Trial Outcomes & Findings for A Study Of The Efficacy And Safety Of CP-601,927 Augmentation Of Antidepressant Therapy In Major Depression (NCT NCT01098240)

Last Updated: 2021-05-03

Results Overview

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).

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

297 participants

Primary outcome timeframe

Week 8 (double-blind baseline ) and week 14 (week 6 of double-blind phase)

Results posted on

2021-05-03

Participant Flow

Participant milestones

Participant milestones
Measure	Open-Label Antidepressant Treatment (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 milligram/day \[mg/d\]), citalopram (Celexa) (20-40 mg/d), fluoxetine (Prozac, Sarafem) (20-60 mg/d), paroxetine controlled-release (CR) (Paxil CR) (37.5-62.5 mg/d), sertraline (Zoloft) (100-200 mg/d), for up to 8 weeks in open-label phase.	CP-601,927 + ADT Participants treated with CP-601,927 1 mg every evening (QPM) for 3 days, then 1 mg twice daily (BID) for 3 days, then 2 mg BID on Day 7 of dosing in the double-blind phase. Dose in participants experiencing intolerable nausea may be reduced to 1 mg BID for 6 weeks and a 7-10 day follow-up period. Background ADT (continued from Open-Label ADT) was applied in the double-blind phase.	Placebo + ADT Placebo matched to CP-601,927 1 mg QPM for 3 days, then CP-601,927 1 mg BID for 3 days, and then CP-601,927 2 mg BID on Day 7 of dosing in the double-blind phase. Dose in participants experiencing intolerable nausea may be reduced to 1 mg BID for 6 weeks and a 7-10 day follow-up period. Background ADT (continued from Open-Label ADT) was applied in the double-blind phase.
Open-Label Phase STARTED	297	0	0
Open-Label Phase COMPLETED	162	0	0
Open-Label Phase NOT COMPLETED	135	0	0
Double-Blind Phase STARTED	0	77	85
Double-Blind Phase COMPLETED	0	60	63
Double-Blind Phase NOT COMPLETED	0	17	22

Reasons for withdrawal

Reasons for withdrawal
Measure	Open-Label Antidepressant Treatment (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 milligram/day \[mg/d\]), citalopram (Celexa) (20-40 mg/d), fluoxetine (Prozac, Sarafem) (20-60 mg/d), paroxetine controlled-release (CR) (Paxil CR) (37.5-62.5 mg/d), sertraline (Zoloft) (100-200 mg/d), for up to 8 weeks in open-label phase.	CP-601,927 + ADT Participants treated with CP-601,927 1 mg every evening (QPM) for 3 days, then 1 mg twice daily (BID) for 3 days, then 2 mg BID on Day 7 of dosing in the double-blind phase. Dose in participants experiencing intolerable nausea may be reduced to 1 mg BID for 6 weeks and a 7-10 day follow-up period. Background ADT (continued from Open-Label ADT) was applied in the double-blind phase.	Placebo + ADT Placebo matched to CP-601,927 1 mg QPM for 3 days, then CP-601,927 1 mg BID for 3 days, and then CP-601,927 2 mg BID on Day 7 of dosing in the double-blind phase. Dose in participants experiencing intolerable nausea may be reduced to 1 mg BID for 6 weeks and a 7-10 day follow-up period. Background ADT (continued from Open-Label ADT) was applied in the double-blind phase.
Open-Label Phase Study Terminated by Sponsor	27	0	0
Open-Label Phase Protocol Violation	4	0	0
Open-Label Phase Lost to Follow-up	13	0	0
Open-Label Phase Other	19	0	0
Open-Label Phase Did Not Meet Entrance Criteria	50	0	0
Open-Label Phase Pregnancy	1	0	0
Open-Label Phase Withdrawal by Subject	9	0	0
Open-Label Phase Adverse Event	12	0	0
Double-Blind Phase Study Terminated by Sponsor	0	5	8
Double-Blind Phase Protocol Violation	0	2	4
Double-Blind Phase Lost to Follow-up	0	2	0
Double-Blind Phase Other	0	2	2
Double-Blind Phase Did Not Meet Entrance Criteria	0	1	0
Double-Blind Phase Insufficient Clinical Response	0	1	2
Double-Blind Phase Withdrawal by Subject	0	1	3
Double-Blind Phase Adverse Event	0	3	3

