Study to Evaluate the Efficacy, Safety and Tolerability of an Oral Aripiprazole/Escitalopram Combination Therapy in Participants With Major Depressive Disorder (MDD)
Study Details
Study Description
Brief Summary
This will be a multicenter, randomized, double-blind study designed to assess the efficacy, safety and tolerability of an oral Aripiprazole/Escitalopram combination therapy in participants with MDD who have demonstrated an incomplete response to a prospective trial of Escitalopram, and report a treatment history for the current MDD episode of an inadequate response to at least one and no more than three adequate trials of an approved antidepressant other than Escitalopram. An inadequate response is defined as less than a 50% reduction in depressive symptom severity as assessed by the participant's self-report on the Massachusetts General Hospital Antidepressant Treatment Response Questionnaire (ATRQ) and evaluated by the investigator as part of the participant's medical and psychiatric history. An adequate trial is defined as an antidepressant treatment for at least 6 weeks duration (or at least 3 weeks for combination treatments) at an approved dose as specified in the ATRQ.
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
|
Phase 3 |
Detailed Description
The study will be organized as follows:
-
Screening Phase
-
Single-blind Prospective Treatment Phase
-
Single-blind Continuation Phase (Responder) or Double-blind Randomization Phase (non-Responder)
-
30 day Post Treatment Follow-up
Assigned Interventions:
-
Escitalopram monotherapy
-
Aripiprazole/Escitalopram combination therapy
-
Aripiprazole monotherapy
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Active Comparator: 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+. |
Drug: Escitalopram
Escitalopram oral capsules.
Drug: Placebo
Study drug matching placebo capsule.
|
Active Comparator: 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+. |
Drug: Escitalopram
Escitalopram oral capsules.
Drug: Placebo
Study drug matching placebo capsule.
|
Active Comparator: 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. |
Drug: Escitalopram
Escitalopram oral capsules.
Drug: Placebo
Study drug matching placebo capsule.
|
Active Comparator: 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. |
Drug: Aripiprazole
Aripiprazole oral capsules.
Other Names:
Drug: Placebo
Study drug matching placebo capsule.
|
Active Comparator: 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. |
Drug: Escitalopram
Escitalopram oral capsules.
Drug: Aripiprazole
Aripiprazole oral capsules.
Other Names:
Drug: Placebo
Study drug matching placebo capsule.
|
Outcome Measures
Primary Outcome Measures
- 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) [Week 8 to Week 14]
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.
Secondary Outcome Measures
- Phase C: Clinical Global Impression - Improvement Scale (CGI-I) Score at The End of Phase C (Week 14) [Week 14]
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.
- 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) [Week 8 to Week 14]
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.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Participants with a current diagnosis of a major depressive episode. The current depressive episode must be ≥ 8 weeks in duration
-
Participants willing to discontinue all prohibited psychotropic medication starting from the time of signing the informed consent and during the study period
-
Participants with a 17-item Hamilton Depression Rating Scale (HAM-D17) total score ≥ 18 at the Baseline Visit for the Prospective Treatment Phase.
Exclusion Criteria:
-
Lack of prior treatment with an antidepressant during the current depressive episode
-
Participants who report treatment with adjunctive or monotherapy antipsychotic treatment during the current depressive episode.
-
Participants experiencing hallucinations, delusions or any psychotic symptomatology in the current depressive episode
-
Participants with epilepsy or significant history of seizure disorders
-
Participants with a clinically significant current diagnosis of borderline, antisocial, paranoid, schizoid, schizotypal or histrionic personality disorder
-
Participants who have received electroconvulsive therapy (ECT) in the last 10 years.
