Trial Outcomes & Findings for Study to Evaluate the Efficacy, Safety and Tolerability of an Oral Aripiprazole/Escitalopram Combination Therapy in Participants With Major Depressive Disorder (MDD) (NCT NCT01111552)
NCT ID: NCT01111552
Last Updated: 2021-10-26
Results Overview
The MADRS assessed severity of depressive symptoms. It ranges from a minimum of 0 to a maximum of 60 (higher scores indicating a greater severity of depressive symptoms). Participants are rated on 10 items (feelings of sadness, lassitude, pessimism, inner tension, suicidality, reduced sleep or appetite, difficulty concentrating, and a lack of interest) each on a 7-point scale from 0 (no symptoms) to 6 (symptoms of maximum severity). A negative change from Week 8 indicates improvement. Last observation carried forward (LOCF) method was used for analyses.
Recruitment status
TERMINATED
Study phase
PHASE3
Target enrollment
237 participants
Primary outcome timeframe
Week 8 to Week 14
Results posted on
2021-10-26
Participant Flow
Participants took part in the study at 69 investigative sites in Australia, Bulgaria, India, Philippines, Romania, Russia, Slovakia, and the United States from 29 July 2010 to 27 September 2011.
A total of 237 major depressive disorder(MDD)participants were enrolled in Phase B(Single-blind Prospective Treatment Phase)to receive escitalopram monotherapy(10 or 20mg/day),of which 54 responders continued to Phase B+(Single-blind Phase B Responders),received escitalopram monotherapy(10 or 20mg/day).66 non-responders were randomized in 1:1:1 ratio to Phase C(Double-blind Randomization Phase),received escitalopram or aripiprazole monotherapy or aripiprazole/escitalopram combination therapy.
Participant milestones
| Measure |
Phase B: Single-blind Prospective Treatment Phase
Escitalopram 10 mg capsule, orally, once daily increased to 20 mg/day at the end of Week 1 based upon tolerability profile, plus one matching placebo capsule, for 8 weeks. No dose reductions were allowed after Week 4 and no dose increments were allowed after Week 3. Participants with incomplete response at the end of the Phase B (Week 8) entered Phase C and the rest of the participants continued to Phase B+.
|
Phase B+: Single-blind Phase B Responders
Participants with response at the end of the Phase B (Week 8) continued treatment with the single-blind escitalopram monotherapy at the dose (10 or 20 mg/day) taken during the final week of Phase B plus one matching placebo capsule, for an additional 6 weeks, in Phase B+.
|
Phase C: Escitalopram Monotherapy
Participants with incomplete response at Week 8 who were randomized to this arm group received escitalopram monotherapy 10 or 20 mg capsule, orally, once daily, whichever dose was taken during the final week of Phase B plus one matching placebo capsule for 6 weeks, in Phase C. No dose adjustments were allowed for escitalopram monotherapy during Phase C.
|
Phase C: Aripiprazole Monotherapy
Participants with incomplete response at Week 8 who were randomized to this arm group received aripiprazole 3, 6, or 12 mg capsule, orally, once daily plus one matching placebo capsule for 6 weeks, in Phase C. Participants were titrated to the aripiprazole target dose of 12 mg/day at Week 9 if the initial 6 mg/day dose was tolerated. No dose increments were allowed after Week 12; however, doses may have been decreased at any week, based upon tolerability.
|
Phase C: Aripiprazole/Escitalopram Combination Therapy
Participants with incomplete response at Week 8 who were randomized to this arm group received aripiprazole 3, 6, or 12 mg capsule, orally, once daily in combination with the escitalopram 10 or 20 mg orally, once daily plus one matching placebo capsule for 6 weeks, in Phase C. No dose adjustments were allowed for escitalopram during Phase C. Participants were titrated to the aripiprazole target dose of 12 mg/day at Week 9 if the initial 6 mg/day dose was tolerated.
|
|---|---|---|---|---|---|
|
Phase B (Day 1 to Week 8)
STARTED
|
237
|
0
|
0
|
0
|
0
|
|
Phase B (Day 1 to Week 8)
COMPLETED
|
120
|
0
|
0
|
0
|
0
|
|
Phase B (Day 1 to Week 8)
NOT COMPLETED
|
117
|
0
|
0
|
0
|
0
|
|
Phase B+ and Phase C (Weeks 9 to 14)
STARTED
|
0
|
54
|
22
|
21
|
23
|
|
Phase B+ and Phase C (Weeks 9 to 14)
COMPLETED
|
0
|
45
|
17
|
17
|
18
|
|
Phase B+ and Phase C (Weeks 9 to 14)
NOT COMPLETED
|
0
|
9
|
5
|
4
|
5
|
Reasons for withdrawal
| Measure |
Phase B: Single-blind Prospective Treatment Phase
Escitalopram 10 mg capsule, orally, once daily increased to 20 mg/day at the end of Week 1 based upon tolerability profile, plus one matching placebo capsule, for 8 weeks. No dose reductions were allowed after Week 4 and no dose increments were allowed after Week 3. Participants with incomplete response at the end of the Phase B (Week 8) entered Phase C and the rest of the participants continued to Phase B+.
|
Phase B+: Single-blind Phase B Responders
Participants with response at the end of the Phase B (Week 8) continued treatment with the single-blind escitalopram monotherapy at the dose (10 or 20 mg/day) taken during the final week of Phase B plus one matching placebo capsule, for an additional 6 weeks, in Phase B+.
|
Phase C: Escitalopram Monotherapy
Participants with incomplete response at Week 8 who were randomized to this arm group received escitalopram monotherapy 10 or 20 mg capsule, orally, once daily, whichever dose was taken during the final week of Phase B plus one matching placebo capsule for 6 weeks, in Phase C. No dose adjustments were allowed for escitalopram monotherapy during Phase C.
|
Phase C: Aripiprazole Monotherapy
Participants with incomplete response at Week 8 who were randomized to this arm group received aripiprazole 3, 6, or 12 mg capsule, orally, once daily plus one matching placebo capsule for 6 weeks, in Phase C. Participants were titrated to the aripiprazole target dose of 12 mg/day at Week 9 if the initial 6 mg/day dose was tolerated. No dose increments were allowed after Week 12; however, doses may have been decreased at any week, based upon tolerability.
