Major Depressive Disorder
Conditions
Keywords
Antidepressant Augmentation
Brief summary
The primary objectives of this study are to: 1) Evaluate the efficacy of CP 601,927 compared to placebo in the augmentation of antidepressant therapy (ADT) in patients with Major Depressive Disorder (MDD) using the Montgomery Asberg Depression Rating Scale (MADRS). 2) Evaluate the safety and tolerability of CP 601,927 in patients with MDD on ADT.
Detailed description
The study was stopped at interim analysis in August 2011, as stopping criteria for futility were met. There was no statistically significant change on the primary efficacy scale in favor of the drug. There was a very small chance that any additional data could change the study overall outcome. There were no concerns regarding subject safety.
Interventions
DRUGCP-601,927
CP-601,927 1-2 mg twice per day, oral 1 mg tablets, for 6 weeks.
OTHERPlacebo
Matching placebo tablets, taken orally, twice per day, for 6 weeks.
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Medically healthy males or females aged 18-65 (inclusive). * Patients must have a primary current diagnosis of MDD without psychotic features. * Patients must be receiving ongoing antidepressant therapy at the time of screening. Duration of the current episode of MDD must be at least 8 weeks prior to enrollment without adequate response to treatment.
Exclusion criteria
* Patients with other psychiatric disorders. * Patients who use tobacco products. * Alcohol or substance abuse or dependence. * Treatment with a monoamine oxidase inhibitor within 10 weeks of enrollment. * Pregnancy or breastfeeding. * Clinically significant abnormalities on laboratory tests, electrocardiogram, or physical or neurologic examination.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Double-blind Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) - Total Score at Week 14 | Week 8 (double-blind baseline ) and week 14 (week 6 of double-blind phase) | MADRS measures the overall severity of depressive symptoms. The MADRS had a 10-item checklist. Items are rated on a scale of 0-6, for a total numeric range of scores from 0 (depressive symptoms absent) to 60 (numerically highest level of depressive symptoms). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Double-blind Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) - Total Score at Weeks 9 Through 13 | Week 8 (double-blind baseline) and weeks 9 through 13 | MADRS measures the overall severity of depressive symptoms. The MADRS had a 10-item checklist. Items are rated on a scale of 0-6, for a total numeric range of scores from 0 (depressive symptoms absent) to 60 (numerically highest level of depressive symptoms). |
| Change From Double-blind Baseline in Hamilton Depression Scale 25-item (HAM-D25) - Total Score at Weeks 9 Through 14 | Weeks 8 (double-blind baseline) through 14 | The HAM-D25 is the 25-item version of a scale used to assess the range of depressive symptoms including depressed mood, work and activities, sleep, suicidal thinking, psychomotor agitation/retardation, appetite, sexual interest, anxiety, somatic symptoms, and cognitive symptoms. The items on the HAM-D were rated on a scale of 0-2 or 0-4, for a total numeric range of scores from 0 (depressive symptoms absent) to 72 (numerically highest level of depressive symptoms). |
| Change From Double-blind Baseline in Bech Melancholia Subscale Score at Weeks 9 Through 14 | Weeks 8 (double-blind baseline) through 14 | The Bech Melancholia is sum of scores on 6 items (items 1, 2, 7, 8, 10 and 13) pertaining to melancholia within HAM-D. The items are rated on a scale of 0-4, higher scores reflecting greater severity. Total possible score is 0-24. |
| Change From Double-blind Baseline in Clinical Global Impression - Severity (CGI-S) at Weeks 9, 10, 12, and 14 | Week 8 (double-blind baseline) and weeks 9, 10, 12, 14 | CGI-S was defined as 7-point clinician rated scale to assess severity of participant's current illness state; range: 1 (normal - not ill at all) to 7 (among the most extremely ill participants). Higher score = more affected. |
| Change From Double-blind Baseline in Sheehan Irritability Scale (SIS) Total Score at Weeks 11 and 14 | Weeks 8 (double-blind baseline), 11 and 14 | The SIS is to rate suffering with regard to irritability symptoms. The degree to which irritability interferes with work, social and family function is also queried. The total SIS score is the sum of 7 items. Each item is rated on a scale of 0-10, for a total numeric range of scores from 0 (not at all) to 70 (extremely). The SIS also records the number of days impaired by irritability. |
| Change From Double-blind Baseline in Sheehan Disability Scale (SDS) Total Score at Weeks 11 and 14 | Weeks 8 (double-blind baseline), 11 and 14 | SDS is defined as a self-administered tool that measures functional impairment including work/school, social life, and family life/home responsibilities. Items are rated on a scale of 0-10 visual analog scale (0=not at all impaired, 10=extremely impaired), for a total numeric range of scores from 0 (not at all impaired) to 30 (extremely impaired). |
| Clinical Global Impression - Improvement (CGI-I) Total Score at Weeks 9, 10, 12 and 14 | Weeks 8 (double-blind baseline) 9, 10, 12 and 14 | CGI-I was defined as a 7-point clinician rated scale ranging from 1 (very much improved) to 7 (very much worse). Improvement was defined as a score of 1 (very much improved), 2 (much improved), or 3 (minimally improved) on the scale. Higher score = more affected. |
| Number of Participants With Remission at Weeks 9, 10, 12 and 14 | Weeks 9, 10, 12 and 14 | Remission was defined as response plus an absolute MADRS total score of less than or equal to 10 plus a CGI-I score less than 2 ('much' or 'very much' improved). |
| Number of Participants With Response at Weeks 9 Through 14 | Weeks 9 through 14 | Response was defined as greater than 50 percent reduction from double-blind baseline in MADRS total score. |