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | Birmingham | Alabama | United States | 35216 | |
2 | Little Rock | Arkansas | United States | 72223 | |
3 | Carson | California | United States | 90746 | |
4 | Garden Grove | California | United States | 95231 | |
5 | Imperial | California | United States | 92251 | |
6 | Mission Viejo | California | United States | 92691 | |
7 | Redlands | California | United States | 92374 | |
8 | San Diego | California | United States | 92128 | |
9 | Atlanta | Georgia | United States | 30308 | |
10 | Atlanta | Georgia | United States | 30328 | |
11 | Hoffman Estates | Illinois | United States | 60169 | |
12 | Terre Haute | Indiana | United States | 47802 | |
13 | Overland Park | Kansas | United States | 66211 | |
14 | Prairie Village | Kansas | United States | 66206 | |
15 | Wichita | Kansas | United States | 67207 | |
16 | Baltimore | Maryland | United States | 21204 | |
17 | New York | New York | United States | 10021 | |
18 | Toledo | Ohio | United States | 43623 | |
19 | Bartlett | Tennessee | United States | 38134 | |
20 | Wichita Falls | Texas | United States | 76309 | |
21 | Brisbane | Queensland | Australia | 4000 | |
22 | Everton Park | Queensland | Australia | 4053 | |
23 | Malvern | Victoria | Australia | 3144 | |
24 | Melbourne | Victoria | Australia | 3004 | |
25 | Fremantle | Western Australia | Australia | 6959 | |
26 | Bourgas | Bulgaria | 8000 | ||
27 | Lovech | Bulgaria | 5500 | ||
28 | Novi Iskar | Bulgaria | 1282 | ||
29 | Pleven | Bulgaria | 5800 | ||
30 | Plovdiv | Bulgaria | 4000 | ||
31 | Rousse | Bulgaria | 7003 | ||
32 | Sofia | Bulgaria | 1113 | ||
33 | Sofia | Bulgaria | 1431 | ||
34 | Sofia | Bulgaria | 1606 | ||
35 | Tsarev Brod | Bulgaria | 9747 | ||
36 | Tserova Koria | Bulgaria | 5047 | ||
37 | Varna | Bulgaria | 9000 | ||
38 | Tirupati | Andhra Pradesh | India | 517507 | |
39 | Vijayawada | Andhra Pradesh | India | 500072 | |
40 | Manipala | Karnataka | India | 576104 | |
41 | Pune | Maharashtra | India | 411004 | |
42 | Ludhiana | Punjab | India | 141001 | |
43 | Chennai | Tamil Nadu | India | 600003 | |
44 | Kanpur | Uttar Pradesh | India | 208005 | |
45 | Quezon City | NCR | Philippines | 1101 | |
46 | Quezon City | NCR | Philippines | 1102 | |
47 | Bucuresti | Romania | 010825 | ||
48 | Bucuresti | Romania | 030455 | ||
49 | Study Site 1 | Bucuresti | Romania | 041914 | |
50 | Study Site 2 | Bucuresti | Romania | 041914 | |
51 | Craiova | Romania | 200620 | ||
52 | Craiova | Romania | 540139 | ||
53 | Iasi | Romania | 700282 | ||
54 | Targoviste | Romania | 130081 | ||
55 | Targu Mures | Romania | 540139 | ||
56 | Michalovce | Slovakia | 07101 | ||
57 | Rimavska Sobota | Slovakia | 97901 | ||
58 | Svidnik | Slovakia | 8901 | ||
59 | Trencin | Slovakia | 91101 | ||
60 | Zlate Moravce | Slovakia | 95301 |
Sponsors and Collaborators
- Otsuka Pharmaceutical Development & Commercialization, Inc.
