging from 1 to 7. Total Negative and Positive Subscale scores each range from 7 to 49; higher score indicates greater severity. |
| Percentage of Responders as Assessed by the Total PANSS Score | Day 85 | A Response is defined as a reduction of at least 20% at day 85 or last visit in total PANSS score relative to Baseline. |
| Number of Patients With Adverse Events | Day 115 | Adverse events, serious adverse events, and adverse events leading to discontinuation throughout the study |
| Number of Patients With Vital Sign Measurements | Day 85 | Vital signs at baseline, day 85 or last visit |
| InterSePT Scale for Suicidal Thinking-Plus (ISST-Plus) Score | Baseline, Day 29, 57, 85, and 115 | InterSePT Scale for Suicidal Thinking-Plus (ISST-Plus) score. Semi-structured interview to assess severity of suicidal ideation and behavior Part I: collects information on 7 days prior to visit; 13 items scored 0 (min) to 2 (max) for suicidality, with a higher score representing a worse outcome Part II: collects information on suicidal behavior since last visit, with nominal categories Yes / No / Unknown (NA) Part III: global rating of status at time of interview; scored 0 (min) to 5 (max) for suicidality, with a higher score representing a worse outcome. Please note that only part III score (severity of suicidal risk) was summarized and reported. |
| Percentage of Responders as Assessed by the Brief Medication Questionnaire (BMQ) | Day 29, Day 57, and Day 85 | The Brief Medication Questionnaire (BMQ) collects information about current schizophrenia medication use. |
| Change From Baseline in the General Psychopathology PANSS Score | Baseline, Day 29, Day 57, Day 85 | The PANSS includes 3 scales and 30 items: 7 items that make up the Positive Scale (eg, delusions, conceptual disorganization, hallucinatory behavior); 7 items that make up the Negative Scale (eg, blunted affect, emotional withdrawal, poor rapport, passive/apathetic social withdrawal); and 16 items that make up the General Psychopathology Scale (eg, somatic concern, anxiety, guilt feelings, mannerisms and posturing, motor retardation, uncooperativeness, disorientation, poor impulse control, preoccupation). Individual items are scored with values ranging from 1 to 7. Total General Psychopathology Subscale score range from 16 to 112; higher score indicates greater severity. |
Countries
United States
Participant flow
Recruitment details
This study was conducted at 6 centers in the USA.
Pre-assignment details
The eligible subjects were randomized in 1:1 ratio to receive either PEAR-004 or sham.
Participants by arm
| Arm | Count |
|---|---|
| PEAR-004 Eligible participants were to access PEAR-004 (an investigational digital therapeutic) on a mobile device (iOS and Android based) as needed to receive suggestions about coping strategies to overcome difficulties in daily life. | 55 |
| Sham Eligible participants were to access a sham control downloaded on a mobile device (iOS and Android based) as needed to delivering notifications prompting the participant to open the sham app, and then display a prescription timer for the remaining duration of app availability. | 55 |
| Total | 110 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 |
| Overall Study | Lost to Follow-up | 3 | 5 |
| Overall Study | Physician Decision | 0 | 2 |
| Overall Study | Protocol Violation | 0 | 2 |
| Overall Study | Withdrawal by Subject | 5 | 2 |
Baseline characteristics
| Characteristic | PEAR-004 | Sham | Total |
|---|---|---|---|
| Age, Continuous | 43.7 Years STANDARD_DEVIATION 10.99 | 45.7 Years STANDARD_DEVIATION 11.6 | 44.7 Years STANDARD_DEVIATION 11.29 |
| Disease duration at baseline | 16.2 Years STANDARD_DEVIATION 11.4 | 18.2 Years STANDARD_DEVIATION 11.56 | 17.2 Years STANDARD_DEVIATION 11.47 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 3 Participants | 0 Participants | 3 Participants |
| Race/Ethnicity, Customized Asian | 3 Participants | 4 Participants | 7 Participants |
| Race/Ethnicity, Customized Black or African American | 28 Participants | 25 Participants | 53 Participants |
| Race/Ethnicity, Customized Native Hawaiian or other Pacific Islander | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Other | 3 Participants | 0 Participants | 3 Participants |
| Race/Ethnicity, Customized White | 18 Participants | 25 Participants | 43 Participants |
| Sex: Female, Male Female | 19 Participants | 19 Participants | 38 Participants |
| Sex: Female, Male Male | 36 Participants | 36 Participants | 72 Participants |