| Population Pharmacokinetics | Weeks 11,12 and 14 | Population pharmacokinetic analysis involved mixed effects modeling using nonlinear mixed effects modeling (NONMEM) software. The intent of this analysis was to establish a basic population pharmacokinetic model for CP-601,927 and to determine inter-individual and residual variability in population clearance, and volume of distribution of drug. Relationship of demographic variables (gender, age, body weight, height and ethnicity), concomitant medications and measures of altered hepatic and renal function were examined by fitting measured CP-601,927 concentrations |
| Plasma CP-601,927 Concentration | Week 11, 12 and 14 | Blood samples were collected for plasma CP-601,927 concentration analysis which was summarized by mean and standard deviation. |
| Change From Double-blind Baseline in Sheehan Disability Scale (SDS) Subscale Score at Weeks 11 and 14 | Weeks 8 (double-blind baseline), 11 and 14 | SDS subscale is defined as a self-administered tool that measures functional impairment in 3-item including work/school, social life, and family life/home responsibilities. Items are rated on a scale of 0-10 visual analog scale, for a total numeric range of scores from 0 (not at all impaired) to 30 (extremely impaired). |
Other
| Measure | Time frame | Description |
|---|---|---|
| The Sheehan Suicidality Tracking Scale (STS) | Week 8 (double-blind baseline) and weeks 9 through 14 | The Sheehan Suicidality Tracking Scale (STS) measures treatment-emergent suicidal ideation as well as behaviors. It can be administered by a clinician or filled in by a participant. Prior to analysis, the STS was mapped to the Columbia Classification Algorithm of Suicide Assessment(C-CASA) categories, which has 9-item including completed suicide, suicide attempt, preparatory acts, suicidal ideation, self-injurious behavior, self-injurious no intent, unknown fatal,unknown non-fatal or other not deliberate. Participants who were mapped to C-CASA items were reported. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Open-Label ADT Participants treated with 1 of 5 allowed antidepressant agents in accordance with current product labeling, targeting the following doses by the end of week 2: escitalopram (Lexapro) (10-20 mg/d), citalopram (Celexa) (20-40 mg/d), fluoxetine (Prozac, Sarafem) (20-60 mg/d), paroxetine CR (Paxil CR) (37.5-62.5 mg/d), sertraline (Zoloft) (100-200 mg/d), for up to 8 weeks in open-label phase. | 297 |
| Total | 297 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Double-Blind Phase | Adverse Event | 0 | 3 | 3 |
| Double-Blind Phase | Did Not Meet Entrance Criteria | 0 | 1 | 0 |
| Double-Blind Phase | Insufficient Clinical Response | 0 | 1 | 2 |
| Double-Blind Phase | Lost to Follow-up | 0 | 2 | 0 |
| Double-Blind Phase | Other | 0 | 2 | 2 |
| Double-Blind Phase | Protocol Violation | 0 | 2 | 4 |
| Double-Blind Phase | Study Terminated by Sponsor | 0 | 5 | 8 |
| Double-Blind Phase | Withdrawal by Subject | 0 | 1 | 3 |
| Open-Label Phase | Adverse Event | 12 | 0 | 0 |
| Open-Label Phase | Did Not Meet Entrance Criteria | 50 | 0 | 0 |
| Open-Label Phase | Lost to Follow-up | 13 | 0 | 0 |
| Open-Label Phase | Other | 19 | 0 | 0 |
| Open-Label Phase | Pregnancy | 1 | 0 | 0 |
| Open-Label Phase | Protocol Violation | 4 | 0 | 0 |
| Open-Label Phase | Study Terminated by Sponsor | 27 | 0 | 0 |
| Open-Label Phase | Withdrawal by Subject | 9 | 0 | 0 |
Baseline characteristics
| Characteristic | Open-Label ADT |
|---|---|
| Age, Customized 18 to 44 years | 113 Participants |
| Age, Customized 45 to 64 years | 181 Participants |
| Age, Customized Greater than or equal to (>=) 65 years | 3 Participants |
| Sex: Female, Male Female | 220 Participants |
| Sex: Female, Male Male | 77 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 210 / 297 | 58 / 77 | 61 / 85 |
| serious Total, serious adverse events | 3 / 297 | 1 / 77 | 1 / 85 |
Outcome results
Primary
Change From Double-blind Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) - Total Score at Week 14
MADRS measures the overall severity of depressive symptoms. The MADRS had a 10-item checklist. Items are rated on a scale of 0-6, for a total numeric range of scores from 0 (depressive symptoms absent) to 60 (numerically highest level of depressive symptoms).
Time frame: Week 8 (double-blind baseline ) and week 14 (week 6 of double-blind phase)
Population: The full analysis set, which was defined as the set of all participants who consumed at least one dose of randomized study medication, was applied for the analysis. Number Analyzed = number of participants with evaluable data at each timeframe.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CP-601,927 + ADT | Change From Double-blind Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) - Total Score at Week 14 | Week 8 (double-blind baseline) | 29.5 Units on a scale | Standard Deviation 6 |
| CP-601,927 + ADT | Change From Double-blind Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) - Total Score at Week 14 | Change at week 14 | -10.3 Units on a scale | Standard Deviation 8.6 |
| Placebo + ADT | Change From Double-blind Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) - Total Score at Week 14 | Week 8 (double-blind baseline) | 29.1 Units on a scale | Standard Deviation 5.54 |
| Placebo + ADT | Change From Double-blind Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) - Total Score at Week 14 | Change at week 14 | -8.8 Units on a scale | Standard Deviation 10.4 |
Secondary
Change From Double-blind Baseline in Bech Melancholia Subscale Score at Weeks 9 Through 14
The Bech Melancholia is sum of scores on 6 items (items 1, 2, 7, 8, 10 and 13) pertaining to melancholia within HAM-D. The items are rated on a scale of 0-4, higher scores reflecting greater severity. Total possible score is 0-24.