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 31-08-256
- 2010-018858-12
Study Results
Participant Flow
Recruitment Details | 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. |
---|---|
Pre-assignment Detail | 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. |
Arm/Group Title | Phase B: Single-blind Prospective Treatment Phase | Phase B+: Single-blind Phase B Responders | Phase C: Escitalopram Monotherapy | Phase C: Aripiprazole Monotherapy | Phase C: Aripiprazole/Escitalopram Combination Therapy |
---|---|---|---|---|---|
Arm/Group Description | 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+. | 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+. | 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. | 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. | 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. |
Period Title: Phase B (Day 1 to Week 8) | |||||
STARTED | 237 | 0 | 0 | 0 | 0 |
COMPLETED | 120 | 0 | 0 | 0 | 0 |
NOT COMPLETED | 117 | 0 | 0 | 0 | 0 |
Period Title: Phase B (Day 1 to Week 8) | |||||
STARTED | 0 | 54 | 22 | 21 | 23 |
COMPLETED | 0 | 45 | 17 | 17 | 18 |
NOT COMPLETED | 0 | 9 | 5 | 4 | 5 |
Baseline Characteristics
Arm/Group Title | Phase B: Single-blind Prospective Treatment Phase |
---|---|
Arm/Group Description | 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+. |
Overall Participants | 237 |
Age (years) [Mean (Standard Deviation) ] | |
Mean (Standard Deviation) [years] |
45.2
(11.3)
|
Sex: Female, Male (Count of Participants) | |
Female |
156
65.8%
|
Male |
81
34.2%
|
Ethnicity (NIH/OMB) (Count of Participants) | |
Hispanic or Latino |
18
7.6%
|
Not Hispanic or Latino |
218
92%
|
Unknown or Not Reported |
1
0.4%
|
Race (NIH/OMB) (Count of Participants) | |
American Indian or Alaska Native |
2
0.8%
|
Asian |
15
6.3%
|
Native Hawaiian or Other Pacific Islander |
0
0%
|
Black or African American |
30
12.7%
|
White |
186
78.5%
|
More than one race |
0
0%
|
Unknown or Not Reported |
4
1.7%
|
Outcome Measures
Title | 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) |
---|---|
Description | 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. |
Time Frame | Week 8 to Week 14 |
Outcome Measure Data
Analysis Population Description |
---|
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. |
Arm/Group Title | Phase C: Escitalopram Monotherapy | Phase C: Aripiprazole Monotherapy | Phase C: Aripiprazole/Escitalopram Combination Therapy |
---|---|---|---|
Arm/Group Description | 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. | 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. | 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. |
Measure Participants | 22 | 21 | 23 |
Least Squares Mean (Standard Error) [score on a scale] |
-8.0
(1.7)
|
-9.6
(1.7)
|
-9.2
(1.6)
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Phase C: Escitalopram Monotherapy, Phase C: Aripiprazole/Escitalopram Combination Therapy |
---|---|---|
Comments | ||
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | =0.595 |
Comments | ||
Method | ANCOVA | |
Comments | ||
Method of Estimation | Estimation Parameter | Treatment Difference |
Estimated Value | -1.3 | |
Confidence Interval |
(2-Sided) 95% -5.9 to 3.4 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Statistical Analysis 2
Statistical Analysis Overview | Comparison Group Selection | Phase C: Aripiprazole Monotherapy, Phase C: Aripiprazole/Escitalopram Combination Therapy |
---|---|---|
Comments | ||
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | =0.869 |
Comments | ||
Method | ANCOVA | |
Comments | ||
Method of Estimation | Estimation Parameter | Treatment Difference |
Estimated Value | 0.4 | |
Confidence Interval |
(2-Sided) 95% -4.4 to 5.1 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Title | Phase C: Clinical Global Impression - Improvement Scale (CGI-I) Score at The End of Phase C (Week 14) |