| Total Positive and Negative Syndrome Scale (PANSS) score at baseline | 73.5 Score STANDARD_DEVIATION 10.25 | 72.7 Score STANDARD_DEVIATION 10.1 | 73.1 Score STANDARD_DEVIATION 10.14 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 55 | 0 / 55 | 0 / 110 |
| other Total, other adverse events | 0 / 55 | 0 / 55 | 0 / 110 |
| serious Total, serious adverse events | 0 / 55 | 1 / 55 | 1 / 110 |
Outcome results
Primary
Change From Baseline in Total Positive and Negative Syndrome Scale (PANSS) Score
The Positive and Negative Syndrome Scale (PANSS) is a well validated, standardized method of evaluating and monitoring psychotic symptoms. The PANSS assesses: positive (hallucinations, delusions, thought disorder), negative (blunted affect, abstract thinking and general symptomatology. The positive and negative subscale each consist of 7 items rated from 1(absent) - 7(extreme) with a minimum score = 7, maximum score = 49. The general subscale consists of 16 items with a minimum score = 16, maximum score = 112. A Total PANSS score (positive+ negative + general scores) has a minimum of 30 and maximum of 210. Higher scores represent more severity in symptoms.
Time frame: Baseline, Day 29, Day 57, Day 85
Population: Full Analysis Set (FAS)
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| PEAR-004 | Change From Baseline in Total Positive and Negative Syndrome Scale (PANSS) Score | Day 57 | -2.5 Score | Standard Error 0.9 |
| PEAR-004 | Change From Baseline in Total Positive and Negative Syndrome Scale (PANSS) Score | Day 29 | -1.6 Score | Standard Error 0.86 |
| PEAR-004 | Change From Baseline in Total Positive and Negative Syndrome Scale (PANSS) Score | Day 85 | -2.6 Score | Standard Error 1.14 |
| Sham | Change From Baseline in Total Positive and Negative Syndrome Scale (PANSS) Score | Day 29 | -2.2 Score | Standard Error 0.84 |
| Sham | Change From Baseline in Total Positive and Negative Syndrome Scale (PANSS) Score | Day 57 | -3.3 Score | Standard Error 0.9 |
| Sham | Change From Baseline in Total Positive and Negative Syndrome Scale (PANSS) Score | Day 85 | -5.3 Score | Standard Error 1.13 |
Comparison: Day 2990% CI: [-1.4, 2.6]
Comparison: Day 5790% CI: [-1.3, 2.9]
Comparison: Day 85p-value: 0.093190% CI: [0.1, 5.4]t-test, 2 sided
Primary
Percent of Dropout
Dropout rate to evaluate retention to assigned study treatment
Time frame: Day 115
Population: Randomized Set
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| PEAR-004 | Percent of Dropout | 8 Participants |
| Sham | Percent of Dropout | 12 Participants |
Secondary
Change From Baseline in the Beck Depression Inventory, Second Ed. (BDI-II) Total Score
Beck Depression Inventory (BDI) is a 21-items self reported inventory with a scale evaluating depressive symptoms and the changes in BDI after treatment compared to baseline. The range of scores is 0 to 63, with higher scores indicating greater severity of depression.
Time frame: Baseline, Day 29, Day 57, Day 85
Population: Full Analysis Set (FAS)
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| PEAR-004 | Change From Baseline in the Beck Depression Inventory, Second Ed. (BDI-II) Total Score | Day 29 | -1.0 Score | Standard Error 1.13 |
| PEAR-004 | Change From Baseline in the Beck Depression Inventory, Second Ed. (BDI-II) Total Score | Day 57 | -4.8 Score | Standard Error 1.14 |
| PEAR-004 | Change From Baseline in the Beck Depression Inventory, Second Ed. (BDI-II) Total Score | Day 85 | -3.4 Score | Standard Error 1.32 |
| Sham | Change From Baseline in the Beck Depression Inventory, Second Ed. (BDI-II) Total Score | Day 29 | -0.1 Score | Standard Error 1.11 |
| Sham | Change From Baseline in the Beck Depression Inventory, Second Ed. (BDI-II) Total Score | Day 57 | -1.5 Score | Standard Error 1.15 |
| Sham | Change From Baseline in the Beck Depression Inventory, Second Ed. (BDI-II) Total Score | Day 85 | -3.2 Score | Standard Error 1.3 |
Secondary
Change From Baseline in the General Psychopathology PANSS Score
The PANSS includes 3 scales and 30 items: 7 items that make up the Positive Scale (eg, delusions, conceptual disorganization, hallucinatory behavior); 7 items that make up the Negative Scale (eg, blunted affect, emotional withdrawal, poor rapport, passive/apathetic social withdrawal); and 16 items that make up the General Psychopathology Scale (eg, somatic concern, anxiety, guilt feelings, mannerisms and posturing, motor retardation, uncooperativeness, disorientation, poor impulse control, preoccupation). Individual items are scored with values ranging from 1 to 7. Total General Psychopathology Subscale score range from 16 to 112; higher score indicates greater severity.