Time frame: Weeks 8 (double-blind baseline) through 14
Population: The full analysis set, which was defined as the set of all participants who consumed at least one dose of randomized study medication, was applied for the analysis. Number Analyzed = number of participants with evaluable data at each timeframe.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CP-601,927 + ADT | Change From Double-blind Baseline in Bech Melancholia Subscale Score at Weeks 9 Through 14 | Change at week 10 | -2.1 Units on a scale | Standard Deviation 3.07 |
| CP-601,927 + ADT | Change From Double-blind Baseline in Bech Melancholia Subscale Score at Weeks 9 Through 14 | Change at week 12 | -3.6 Units on a scale | Standard Deviation 3.65 |
| CP-601,927 + ADT | Change From Double-blind Baseline in Bech Melancholia Subscale Score at Weeks 9 Through 14 | Change at week 9 | -1.3 Units on a scale | Standard Deviation 2.31 |
| CP-601,927 + ADT | Change From Double-blind Baseline in Bech Melancholia Subscale Score at Weeks 9 Through 14 | Change at week 13 | -3.8 Units on a scale | Standard Deviation 3.56 |
| CP-601,927 + ADT | Change From Double-blind Baseline in Bech Melancholia Subscale Score at Weeks 9 Through 14 | Change at week 11 | -3.0 Units on a scale | Standard Deviation 3.55 |
| CP-601,927 + ADT | Change From Double-blind Baseline in Bech Melancholia Subscale Score at Weeks 9 Through 14 | Change at week 14 | -4.3 Units on a scale | Standard Deviation 3.87 |
| CP-601,927 + ADT | Change From Double-blind Baseline in Bech Melancholia Subscale Score at Weeks 9 Through 14 | Week 8 (double-blind baseline) | 11.6 Units on a scale | Standard Deviation 1.9 |
| Placebo + ADT | Change From Double-blind Baseline in Bech Melancholia Subscale Score at Weeks 9 Through 14 | Change at week 14 | -3.7 Units on a scale | Standard Deviation 4.15 |
| Placebo + ADT | Change From Double-blind Baseline in Bech Melancholia Subscale Score at Weeks 9 Through 14 | Week 8 (double-blind baseline) | 11.6 Units on a scale | Standard Deviation 2.05 |
| Placebo + ADT | Change From Double-blind Baseline in Bech Melancholia Subscale Score at Weeks 9 Through 14 | Change at week 9 | -1.5 Units on a scale | Standard Deviation 2.48 |
| Placebo + ADT | Change From Double-blind Baseline in Bech Melancholia Subscale Score at Weeks 9 Through 14 | Change at week 10 | -2.0 Units on a scale | Standard Deviation 2.87 |
| Placebo + ADT | Change From Double-blind Baseline in Bech Melancholia Subscale Score at Weeks 9 Through 14 | Change at week 11 | -2.7 Units on a scale | Standard Deviation 3.38 |
| Placebo + ADT | Change From Double-blind Baseline in Bech Melancholia Subscale Score at Weeks 9 Through 14 | Change at week 12 | -3.0 Units on a scale | Standard Deviation 3.4 |
| Placebo + ADT | Change From Double-blind Baseline in Bech Melancholia Subscale Score at Weeks 9 Through 14 | Change at week 13 | -3.2 Units on a scale | Standard Deviation 3.69 |
Secondary
Change From Double-blind Baseline in Clinical Global Impression - Severity (CGI-S) at Weeks 9, 10, 12, and 14
CGI-S was defined as 7-point clinician rated scale to assess severity of participant's current illness state; range: 1 (normal - not ill at all) to 7 (among the most extremely ill participants). Higher score = more affected.