|
Phase C: Aripiprazole/Escitalopram Combination Therapy
Participants with incomplete response at Week 8 who were randomized to this arm group received aripiprazole 3, 6, or 12 mg capsule, orally, once daily in combination with the escitalopram 10 or 20 mg orally, once daily plus one matching placebo capsule for 6 weeks, in Phase C. No dose adjustments were allowed for escitalopram during Phase C. Participants were titrated to the aripiprazole target dose of 12 mg/day at Week 9 if the initial 6 mg/day dose was tolerated.
|
|---|---|---|---|---|---|
|
Phase B (Day 1 to Week 8)
Lost to Follow-up
|
9
|
0
|
0
|
0
|
0
|
|
Phase B (Day 1 to Week 8)
Adverse Event
|
4
|
0
|
0
|
0
|
0
|
|
Phase B (Day 1 to Week 8)
Sponsor Discontinued Study
|
89
|
0
|
0
|
0
|
0
|
|
Phase B (Day 1 to Week 8)
Participant Met Withdrawal Criteria
|
3
|
0
|
0
|
0
|
0
|
|
Phase B (Day 1 to Week 8)
Investigator Withdrew Participant
|
3
|
0
|
0
|
0
|
0
|
|
Phase B (Day 1 to Week 8)
Participant Withdrew Consent
|
7
|
0
|
0
|
0
|
0
|
|
Phase B (Day 1 to Week 8)
Protocol Deviation
|
1
|
0
|
0
|
0
|
0
|
|
Phase B (Day 1 to Week 8)
Lack of Efficacy as Determined by Investigator
|
1
|
0
|
0
|
0
|
0
|
|
Phase B+ and Phase C (Weeks 9 to 14)
Adverse Event
|
0
|
0
|
0
|
1
|
0
|
|
Phase B+ and Phase C (Weeks 9 to 14)
Sponsor Discontinued Study
|
0
|
5
|
4
|
3
|
5
|
|
Phase B+ and Phase C (Weeks 9 to 14)
Participant Met Withdrawal Criteria
|
0
|
2
|
0
|
0
|
0
|
|
Phase B+ and Phase C (Weeks 9 to 14)
Investigator Withdrew Participant
|
0
|
1
|
0
|
0
|
0
|
|
Phase B+ and Phase C (Weeks 9 to 14)
Participant Withdrew Consent
|
0
|
1
|
0
|
0
|
0
|
|
Phase B+ and Phase C (Weeks 9 to 14)
Protocol Deviation
|
0
|
0
|
1
|
0
|
0
|
Baseline Characteristics
Study to Evaluate the Efficacy, Safety and Tolerability of an Oral Aripiprazole/Escitalopram Combination Therapy in Participants With Major Depressive Disorder (MDD)
Baseline characteristics by cohort
| Measure |
Phase B: Single-blind Prospective Treatment Phase
n=237 Participants
Escitalopram 10 mg capsule, orally, once daily increased to 20 mg/day at the end of Week 1 based upon tolerability profile, plus one matching placebo capsule, for 8 weeks. No dose reductions were allowed after Week 4 and no dose increments were allowed after Week 3. Participants with incomplete response at the end of the Phase B (Week 8) entered Phase C and the rest of the participants continued to Phase B+.
|
|---|---|
|
Age, Continuous
|
45.2 years
STANDARD_DEVIATION 11.3 • n=5 Participants
|
|
Sex: Female, Male
Female
|
156 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
81 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
18 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
218 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
2 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
15 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
30 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
186 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
4 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Week 8 to Week 14Population: Intent-to-treat (ITT) Sample included all participants in the Randomized Sample who received at least one dose of double-blind trial medication and had at least one post-randomization efficacy evaluation in Phase C.
The MADRS assessed severity of depressive symptoms. It ranges from a minimum of 0 to a maximum of 60 (higher scores indicating a greater severity of depressive symptoms). Participants are rated on 10 items (feelings of sadness, lassitude, pessimism, inner tension, suicidality, reduced sleep or appetite, difficulty concentrating, and a lack of interest) each on a 7-point scale from 0 (no symptoms) to 6 (symptoms of maximum severity). A negative change from Week 8 indicates improvement. Last observation carried forward (LOCF) method was used for analyses.
Outcome measures
| Measure |
Phase C: Escitalopram Monotherapy
n=22 Participants
Participants with incomplete response at Week 8 who were randomized to this arm group received escitalopram monotherapy 10 or 20 mg capsule, orally, once daily, whichever dose was taken during the final week of Phase B plus one matching placebo capsule for 6 weeks, in Phase C. No dose adjustments were allowed for escitalopram monotherapy during Phase C.
|
Phase C: Aripiprazole Monotherapy
n=21 Participants
Participants with incomplete response at Week 8 who were randomized to this arm group received aripiprazole 3, 6, or 12 mg capsule, orally, once daily plus one matching placebo capsule for 6 weeks, in Phase C. Participants were titrated to the aripiprazole target dose of 12 mg/day at Week 9 if the initial 6 mg/day dose was tolerated. No dose increments were allowed after Week 12; however, doses may have been decreased at any week, based upon tolerability.
|
Phase C: Aripiprazole/Escitalopram Combination Therapy
n=23 Participants
Participants with incomplete response at Week 8 who were randomized to this arm group received aripiprazole 3, 6, or 12 mg capsule, orally, once daily in combination with the escitalopram 10 or 20 mg orally, once daily plus one matching placebo capsule for 6 weeks, in Phase C. No dose adjustments were allowed for escitalopram during Phase C. Participants were titrated to the aripiprazole target dose of 12 mg/day at Week 9 if the initial 6 mg/day dose was tolerated.
|
|---|---|---|---|
|
Phase C: Mean Change From End of Phase B (Week 8) in the Montgomery-Asberg Depression Rating Scale (MADRS) Total Score to End of Phase C (Week 14)
|
-8.0 score on a scale
Standard Error 1.7
|
-9.6 score on a scale
Standard Error 1.7
|
-9.2 score on a scale
Standard Error 1.6
|
SECONDARY outcome
Timeframe: Week 14Population: ITT Sample included all participants in the Randomized Sample who received at least one dose of double-blind trial medication and had at least one post-randomization efficacy evaluation in Phase C.