---|---|
Description | 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. |
Time Frame | Week 14 |
Outcome Measure Data
Analysis Population Description |
---|
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. |
Arm/Group Title | Phase C: Escitalopram Monotherapy | Phase C: Aripiprazole Monotherapy | Phase C: Aripiprazole/Escitalopram Combination Therapy |
---|---|---|---|
Arm/Group Description | 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. | 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. | 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. |
Measure Participants | 22 | 21 | 23 |
Mean (Standard Error) [score on a scale] |
2.4
(0.3)
|
2.3
(0.2)
|
2.3
(0.2)
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Phase C: Escitalopram Monotherapy, Phase C: Aripiprazole/Escitalopram Combination Therapy |
---|---|---|
Comments | ||
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | =0.856 |
Comments | ||
Method | Cochran-Mantel-Haenszel | |
Comments | Cochran-Mantel-Haenszel Row Mean Scores Test was used to determine the p-value. | |
Method of Estimation | Estimation Parameter | Treatment Difference |
Estimated Value | -0.1 | |
Confidence Interval |
(2-Sided) 95% -0.7 to 0.6 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Statistical Analysis 2
Statistical Analysis Overview | Comparison Group Selection | Phase C: Aripiprazole Monotherapy, Phase C: Aripiprazole/Escitalopram Combination Therapy |
---|---|---|
Comments | ||
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | =0.838 |
Comments | ||
Method | Cochran-Mantel-Haenszel | |
Comments | Cochran-Mantel-Haenszel Row Mean Scores Test was used to determine the p-value. | |
Method of Estimation | Estimation Parameter | Treatment Difference |
Estimated Value | 0.1 | |
Confidence Interval |
(2-Sided) 95% -0.6 to 0.7 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Title | 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) |
---|---|
Description | 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. |
Time Frame | Week 8 to Week 14 |
Outcome Measure Data
Analysis Population Description |
---|
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. |
Arm/Group Title | Phase C: Escitalopram Monotherapy | Phase C: Aripiprazole Monotherapy | Phase C: Aripiprazole/Escitalopram Combination Therapy |
---|---|---|---|
Arm/Group Description | 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. | 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. | 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. |
Measure Participants | 22 | 21 | 23 |
Least Squares Mean (Standard Error) [score on a scale] |
-0.9
(0.5)
|
-1.4
(0.5)
|
-1.2
(0.5)
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Phase C: Escitalopram Monotherapy, Phase C: Aripiprazole/Escitalopram Combination Therapy |
---|---|---|
Comments | ||
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | =0.765 |
Comments | ||
Method | ANCOVA | |
Comments | ||
Method of Estimation | Estimation Parameter | Treatment Difference |
Estimated Value | -0.2 | |
Confidence Interval |
(2-Sided) 95% -1.6 to 1.2 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Statistical Analysis 2
Statistical Analysis Overview | Comparison Group Selection | Phase C: Aripiprazole Monotherapy, Phase C: Aripiprazole/Escitalopram Combination Therapy |
---|---|---|
Comments | ||
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | =0.760 |
Comments | ||
Method | ANCOVA | |
Comments | ||
Method of Estimation | Estimation Parameter | Treatment Difference |
Estimated Value | 0.2 | |
Confidence Interval |
(2-Sided) 95% -1.2 to 1.6 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Adverse Events
Time Frame | From first dose of study drug through end of study (up to 22 weeks) | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