Time frame: Week 8 (double-blind baseline) and weeks 9, 10, 12, 14
Population: The full analysis set, which was defined as the set of all participants who consumed at least one dose of randomized study medication, was applied for the analysis. Number Analyzed = number of participants with evaluable data at each timeframe.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CP-601,927 + ADT | Change From Double-blind Baseline in Clinical Global Impression - Severity (CGI-S) at Weeks 9, 10, 12, and 14 | Change at week 9 | -0.2 Units on a scale | Standard Deviation 0.49 |
| CP-601,927 + ADT | Change From Double-blind Baseline in Clinical Global Impression - Severity (CGI-S) at Weeks 9, 10, 12, and 14 | Change at week 12 | -0.8 Units on a scale | Standard Deviation 1.01 |
| CP-601,927 + ADT | Change From Double-blind Baseline in Clinical Global Impression - Severity (CGI-S) at Weeks 9, 10, 12, and 14 | Change at week 10 | -0.5 Units on a scale | Standard Deviation 0.81 |
| CP-601,927 + ADT | Change From Double-blind Baseline in Clinical Global Impression - Severity (CGI-S) at Weeks 9, 10, 12, and 14 | Change at week 14 | -1.1 Units on a scale | Standard Deviation 1.11 |
| CP-601,927 + ADT | Change From Double-blind Baseline in Clinical Global Impression - Severity (CGI-S) at Weeks 9, 10, 12, and 14 | Week 8 (double-blind baseline) | 4.2 Units on a scale | Standard Deviation 0.59 |
| Placebo + ADT | Change From Double-blind Baseline in Clinical Global Impression - Severity (CGI-S) at Weeks 9, 10, 12, and 14 | Change at week 14 | -1.0 Units on a scale | Standard Deviation 1.18 |
| Placebo + ADT | Change From Double-blind Baseline in Clinical Global Impression - Severity (CGI-S) at Weeks 9, 10, 12, and 14 | Week 8 (double-blind baseline) | 4.2 Units on a scale | Standard Deviation 0.67 |
| Placebo + ADT | Change From Double-blind Baseline in Clinical Global Impression - Severity (CGI-S) at Weeks 9, 10, 12, and 14 | Change at week 9 | -0.2 Units on a scale | Standard Deviation 0.6 |
| Placebo + ADT | Change From Double-blind Baseline in Clinical Global Impression - Severity (CGI-S) at Weeks 9, 10, 12, and 14 | Change at week 10 | -0.5 Units on a scale | Standard Deviation 0.83 |
| Placebo + ADT | Change From Double-blind Baseline in Clinical Global Impression - Severity (CGI-S) at Weeks 9, 10, 12, and 14 | Change at week 12 | -0.7 Units on a scale | Standard Deviation 1.14 |
Secondary
Change From Double-blind Baseline in Hamilton Depression Scale 25-item (HAM-D25) - Total Score at Weeks 9 Through 14
The HAM-D25 is the 25-item version of a scale used to assess the range of depressive symptoms including depressed mood, work and activities, sleep, suicidal thinking, psychomotor agitation/retardation, appetite, sexual interest, anxiety, somatic symptoms, and cognitive symptoms. The items on the HAM-D were rated on a scale of 0-2 or 0-4, for a total numeric range of scores from 0 (depressive symptoms absent) to 72 (numerically highest level of depressive symptoms).
Time frame: Weeks 8 (double-blind baseline) through 14
Population: The full analysis set, which was defined as the set of all participants who consumed at least one dose of randomized study medication, was applied for the analysis. Number Analyzed = number of participants with evaluable data at each timeframe.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CP-601,927 + ADT | Change From Double-blind Baseline in Hamilton Depression Scale 25-item (HAM-D25) - Total Score at Weeks 9 Through 14 | Change at week 10 | -4.4 Units on a scale | Standard Deviation 6.57 |
| CP-601,927 + ADT | Change From Double-blind Baseline in Hamilton Depression Scale 25-item (HAM-D25) - Total Score at Weeks 9 Through 14 | Change at week 12 | -7.6 Units on a scale | Standard Deviation 7.63 |
| CP-601,927 + ADT | Change From Double-blind Baseline in Hamilton Depression Scale 25-item (HAM-D25) - Total Score at Weeks 9 Through 14 | Change at week 9 | -3.0 Units on a scale | Standard Deviation 4.49 |
| CP-601,927 + ADT | Change From Double-blind Baseline in Hamilton Depression Scale 25-item (HAM-D25) - Total Score at Weeks 9 Through 14 | Change at week 13 | -8.0 Units on a scale | Standard Deviation 7.22 |
| CP-601,927 + ADT | Change From Double-blind Baseline in Hamilton Depression Scale 25-item (HAM-D25) - Total Score at Weeks 9 Through 14 | Change at week 14 | -9.1 Units on a scale | Standard Deviation 7.76 |
| CP-601,927 + ADT | Change From Double-blind Baseline in Hamilton Depression Scale 25-item (HAM-D25) - Total Score at Weeks 9 Through 14 | Change at week 11 | -5.9 Units on a scale | Standard Deviation 7.4 |
| CP-601,927 + ADT | Change From Double-blind Baseline in Hamilton Depression Scale 25-item (HAM-D25) - Total Score at Weeks 9 Through 14 | Week 8 (double-blind baseline) | 26.4 Units on a scale | Standard Deviation 4.25 |
| Placebo + ADT | Change From Double-blind Baseline in Hamilton Depression Scale 25-item (HAM-D25) - Total Score at Weeks 9 Through 14 | Change at week 13 | -7.3 Units on a scale | Standard Deviation 7.9 |
| Placebo + ADT | Change From Double-blind Baseline in Hamilton Depression Scale 25-item (HAM-D25) - Total Score at Weeks 9 Through 14 | Week 8 (double-blind baseline) | 26.3 Units on a scale | Standard Deviation 4.96 |
| Placebo + ADT | Change From Double-blind Baseline in Hamilton Depression Scale 25-item (HAM-D25) - Total Score at Weeks 9 Through 14 | Change at week 9 | -3.0 Units on a scale | Standard Deviation 5.25 |
| Placebo + ADT | Change From Double-blind Baseline in Hamilton Depression Scale 25-item (HAM-D25) - Total Score at Weeks 9 Through 14 | Change at week 10 | -4.7 Units on a scale | Standard Deviation 5.78 |
| Placebo + ADT | Change From Double-blind Baseline in Hamilton Depression Scale 25-item (HAM-D25) - Total Score at Weeks 9 Through 14 | Change at week 11 | -6.4 Units on a scale | Standard Deviation 7.06 |
| Placebo + ADT | Change From Double-blind Baseline in Hamilton Depression Scale 25-item (HAM-D25) - Total Score at Weeks 9 Through 14 | Change at week 12 | -6.7 Units on a scale | Standard Deviation 7.67 |
| Placebo + ADT | Change From Double-blind Baseline in Hamilton Depression Scale 25-item (HAM-D25) - Total Score at Weeks 9 Through 14 | Change at week 14 | -8.4 Units on a scale | Standard Deviation 8.99 |
Secondary
Change From Double-blind Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) - Total Score at Weeks 9 Through 13
MADRS measures the overall severity of depressive symptoms. The MADRS had a 10-item checklist. Items are rated on a scale of 0-6, for a total numeric range of scores from 0 (depressive symptoms absent) to 60 (numerically highest level of depressive symptoms).
