Trial Outcomes & Findings for Incomplete Response in Late Life Depression: Getting to Remission (IRL GREY) (NCT NCT00892047)

NCT ID: NCT00892047

Last Updated: 2015-12-17

Results Overview

The Montgomery-Asberg Depression Rating Scale (MADRS) is a clinician rated ten item instrument assessing depression symptoms. Possible scores range from 0-60; higher scores indicate greater severity of depression. Remission defined as score of 10 or less based on the MADRS.

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 468 participants
• Primary outcome timeframe: 12 weeks
• Results posted on: 2015-12-17

Participant Flow

Participants were recruited at 3 Centers (University of Pittsburgh, Centre for Addiction and Mental Health in Toronto, Canada, and Washington University). The first participant was enrolled July 2009, last finished August 2014.

468 signed consent. 181 were randomized. Of these 181, 91 randomized to venlafaxine plus aripirazol and 90 to venlafaxine plus placebo. Prior to randomization, 191 responded to venlafaxine; 40 withdrew consent; 41 withdrawn by PI, possible AE, 14 non-compliance; 1 death.

Participant milestones

Measure	1: Venlafaxine Plus Aripiprazole antidepressant (venlafaxine) plus aripiprazol or venlafaxine plus placebo venlafaxine XR plus aripiprazole: Dosage varies. Subject remains on antidepressant throughout the 36 week study and also receives aripiprazole 2mg to 15mg daily for up to 24 weeks.	2: Placebo Comparator antidepressant (venlafaxine) plus aripiprazol or venlafaxine plus placebo venlafaxine plus placebo: Dosage varies. Subject remains on antidepressant throughout the 36 week study and also receives placebo for up to 24 weeks.
Overall Study STARTED	91	90
Overall Study COMPLETED	87	83
Overall Study NOT COMPLETED	4	7

Reasons for withdrawal

Measure	1: Venlafaxine Plus Aripiprazole antidepressant (venlafaxine) plus aripiprazol or venlafaxine plus placebo venlafaxine XR plus aripiprazole: Dosage varies. Subject remains on antidepressant throughout the 36 week study and also receives aripiprazole 2mg to 15mg daily for up to 24 weeks.	2: Placebo Comparator antidepressant (venlafaxine) plus aripiprazol or venlafaxine plus placebo venlafaxine plus placebo: Dosage varies. Subject remains on antidepressant throughout the 36 week study and also receives placebo for up to 24 weeks.
Overall Study Adverse Event	2	2
Overall Study subject burden	2	3
Overall Study Lack of Efficacy	0	2

Baseline Characteristics

Incomplete Response in Late Life Depression: Getting to Remission (IRL GREY)

Baseline characteristics by cohort

Measure	1: Venlafaxine Plus Aripiprazole n=91 Participants antidepressant (venlafaxine) plus aripiprazol or venlafaxine plus placebo venlafaxine XR plus aripiprazole: Dosage varies. Subject remains on antidepressant throughout the 36 week study. Will be randomized to aripiprazole or placebo for up to 24 weeks.	2: Placebo Comparator n=90 Participants antidepressant (venlafaxine) plus aripiprazol or venlafaxine plus placebo venlafaxine plus placebo: Dosage varies. Subject remains on antidepressant throughout the 36 week study. Will be randomized to aripiprazole or placebo for up to 24 weeks.	Total n=181 Participants Total of all reporting groups
Age, Continuous	66.4 years n=5 Participants	65.7 years n=7 Participants	66.0 years n=5 Participants
Sex: Female, Male Female	52 Participants n=5 Participants	51 Participants n=7 Participants	103 Participants n=5 Participants
Sex: Female, Male Male	39 Participants n=5 Participants	39 Participants n=7 Participants	78 Participants n=5 Participants

PRIMARY outcome

Timeframe: 12 weeks

The Montgomery-Asberg Depression Rating Scale (MADRS) is a clinician rated ten item instrument assessing depression symptoms. Possible scores range from 0-60; higher scores indicate greater severity of depression. Remission defined as score of 10 or less based on the MADRS.

