Trial Outcomes & Findings for Sustaining Remission of Psychotic Depression (NCT NCT01427608)

NCT ID: NCT01427608

Last Updated: 2019-03-05

Results Overview

Relapse criteria include at least one of the following: 1)Structured Clinical Interview for Diagnostic Statistical Manual #4 Trade Revision (DSM-IV-TR) Axis 1 Disorders (SCID) symptoms of major depression maintained over two weeks 2)17-item Hamilton Depression Rating Scale score of \>17 maintained for more than one week + a mean increase of 5 points from entry into randomized phase 3)Re-emergence of psychosis for more than one week, with a SADS (Schedule for Affective Disorders and Schizophrenia) score of \>2 on delusion or hallucination severity items 4)Significant clinical worsening defined as either emergence of high-risk of suicide, and/or development of mania for greater than one week, and/or psychiatric hospitalization.

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 269 participants
• Primary outcome timeframe: From entry into randomized phase (baseline) and 36 weeks or earlier relapse
• Results posted on: 2019-03-05

Participant Flow

269 participants were enrolled in the open-label phase. However, only 126 participants were eligible and consented to participate in the RCT phase. Reasons for not being eligible for the RCT phase included failure to achive remission criteria, discontinuation of treatment prior to the RCT, or decision by the participant not to consent to the RCT.

Participant milestones

Measure	Sertraline + Olanzapine Randomized to continue with sertraline and olanzapine under double-blind conditions	Sertraline + Placebo Randomized to continue with sertraline and substitute placebo for olanzapine under double-blind conditions
Overall Study STARTED	64	62
Overall Study COMPLETED	43	24
Overall Study NOT COMPLETED	21	38

Reasons for withdrawal

Measure	Sertraline + Olanzapine Randomized to continue with sertraline and olanzapine under double-blind conditions	Sertraline + Placebo Randomized to continue with sertraline and substitute placebo for olanzapine under double-blind conditions
Overall Study Death	1	0
Overall Study Withdrawal by Subject	7	3
Overall Study Relapsed-all cause	13	34
Overall Study Events not attributed to study meds	0	1

Baseline Characteristics

Sustaining Remission of Psychotic Depression

Baseline characteristics by cohort

Measure	Sertraline + Olanzapine n=64 Participants Randomized to continue with sertraline and olanzapine under double-blind conditions	Sertraline + Placebo n=62 Participants Randomized to continue with sertraline and substitute placebo for olanzapine under double-blind conditions	Total n=126 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	45 Participants n=5 Participants	42 Participants n=7 Participants	87 Participants n=5 Participants
Age, Categorical >=65 years	19 Participants n=5 Participants	20 Participants n=7 Participants	39 Participants n=5 Participants
Age, Continuous	55.0 years STANDARD_DEVIATION 15.1 • n=5 Participants	55.7 years STANDARD_DEVIATION 14.9 • n=7 Participants	55.3 years STANDARD_DEVIATION 14.8 • n=5 Participants
Sex: Female, Male Female	37 Participants n=5 Participants	41 Participants n=7 Participants	78 Participants n=5 Participants
Sex: Female, Male Male	27 Participants n=5 Participants	21 Participants n=7 Participants	48 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	6 Participants n=5 Participants	9 Participants n=7 Participants	15 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	58 Participants n=5 Participants	53 Participants n=7 Participants	111 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	4 Participants n=5 Participants	3 Participants n=7 Participants	7 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	6 Participants n=5 Participants	9 Participants n=7 Participants	15 Participants n=5 Participants
Race (NIH/OMB) White	54 Participants n=5 Participants	49 Participants n=7 Participants	103 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Region of Enrollment Canada	24 participants n=5 Participants	23 participants n=7 Participants	47 participants n=5 Participants
Region of Enrollment United States	40 participants n=5 Participants	39 participants n=7 Participants	79 participants n=5 Participants
Hamilton Depression Rating Scale 17-Item Total Score	5.3 units on a scale STANDARD_DEVIATION 3.6 • n=5 Participants	5.6 units on a scale STANDARD_DEVIATION 3.6 • n=7 Participants	5.5 units on a scale STANDARD_DEVIATION 3.6 • n=5 Participants
Weight	178.6 pounds STANDARD_DEVIATION 39.4 • n=5 Participants	182.5 pounds STANDARD_DEVIATION 39.8 • n=7 Participants	180.5 pounds STANDARD_DEVIATION 39.5 • n=5 Participants
Total Cholesterol level	209.0 mg/dL STANDARD_DEVIATION 51.3 • n=5 Participants	220.4 mg/dL STANDARD_DEVIATION 46.8 • n=7 Participants	214.7 mg/dL STANDARD_DEVIATION 49.3 • n=5 Participants
Triglycerides	134 mg/dL n=5 Participants	121 mg/dL n=7 Participants	127 mg/dL n=5 Participants