Time frame: Week 8 (double-blind baseline) and weeks 9 through 13
Population: The full analysis set, which was defined as the set of all participants who consumed at least one dose of randomized study medication, was applied for the analysis. Number Analyzed = number of participants with evaluable data at each timeframe.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CP-601,927 + ADT | Change From Double-blind Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) - Total Score at Weeks 9 Through 13 | Week 8 (double-blind baseline) | 29.5 Units on a scale | Standard Deviation 6 |
| CP-601,927 + ADT | Change From Double-blind Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) - Total Score at Weeks 9 Through 13 | Change at Week 9 | -2.4 Units on a scale | Standard Deviation 4.68 |
| CP-601,927 + ADT | Change From Double-blind Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) - Total Score at Weeks 9 Through 13 | Change at Week 10 | -4.7 Units on a scale | Standard Deviation 6.65 |
| CP-601,927 + ADT | Change From Double-blind Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) - Total Score at Weeks 9 Through 13 | Change at Week 11 | -7.0 Units on a scale | Standard Deviation 7.78 |
| CP-601,927 + ADT | Change From Double-blind Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) - Total Score at Weeks 9 Through 13 | Change at Week 12 | -8.5 Units on a scale | Standard Deviation 8.08 |
| CP-601,927 + ADT | Change From Double-blind Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) - Total Score at Weeks 9 Through 13 | Change at week 13 | -8.6 Units on a scale | Standard Deviation 8.16 |
| Placebo + ADT | Change From Double-blind Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) - Total Score at Weeks 9 Through 13 | Change at Week 12 | -7.4 Units on a scale | Standard Deviation 8.83 |
| Placebo + ADT | Change From Double-blind Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) - Total Score at Weeks 9 Through 13 | Week 8 (double-blind baseline) | 29.1 Units on a scale | Standard Deviation 5.54 |
| Placebo + ADT | Change From Double-blind Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) - Total Score at Weeks 9 Through 13 | Change at Week 11 | -6.0 Units on a scale | Standard Deviation 8.06 |
| Placebo + ADT | Change From Double-blind Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) - Total Score at Weeks 9 Through 13 | Change at Week 9 | -3.3 Units on a scale | Standard Deviation 5.35 |
| Placebo + ADT | Change From Double-blind Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) - Total Score at Weeks 9 Through 13 | Change at week 13 | -7.9 Units on a scale | Standard Deviation 9.37 |
| Placebo + ADT | Change From Double-blind Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) - Total Score at Weeks 9 Through 13 | Change at Week 10 | -4.6 Units on a scale | Standard Deviation 6.85 |
Secondary
Change From Double-blind Baseline in Sheehan Disability Scale (SDS) Subscale Score at Weeks 11 and 14
SDS subscale is defined as a self-administered tool that measures functional impairment in 3-item including work/school, social life, and family life/home responsibilities. Items are rated on a scale of 0-10 visual analog scale, for a total numeric range of scores from 0 (not at all impaired) to 30 (extremely impaired).
Time frame: Weeks 8 (double-blind baseline), 11 and 14
Population: The full analysis set, which was defined as the set of all participants who consumed at least one dose of randomized study medication, was applied for the analysis. Number Analyzed = number of participants with evaluable data at each timeframe.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CP-601,927 + ADT | Change From Double-blind Baseline in Sheehan Disability Scale (SDS) Subscale Score at Weeks 11 and 14 | Week 8 (double-blind baseline) | 6.0 Units on a scale | Standard Deviation 2.22 |
| CP-601,927 + ADT | Change From Double-blind Baseline in Sheehan Disability Scale (SDS) Subscale Score at Weeks 11 and 14 | Change at week 11 | -2.1 Units on a scale | Standard Deviation 2.86 |
| CP-601,927 + ADT | Change From Double-blind Baseline in Sheehan Disability Scale (SDS) Subscale Score at Weeks 11 and 14 | Change at week 14 | -2.1 Units on a scale | Standard Deviation 2.88 |
| Placebo + ADT | Change From Double-blind Baseline in Sheehan Disability Scale (SDS) Subscale Score at Weeks 11 and 14 | Week 8 (double-blind baseline) | 5.5 Units on a scale | Standard Deviation 2.66 |
| Placebo + ADT | Change From Double-blind Baseline in Sheehan Disability Scale (SDS) Subscale Score at Weeks 11 and 14 | Change at week 11 | -0.9 Units on a scale | Standard Deviation 2.1 |
| Placebo + ADT | Change From Double-blind Baseline in Sheehan Disability Scale (SDS) Subscale Score at Weeks 11 and 14 | Change at week 14 | -1.9 Units on a scale | Standard Deviation 2.66 |
Secondary
Change From Double-blind Baseline in Sheehan Disability Scale (SDS) Total Score at Weeks 11 and 14
SDS is defined as a self-administered tool that measures functional impairment including work/school, social life, and family life/home responsibilities. Items are rated on a scale of 0-10 visual analog scale (0=not at all impaired, 10=extremely impaired), for a total numeric range of scores from 0 (not at all impaired) to 30 (extremely impaired).