The CGI-I is a 7-point scale that requires the clinician to assess how much the participant's illness has improved or worsened relative to a baseline state at the beginning of the intervention and rated as: 1=very much improved; 2=much improved; 3=minimally improved; 4=no change; 5=minimally worse; 6=much worse; 7=very much worse. Last observation carried forward (LOCF) method was used for analyses.
Outcome measures
| Measure |
Phase C: Escitalopram Monotherapy
n=22 Participants
Participants with incomplete response at Week 8 who were randomized to this arm group received escitalopram monotherapy 10 or 20 mg capsule, orally, once daily, whichever dose was taken during the final week of Phase B plus one matching placebo capsule for 6 weeks, in Phase C. No dose adjustments were allowed for escitalopram monotherapy during Phase C.
|
Phase C: Aripiprazole Monotherapy
n=21 Participants
Participants with incomplete response at Week 8 who were randomized to this arm group received aripiprazole 3, 6, or 12 mg capsule, orally, once daily plus one matching placebo capsule for 6 weeks, in Phase C. Participants were titrated to the aripiprazole target dose of 12 mg/day at Week 9 if the initial 6 mg/day dose was tolerated. No dose increments were allowed after Week 12; however, doses may have been decreased at any week, based upon tolerability.
|
Phase C: Aripiprazole/Escitalopram Combination Therapy
n=23 Participants
Participants with incomplete response at Week 8 who were randomized to this arm group received aripiprazole 3, 6, or 12 mg capsule, orally, once daily in combination with the escitalopram 10 or 20 mg orally, once daily plus one matching placebo capsule for 6 weeks, in Phase C. No dose adjustments were allowed for escitalopram during Phase C. Participants were titrated to the aripiprazole target dose of 12 mg/day at Week 9 if the initial 6 mg/day dose was tolerated.
|
|---|---|---|---|
|
Phase C: Clinical Global Impression - Improvement Scale (CGI-I) Score at The End of Phase C (Week 14)
|
2.4 score on a scale
Standard Error 0.3
|
2.3 score on a scale
Standard Error 0.2
|
2.3 score on a scale
Standard Error 0.2
|
SECONDARY outcome
Timeframe: Week 8 to Week 14Population: ITT Sample included all participants in the Randomized Sample who received at least one dose of double-blind trial medication and had at least one post-randomization efficacy evaluation in Phase C. Number analyzed is the number of participants with data available for analysis.
The SDS is a 3-item clinician-rated questionnaire used to evaluate impairments in the domains of work, social life/leisure, and family life/home responsibility. All items are rated on an 11-point continuum (0= no impairment to 10= most severe) with the total SDS score ranging from 0 (no impairment) to 30 (most severe). A negative change from Week 8 indicates improvement. Last observation carried forward (LOCF) method was used for analyses.
Outcome measures
| Measure |
Phase C: Escitalopram Monotherapy
n=22 Participants
Participants with incomplete response at Week 8 who were randomized to this arm group received escitalopram monotherapy 10 or 20 mg capsule, orally, once daily, whichever dose was taken during the final week of Phase B plus one matching placebo capsule for 6 weeks, in Phase C. No dose adjustments were allowed for escitalopram monotherapy during Phase C.
|
Phase C: Aripiprazole Monotherapy
n=21 Participants
Participants with incomplete response at Week 8 who were randomized to this arm group received aripiprazole 3, 6, or 12 mg capsule, orally, once daily plus one matching placebo capsule for 6 weeks, in Phase C. Participants were titrated to the aripiprazole target dose of 12 mg/day at Week 9 if the initial 6 mg/day dose was tolerated. No dose increments were allowed after Week 12; however, doses may have been decreased at any week, based upon tolerability.
|
Phase C: Aripiprazole/Escitalopram Combination Therapy
n=23 Participants
Participants with incomplete response at Week 8 who were randomized to this arm group received aripiprazole 3, 6, or 12 mg capsule, orally, once daily in combination with the escitalopram 10 or 20 mg orally, once daily plus one matching placebo capsule for 6 weeks, in Phase C. No dose adjustments were allowed for escitalopram during Phase C. Participants were titrated to the aripiprazole target dose of 12 mg/day at Week 9 if the initial 6 mg/day dose was tolerated.
|
|---|---|---|---|
|
Phase C: Mean Change From End of Phase B (Week 8) in the Sheehan Disability Scale (SDS) Mean Score to End of Phase C (Week 14)
|
-0.9 score on a scale
Standard Error 0.5
|
-1.4 score on a scale
Standard Error 0.5
|
-1.2 score on a scale
Standard Error 0.5
|
Adverse Events
Phase B: Single-blind Prospective Treatment Phase
Serious events: 2 serious events
Other events: 53 other events
Deaths: 0 deaths
Phase B+: Single-blind Phase B Responders
Serious events: 1 serious events
Other events: 7 other events
Deaths: 0 deaths
Phase C: Escitalopram Monotherapy
Serious events: 1 serious events
Other events: 5 other events
Deaths: 0 deaths
Phase C: Aripiprazole Monotherapy
Serious events: 0 serious events
Other events: 10 other events
Deaths: 0 deaths
Phase C: Aripiprazole/Escitalopram Combination Therapy
Serious events: 0 serious events
Other events: 11 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Phase B: Single-blind Prospective Treatment Phase
n=237 participants at risk
Escitalopram 10 mg capsule, orally, once daily increased to 20 mg/day at the end of Week 1 based upon tolerability profile, plus one matching placebo capsule, for 8 weeks. No dose reductions were allowed after Week 4 and no dose increments were allowed after Week 3. Participants with incomplete response at the end of the Phase B (Week 8) entered Phase C and the rest of the participants continued to Phase B+.
|
Phase B+: Single-blind Phase B Responders
n=54 participants at risk
Participants with response at the end of the Phase B (Week 8) continued treatment with the single-blind escitalopram monotherapy at the dose (10 or 20 mg/day) taken during the final week of Phase B plus one matching placebo capsule, for an additional 6 weeks, in Phase B+.