PRIMARY outcome

Timeframe: From entry into randomized phase (baseline) and 36 weeks or earlier relapse

Relapse criteria include at least one of the following:

1)Structured Clinical Interview for Diagnostic Statistical Manual #4 Trade Revision (DSM-IV-TR) Axis 1 Disorders (SCID) symptoms of major depression maintained over two weeks 2)17-item Hamilton Depression Rating Scale score of >17 maintained for more than one week + a mean increase of 5 points from entry into randomized phase 3)Re-emergence of psychosis for more than one week, with a SADS (Schedule for Affective Disorders and Schizophrenia) score of >2 on delusion or hallucination severity items 4)Significant clinical worsening defined as either emergence of high-risk of suicide, and/or development of mania for greater than one week, and/or psychiatric hospitalization.

Outcome measures

Measure	Sertraline + Olanzapine n=64 Participants Randomized to continue with sertraline and olanzapine under double-blind conditions	Sertraline + Placebo n=62 Participants Randomized to continue with sertraline and substitute placebo for olanzapine under double-blind conditions
Number of Subjects at Risk of Relapse During the Randomized Phase.	13 Participants	34 Participants

SECONDARY outcome

Timeframe: From entry into randomized phase (baseline) and 36 weeks

Change in weight from entry into randomized phase (baseline) and 36 weeks.

Outcome measures

Measure	Sertraline + Olanzapine n=64 Participants Randomized to continue with sertraline and olanzapine under double-blind conditions	Sertraline + Placebo n=62 Participants Randomized to continue with sertraline and substitute placebo for olanzapine under double-blind conditions
Changes in Metabolic Measures: Weight	5.70 pounds Interval 3.3 to 8.11	-3.11 pounds Interval -5.41 to -0.81

SECONDARY outcome

Timeframe: From entry into randomized phase (baseline) and 36 weeks

Change in cholesterol from entry into randomized phase (baseline) and 36 weeks.

Outcome measures

Measure	Sertraline + Olanzapine n=64 Participants Randomized to continue with sertraline and olanzapine under double-blind conditions	Sertraline + Placebo n=62 Participants Randomized to continue with sertraline and substitute placebo for olanzapine under double-blind conditions
Changes in Metabolic Measure: Cholesterol	-0.46 mg/dL Interval -14.9 to 5.57	-22.28 mg/dL Interval -32.71 to -11.86

SECONDARY outcome

Timeframe: From entry into randomized phase (baseline) and 36 weeks

Change in triglycerides from entry into randomized phase (baseline) and 36 weeks.

Outcome measures

Measure	Sertraline + Olanzapine n=64 Participants Randomized to continue with sertraline and olanzapine under double-blind conditions	Sertraline + Placebo n=62 Participants Randomized to continue with sertraline and substitute placebo for olanzapine under double-blind conditions
Changes in Metabolic Measures: Triglycerides	-3.85 mg/dL Interval -31.68 to 23.99	-18.18 mg/dL Interval -30.05 to -6.31

Adverse Events

Sertraline + Olanzapine

Serious events: 11 serious events

Other events: 29 other events

Deaths: 1 deaths

Sertraline + Placebo

Serious events: 12 serious events

Other events: 23 other events

Deaths: 0 deaths

Serious adverse events

Measure	Sertraline + Olanzapine n=64 participants at risk Randomized to continue with sertraline and olanzapine under double-blind conditions	Sertraline + Placebo n=62 participants at risk Randomized to continue with sertraline and substitute placebo for olanzapine under double-blind conditions
Surgical and medical procedures Hospitalisation	17.2% 11/64 • Number of events 11 • 36 Weeks of RCT Phase Are based on items of the Udvalg for Kliniske Undersogelser Side effect scale (UKU), based on the following system: 1) Items with an increase of ≥2 points from baseline and items rated as a 3 on the UKU that were rated \<3 at baseline. Exceptions include the following items: 35=Weight Gain, 36= Weight Loss. 2) Weight gain and weight loss AEs were determined by the following definitions: a. weight gain of \>7% from pre-morbid weight, b. weight loss of \>7% from pre-morbid weight in the RCT phase.	19.4% 12/62 • Number of events 12 • 36 Weeks of RCT Phase Are based on items of the Udvalg for Kliniske Undersogelser Side effect scale (UKU), based on the following system: 1) Items with an increase of ≥2 points from baseline and items rated as a 3 on the UKU that were rated \<3 at baseline. Exceptions include the following items: 35=Weight Gain, 36= Weight Loss. 2) Weight gain and weight loss AEs were determined by the following definitions: a. weight gain of \>7% from pre-morbid weight, b. weight loss of \>7% from pre-morbid weight in the RCT phase.