Baseline Characteristics

A Study Of The Efficacy And Safety Of CP-601,927 Augmentation Of Antidepressant Therapy In Major Depression

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Open-Label ADT n=297 Participants 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.
Age, Customized 18 to 44 years	113 Participants n=5 Participants
Age, Customized 45 to 64 years	181 Participants n=5 Participants
Age, Customized Greater than or equal to (>=) 65 years	3 Participants n=5 Participants
Sex: Female, Male Female	220 Participants n=5 Participants
Sex: Female, Male Male	77 Participants n=5 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	CP-601,927 + ADT n=77 Participants Participants treated with CP-601,927 1 mg QPM for 3 days, then 1 mg BID for 3 days, then 2 mg BID on Day 7 of dosing in the double-blind phase. Dose in participants experiencing intolerable nausea may be reduced to 1 mg BID for 6 weeks and a 7-10 day follow-up period. Background ADT (continued from Open-Label ADT) was applied in the double-blind phase.	Placebo + ADT n=85 Participants Placebo matched to CP-601,927 1 mg QPM for 3 days, then CP-601,927 1 mg BID for 3 days, and then CP-601,927 2 mg BID on Day 7 of dosing in the double-blind phase. Dose in participants experiencing intolerable nausea may be reduced to 1 mg BID for 6 weeks and a 7-10 day follow-up period. Background ADT (continued from Open-Label ADT) was applied in the double-blind phase.
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 6.00	29.1 Units on a scale Standard Deviation 5.54
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 8.60	-8.8 Units on a scale Standard Deviation 10.40

SECONDARY outcome

Timeframe: Week 8 (double-blind baseline) and weeks 9 through 13

Outcome measures

Outcome measures
Measure	CP-601,927 + ADT n=77 Participants Participants treated with CP-601,927 1 mg QPM for 3 days, then 1 mg BID for 3 days, then 2 mg BID on Day 7 of dosing in the double-blind phase. Dose in participants experiencing intolerable nausea may be reduced to 1 mg BID for 6 weeks and a 7-10 day follow-up period. Background ADT (continued from Open-Label ADT) was applied in the double-blind phase.	Placebo + ADT n=85 Participants Placebo matched to CP-601,927 1 mg QPM for 3 days, then CP-601,927 1 mg BID for 3 days, and then CP-601,927 2 mg BID on Day 7 of dosing in the double-blind phase. Dose in participants experiencing intolerable nausea may be reduced to 1 mg BID for 6 weeks and a 7-10 day follow-up period. Background ADT (continued from Open-Label ADT) was applied in the double-blind phase.
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	-6.0 Units on a scale Standard Deviation 8.06
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 6.00	29.1 Units on a scale Standard Deviation 5.54
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	-3.3 Units on a scale Standard Deviation 5.35
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	-4.6 Units on a scale Standard Deviation 6.85
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	-7.4 Units on a scale Standard Deviation 8.83
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	-7.9 Units on a scale Standard Deviation 9.37

SECONDARY outcome

Timeframe: 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).

Outcome measures

Outcome measures
Measure	CP-601,927 + ADT n=77 Participants Participants treated with CP-601,927 1 mg QPM for 3 days, then 1 mg BID for 3 days, then 2 mg BID on Day 7 of dosing in the double-blind phase. Dose in participants experiencing intolerable nausea may be reduced to 1 mg BID for 6 weeks and a 7-10 day follow-up period. Background ADT (continued from Open-Label ADT) was applied in the double-blind phase.	Placebo + ADT n=85 Participants Placebo matched to CP-601,927 1 mg QPM for 3 days, then CP-601,927 1 mg BID for 3 days, and then CP-601,927 2 mg BID on Day 7 of dosing in the double-blind phase. Dose in participants experiencing intolerable nausea may be reduced to 1 mg BID for 6 weeks and a 7-10 day follow-up period. Background ADT (continued from Open-Label ADT) was applied in the double-blind phase.
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	26.3 Units on a scale Standard Deviation 4.96
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	-3.0 Units on a scale Standard Deviation 5.25
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	-4.7 Units on a scale Standard Deviation 5.78
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 7.40	-6.4 Units on a scale Standard Deviation 7.06
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	-6.7 Units on a scale Standard Deviation 7.67
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	-7.3 Units on a scale Standard Deviation 7.90
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	-8.4 Units on a scale Standard Deviation 8.99