Time frame: Baseline, Day 29, Day 57, Day 85
Population: Full Analysis Set (FAS)
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| PEAR-004 | Change From Baseline in the General Psychopathology PANSS Score | Day 29 | -0.8 Score | Standard Error 0.61 |
| PEAR-004 | Change From Baseline in the General Psychopathology PANSS Score | Day 57 | -1.4 Score | Standard Error 0.63 |
| PEAR-004 | Change From Baseline in the General Psychopathology PANSS Score | Day 85 | -1.2 Score | Standard Error 0.76 |
| Sham | Change From Baseline in the General Psychopathology PANSS Score | Day 29 | -1.4 Score | Standard Error 0.59 |
| Sham | Change From Baseline in the General Psychopathology PANSS Score | Day 57 | -1.5 Score | Standard Error 0.63 |
| Sham | Change From Baseline in the General Psychopathology PANSS Score | Day 85 | -2.8 Score | Standard Error 0.75 |
Comparison: Day 2990% CI: [-0.9, 1.9]
Comparison: Day 5790% CI: [-1.4, 1.6]
Comparison: Day 85p-value: 0.136890% CI: [-0.2, 3.4]t-test, 2 sided
Secondary
Change From Baseline in the Motivation and Pleasure Self-report (MAP-SR) Score
The MAP-SR is a 15-item self-report measure that provides a total score index of current motivation/pleasure negative symptoms. Responses are given on a 5-point scale where 0 = no pleasure or motivation and 4 = extreme pleasure or motivation. Total scores range from 0 to 60 and higher scores indicate greater motivation and pleasure during everyday activities.
Time frame: Baseline, Day 29, Day 57, Day 85
Population: Full Analysis Set (FAS)
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| PEAR-004 | Change From Baseline in the Motivation and Pleasure Self-report (MAP-SR) Score | Day 29 | 0.8 Score | Standard Error 1.05 |
| PEAR-004 | Change From Baseline in the Motivation and Pleasure Self-report (MAP-SR) Score | Day 57 | -0.5 Score | Standard Error 1.41 |
| PEAR-004 | Change From Baseline in the Motivation and Pleasure Self-report (MAP-SR) Score | Day 851.43 | -1.2 Score | Standard Error 1.26 |
| Sham | Change From Baseline in the Motivation and Pleasure Self-report (MAP-SR) Score | Day 29 | 1.6 Score | Standard Error 1.02 |
| Sham | Change From Baseline in the Motivation and Pleasure Self-report (MAP-SR) Score | Day 57 | 1.1 Score | Standard Error 1.43 |
| Sham | Change From Baseline in the Motivation and Pleasure Self-report (MAP-SR) Score | Day 851.43 | 2.8 Score | Standard Error 1.25 |
Comparison: Day 2990% CI: [-3.2, 1.6]
Comparison: Day 5790% CI: [-4.9, 1.7]
Comparison: Day 85p-value: 0.024590% CI: [-7, -1.1]t-test, 2 sided
Secondary
Change From Baseline in the Negative PANSS Score
The PANSS includes 3 scales and 30 items: 7 items that make up the Positive Scale (eg, delusions, conceptual disorganization, hallucinatory behavior); 7 items that make up the Negative Scale (eg, blunted affect, emotional withdrawal, poor rapport, passive/apathetic social withdrawal); and 16 items that make up the General Psychopathology Scale (eg, somatic concern, anxiety, guilt feelings, mannerisms and posturing, motor retardation, uncooperativeness, disorientation, poor impulse control, preoccupation). Individual items are scored with values ranging from 1 to 7. Total Negative and Positive Subscale scores each range from 7 to 49; higher score indicates greater severity.