|
Phase C: Escitalopram Monotherapy
n=22 participants at risk
Participants with incomplete response at Week 8 who were randomized to this arm group received escitalopram monotherapy 10 or 20 mg capsule, orally, once daily, whichever dose was taken during the final week of Phase B plus one matching placebo capsule for 6 weeks, in Phase C. No dose adjustments were allowed for escitalopram monotherapy during Phase C.
|
Phase C: Aripiprazole Monotherapy
n=21 participants at risk
Participants with incomplete response at Week 8 who were randomized to this arm group received aripiprazole 3, 6, or 12 mg capsule, orally, once daily plus one matching placebo capsule for 6 weeks, in Phase C. Participants were titrated to the aripiprazole target dose of 12 mg/day at Week 9 if the initial 6 mg/day dose was tolerated. No dose increments were allowed after Week 12; however, doses may have been decreased at any week, based upon tolerability.
|
Phase C: Aripiprazole/Escitalopram Combination Therapy
n=23 participants at risk
Participants with incomplete response at Week 8 who were randomized to this arm group received aripiprazole 3, 6, or 12 mg capsule, orally, once daily in combination with the escitalopram 10 or 20 mg orally, once daily plus one matching placebo capsule for 6 weeks, in Phase C. No dose adjustments were allowed for escitalopram during Phase C. Participants were titrated to the aripiprazole target dose of 12 mg/day at Week 9 if the initial 6 mg/day dose was tolerated.
|
|---|---|---|---|---|---|
|
Investigations
Alanine aminotransferase increased
|
0.00%
0/237 • From first dose of study drug through end of study (up to 22 weeks)
Phase B Sample included all participants who took at least one dose of escitalopram as indicated on the dosing record. Phase B+ Sample included all participants who responded at the end of Phase B (were therefore not randomized) and who continued on single-blind escitalopram beyond Week 8. Randomized Sample included all participants who were randomized in Phase C.
|
0.00%
0/54 • From first dose of study drug through end of study (up to 22 weeks)
Phase B Sample included all participants who took at least one dose of escitalopram as indicated on the dosing record. Phase B+ Sample included all participants who responded at the end of Phase B (were therefore not randomized) and who continued on single-blind escitalopram beyond Week 8. Randomized Sample included all participants who were randomized in Phase C.
|
4.5%
1/22 • From first dose of study drug through end of study (up to 22 weeks)
Phase B Sample included all participants who took at least one dose of escitalopram as indicated on the dosing record. Phase B+ Sample included all participants who responded at the end of Phase B (were therefore not randomized) and who continued on single-blind escitalopram beyond Week 8. Randomized Sample included all participants who were randomized in Phase C.
|
0.00%
0/21 • From first dose of study drug through end of study (up to 22 weeks)
Phase B Sample included all participants who took at least one dose of escitalopram as indicated on the dosing record. Phase B+ Sample included all participants who responded at the end of Phase B (were therefore not randomized) and who continued on single-blind escitalopram beyond Week 8. Randomized Sample included all participants who were randomized in Phase C.
|
0.00%
0/23 • From first dose of study drug through end of study (up to 22 weeks)
Phase B Sample included all participants who took at least one dose of escitalopram as indicated on the dosing record. Phase B+ Sample included all participants who responded at the end of Phase B (were therefore not randomized) and who continued on single-blind escitalopram beyond Week 8. Randomized Sample included all participants who were randomized in Phase C.
|
|
Respiratory, thoracic and mediastinal disorders
Asthma
|
0.00%
0/237 • From first dose of study drug through end of study (up to 22 weeks)
Phase B Sample included all participants who took at least one dose of escitalopram as indicated on the dosing record. Phase B+ Sample included all participants who responded at the end of Phase B (were therefore not randomized) and who continued on single-blind escitalopram beyond Week 8. Randomized Sample included all participants who were randomized in Phase C.
|
1.9%
1/54 • From first dose of study drug through end of study (up to 22 weeks)
Phase B Sample included all participants who took at least one dose of escitalopram as indicated on the dosing record. Phase B+ Sample included all participants who responded at the end of Phase B (were therefore not randomized) and who continued on single-blind escitalopram beyond Week 8. Randomized Sample included all participants who were randomized in Phase C.
|
0.00%
0/22 • From first dose of study drug through end of study (up to 22 weeks)
Phase B Sample included all participants who took at least one dose of escitalopram as indicated on the dosing record. Phase B+ Sample included all participants who responded at the end of Phase B (were therefore not randomized) and who continued on single-blind escitalopram beyond Week 8. Randomized Sample included all participants who were randomized in Phase C.
|
0.00%
0/21 • From first dose of study drug through end of study (up to 22 weeks)
Phase B Sample included all participants who took at least one dose of escitalopram as indicated on the dosing record. Phase B+ Sample included all participants who responded at the end of Phase B (were therefore not randomized) and who continued on single-blind escitalopram beyond Week 8. Randomized Sample included all participants who were randomized in Phase C.
|
0.00%
0/23 • From first dose of study drug through end of study (up to 22 weeks)
Phase B Sample included all participants who took at least one dose of escitalopram as indicated on the dosing record. Phase B+ Sample included all participants who responded at the end of Phase B (were therefore not randomized) and who continued on single-blind escitalopram beyond Week 8. Randomized Sample included all participants who were randomized in Phase C.
|
|
Psychiatric disorders
Depression
|
0.42%
1/237 • From first dose of study drug through end of study (up to 22 weeks)
Phase B Sample included all participants who took at least one dose of escitalopram as indicated on the dosing record. Phase B+ Sample included all participants who responded at the end of Phase B (were therefore not randomized) and who continued on single-blind escitalopram beyond Week 8. Randomized Sample included all participants who were randomized in Phase C.
|
0.00%
0/54 • From first dose of study drug through end of study (up to 22 weeks)
Phase B Sample included all participants who took at least one dose of escitalopram as indicated on the dosing record. Phase B+ Sample included all participants who responded at the end of Phase B (were therefore not randomized) and who continued on single-blind escitalopram beyond Week 8. Randomized Sample included all participants who were randomized in Phase C.