Time frame: Weeks 8 (double-blind baseline), 11 and 14
Population: The full analysis set, which was defined as the set of all participants who consumed at least one dose of randomized study medication, was applied for the analysis. Number Analyzed = number of participants with evaluable data at each timeframe.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CP-601,927 + ADT | Change From Double-blind Baseline in Sheehan Disability Scale (SDS) Total Score at Weeks 11 and 14 | Week 8 (double-blind baseline) | 19.0 Units on a scale | Standard Deviation 5.88 |
| CP-601,927 + ADT | Change From Double-blind Baseline in Sheehan Disability Scale (SDS) Total Score at Weeks 11 and 14 | Change at week 11 | -5.6 Units on a scale | Standard Deviation 6.98 |
| CP-601,927 + ADT | Change From Double-blind Baseline in Sheehan Disability Scale (SDS) Total Score at Weeks 11 and 14 | Change at week 14 | -6.6 Units on a scale | Standard Deviation 7.98 |
| Placebo + ADT | Change From Double-blind Baseline in Sheehan Disability Scale (SDS) Total Score at Weeks 11 and 14 | Week 8 (double-blind baseline) | 18.5 Units on a scale | Standard Deviation 5.3 |
| Placebo + ADT | Change From Double-blind Baseline in Sheehan Disability Scale (SDS) Total Score at Weeks 11 and 14 | Change at week 11 | -3.8 Units on a scale | Standard Deviation 6.33 |
| Placebo + ADT | Change From Double-blind Baseline in Sheehan Disability Scale (SDS) Total Score at Weeks 11 and 14 | Change at week 14 | -5.7 Units on a scale | Standard Deviation 8.21 |
Secondary
Change From Double-blind Baseline in Sheehan Irritability Scale (SIS) Total Score at Weeks 11 and 14
The SIS is to rate suffering with regard to irritability symptoms. The degree to which irritability interferes with work, social and family function is also queried. The total SIS score is the sum of 7 items. Each item is rated on a scale of 0-10, for a total numeric range of scores from 0 (not at all) to 70 (extremely). The SIS also records the number of days impaired by irritability.
Time frame: Weeks 8 (double-blind baseline), 11 and 14
Population: The full analysis set, which was defined as the set of all participants who consumed at least one dose of randomized study medication, was applied for the analysis. Number Analyzed = number of participants with evaluable data at each timeframe.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CP-601,927 + ADT | Change From Double-blind Baseline in Sheehan Irritability Scale (SIS) Total Score at Weeks 11 and 14 | Week 8 (double-blind baseline) | 36.1 Units on a scale | Standard Deviation 13.21 |
| CP-601,927 + ADT | Change From Double-blind Baseline in Sheehan Irritability Scale (SIS) Total Score at Weeks 11 and 14 | Change at week 11 | -9.3 Units on a scale | Standard Deviation 14.41 |
| CP-601,927 + ADT | Change From Double-blind Baseline in Sheehan Irritability Scale (SIS) Total Score at Weeks 11 and 14 | Change at week 14 | -12.3 Units on a scale | Standard Deviation 15.8 |
| Placebo + ADT | Change From Double-blind Baseline in Sheehan Irritability Scale (SIS) Total Score at Weeks 11 and 14 | Week 8 (double-blind baseline) | 34.8 Units on a scale | Standard Deviation 13.68 |
| Placebo + ADT | Change From Double-blind Baseline in Sheehan Irritability Scale (SIS) Total Score at Weeks 11 and 14 | Change at week 11 | -7.3 Units on a scale | Standard Deviation 13.7 |
| Placebo + ADT | Change From Double-blind Baseline in Sheehan Irritability Scale (SIS) Total Score at Weeks 11 and 14 | Change at week 14 | -10.4 Units on a scale | Standard Deviation 17.11 |
Secondary
Clinical Global Impression - Improvement (CGI-I) Total Score at Weeks 9, 10, 12 and 14
CGI-I was defined as a 7-point clinician rated scale ranging from 1 (very much improved) to 7 (very much worse). Improvement was defined as a score of 1 (very much improved), 2 (much improved), or 3 (minimally improved) on the scale. Higher score = more affected.
Time frame: Weeks 8 (double-blind baseline) 9, 10, 12 and 14
Population: The full analysis set, which was defined as the set of all participants who consumed at least one dose of randomized study medication, was applied for the analysis. Number Analyzed = number of participants with evaluable data at each timeframe.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CP-601,927 + ADT | Clinical Global Impression - Improvement (CGI-I) Total Score at Weeks 9, 10, 12 and 14 | Week 9 | 3.4 Units on a scale | Standard Deviation 0.84 |
| CP-601,927 + ADT | Clinical Global Impression - Improvement (CGI-I) Total Score at Weeks 9, 10, 12 and 14 | Week 12 | 2.7 Units on a scale | Standard Deviation 1.05 |
| CP-601,927 + ADT | Clinical Global Impression - Improvement (CGI-I) Total Score at Weeks 9, 10, 12 and 14 | Week 10 | 3.2 Units on a scale | Standard Deviation 0.92 |
| CP-601,927 + ADT | Clinical Global Impression - Improvement (CGI-I) Total Score at Weeks 9, 10, 12 and 14 | Week 14 | 2.5 Units on a scale | Standard Deviation 1.05 |
| CP-601,927 + ADT | Clinical Global Impression - Improvement (CGI-I) Total Score at Weeks 9, 10, 12 and 14 | Week 8 (double-blind baseline) | 3.7 Units on a scale | Standard Deviation 0.77 |
| Placebo + ADT | Clinical Global Impression - Improvement (CGI-I) Total Score at Weeks 9, 10, 12 and 14 | Week 14 | 2.7 Units on a scale | Standard Deviation 1.03 |
| Placebo + ADT | Clinical Global Impression - Improvement (CGI-I) Total Score at Weeks 9, 10, 12 and 14 | Week 8 (double-blind baseline) | 3.5 Units on a scale | Standard Deviation 0.66 |
| Placebo + ADT | Clinical Global Impression - Improvement (CGI-I) Total Score at Weeks 9, 10, 12 and 14 | Week 9 | 3.2 Units on a scale | Standard Deviation 0.78 |
| Placebo + ADT | Clinical Global Impression - Improvement (CGI-I) Total Score at Weeks 9, 10, 12 and 14 | Week 10 | 3.1 Units on a scale | Standard Deviation 0.88 |
| Placebo + ADT | Clinical Global Impression - Improvement (CGI-I) Total Score at Weeks 9, 10, 12 and 14 | Week 12 | 2.8 Units on a scale | Standard Deviation 1.07 |
Secondary
Number of Participants With Remission at Weeks 9, 10, 12 and 14
Remission was defined as response plus an absolute MADRS total score of less than or equal to 10 plus a CGI-I score less than 2 ('much' or 'very much' improved).