Other adverse events

Measure	Sertraline + Olanzapine n=64 participants at risk Randomized to continue with sertraline and olanzapine under double-blind conditions	Sertraline + Placebo n=62 participants at risk Randomized to continue with sertraline and substitute placebo for olanzapine under double-blind conditions
Psychiatric disorders Abnormal dreams	1.6% 1/64 • Number of events 2 • 36 Weeks of RCT Phase Are based on items of the Udvalg for Kliniske Undersogelser Side effect scale (UKU), based on the following system: 1) Items with an increase of ≥2 points from baseline and items rated as a 3 on the UKU that were rated \<3 at baseline. Exceptions include the following items: 35=Weight Gain, 36= Weight Loss. 2) Weight gain and weight loss AEs were determined by the following definitions: a. weight gain of \>7% from pre-morbid weight, b. weight loss of \>7% from pre-morbid weight in the RCT phase.	1.6% 1/62 • Number of events 1 • 36 Weeks of RCT Phase Are based on items of the Udvalg for Kliniske Undersogelser Side effect scale (UKU), based on the following system: 1) Items with an increase of ≥2 points from baseline and items rated as a 3 on the UKU that were rated \<3 at baseline. Exceptions include the following items: 35=Weight Gain, 36= Weight Loss. 2) Weight gain and weight loss AEs were determined by the following definitions: a. weight gain of \>7% from pre-morbid weight, b. weight loss of \>7% from pre-morbid weight in the RCT phase.
Gastrointestinal disorders Constipation	0.00% 0/64 • 36 Weeks of RCT Phase Are based on items of the Udvalg for Kliniske Undersogelser Side effect scale (UKU), based on the following system: 1) Items with an increase of ≥2 points from baseline and items rated as a 3 on the UKU that were rated \<3 at baseline. Exceptions include the following items: 35=Weight Gain, 36= Weight Loss. 2) Weight gain and weight loss AEs were determined by the following definitions: a. weight gain of \>7% from pre-morbid weight, b. weight loss of \>7% from pre-morbid weight in the RCT phase.	1.6% 1/62 • Number of events 1 • 36 Weeks of RCT Phase Are based on items of the Udvalg for Kliniske Undersogelser Side effect scale (UKU), based on the following system: 1) Items with an increase of ≥2 points from baseline and items rated as a 3 on the UKU that were rated \<3 at baseline. Exceptions include the following items: 35=Weight Gain, 36= Weight Loss. 2) Weight gain and weight loss AEs were determined by the following definitions: a. weight gain of \>7% from pre-morbid weight, b. weight loss of \>7% from pre-morbid weight in the RCT phase.
Psychiatric disorders Depression	1.6% 1/64 • Number of events 1 • 36 Weeks of RCT Phase Are based on items of the Udvalg for Kliniske Undersogelser Side effect scale (UKU), based on the following system: 1) Items with an increase of ≥2 points from baseline and items rated as a 3 on the UKU that were rated \<3 at baseline. Exceptions include the following items: 35=Weight Gain, 36= Weight Loss. 2) Weight gain and weight loss AEs were determined by the following definitions: a. weight gain of \>7% from pre-morbid weight, b. weight loss of \>7% from pre-morbid weight in the RCT phase.	0.00% 0/62 • 36 Weeks of RCT Phase Are based on items of the Udvalg for Kliniske Undersogelser Side effect scale (UKU), based on the following system: 1) Items with an increase of ≥2 points from baseline and items rated as a 3 on the UKU that were rated \<3 at baseline. Exceptions include the following items: 35=Weight Gain, 36= Weight Loss. 2) Weight gain and weight loss AEs were determined by the following definitions: a. weight gain of \>7% from pre-morbid weight, b. weight loss of \>7% from pre-morbid weight in the RCT phase.
Gastrointestinal disorders Diarrhoea	6.2% 4/64 • Number of events 4 • 36 Weeks of RCT Phase Are based on items of the Udvalg for Kliniske Undersogelser Side effect scale (UKU), based on the following system: 1) Items with an increase of ≥2 points from baseline and items rated as a 3 on the UKU that were rated \<3 at baseline. Exceptions include the following items: 35=Weight Gain, 36= Weight Loss. 2) Weight gain and weight loss AEs were determined by the following definitions: a. weight gain of \>7% from pre-morbid weight, b. weight loss of \>7% from pre-morbid weight in the RCT phase.	1.6% 1/62 • Number of events 2 • 36 Weeks of RCT Phase Are based on items of the Udvalg for Kliniske Undersogelser Side effect scale (UKU), based on the following system: 1) Items with an increase of ≥2 points from baseline and items rated as a 3 on the UKU that were rated \<3 at baseline. Exceptions include the following items: 35=Weight Gain, 36= Weight Loss. 2) Weight gain and weight loss AEs were determined by the following definitions: a. weight gain of \>7% from pre-morbid weight, b. weight loss of \>7% from pre-morbid weight in the RCT phase.