|
0.00%
0/22 • From first dose of study drug through end of study (up to 22 weeks)
Phase B Sample included all participants who took at least one dose of escitalopram as indicated on the dosing record. Phase B+ Sample included all participants who responded at the end of Phase B (were therefore not randomized) and who continued on single-blind escitalopram beyond Week 8. Randomized Sample included all participants who were randomized in Phase C.
|
0.00%
0/21 • From first dose of study drug through end of study (up to 22 weeks)
Phase B Sample included all participants who took at least one dose of escitalopram as indicated on the dosing record. Phase B+ Sample included all participants who responded at the end of Phase B (were therefore not randomized) and who continued on single-blind escitalopram beyond Week 8. Randomized Sample included all participants who were randomized in Phase C.
|
0.00%
0/23 • From first dose of study drug through end of study (up to 22 weeks)
Phase B Sample included all participants who took at least one dose of escitalopram as indicated on the dosing record. Phase B+ Sample included all participants who responded at the end of Phase B (were therefore not randomized) and who continued on single-blind escitalopram beyond Week 8. Randomized Sample included all participants who were randomized in Phase C.
|
|
Social circumstances
Physical assault
|
0.42%
1/237 • From first dose of study drug through end of study (up to 22 weeks)
Phase B Sample included all participants who took at least one dose of escitalopram as indicated on the dosing record. Phase B+ Sample included all participants who responded at the end of Phase B (were therefore not randomized) and who continued on single-blind escitalopram beyond Week 8. Randomized Sample included all participants who were randomized in Phase C.
|
0.00%
0/54 • From first dose of study drug through end of study (up to 22 weeks)
Phase B Sample included all participants who took at least one dose of escitalopram as indicated on the dosing record. Phase B+ Sample included all participants who responded at the end of Phase B (were therefore not randomized) and who continued on single-blind escitalopram beyond Week 8. Randomized Sample included all participants who were randomized in Phase C.
|
0.00%
0/22 • From first dose of study drug through end of study (up to 22 weeks)
Phase B Sample included all participants who took at least one dose of escitalopram as indicated on the dosing record. Phase B+ Sample included all participants who responded at the end of Phase B (were therefore not randomized) and who continued on single-blind escitalopram beyond Week 8. Randomized Sample included all participants who were randomized in Phase C.
|
0.00%
0/21 • From first dose of study drug through end of study (up to 22 weeks)
Phase B Sample included all participants who took at least one dose of escitalopram as indicated on the dosing record. Phase B+ Sample included all participants who responded at the end of Phase B (were therefore not randomized) and who continued on single-blind escitalopram beyond Week 8. Randomized Sample included all participants who were randomized in Phase C.
|
0.00%
0/23 • From first dose of study drug through end of study (up to 22 weeks)
Phase B Sample included all participants who took at least one dose of escitalopram as indicated on the dosing record. Phase B+ Sample included all participants who responded at the end of Phase B (were therefore not randomized) and who continued on single-blind escitalopram beyond Week 8. Randomized Sample included all participants who were randomized in Phase C.
|
Other adverse events
| Measure |
Phase B: Single-blind Prospective Treatment Phase
n=237 participants at risk
Escitalopram 10 mg capsule, orally, once daily increased to 20 mg/day at the end of Week 1 based upon tolerability profile, plus one matching placebo capsule, for 8 weeks. No dose reductions were allowed after Week 4 and no dose increments were allowed after Week 3. Participants with incomplete response at the end of the Phase B (Week 8) entered Phase C and the rest of the participants continued to Phase B+.
|
Phase B+: Single-blind Phase B Responders
n=54 participants at risk
Participants with response at the end of the Phase B (Week 8) continued treatment with the single-blind escitalopram monotherapy at the dose (10 or 20 mg/day) taken during the final week of Phase B plus one matching placebo capsule, for an additional 6 weeks, in Phase B+.
|
Phase C: Escitalopram Monotherapy
n=22 participants at risk
Participants with incomplete response at Week 8 who were randomized to this arm group received escitalopram monotherapy 10 or 20 mg capsule, orally, once daily, whichever dose was taken during the final week of Phase B plus one matching placebo capsule for 6 weeks, in Phase C. No dose adjustments were allowed for escitalopram monotherapy during Phase C.
|
Phase C: Aripiprazole Monotherapy
n=21 participants at risk
Participants with incomplete response at Week 8 who were randomized to this arm group received aripiprazole 3, 6, or 12 mg capsule, orally, once daily plus one matching placebo capsule for 6 weeks, in Phase C. Participants were titrated to the aripiprazole target dose of 12 mg/day at Week 9 if the initial 6 mg/day dose was tolerated. No dose increments were allowed after Week 12; however, doses may have been decreased at any week, based upon tolerability.
|
Phase C: Aripiprazole/Escitalopram Combination Therapy
n=23 participants at risk
Participants with incomplete response at Week 8 who were randomized to this arm group received aripiprazole 3, 6, or 12 mg capsule, orally, once daily in combination with the escitalopram 10 or 20 mg orally, once daily plus one matching placebo capsule for 6 weeks, in Phase C. No dose adjustments were allowed for escitalopram during Phase C. Participants were titrated to the aripiprazole target dose of 12 mg/day at Week 9 if the initial 6 mg/day dose was tolerated.
|
|---|---|---|---|---|---|
|
Infections and infestations
Upper Respiratory Tract Infection
|
2.1%
5/237 • From first dose of study drug through end of study (up to 22 weeks)
Phase B Sample included all participants who took at least one dose of escitalopram as indicated on the dosing record. Phase B+ Sample included all participants who responded at the end of Phase B (were therefore not randomized) and who continued on single-blind escitalopram beyond Week 8. Randomized Sample included all participants who were randomized in Phase C.
|
1.9%
1/54 • From first dose of study drug through end of study (up to 22 weeks)
Phase B Sample included all participants who took at least one dose of escitalopram as indicated on the dosing record. Phase B+ Sample included all participants who responded at the end of Phase B (were therefore not randomized) and who continued on single-blind escitalopram beyond Week 8. Randomized Sample included all participants who were randomized in Phase C.