Outcome measures

Measure	1: Venlafaxine Plus Aripiprazole n=91 Participants antidepressant (venlafaxine) plus aripiprazol or venlafaxine plus placebo venlafaxine XR plus aripiprazole: Dosage of venlafaxine ranged from 150mg to 300mg. Dose of aripirpazole ranged from 2mg to 15mg. Subject remained on venlafaxine throughout the 36 week study. Subject remained on aripiprazole or placebo for up to 24 weeks.	2: Placebo Comparator n=90 Participants antidepressant (venlafaxine) plus aripiprazol or venlafaxine plus placebo venlafaxine XR plus aripiprazole: Dosage of venlafaxine ranged from 150mg to 300mg. Dose of aripirpazole ranged from 2mg to 15mg. Subject remained on venlafaxine throughout the 36 week study. Subject remained on aripiprazole or placebo for up to 24 weeks.
Percentage of Subjects Who Met Criteria for Remission Based on the Montgomery-Asberg Depression Rating Scale (MADRS)	44 percentage of participants	29 percentage of participants

PRIMARY outcome

Timeframe: 12 weeks

Percentage of participants who developed clinically significant akathisia.

Outcome measures

Measure	1: Venlafaxine Plus Aripiprazole n=91 Participants antidepressant (venlafaxine) plus aripiprazol or venlafaxine plus placebo venlafaxine XR plus aripiprazole: Dosage of venlafaxine ranged from 150mg to 300mg. Dose of aripirpazole ranged from 2mg to 15mg. Subject remained on venlafaxine throughout the 36 week study. Subject remained on aripiprazole or placebo for up to 24 weeks.	2: Placebo Comparator n=90 Participants antidepressant (venlafaxine) plus aripiprazol or venlafaxine plus placebo venlafaxine XR plus aripiprazole: Dosage of venlafaxine ranged from 150mg to 300mg. Dose of aripirpazole ranged from 2mg to 15mg. Subject remained on venlafaxine throughout the 36 week study. Subject remained on aripiprazole or placebo for up to 24 weeks.
Akathisia	26.7 percentage of participants	12.2 percentage of participants

PRIMARY outcome

Timeframe: Baseline through12 weeks

Population: The number of participants analyzed is lower due to missing data attributable to dropouts. The information obtained is from figure 3B in the manuscript

Weight change in kilograms

Outcome measures

Measure	1: Venlafaxine Plus Aripiprazole n=84 Participants antidepressant (venlafaxine) plus aripiprazol or venlafaxine plus placebo venlafaxine XR plus aripiprazole: Dosage of venlafaxine ranged from 150mg to 300mg. Dose of aripirpazole ranged from 2mg to 15mg. Subject remained on venlafaxine throughout the 36 week study. Subject remained on aripiprazole or placebo for up to 24 weeks.	2: Placebo Comparator n=85 Participants antidepressant (venlafaxine) plus aripiprazol or venlafaxine plus placebo venlafaxine XR plus aripiprazole: Dosage of venlafaxine ranged from 150mg to 300mg. Dose of aripirpazole ranged from 2mg to 15mg. Subject remained on venlafaxine throughout the 36 week study. Subject remained on aripiprazole or placebo for up to 24 weeks.
Weight	1.93 kilograms Standard Deviation 3.00	0.01 kilograms Standard Deviation 3.15

PRIMARY outcome

Timeframe: 12weeks

Population: We have a lower number of participants analyzed due to dropouts and missed assessments.

Percentage of participants who develop signs of parkinsonism

Outcome measures

Measure	1: Venlafaxine Plus Aripiprazole n=86 Participants antidepressant (venlafaxine) plus aripiprazol or venlafaxine plus placebo venlafaxine XR plus aripiprazole: Dosage of venlafaxine ranged from 150mg to 300mg. Dose of aripirpazole ranged from 2mg to 15mg. Subject remained on venlafaxine throughout the 36 week study. Subject remained on aripiprazole or placebo for up to 24 weeks.	2: Placebo Comparator n=81 Participants antidepressant (venlafaxine) plus aripiprazol or venlafaxine plus placebo venlafaxine XR plus aripiprazole: Dosage of venlafaxine ranged from 150mg to 300mg. Dose of aripirpazole ranged from 2mg to 15mg. Subject remained on venlafaxine throughout the 36 week study. Subject remained on aripiprazole or placebo for up to 24 weeks.
Parkinsonism	17.4 percentage of participants	2.5 percentage of participants