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	CP-601,927 + ADT n=77 Participants Participants treated with CP-601,927 1 mg QPM for 3 days, then 1 mg BID for 3 days, then 2 mg BID on Day 7 of dosing in the double-blind phase. Dose in participants experiencing intolerable nausea may be reduced to 1 mg BID for 6 weeks and a 7-10 day follow-up period. Background ADT (continued from Open-Label ADT) was applied in the double-blind phase.	Placebo + ADT n=85 Participants Placebo matched to CP-601,927 1 mg QPM for 3 days, then CP-601,927 1 mg BID for 3 days, and then CP-601,927 2 mg BID on Day 7 of dosing in the double-blind phase. Dose in participants experiencing intolerable nausea may be reduced to 1 mg BID for 6 weeks and a 7-10 day follow-up period. Background ADT (continued from Open-Label ADT) was applied in the double-blind phase.
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	-1.5 Units on a scale Standard Deviation 2.48
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 1.90	11.6 Units on a scale Standard Deviation 2.05
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	-2.0 Units on a scale Standard Deviation 2.87
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	-2.7 Units on a scale Standard Deviation 3.38
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	-3.0 Units on a scale Standard Deviation 3.40
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	-3.2 Units on a scale Standard Deviation 3.69
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	-3.7 Units on a scale Standard Deviation 4.15

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	CP-601,927 + ADT n=77 Participants Participants treated with CP-601,927 1 mg QPM for 3 days, then 1 mg BID for 3 days, then 2 mg BID on Day 7 of dosing in the double-blind phase. Dose in participants experiencing intolerable nausea may be reduced to 1 mg BID for 6 weeks and a 7-10 day follow-up period. Background ADT (continued from Open-Label ADT) was applied in the double-blind phase.	Placebo + ADT n=85 Participants Placebo matched to CP-601,927 1 mg QPM for 3 days, then CP-601,927 1 mg BID for 3 days, and then CP-601,927 2 mg BID on Day 7 of dosing in the double-blind phase. Dose in participants experiencing intolerable nausea may be reduced to 1 mg BID for 6 weeks and a 7-10 day follow-up period. Background ADT (continued from Open-Label ADT) was applied in the double-blind phase.
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	-0.5 Units on a scale Standard Deviation 0.83
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	4.2 Units on a scale Standard Deviation 0.67
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	-0.2 Units on a scale Standard Deviation 0.60
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	-0.7 Units on a scale Standard Deviation 1.14
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	-1.0 Units on a scale Standard Deviation 1.18

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	CP-601,927 + ADT n=77 Participants Participants treated with CP-601,927 1 mg QPM for 3 days, then 1 mg BID for 3 days, then 2 mg BID on Day 7 of dosing in the double-blind phase. Dose in participants experiencing intolerable nausea may be reduced to 1 mg BID for 6 weeks and a 7-10 day follow-up period. Background ADT (continued from Open-Label ADT) was applied in the double-blind phase.	Placebo + ADT n=85 Participants Placebo matched to CP-601,927 1 mg QPM for 3 days, then CP-601,927 1 mg BID for 3 days, and then CP-601,927 2 mg BID on Day 7 of dosing in the double-blind phase. Dose in participants experiencing intolerable nausea may be reduced to 1 mg BID for 6 weeks and a 7-10 day follow-up period. Background ADT (continued from Open-Label ADT) was applied in the double-blind phase.
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	34.8 Units on a scale Standard Deviation 13.68
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	-7.3 Units on a scale Standard Deviation 13.70
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 15.80	-10.4 Units on a scale Standard Deviation 17.11

SECONDARY outcome

Timeframe: 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).