Time frame: Weeks 9, 10, 12 and 14
Population: The full analysis set, which was defined as the set of all participants who consumed at least one dose of randomized study medication, was applied for the analysis. Number Analyzed = number of participants with evaluable data at each timeframe.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| CP-601,927 + ADT | Number of Participants With Remission at Weeks 9, 10, 12 and 14 | Week 9 | 1 Participants |
| CP-601,927 + ADT | Number of Participants With Remission at Weeks 9, 10, 12 and 14 | Week 10 | 4 Participants |
| CP-601,927 + ADT | Number of Participants With Remission at Weeks 9, 10, 12 and 14 | Week 12 | 5 Participants |
| CP-601,927 + ADT | Number of Participants With Remission at Weeks 9, 10, 12 and 14 | Week 14 | 9 Participants |
| Placebo + ADT | Number of Participants With Remission at Weeks 9, 10, 12 and 14 | Week 14 | 11 Participants |
| Placebo + ADT | Number of Participants With Remission at Weeks 9, 10, 12 and 14 | Week 9 | 0 Participants |
| Placebo + ADT | Number of Participants With Remission at Weeks 9, 10, 12 and 14 | Week 12 | 9 Participants |
| Placebo + ADT | Number of Participants With Remission at Weeks 9, 10, 12 and 14 | Week 10 | 1 Participants |
Secondary
Number of Participants With Response at Weeks 9 Through 14
Response was defined as greater than 50 percent reduction from double-blind baseline in MADRS total score.
Time frame: Weeks 9 through 14
Population: The full analysis set, which was defined as the set of all participants who consumed at least one dose of randomized study medication, was applied for the analysis. Number Analyzed = number of participants with evaluable data at each timeframe.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| CP-601,927 + ADT | Number of Participants With Response at Weeks 9 Through 14 | Week 9 | 3 Participants |
| CP-601,927 + ADT | Number of Participants With Response at Weeks 9 Through 14 | Week 10 | 8 Participants |
| CP-601,927 + ADT | Number of Participants With Response at Weeks 9 Through 14 | Week 11 | 15 Participants |
| CP-601,927 + ADT | Number of Participants With Response at Weeks 9 Through 14 | Week 12 | 18 Participants |
| CP-601,927 + ADT | Number of Participants With Response at Weeks 9 Through 14 | Week 13 | 23 Participants |
| CP-601,927 + ADT | Number of Participants With Response at Weeks 9 Through 14 | Week 14 | 22 Participants |
| Placebo + ADT | Number of Participants With Response at Weeks 9 Through 14 | Week 13 | 20 Participants |
| Placebo + ADT | Number of Participants With Response at Weeks 9 Through 14 | Week 9 | 4 Participants |
| Placebo + ADT | Number of Participants With Response at Weeks 9 Through 14 | Week 12 | 16 Participants |
| Placebo + ADT | Number of Participants With Response at Weeks 9 Through 14 | Week 10 | 8 Participants |
| Placebo + ADT | Number of Participants With Response at Weeks 9 Through 14 | Week 14 | 20 Participants |
| Placebo + ADT | Number of Participants With Response at Weeks 9 Through 14 | Week 11 | 10 Participants |
Secondary
Plasma CP-601,927 Concentration
Blood samples were collected for plasma CP-601,927 concentration analysis which was summarized by mean and standard deviation.
Time frame: Week 11, 12 and 14
Population: All randomized participants with at least one dose of study medication in DB (double blind) phase and one valid plasma concentration measurement collected during the DB phase was be included in the analyses of the PK endpoints. Number Analyzed = number of participants with evaluable data at each timeframe.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CP-601,927 + ADT | Plasma CP-601,927 Concentration | Week 11 at 1 Hour | 5.80 ng/mL | Standard Deviation 3.42 |
| CP-601,927 + ADT | Plasma CP-601,927 Concentration | Week 11 at 2 Hours | 5.90 ng/mL | Standard Deviation 3.13 |
| CP-601,927 + ADT | Plasma CP-601,927 Concentration | Week 12 | 6.24 ng/mL | Standard Deviation 3.85 |
| CP-601,927 + ADT | Plasma CP-601,927 Concentration | Week 14 at 1 Hour | 5.36 ng/mL | Standard Deviation 3.83 |
| CP-601,927 + ADT | Plasma CP-601,927 Concentration | Week 14 at 2 Hour | 5.39 ng/mL | Standard Deviation 3.89 |
Secondary
Population Pharmacokinetics
Population pharmacokinetic analysis involved mixed effects modeling using nonlinear mixed effects modeling (NONMEM) software. The intent of this analysis was to establish a basic population pharmacokinetic model for CP-601,927 and to determine inter-individual and residual variability in population clearance, and volume of distribution of drug. Relationship of demographic variables (gender, age, body weight, height and ethnicity), concomitant medications and measures of altered hepatic and renal function were examined by fitting measured CP-601,927 concentrations
Time frame: Weeks 11,12 and 14
Population: Data for this outcome measure was not collected and reported because the planned analysis (data collection) was not done as the study was stopped early for futility.