Time frame: Baseline, Day 29, Day 57, Day 85
Population: Full Analysis Set (FAS)
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| PEAR-004 | Change From Baseline in the Negative PANSS Score | Day 57 | -0.3 Score | Standard Error 0.32 |
| PEAR-004 | Change From Baseline in the Negative PANSS Score | Day 29 | -0.5 Score | Standard Error 0.31 |
| PEAR-004 | Change From Baseline in the Negative PANSS Score | Day 85 | -0.4 Score | Standard Error 0.41 |
| Sham | Change From Baseline in the Negative PANSS Score | Day 29 | -0.4 Score | Standard Error 0.3 |
| Sham | Change From Baseline in the Negative PANSS Score | Day 57 | -0.5 Score | Standard Error 0.32 |
| Sham | Change From Baseline in the Negative PANSS Score | Day 85 | -0.9 Score | Standard Error 0.41 |
Comparison: Day 2990% CI: [-0.8, 0.6]
Comparison: Day 5790% CI: [-0.6, 0.9]
p-value: 0.379890% CI: [-0.5, 1.5]t-test, 2 sided
Secondary
Change From Baseline in the Positive PANSS Score
The PANSS includes 3 scales and 30 items: 7 items that make up the Positive Scale (eg, delusions, conceptual disorganization, hallucinatory behavior); 7 items that make up the Negative Scale (eg, blunted affect, emotional withdrawal, poor rapport, passive/apathetic social withdrawal); and 16 items that make up the General Psychopathology Scale (eg, somatic concern, anxiety, guilt feelings, mannerisms and posturing, motor retardation, uncooperativeness, disorientation, poor impulse control, preoccupation). Individual items are scored with values ranging from 1 to 7. Total Negative and Positive Subscale scores each range from 7 to 49; higher score indicates greater severity.
Time frame: Baseline, Day 29, Day 57, Day 85
Population: Full Analysis Set (FAS)
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| PEAR-004 | Change From Baseline in the Positive PANSS Score | Day 85 | -1.0 Score | Standard Error 0.46 |
| PEAR-004 | Change From Baseline in the Positive PANSS Score | Day 29 | -0.2 Score | Standard Error 0.36 |
| PEAR-004 | Change From Baseline in the Positive PANSS Score | Day 57 | -0.8 Score | Standard Error 0.38 |
| Sham | Change From Baseline in the Positive PANSS Score | Day 29 | -0.4 Score | Standard Error 0.35 |
| Sham | Change From Baseline in the Positive PANSS Score | Day 57 | -1.4 Score | Standard Error 0.38 |
| Sham | Change From Baseline in the Positive PANSS Score | Day 85 | -1.8 Score | Standard Error 0.45 |
Comparison: Day 2990% CI: [-0.6, 1]
Comparison: Day 5790% CI: [-0.3, 1.5]
Comparison: Day 85p-value: 0.206990% CI: [-0.3, 1.9]t-test, 2 sided
Secondary
Change From Baseline in the World Health Organization Quality of Life (WHOQOL-BREF) Scale
The WHOQOL-BREF is a 26-item, self-report questionnaire and short version of WHOQOL-100, consisting of 4 domains: physical health (7 items) (Domain 1), psychological health (6 items) (Domian 2), social relationships (3 items) (Domain 3), and environmental health (8 items) (Domain 4); it also contains QOL and general health items. Domain scores are scaled in a positive direction (i.e. higher scores denote higher quality of life). The mean score of items within each domain is used to calculate the domain score. Each individual item of the WHOQOL-BREF is scored from 1=not at all to 5=completely on a response scale, which is stipulated as a 5-point ordinal scale. The scores are then transformed linearly to a scale of 0 (the worse quality of life) to 100 (the worse quality of life).