Outcome measures

Outcome measures
Measure	CP-601,927 + ADT n=77 Participants Participants treated with CP-601,927 1 mg QPM for 3 days, then 1 mg BID for 3 days, then 2 mg BID on Day 7 of dosing in the double-blind phase. Dose in participants experiencing intolerable nausea may be reduced to 1 mg BID for 6 weeks and a 7-10 day follow-up period. Background ADT (continued from Open-Label ADT) was applied in the double-blind phase.	Placebo + ADT n=85 Participants Placebo matched to CP-601,927 1 mg QPM for 3 days, then CP-601,927 1 mg BID for 3 days, and then CP-601,927 2 mg BID on Day 7 of dosing in the double-blind phase. Dose in participants experiencing intolerable nausea may be reduced to 1 mg BID for 6 weeks and a 7-10 day follow-up period. Background ADT (continued from Open-Label ADT) was applied in the double-blind phase.
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	18.5 Units on a scale Standard Deviation 5.30
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	-3.8 Units on a scale Standard Deviation 6.33
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	-5.7 Units on a scale Standard Deviation 8.21

SECONDARY outcome

Timeframe: 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).

Outcome measures

Outcome measures
Measure	CP-601,927 + ADT n=77 Participants Participants treated with CP-601,927 1 mg QPM for 3 days, then 1 mg BID for 3 days, then 2 mg BID on Day 7 of dosing in the double-blind phase. Dose in participants experiencing intolerable nausea may be reduced to 1 mg BID for 6 weeks and a 7-10 day follow-up period. Background ADT (continued from Open-Label ADT) was applied in the double-blind phase.	Placebo + ADT n=85 Participants Placebo matched to CP-601,927 1 mg QPM for 3 days, then CP-601,927 1 mg BID for 3 days, and then CP-601,927 2 mg BID on Day 7 of dosing in the double-blind phase. Dose in participants experiencing intolerable nausea may be reduced to 1 mg BID for 6 weeks and a 7-10 day follow-up period. Background ADT (continued from Open-Label ADT) was applied in the double-blind phase.
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	5.5 Units on a scale Standard Deviation 2.66
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	-0.9 Units on a scale Standard Deviation 2.10
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	-1.9 Units on a scale Standard Deviation 2.66

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	CP-601,927 + ADT n=77 Participants Participants treated with CP-601,927 1 mg QPM for 3 days, then 1 mg BID for 3 days, then 2 mg BID on Day 7 of dosing in the double-blind phase. Dose in participants experiencing intolerable nausea may be reduced to 1 mg BID for 6 weeks and a 7-10 day follow-up period. Background ADT (continued from Open-Label ADT) was applied in the double-blind phase.	Placebo + ADT n=85 Participants Placebo matched to CP-601,927 1 mg QPM for 3 days, then CP-601,927 1 mg BID for 3 days, and then CP-601,927 2 mg BID on Day 7 of dosing in the double-blind phase. Dose in participants experiencing intolerable nausea may be reduced to 1 mg BID for 6 weeks and a 7-10 day follow-up period. Background ADT (continued from Open-Label ADT) was applied in the double-blind phase.
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	3.5 Units on a scale Standard Deviation 0.66
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	3.2 Units on a scale Standard Deviation 0.78
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	3.1 Units on a scale Standard Deviation 0.88
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	2.8 Units on a scale Standard Deviation 1.07
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	2.7 Units on a scale Standard Deviation 1.03

SECONDARY outcome

Timeframe: 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).

Outcome measures

Outcome measures
Measure	CP-601,927 + ADT n=76 Participants Participants treated with CP-601,927 1 mg QPM for 3 days, then 1 mg BID for 3 days, then 2 mg BID on Day 7 of dosing in the double-blind phase. Dose in participants experiencing intolerable nausea may be reduced to 1 mg BID for 6 weeks and a 7-10 day follow-up period. Background ADT (continued from Open-Label ADT) was applied in the double-blind phase.	Placebo + ADT n=82 Participants Placebo matched to CP-601,927 1 mg QPM for 3 days, then CP-601,927 1 mg BID for 3 days, and then CP-601,927 2 mg BID on Day 7 of dosing in the double-blind phase. Dose in participants experiencing intolerable nausea may be reduced to 1 mg BID for 6 weeks and a 7-10 day follow-up period. Background ADT (continued from Open-Label ADT) was applied in the double-blind phase.
Number of Participants With Remission at Weeks 9, 10, 12 and 14 Week 9	1 Participants	0 Participants
Number of Participants With Remission at Weeks 9, 10, 12 and 14 Week 10	4 Participants	1 Participants
Number of Participants With Remission at Weeks 9, 10, 12 and 14 Week 12	5 Participants	9 Participants
Number of Participants With Remission at Weeks 9, 10, 12 and 14 Week 14	9 Participants	11 Participants

SECONDARY outcome

Timeframe: Weeks 9 through 14

Response was defined as greater than 50 percent reduction from double-blind baseline in MADRS total score.