|
0.00%
0/22 • From first dose of study drug through end of study (up to 22 weeks)
Phase B Sample included all participants who took at least one dose of escitalopram as indicated on the dosing record. Phase B+ Sample included all participants who responded at the end of Phase B (were therefore not randomized) and who continued on single-blind escitalopram beyond Week 8. Randomized Sample included all participants who were randomized in Phase C.
|
9.5%
2/21 • From first dose of study drug through end of study (up to 22 weeks)
Phase B Sample included all participants who took at least one dose of escitalopram as indicated on the dosing record. Phase B+ Sample included all participants who responded at the end of Phase B (were therefore not randomized) and who continued on single-blind escitalopram beyond Week 8. Randomized Sample included all participants who were randomized in Phase C.
|
8.7%
2/23 • From first dose of study drug through end of study (up to 22 weeks)
Phase B Sample included all participants who took at least one dose of escitalopram as indicated on the dosing record. Phase B+ Sample included all participants who responded at the end of Phase B (were therefore not randomized) and who continued on single-blind escitalopram beyond Week 8. Randomized Sample included all participants who were randomized in Phase C.
|
|
Nervous system disorders
Akathisia
|
0.00%
0/237 • From first dose of study drug through end of study (up to 22 weeks)
Phase B Sample included all participants who took at least one dose of escitalopram as indicated on the dosing record. Phase B+ Sample included all participants who responded at the end of Phase B (were therefore not randomized) and who continued on single-blind escitalopram beyond Week 8. Randomized Sample included all participants who were randomized in Phase C.
|
0.00%
0/54 • From first dose of study drug through end of study (up to 22 weeks)
Phase B Sample included all participants who took at least one dose of escitalopram as indicated on the dosing record. Phase B+ Sample included all participants who responded at the end of Phase B (were therefore not randomized) and who continued on single-blind escitalopram beyond Week 8. Randomized Sample included all participants who were randomized in Phase C.
|
0.00%
0/22 • From first dose of study drug through end of study (up to 22 weeks)
Phase B Sample included all participants who took at least one dose of escitalopram as indicated on the dosing record. Phase B+ Sample included all participants who responded at the end of Phase B (were therefore not randomized) and who continued on single-blind escitalopram beyond Week 8. Randomized Sample included all participants who were randomized in Phase C.
|
9.5%
2/21 • From first dose of study drug through end of study (up to 22 weeks)
Phase B Sample included all participants who took at least one dose of escitalopram as indicated on the dosing record. Phase B+ Sample included all participants who responded at the end of Phase B (were therefore not randomized) and who continued on single-blind escitalopram beyond Week 8. Randomized Sample included all participants who were randomized in Phase C.
|
8.7%
2/23 • From first dose of study drug through end of study (up to 22 weeks)
Phase B Sample included all participants who took at least one dose of escitalopram as indicated on the dosing record. Phase B+ Sample included all participants who responded at the end of Phase B (were therefore not randomized) and who continued on single-blind escitalopram beyond Week 8. Randomized Sample included all participants who were randomized in Phase C.
|
|
Nervous system disorders
Dizziness
|
3.4%
8/237 • From first dose of study drug through end of study (up to 22 weeks)
Phase B Sample included all participants who took at least one dose of escitalopram as indicated on the dosing record. Phase B+ Sample included all participants who responded at the end of Phase B (were therefore not randomized) and who continued on single-blind escitalopram beyond Week 8. Randomized Sample included all participants who were randomized in Phase C.
|
0.00%
0/54 • From first dose of study drug through end of study (up to 22 weeks)
Phase B Sample included all participants who took at least one dose of escitalopram as indicated on the dosing record. Phase B+ Sample included all participants who responded at the end of Phase B (were therefore not randomized) and who continued on single-blind escitalopram beyond Week 8. Randomized Sample included all participants who were randomized in Phase C.
|
4.5%
1/22 • From first dose of study drug through end of study (up to 22 weeks)
Phase B Sample included all participants who took at least one dose of escitalopram as indicated on the dosing record. Phase B+ Sample included all participants who responded at the end of Phase B (were therefore not randomized) and who continued on single-blind escitalopram beyond Week 8. Randomized Sample included all participants who were randomized in Phase C.
|
19.0%
4/21 • From first dose of study drug through end of study (up to 22 weeks)
Phase B Sample included all participants who took at least one dose of escitalopram as indicated on the dosing record. Phase B+ Sample included all participants who responded at the end of Phase B (were therefore not randomized) and who continued on single-blind escitalopram beyond Week 8. Randomized Sample included all participants who were randomized in Phase C.
|
4.3%
1/23 • From first dose of study drug through end of study (up to 22 weeks)
Phase B Sample included all participants who took at least one dose of escitalopram as indicated on the dosing record. Phase B+ Sample included all participants who responded at the end of Phase B (were therefore not randomized) and who continued on single-blind escitalopram beyond Week 8. Randomized Sample included all participants who were randomized in Phase C.
|
|
Gastrointestinal disorders
Constipation
|
0.42%
1/237 • From first dose of study drug through end of study (up to 22 weeks)
Phase B Sample included all participants who took at least one dose of escitalopram as indicated on the dosing record. Phase B+ Sample included all participants who responded at the end of Phase B (were therefore not randomized) and who continued on single-blind escitalopram beyond Week 8. Randomized Sample included all participants who were randomized in Phase C.
|
0.00%
0/54 • From first dose of study drug through end of study (up to 22 weeks)
Phase B Sample included all participants who took at least one dose of escitalopram as indicated on the dosing record. Phase B+ Sample included all participants who responded at the end of Phase B (were therefore not randomized) and who continued on single-blind escitalopram beyond Week 8. Randomized Sample included all participants who were randomized in Phase C.
|
9.1%
2/22 • From first dose of study drug through end of study (up to 22 weeks)
Phase B Sample included all participants who took at least one dose of escitalopram as indicated on the dosing record. Phase B+ Sample included all participants who responded at the end of Phase B (were therefore not randomized) and who continued on single-blind escitalopram beyond Week 8. Randomized Sample included all participants who were randomized in Phase C.