Time frame: Baseline, Day 29, Day 57, Day 85
Population: Full Analysis Set (FAS)
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| PEAR-004 | Change From Baseline in the World Health Organization Quality of Life (WHOQOL-BREF) Scale | Day 29-Domain 2 | -0.6 Score | Standard Error 0.4 |
| PEAR-004 | Change From Baseline in the World Health Organization Quality of Life (WHOQOL-BREF) Scale | Day 85-Domain 2 | -0.5 Score | Standard Error 0.43 |
| PEAR-004 | Change From Baseline in the World Health Organization Quality of Life (WHOQOL-BREF) Scale | Day 57-Domain 2 | -0.7 Score | Standard Error 0.37 |
| PEAR-004 | Change From Baseline in the World Health Organization Quality of Life (WHOQOL-BREF) Scale | Day 29-Domain 3 | -0.3 Score | Standard Error 0.28 |
| PEAR-004 | Change From Baseline in the World Health Organization Quality of Life (WHOQOL-BREF) Scale | Day 85-Domain 1 | 0.2 Score | Standard Error 0.45 |
| PEAR-004 | Change From Baseline in the World Health Organization Quality of Life (WHOQOL-BREF) Scale | Day 57-Domain 3 | -0.3 Score | Standard Error 0.33 |
| PEAR-004 | Change From Baseline in the World Health Organization Quality of Life (WHOQOL-BREF) Scale | Day 57-Domain 1 | -0.3 Score | Standard Error 0.44 |
| PEAR-004 | Change From Baseline in the World Health Organization Quality of Life (WHOQOL-BREF) Scale | Day 85-Domain 3 | 0.5 Score | Standard Error 0.33 |
| PEAR-004 | Change From Baseline in the World Health Organization Quality of Life (WHOQOL-BREF) Scale | Day 57-Domain 4 | -0.5 Score | Standard Error 0.61 |
| PEAR-004 | Change From Baseline in the World Health Organization Quality of Life (WHOQOL-BREF) Scale | Day 29-Domain 4 | -0.2 Score | Standard Error 0.61 |
| PEAR-004 | Change From Baseline in the World Health Organization Quality of Life (WHOQOL-BREF) Scale | Day 85-Domain 4 | -0.1 Score | Standard Error 0.69 |
| PEAR-004 | Change From Baseline in the World Health Organization Quality of Life (WHOQOL-BREF) Scale | Day 29-Domain 1 | -0.1 Score | Standard Error 0.37 |
| Sham | Change From Baseline in the World Health Organization Quality of Life (WHOQOL-BREF) Scale | Day 85-Domain 4 | 1.1 Score | Standard Error 0.68 |
| Sham | Change From Baseline in the World Health Organization Quality of Life (WHOQOL-BREF) Scale | Day 29-Domain 1 | 0.1 Score | Standard Error 0.36 |
| Sham | Change From Baseline in the World Health Organization Quality of Life (WHOQOL-BREF) Scale | Day 57-Domain 1 | -0.3 Score | Standard Error 0.45 |
| Sham | Change From Baseline in the World Health Organization Quality of Life (WHOQOL-BREF) Scale | Day 85-Domain 1 | 0.1 Score | Standard Error 0.45 |
| Sham | Change From Baseline in the World Health Organization Quality of Life (WHOQOL-BREF) Scale | Day 57-Domain 2 | -0.6 Score | Standard Error 0.38 |
| Sham | Change From Baseline in the World Health Organization Quality of Life (WHOQOL-BREF) Scale | Day 57-Domain 3 | 0.1 Score | Standard Error 0.33 |
| Sham | Change From Baseline in the World Health Organization Quality of Life (WHOQOL-BREF) Scale | Day 29-Domain 2 | -0.1 Score | Standard Error 0.39 |
| Sham | Change From Baseline in the World Health Organization Quality of Life (WHOQOL-BREF) Scale | Day 85-Domain 2 | 0.1 Score | Standard Error 0.42 |
| Sham | Change From Baseline in the World Health Organization Quality of Life (WHOQOL-BREF) Scale | Day 29-Domain 3 | 0.1 Score | Standard Error 0.27 |
| Sham | Change From Baseline in the World Health Organization Quality of Life (WHOQOL-BREF) Scale | Day 85-Domain 3 | 0.3 Score | Standard Error 0.33 |
| Sham | Change From Baseline in the World Health Organization Quality of Life (WHOQOL-BREF) Scale | Day 29-Domain 4 | -0.9 Score | Standard Error 0.6 |
| Sham | Change From Baseline in the World Health Organization Quality of Life (WHOQOL-BREF) Scale | Day 57-Domain 4 | -0.7 Score | Standard Error 0.61 |
Comparison: Day 29-Domain 190% CI: [-1, 0.7]
Secondary
InterSePT Scale for Suicidal Thinking-Plus (ISST-Plus) Score
InterSePT Scale for Suicidal Thinking-Plus (ISST-Plus) score. Semi-structured interview to assess severity of suicidal ideation and behavior Part I: collects information on 7 days prior to visit; 13 items scored 0 (min) to 2 (max) for suicidality, with a higher score representing a worse outcome Part II: collects information on suicidal behavior since last visit, with nominal categories Yes / No / Unknown (NA) Part III: global rating of status at time of interview; scored 0 (min) to 5 (max) for suicidality, with a higher score representing a worse outcome. Please note that only part III score (severity of suicidal risk) was summarized and reported.