Outcome measures

Outcome measures
Measure	CP-601,927 + ADT n=76 Participants Participants treated with CP-601,927 1 mg QPM for 3 days, then 1 mg BID for 3 days, then 2 mg BID on Day 7 of dosing in the double-blind phase. Dose in participants experiencing intolerable nausea may be reduced to 1 mg BID for 6 weeks and a 7-10 day follow-up period. Background ADT (continued from Open-Label ADT) was applied in the double-blind phase.	Placebo + ADT n=82 Participants Placebo matched to CP-601,927 1 mg QPM for 3 days, then CP-601,927 1 mg BID for 3 days, and then CP-601,927 2 mg BID on Day 7 of dosing in the double-blind phase. Dose in participants experiencing intolerable nausea may be reduced to 1 mg BID for 6 weeks and a 7-10 day follow-up period. Background ADT (continued from Open-Label ADT) was applied in the double-blind phase.
Number of Participants With Response at Weeks 9 Through 14 Week 9	3 Participants	4 Participants
Number of Participants With Response at Weeks 9 Through 14 Week 10	8 Participants	8 Participants
Number of Participants With Response at Weeks 9 Through 14 Week 11	15 Participants	10 Participants
Number of Participants With Response at Weeks 9 Through 14 Week 12	18 Participants	16 Participants
Number of Participants With Response at Weeks 9 Through 14 Week 13	23 Participants	20 Participants
Number of Participants With Response at Weeks 9 Through 14 Week 14	22 Participants	20 Participants

SECONDARY outcome

Timeframe: 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.

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

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 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.

Blood samples were collected for plasma CP-601,927 concentration analysis which was summarized by mean and standard deviation.

Outcome measures

Outcome measures
Measure	CP-601,927 + ADT n=60 Participants Participants treated with CP-601,927 1 mg QPM for 3 days, then 1 mg BID for 3 days, then 2 mg BID on Day 7 of dosing in the double-blind phase. Dose in participants experiencing intolerable nausea may be reduced to 1 mg BID for 6 weeks and a 7-10 day follow-up period. Background ADT (continued from Open-Label ADT) was applied in the double-blind phase.	Placebo + ADT Placebo matched to CP-601,927 1 mg QPM for 3 days, then CP-601,927 1 mg BID for 3 days, and then CP-601,927 2 mg BID on Day 7 of dosing in the double-blind phase. Dose in participants experiencing intolerable nausea may be reduced to 1 mg BID for 6 weeks and a 7-10 day follow-up period. Background ADT (continued from Open-Label ADT) was applied in the double-blind phase.
Plasma CP-601,927 Concentration Week 11 at 1 Hour	5.80 ng/mL Standard Deviation 3.42	—
Plasma CP-601,927 Concentration Week 11 at 2 Hours	5.90 ng/mL Standard Deviation 3.13	—
Plasma CP-601,927 Concentration Week 12	6.24 ng/mL Standard Deviation 3.85	—
Plasma CP-601,927 Concentration Week 14 at 1 Hour	5.36 ng/mL Standard Deviation 3.83	—
Plasma CP-601,927 Concentration Week 14 at 2 Hour	5.39 ng/mL Standard Deviation 3.89	—