SECONDARY outcome

Timeframe: 12 weeks

Population: It is a smaller number of participants restricted to those who did not report any suicidal ideation at baseline. This is in Table 3of the manuscript

percentage of participants who reported suicidal ideation during treatment but not at baseline

Outcome measures

Measure	1: Venlafaxine Plus Aripiprazole n=61 Participants antidepressant (venlafaxine) plus aripiprazol or venlafaxine plus placebo venlafaxine XR plus aripiprazole: Dosage of venlafaxine ranged from 150mg to 300mg. Dose of aripirpazole ranged from 2mg to 15mg. Subject remained on venlafaxine throughout the 36 week study. Subject remained on aripiprazole or placebo for up to 24 weeks.	2: Placebo Comparator n=65 Participants antidepressant (venlafaxine) plus aripiprazol or venlafaxine plus placebo venlafaxine XR plus aripiprazole: Dosage of venlafaxine ranged from 150mg to 300mg. Dose of aripirpazole ranged from 2mg to 15mg. Subject remained on venlafaxine throughout the 36 week study. Subject remained on aripiprazole or placebo for up to 24 weeks.
Emergent Suicidal Ideation in Those With no Ideation at the Start of Treatment	21.3 percent of participants	29.2 percent of participants

SECONDARY outcome

Timeframe: 12 weeks

Population: We had a smaller number of participant observations due to dropouts and missing data. This data is in Table 3 of the manuscript.

percentage of participants

Outcome measures

Measure	1: Venlafaxine Plus Aripiprazole n=78 Participants antidepressant (venlafaxine) plus aripiprazol or venlafaxine plus placebo venlafaxine XR plus aripiprazole: Dosage of venlafaxine ranged from 150mg to 300mg. Dose of aripirpazole ranged from 2mg to 15mg. Subject remained on venlafaxine throughout the 36 week study. Subject remained on aripiprazole or placebo for up to 24 weeks.	2: Placebo Comparator n=79 Participants antidepressant (venlafaxine) plus aripiprazol or venlafaxine plus placebo venlafaxine XR plus aripiprazole: Dosage of venlafaxine ranged from 150mg to 300mg. Dose of aripirpazole ranged from 2mg to 15mg. Subject remained on venlafaxine throughout the 36 week study. Subject remained on aripiprazole or placebo for up to 24 weeks.
QTc Prolongation on EKG (to Greater or Equal to 480 Msec)	1.3 percent of participants	0 percent of participants

Adverse Events

1: Venlafaxine Plus Aripiprazole

Serious events: 4 serious events

Other events: 0 other events

Deaths: 0 deaths

2: Placebo Comparator

Serious events: 2 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Measure	1: Venlafaxine Plus Aripiprazole n=91 participants at risk antidepressant (venlafaxine) plus aripiprazol or venlafaxine plus placebo venlafaxine XR plus aripiprazole: Dosage varies. Subject remains on antidepressant throughout the 36 week study and also receives aripiprazole 2mg to 15mg daily for up to 24 weeks.	2: Placebo Comparator n=90 participants at risk antidepressant (venlafaxine) plus aripiprazol or venlafaxine plus placebo venlafaxine plus placebo: Dosage varies. Subject remains on antidepressant throughout the 36 week study and also receives placebo for up to 24 weeks.
Psychiatric disorders completed suicide	1.1% 1/91 • Number of events 1	0.00% 0/90
Cardiac disorders hospitalization for MI or CHF	1.1% 1/91 • Number of events 1	1.1% 1/90 • Number of events 1
Nervous system disorders stroke	1.1% 1/91 • Number of events 1	0.00% 0/90
Gastrointestinal disorders diverticulitis or excessive vonmiting	1.1% 1/91 • Number of events 1	1.1% 1/90 • Number of events 1

Other adverse events

Adverse event data not reported

Additional Information

Charles F. Reynolds III, MD

University of Pittsburgh

Phone: 412-246-6414

Email: reynoldscf@upmc.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place