Time frame: Baseline, Day 29, 57, 85, and 115
Population: The number of subjects analyzed at different visits may differ from the overall number analyzed within a treatment group because some patients missed some visits.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PEAR-004 | InterSePT Scale for Suicidal Thinking-Plus (ISST-Plus) Score | Day 85 | 0.1 scores on a scale | Standard Deviation 0.45 |
| PEAR-004 | InterSePT Scale for Suicidal Thinking-Plus (ISST-Plus) Score | Baseline | 0.0 scores on a scale | Standard Deviation 0 |
| PEAR-004 | InterSePT Scale for Suicidal Thinking-Plus (ISST-Plus) Score | Day 1 | 0.1 scores on a scale | Standard Deviation 0.31 |
| PEAR-004 | InterSePT Scale for Suicidal Thinking-Plus (ISST-Plus) Score | Day 29 | 0.0 scores on a scale | Standard Deviation 0.28 |
| PEAR-004 | InterSePT Scale for Suicidal Thinking-Plus (ISST-Plus) Score | Day 57 | 0.1 scores on a scale | Standard Deviation 0.44 |
| PEAR-004 | InterSePT Scale for Suicidal Thinking-Plus (ISST-Plus) Score | Day 115 / End Of Study | 0.1 scores on a scale | Standard Deviation 0.43 |
| Sham | InterSePT Scale for Suicidal Thinking-Plus (ISST-Plus) Score | Day 1 | 0.0 scores on a scale | Standard Deviation 0.14 |
| Sham | InterSePT Scale for Suicidal Thinking-Plus (ISST-Plus) Score | Day 85 | 0.1 scores on a scale | Standard Deviation 0.32 |
| Sham | InterSePT Scale for Suicidal Thinking-Plus (ISST-Plus) Score | Day 115 / End Of Study | 0.1 scores on a scale | Standard Deviation 0.45 |
| Sham | InterSePT Scale for Suicidal Thinking-Plus (ISST-Plus) Score | Day 57 | 0.0 scores on a scale | Standard Deviation 0 |
| Sham | InterSePT Scale for Suicidal Thinking-Plus (ISST-Plus) Score | Baseline | 0.1 scores on a scale | Standard Deviation 0.24 |
| Sham | InterSePT Scale for Suicidal Thinking-Plus (ISST-Plus) Score | Day 29 | 0.1 scores on a scale | Standard Deviation 0.41 |
Secondary
Number of Patients With Adverse Events
Adverse events, serious adverse events, and adverse events leading to discontinuation throughout the study
Time frame: Day 115
Population: Safety Set (SAF)
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| PEAR-004 | Number of Patients With Adverse Events | Study drug-related AEs | 1 Participants |
| PEAR-004 | Number of Patients With Adverse Events | AEs leading to discontinuation of study treatment | 0 Participants |
| PEAR-004 | Number of Patients With Adverse Events | Participants with at least one AE | 12 Participants |
| PEAR-004 | Number of Patients With Adverse Events | Study-drug related AEs leading to treatment disc. | 0 Participants |
| PEAR-004 | Number of Patients With Adverse Events | Participants with at least one SAE | 0 Participants |
| Sham | Number of Patients With Adverse Events | Study-drug related AEs leading to treatment disc. | 0 Participants |
| Sham | Number of Patients With Adverse Events | Study drug-related AEs | 0 Participants |
| Sham | Number of Patients With Adverse Events | Participants with at least one SAE | 1 Participants |
| Sham | Number of Patients With Adverse Events | AEs leading to discontinuation of study treatment | 0 Participants |
| Sham | Number of Patients With Adverse Events | Participants with at least one AE | 10 Participants |
Secondary
Number of Patients With Vital Sign Measurements
Vital signs at baseline, day 85 or last visit
Time frame: Day 85
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| PEAR-004 | Number of Patients With Vital Sign Measurements | 55 Number of participants |
| Sham | Number of Patients With Vital Sign Measurements | 55 Number of participants |
Secondary
Percentage Change From Baseline in Total PANSS Score (Within Assigned Treatment Group)
The Positive and Negative Syndrome Scale (PANSS) is a well validated, standardized method of evaluating and monitoring psychotic symptoms. The PANSS assesses: positive (hallucinations, delusions, thought disorder), negative (blunted affect, abstract thinking and general symptomatology. The positive and negative subscale each consist of 7 items rated from 1(absent) - 7(extreme) with a minimum score = 7, maximum score = 49. The general subscale consists of 16 items with a minimum score = 16, maximum score = 112. A Total PANSS score (positive+ negative + general scores) has a minimum of 30 and maximum of 210. Higher scores represent more severity in symptoms.