|
0.00%
0/21 • From first dose of study drug through end of study (up to 22 weeks)
Phase B Sample included all participants who took at least one dose of escitalopram as indicated on the dosing record. Phase B+ Sample included all participants who responded at the end of Phase B (were therefore not randomized) and who continued on single-blind escitalopram beyond Week 8. Randomized Sample included all participants who were randomized in Phase C.
|
4.3%
1/23 • From first dose of study drug through end of study (up to 22 weeks)
Phase B Sample included all participants who took at least one dose of escitalopram as indicated on the dosing record. Phase B+ Sample included all participants who responded at the end of Phase B (were therefore not randomized) and who continued on single-blind escitalopram beyond Week 8. Randomized Sample included all participants who were randomized in Phase C.
|
|
Gastrointestinal disorders
Diarrhoea
|
4.2%
10/237 • From first dose of study drug through end of study (up to 22 weeks)
Phase B Sample included all participants who took at least one dose of escitalopram as indicated on the dosing record. Phase B+ Sample included all participants who responded at the end of Phase B (were therefore not randomized) and who continued on single-blind escitalopram beyond Week 8. Randomized Sample included all participants who were randomized in Phase C.
|
3.7%
2/54 • From first dose of study drug through end of study (up to 22 weeks)
Phase B Sample included all participants who took at least one dose of escitalopram as indicated on the dosing record. Phase B+ Sample included all participants who responded at the end of Phase B (were therefore not randomized) and who continued on single-blind escitalopram beyond Week 8. Randomized Sample included all participants who were randomized in Phase C.
|
0.00%
0/22 • From first dose of study drug through end of study (up to 22 weeks)
Phase B Sample included all participants who took at least one dose of escitalopram as indicated on the dosing record. Phase B+ Sample included all participants who responded at the end of Phase B (were therefore not randomized) and who continued on single-blind escitalopram beyond Week 8. Randomized Sample included all participants who were randomized in Phase C.
|
14.3%
3/21 • From first dose of study drug through end of study (up to 22 weeks)
Phase B Sample included all participants who took at least one dose of escitalopram as indicated on the dosing record. Phase B+ Sample included all participants who responded at the end of Phase B (were therefore not randomized) and who continued on single-blind escitalopram beyond Week 8. Randomized Sample included all participants who were randomized in Phase C.
|
0.00%
0/23 • From first dose of study drug through end of study (up to 22 weeks)
Phase B Sample included all participants who took at least one dose of escitalopram as indicated on the dosing record. Phase B+ Sample included all participants who responded at the end of Phase B (were therefore not randomized) and who continued on single-blind escitalopram beyond Week 8. Randomized Sample included all participants who were randomized in Phase C.
|
|
Investigations
Weight increased
|
0.84%
2/237 • From first dose of study drug through end of study (up to 22 weeks)
Phase B Sample included all participants who took at least one dose of escitalopram as indicated on the dosing record. Phase B+ Sample included all participants who responded at the end of Phase B (were therefore not randomized) and who continued on single-blind escitalopram beyond Week 8. Randomized Sample included all participants who were randomized in Phase C.
|
3.7%
2/54 • From first dose of study drug through end of study (up to 22 weeks)
Phase B Sample included all participants who took at least one dose of escitalopram as indicated on the dosing record. Phase B+ Sample included all participants who responded at the end of Phase B (were therefore not randomized) and who continued on single-blind escitalopram beyond Week 8. Randomized Sample included all participants who were randomized in Phase C.
|
0.00%
0/22 • From first dose of study drug through end of study (up to 22 weeks)
Phase B Sample included all participants who took at least one dose of escitalopram as indicated on the dosing record. Phase B+ Sample included all participants who responded at the end of Phase B (were therefore not randomized) and who continued on single-blind escitalopram beyond Week 8. Randomized Sample included all participants who were randomized in Phase C.
|
0.00%
0/21 • From first dose of study drug through end of study (up to 22 weeks)
Phase B Sample included all participants who took at least one dose of escitalopram as indicated on the dosing record. Phase B+ Sample included all participants who responded at the end of Phase B (were therefore not randomized) and who continued on single-blind escitalopram beyond Week 8. Randomized Sample included all participants who were randomized in Phase C.
|
8.7%
2/23 • From first dose of study drug through end of study (up to 22 weeks)
Phase B Sample included all participants who took at least one dose of escitalopram as indicated on the dosing record. Phase B+ Sample included all participants who responded at the end of Phase B (were therefore not randomized) and who continued on single-blind escitalopram beyond Week 8. Randomized Sample included all participants who were randomized in Phase C.
|
|
Nervous system disorders
Headache
|
8.4%
20/237 • From first dose of study drug through end of study (up to 22 weeks)
Phase B Sample included all participants who took at least one dose of escitalopram as indicated on the dosing record. Phase B+ Sample included all participants who responded at the end of Phase B (were therefore not randomized) and who continued on single-blind escitalopram beyond Week 8. Randomized Sample included all participants who were randomized in Phase C.
|
3.7%
2/54 • From first dose of study drug through end of study (up to 22 weeks)
Phase B Sample included all participants who took at least one dose of escitalopram as indicated on the dosing record. Phase B+ Sample included all participants who responded at the end of Phase B (were therefore not randomized) and who continued on single-blind escitalopram beyond Week 8. Randomized Sample included all participants who were randomized in Phase C.
|
4.5%
1/22 • From first dose of study drug through end of study (up to 22 weeks)
Phase B Sample included all participants who took at least one dose of escitalopram as indicated on the dosing record. Phase B+ Sample included all participants who responded at the end of Phase B (were therefore not randomized) and who continued on single-blind escitalopram beyond Week 8. Randomized Sample included all participants who were randomized in Phase C.
|
0.00%
0/21 • From first dose of study drug through end of study (up to 22 weeks)
Phase B Sample included all participants who took at least one dose of escitalopram as indicated on the dosing record. Phase B+ Sample included all participants who responded at the end of Phase B (were therefore not randomized) and who continued on single-blind escitalopram beyond Week 8. Randomized Sample included all participants who were randomized in Phase C.
|
8.7%
2/23 • From first dose of study drug through end of study (up to 22 weeks)
Phase B Sample included all participants who took at least one dose of escitalopram as indicated on the dosing record. Phase B+ Sample included all participants who responded at the end of Phase B (were therefore not randomized) and who continued on single-blind escitalopram beyond Week 8. Randomized Sample included all participants who were randomized in Phase C.