Adverse Event Reporting Description | 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. | |||||||||
Arm/Group Title | Phase B: Single-blind Prospective Treatment Phase | Phase B+: Single-blind Phase B Responders | Phase C: Escitalopram Monotherapy | Phase C: Aripiprazole Monotherapy | Phase C: Aripiprazole/Escitalopram Combination Therapy | |||||
Arm/Group Description | 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+. | 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+. | 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. | 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. | 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. | |||||
All Cause Mortality |
||||||||||
Phase B: Single-blind Prospective Treatment Phase | Phase B+: Single-blind Phase B Responders | Phase C: Escitalopram Monotherapy | Phase C: Aripiprazole Monotherapy | Phase C: Aripiprazole/Escitalopram Combination Therapy | ||||||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 0/237 (0%) | 0/54 (0%) | 0/22 (0%) | 0/21 (0%) | 0/23 (0%) | |||||
Serious Adverse Events |
||||||||||
Phase B: Single-blind Prospective Treatment Phase | Phase B+: Single-blind Phase B Responders | Phase C: Escitalopram Monotherapy | Phase C: Aripiprazole Monotherapy | Phase C: Aripiprazole/Escitalopram Combination Therapy | ||||||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 2/237 (0.8%) | 1/54 (1.9%) | 1/22 (4.5%) | 0/21 (0%) | 0/23 (0%) | |||||
Investigations | ||||||||||
Alanine aminotransferase increased | 0/237 (0%) | 0/54 (0%) | 1/22 (4.5%) | 0/21 (0%) | 0/23 (0%) | |||||
Psychiatric disorders | ||||||||||
Depression | 1/237 (0.4%) | 0/54 (0%) | 0/22 (0%) | 0/21 (0%) | 0/23 (0%) | |||||
Respiratory, thoracic and mediastinal disorders | ||||||||||
Asthma | 0/237 (0%) | 1/54 (1.9%) | 0/22 (0%) | 0/21 (0%) | 0/23 (0%) | |||||
Social circumstances | ||||||||||
Physical assault | 1/237 (0.4%) | 0/54 (0%) | 0/22 (0%) | 0/21 (0%) | 0/23 (0%) | |||||
Other (Not Including Serious) Adverse Events |
||||||||||
Phase B: Single-blind Prospective Treatment Phase | Phase B+: Single-blind Phase B Responders | Phase C: Escitalopram Monotherapy | Phase C: Aripiprazole Monotherapy | Phase C: Aripiprazole/Escitalopram Combination Therapy | ||||||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 53/237 (22.4%) | 7/54 (13%) | 5/22 (22.7%) | 10/21 (47.6%) | 11/23 (47.8%) | |||||
Gastrointestinal disorders | ||||||||||
Nausea | 18/237 (7.6%) | 0/54 (0%) | 2/22 (9.1%) | 1/21 (4.8%) | 1/23 (4.3%) | |||||
Constipation | 1/237 (0.4%) | 0/54 (0%) | 2/22 (9.1%) | 0/21 (0%) | 1/23 (4.3%) | |||||
Diarrhoea | 10/237 (4.2%) | 2/54 (3.7%) | 0/22 (0%) | 3/21 (14.3%) | 0/23 (0%) | |||||
Infections and infestations | ||||||||||
Upper Respiratory Tract Infection | 5/237 (2.1%) | 1/54 (1.9%) | 0/22 (0%) | 2/21 (9.5%) | 2/23 (8.7%) | |||||
Investigations | ||||||||||
Weight increased | 2/237 (0.8%) | 2/54 (3.7%) | 0/22 (0%) | 0/21 (0%) | 2/23 (8.7%) | |||||
Nervous system disorders | ||||||||||
Akathisia | 0/237 (0%) | 0/54 (0%) | 0/22 (0%) | 2/21 (9.5%) | 2/23 (8.7%) | |||||
Dizziness | 8/237 (3.4%) | 0/54 (0%) | 1/22 (4.5%) | 4/21 (19%) | 1/23 (4.3%) | |||||
Headache | 20/237 (8.4%) | 2/54 (3.7%) | 1/22 (4.5%) | 0/21 (0%) | 2/23 (8.7%) | |||||
Psychiatric disorders | ||||||||||
Restlessness | 0/237 (0%) | 0/54 (0%) | 0/22 (0%) | 1/21 (4.8%) | 2/23 (8.7%) | |||||
Respiratory, thoracic and mediastinal disorders | ||||||||||
Oropharyngeal pain | 1/237 (0.4%) | 0/54 (0%) | 2/22 (9.1%) | 0/21 (0%) | 1/23 (4.3%) |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
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.
Results Point of Contact
Name/Title | Global Clinical Development |
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Organization | Otsuka Pharmaceutical Development & Commercialization, Inc. |
Phone | 1-609-524-6788 |
clinicaltransparency@otsuka-us.com |
- 31-08-256
- 2010-018858-12