Time frame: Baseline, Day 29, Day 57, Day 85
Population: Full Analysis Set (FAS)
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| PEAR-004 | Percentage Change From Baseline in Total PANSS Score (Within Assigned Treatment Group) | Day 85 | -3.7 Score | Standard Error 1.57 |
| PEAR-004 | Percentage Change From Baseline in Total PANSS Score (Within Assigned Treatment Group) | Day 29 | -2.0 Score | Standard Error 1.21 |
| PEAR-004 | Percentage Change From Baseline in Total PANSS Score (Within Assigned Treatment Group) | Day 57 | -3.6 Score | Standard Error 1.28 |
| Sham | Percentage Change From Baseline in Total PANSS Score (Within Assigned Treatment Group) | Day 29 | -3.0 Score | Standard Error 1.18 |
| Sham | Percentage Change From Baseline in Total PANSS Score (Within Assigned Treatment Group) | Day 57 | -4.4 Score | Standard Error 1.29 |
| Sham | Percentage Change From Baseline in Total PANSS Score (Within Assigned Treatment Group) | Day 85 | -7.1 Score | Standard Error 1.55 |
Secondary
Percentage of Responders as Assessed by the Brief Medication Questionnaire (BMQ)
The Brief Medication Questionnaire (BMQ) collects information about current schizophrenia medication use.
Time frame: Day 29, Day 57, and Day 85
Population: Full Analysis Set (FAS)
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| PEAR-004 | Percentage of Responders as Assessed by the Brief Medication Questionnaire (BMQ) | Day 29 | 52 Participants |
| PEAR-004 | Percentage of Responders as Assessed by the Brief Medication Questionnaire (BMQ) | Day 85 | 48 Participants |
| PEAR-004 | Percentage of Responders as Assessed by the Brief Medication Questionnaire (BMQ) | Day 57 | 49 Participants |
| PEAR-004 | Percentage of Responders as Assessed by the Brief Medication Questionnaire (BMQ) | Day 115 / End of Study | 54 Participants |
| PEAR-004 | Percentage of Responders as Assessed by the Brief Medication Questionnaire (BMQ) | Day 1 | 53 Participants |
| Sham | Percentage of Responders as Assessed by the Brief Medication Questionnaire (BMQ) | Day 115 / End of Study | 52 Participants |
| Sham | Percentage of Responders as Assessed by the Brief Medication Questionnaire (BMQ) | Day 1 | 54 Participants |
| Sham | Percentage of Responders as Assessed by the Brief Medication Questionnaire (BMQ) | Day 29 | 53 Participants |
| Sham | Percentage of Responders as Assessed by the Brief Medication Questionnaire (BMQ) | Day 57 | 46 Participants |
| Sham | Percentage of Responders as Assessed by the Brief Medication Questionnaire (BMQ) | Day 85 | 48 Participants |
Secondary
Percentage of Responders as Assessed by the Total PANSS Score
A Response is defined as a reduction of at least 20% at day 85 or last visit in total PANSS score relative to Baseline.
Time frame: Day 85
Population: Full Analysis Set (FAS)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| PEAR-004 | Percentage of Responders as Assessed by the Total PANSS Score | 2 Participants |
| Sham | Percentage of Responders as Assessed by the Total PANSS Score | 9 Participants |