|
|
Psychiatric disorders
Restlessness
|
0.00%
0/237 • From first dose of study drug through end of study (up to 22 weeks)
Phase B Sample included all participants who took at least one dose of escitalopram as indicated on the dosing record. Phase B+ Sample included all participants who responded at the end of Phase B (were therefore not randomized) and who continued on single-blind escitalopram beyond Week 8. Randomized Sample included all participants who were randomized in Phase C.
|
0.00%
0/54 • From first dose of study drug through end of study (up to 22 weeks)
Phase B Sample included all participants who took at least one dose of escitalopram as indicated on the dosing record. Phase B+ Sample included all participants who responded at the end of Phase B (were therefore not randomized) and who continued on single-blind escitalopram beyond Week 8. Randomized Sample included all participants who were randomized in Phase C.
|
0.00%
0/22 • From first dose of study drug through end of study (up to 22 weeks)
Phase B Sample included all participants who took at least one dose of escitalopram as indicated on the dosing record. Phase B+ Sample included all participants who responded at the end of Phase B (were therefore not randomized) and who continued on single-blind escitalopram beyond Week 8. Randomized Sample included all participants who were randomized in Phase C.
|
4.8%
1/21 • From first dose of study drug through end of study (up to 22 weeks)
Phase B Sample included all participants who took at least one dose of escitalopram as indicated on the dosing record. Phase B+ Sample included all participants who responded at the end of Phase B (were therefore not randomized) and who continued on single-blind escitalopram beyond Week 8. Randomized Sample included all participants who were randomized in Phase C.
|
8.7%
2/23 • From first dose of study drug through end of study (up to 22 weeks)
Phase B Sample included all participants who took at least one dose of escitalopram as indicated on the dosing record. Phase B+ Sample included all participants who responded at the end of Phase B (were therefore not randomized) and who continued on single-blind escitalopram beyond Week 8. Randomized Sample included all participants who were randomized in Phase C.
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
0.42%
1/237 • From first dose of study drug through end of study (up to 22 weeks)
Phase B Sample included all participants who took at least one dose of escitalopram as indicated on the dosing record. Phase B+ Sample included all participants who responded at the end of Phase B (were therefore not randomized) and who continued on single-blind escitalopram beyond Week 8. Randomized Sample included all participants who were randomized in Phase C.
|
0.00%
0/54 • From first dose of study drug through end of study (up to 22 weeks)
Phase B Sample included all participants who took at least one dose of escitalopram as indicated on the dosing record. Phase B+ Sample included all participants who responded at the end of Phase B (were therefore not randomized) and who continued on single-blind escitalopram beyond Week 8. Randomized Sample included all participants who were randomized in Phase C.
|
9.1%
2/22 • From first dose of study drug through end of study (up to 22 weeks)
Phase B Sample included all participants who took at least one dose of escitalopram as indicated on the dosing record. Phase B+ Sample included all participants who responded at the end of Phase B (were therefore not randomized) and who continued on single-blind escitalopram beyond Week 8. Randomized Sample included all participants who were randomized in Phase C.
|
0.00%
0/21 • From first dose of study drug through end of study (up to 22 weeks)
Phase B Sample included all participants who took at least one dose of escitalopram as indicated on the dosing record. Phase B+ Sample included all participants who responded at the end of Phase B (were therefore not randomized) and who continued on single-blind escitalopram beyond Week 8. Randomized Sample included all participants who were randomized in Phase C.
|
4.3%
1/23 • From first dose of study drug through end of study (up to 22 weeks)
Phase B Sample included all participants who took at least one dose of escitalopram as indicated on the dosing record. Phase B+ Sample included all participants who responded at the end of Phase B (were therefore not randomized) and who continued on single-blind escitalopram beyond Week 8. Randomized Sample included all participants who were randomized in Phase C.
|
|
Gastrointestinal disorders
Nausea
|
7.6%
18/237 • From first dose of study drug through end of study (up to 22 weeks)
Phase B Sample included all participants who took at least one dose of escitalopram as indicated on the dosing record. Phase B+ Sample included all participants who responded at the end of Phase B (were therefore not randomized) and who continued on single-blind escitalopram beyond Week 8. Randomized Sample included all participants who were randomized in Phase C.
|
0.00%
0/54 • From first dose of study drug through end of study (up to 22 weeks)
Phase B Sample included all participants who took at least one dose of escitalopram as indicated on the dosing record. Phase B+ Sample included all participants who responded at the end of Phase B (were therefore not randomized) and who continued on single-blind escitalopram beyond Week 8. Randomized Sample included all participants who were randomized in Phase C.
|
9.1%
2/22 • From first dose of study drug through end of study (up to 22 weeks)
Phase B Sample included all participants who took at least one dose of escitalopram as indicated on the dosing record. Phase B+ Sample included all participants who responded at the end of Phase B (were therefore not randomized) and who continued on single-blind escitalopram beyond Week 8. Randomized Sample included all participants who were randomized in Phase C.
|
4.8%
1/21 • From first dose of study drug through end of study (up to 22 weeks)
Phase B Sample included all participants who took at least one dose of escitalopram as indicated on the dosing record. Phase B+ Sample included all participants who responded at the end of Phase B (were therefore not randomized) and who continued on single-blind escitalopram beyond Week 8. Randomized Sample included all participants who were randomized in Phase C.
|
4.3%
1/23 • From first dose of study drug through end of study (up to 22 weeks)
Phase B Sample included all participants who took at least one dose of escitalopram as indicated on the dosing record. Phase B+ Sample included all participants who responded at the end of Phase B (were therefore not randomized) and who continued on single-blind escitalopram beyond Week 8. Randomized Sample included all participants who were randomized in Phase C.
|
Additional Information
Global Clinical Development
Otsuka Pharmaceutical Development & Commercialization, Inc.
Phone: 1-609-524-6788
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee A disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 90 days from the time submitted to the sponsor for review. The sponsor cannot require changes to the communication and cannot extend the embargo.
- Publication restrictions are in place
Restriction type: OTHER