Other Pre-specified
The Sheehan Suicidality Tracking Scale (STS)
The Sheehan Suicidality Tracking Scale (STS) measures treatment-emergent suicidal ideation as well as behaviors. It can be administered by a clinician or filled in by a participant. Prior to analysis, the STS was mapped to the Columbia Classification Algorithm of Suicide Assessment(C-CASA) categories, which has 9-item including completed suicide, suicide attempt, preparatory acts, suicidal ideation, self-injurious behavior, self-injurious no intent, unknown fatal,unknown non-fatal or other not deliberate. Participants who were mapped to C-CASA items were reported.
Time frame: Week 8 (double-blind baseline) and weeks 9 through 14
Population: The full analysis set, which was defined as the set of all participants who consumed at least one dose of randomized study medication, was applied for the analysis. Number Analyzed = number of participants with evaluable data at each timeframe.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| CP-601,927 + ADT | The Sheehan Suicidality Tracking Scale (STS) | Week 12: no suicidal behavior and risk | 57 Participants |
| CP-601,927 + ADT | The Sheehan Suicidality Tracking Scale (STS) | Week 13: suicidal ideation | 5 Participants |
| CP-601,927 + ADT | The Sheehan Suicidality Tracking Scale (STS) | Week 13: no suicidal behavior and risk | 57 Participants |
| CP-601,927 + ADT | The Sheehan Suicidality Tracking Scale (STS) | Week 14: suicidal ideation | 5 Participants |
| CP-601,927 + ADT | The Sheehan Suicidality Tracking Scale (STS) | Week 14: no suicidal behavior and risk | 70 Participants |
| CP-601,927 + ADT | The Sheehan Suicidality Tracking Scale (STS) | Week 8: suicidal ideation | 11 Participants |
| CP-601,927 + ADT | The Sheehan Suicidality Tracking Scale (STS) | Week 8: no suicidal behavior and risk | 66 Participants |
| CP-601,927 + ADT | The Sheehan Suicidality Tracking Scale (STS) | Week 9: suicidal ideation | 10 Participants |
| CP-601,927 + ADT | The Sheehan Suicidality Tracking Scale (STS) | Week 9: self-injurious, no intent | 1 Participants |
| CP-601,927 + ADT | The Sheehan Suicidality Tracking Scale (STS) | Week 9: no suicidal behavior and risk | 61 Participants |
| CP-601,927 + ADT | The Sheehan Suicidality Tracking Scale (STS) | Week 10: suicidal ideation | 12 Participants |
| CP-601,927 + ADT | The Sheehan Suicidality Tracking Scale (STS) | Week 10: no suicidal behavior and risk | 57 Participants |
| CP-601,927 + ADT | The Sheehan Suicidality Tracking Scale (STS) | Week 11: suicidal ideation | 8 Participants |
| CP-601,927 + ADT | The Sheehan Suicidality Tracking Scale (STS) | Week 11: no suicidal behavior and risk | 56 Participants |
| CP-601,927 + ADT | The Sheehan Suicidality Tracking Scale (STS) | Week 12: suicidal ideation | 6 Participants |
| Placebo + ADT | The Sheehan Suicidality Tracking Scale (STS) | Week 12: no suicidal behavior and risk | 65 Participants |
| Placebo + ADT | The Sheehan Suicidality Tracking Scale (STS) | Week 9: self-injurious, no intent | 0 Participants |
| Placebo + ADT | The Sheehan Suicidality Tracking Scale (STS) | Week 13: suicidal ideation | 5 Participants |
| Placebo + ADT | The Sheehan Suicidality Tracking Scale (STS) | Week 11: suicidal ideation | 5 Participants |
| Placebo + ADT | The Sheehan Suicidality Tracking Scale (STS) | Week 13: no suicidal behavior and risk | 58 Participants |
| Placebo + ADT | The Sheehan Suicidality Tracking Scale (STS) | Week 9: no suicidal behavior and risk | 71 Participants |
| Placebo + ADT | The Sheehan Suicidality Tracking Scale (STS) | Week 14: suicidal ideation | 6 Participants |
| Placebo + ADT | The Sheehan Suicidality Tracking Scale (STS) | Week 12: suicidal ideation | 5 Participants |
| Placebo + ADT | The Sheehan Suicidality Tracking Scale (STS) | Week 14: no suicidal behavior and risk | 75 Participants |
| Placebo + ADT | The Sheehan Suicidality Tracking Scale (STS) | Week 10: suicidal ideation | 7 Participants |
| Placebo + ADT | The Sheehan Suicidality Tracking Scale (STS) | Week 8: suicidal ideation | 13 Participants |
| Placebo + ADT | The Sheehan Suicidality Tracking Scale (STS) | Week 11: no suicidal behavior and risk | 66 Participants |
| Placebo + ADT | The Sheehan Suicidality Tracking Scale (STS) | Week 8: no suicidal behavior and risk | 72 Participants |
| Placebo + ADT | The Sheehan Suicidality Tracking Scale (STS) | Week 10: no suicidal behavior and risk | 67 Participants |
| Placebo + ADT | The Sheehan Suicidality Tracking Scale (STS) | Week 9: suicidal ideation | 8 Participants |