OTHER_PRE_SPECIFIED outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	CP-601,927 + ADT n=77 Participants Participants treated with CP-601,927 1 mg QPM for 3 days, then 1 mg BID for 3 days, then 2 mg BID on Day 7 of dosing in the double-blind phase. Dose in participants experiencing intolerable nausea may be reduced to 1 mg BID for 6 weeks and a 7-10 day follow-up period. Background ADT (continued from Open-Label ADT) was applied in the double-blind phase.	Placebo + ADT n=85 Participants Placebo matched to CP-601,927 1 mg QPM for 3 days, then CP-601,927 1 mg BID for 3 days, and then CP-601,927 2 mg BID on Day 7 of dosing in the double-blind phase. Dose in participants experiencing intolerable nausea may be reduced to 1 mg BID for 6 weeks and a 7-10 day follow-up period. Background ADT (continued from Open-Label ADT) was applied in the double-blind phase.
The Sheehan Suicidality Tracking Scale (STS) Week 8: suicidal ideation	11 Participants	13 Participants
The Sheehan Suicidality Tracking Scale (STS) Week 10: suicidal ideation	12 Participants	7 Participants
The Sheehan Suicidality Tracking Scale (STS) Week 10: no suicidal behavior and risk	57 Participants	67 Participants
The Sheehan Suicidality Tracking Scale (STS) Week 8: no suicidal behavior and risk	66 Participants	72 Participants
The Sheehan Suicidality Tracking Scale (STS) Week 9: suicidal ideation	10 Participants	8 Participants
The Sheehan Suicidality Tracking Scale (STS) Week 9: self-injurious, no intent	1 Participants	0 Participants
The Sheehan Suicidality Tracking Scale (STS) Week 9: no suicidal behavior and risk	61 Participants	71 Participants
The Sheehan Suicidality Tracking Scale (STS) Week 11: suicidal ideation	8 Participants	5 Participants
The Sheehan Suicidality Tracking Scale (STS) Week 11: no suicidal behavior and risk	56 Participants	66 Participants
The Sheehan Suicidality Tracking Scale (STS) Week 12: suicidal ideation	6 Participants	5 Participants
The Sheehan Suicidality Tracking Scale (STS) Week 12: no suicidal behavior and risk	57 Participants	65 Participants
The Sheehan Suicidality Tracking Scale (STS) Week 13: suicidal ideation	5 Participants	5 Participants
The Sheehan Suicidality Tracking Scale (STS) Week 13: no suicidal behavior and risk	57 Participants	58 Participants
The Sheehan Suicidality Tracking Scale (STS) Week 14: suicidal ideation	5 Participants	6 Participants
The Sheehan Suicidality Tracking Scale (STS) Week 14: no suicidal behavior and risk	70 Participants	75 Participants

Adverse Events

Open-Label ADT

Serious events: 3 serious events

Other events: 210 other events

Deaths: 0 deaths

CP-601,927 + ADT

Serious events: 1 serious events

Other events: 58 other events

Deaths: 0 deaths

Placebo + ADT

Serious events: 1 serious events

Other events: 61 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Open-Label ADT n=297 participants at risk 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.	CP-601,927 + ADT n=77 participants at risk Participants treated with CP-601,927 1 mg QPM for 3 days, then 1 mg BID for 3 days, then 2 mg BID on Day 7 of dosing in the double-blind phase. Dose in participants experiencing intolerable nausea may be reduced to 1 mg BID for 6 weeks and a 7-10 day follow-up period. Background ADT (continued from Open-Label ADT) was applied in the double-blind phase.	Placebo + ADT n=85 participants at risk Placebo matched to CP-601,927 1 mg QPM for 3 days, then CP-601,927 1 mg BID for 3 days, and then CP-601,927 2 mg BID on Day 7 of dosing in the double-blind phase. Dose in participants experiencing intolerable nausea may be reduced to 1 mg BID for 6 weeks and a 7-10 day follow-up period. Background ADT (continued from Open-Label ADT) was applied in the double-blind phase.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Thyroid cancer	0.00% 0/297 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	1.3% 1/77 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/85 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Psychiatric disorders Suicide attempt	0.00% 0/297 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/77 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	1.2% 1/85 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Cardiac disorders Atrial fibrillation	0.34% 1/297 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/77 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/85 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Infections and infestations Pneumonia	0.34% 1/297 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/77 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/85 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Pregnancy, puerperium and perinatal conditions Pregnancy	0.34% 1/297 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/77 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/85 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Psychiatric disorders Suicidal ideation	0.34% 1/297 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/77 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/85 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.

Other adverse events

Additional Information

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Results disclosure agreements

Principal investigator is a sponsor employee Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
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Restriction type: OTHER