Nervous system disorders Dizziness postural	7.8% 5/64 • Number of events 5 • 36 Weeks of RCT Phase Are based on items of the Udvalg for Kliniske Undersogelser Side effect scale (UKU), based on the following system: 1) Items with an increase of ≥2 points from baseline and items rated as a 3 on the UKU that were rated \<3 at baseline. Exceptions include the following items: 35=Weight Gain, 36= Weight Loss. 2) Weight gain and weight loss AEs were determined by the following definitions: a. weight gain of \>7% from pre-morbid weight, b. weight loss of \>7% from pre-morbid weight in the RCT phase.	3.2% 2/62 • Number of events 2 • 36 Weeks of RCT Phase Are based on items of the Udvalg for Kliniske Undersogelser Side effect scale (UKU), based on the following system: 1) Items with an increase of ≥2 points from baseline and items rated as a 3 on the UKU that were rated \<3 at baseline. Exceptions include the following items: 35=Weight Gain, 36= Weight Loss. 2) Weight gain and weight loss AEs were determined by the following definitions: a. weight gain of \>7% from pre-morbid weight, b. weight loss of \>7% from pre-morbid weight in the RCT phase.
Gastrointestinal disorders Dry mouth	0.00% 0/64 • 36 Weeks of RCT Phase Are based on items of the Udvalg for Kliniske Undersogelser Side effect scale (UKU), based on the following system: 1) Items with an increase of ≥2 points from baseline and items rated as a 3 on the UKU that were rated \<3 at baseline. Exceptions include the following items: 35=Weight Gain, 36= Weight Loss. 2) Weight gain and weight loss AEs were determined by the following definitions: a. weight gain of \>7% from pre-morbid weight, b. weight loss of \>7% from pre-morbid weight in the RCT phase.	1.6% 1/62 • Number of events 1 • 36 Weeks of RCT Phase Are based on items of the Udvalg for Kliniske Undersogelser Side effect scale (UKU), based on the following system: 1) Items with an increase of ≥2 points from baseline and items rated as a 3 on the UKU that were rated \<3 at baseline. Exceptions include the following items: 35=Weight Gain, 36= Weight Loss. 2) Weight gain and weight loss AEs were determined by the following definitions: a. weight gain of \>7% from pre-morbid weight, b. weight loss of \>7% from pre-morbid weight in the RCT phase.
General disorders Fatigue	3.1% 2/64 • Number of events 2 • 36 Weeks of RCT Phase Are based on items of the Udvalg for Kliniske Undersogelser Side effect scale (UKU), based on the following system: 1) Items with an increase of ≥2 points from baseline and items rated as a 3 on the UKU that were rated \<3 at baseline. Exceptions include the following items: 35=Weight Gain, 36= Weight Loss. 2) Weight gain and weight loss AEs were determined by the following definitions: a. weight gain of \>7% from pre-morbid weight, b. weight loss of \>7% from pre-morbid weight in the RCT phase.	1.6% 1/62 • Number of events 1 • 36 Weeks of RCT Phase Are based on items of the Udvalg for Kliniske Undersogelser Side effect scale (UKU), based on the following system: 1) Items with an increase of ≥2 points from baseline and items rated as a 3 on the UKU that were rated \<3 at baseline. Exceptions include the following items: 35=Weight Gain, 36= Weight Loss. 2) Weight gain and weight loss AEs were determined by the following definitions: a. weight gain of \>7% from pre-morbid weight, b. weight loss of \>7% from pre-morbid weight in the RCT phase.
Nervous system disorders Headache	4.7% 3/64 • Number of events 3 • 36 Weeks of RCT Phase Are based on items of the Udvalg for Kliniske Undersogelser Side effect scale (UKU), based on the following system: 1) Items with an increase of ≥2 points from baseline and items rated as a 3 on the UKU that were rated \<3 at baseline. Exceptions include the following items: 35=Weight Gain, 36= Weight Loss. 2) Weight gain and weight loss AEs were determined by the following definitions: a. weight gain of \>7% from pre-morbid weight, b. weight loss of \>7% from pre-morbid weight in the RCT phase.	1.6% 1/62 • Number of events 1 • 36 Weeks of RCT Phase Are based on items of the Udvalg for Kliniske Undersogelser Side effect scale (UKU), based on the following system: 1) Items with an increase of ≥2 points from baseline and items rated as a 3 on the UKU that were rated \<3 at baseline. Exceptions include the following items: 35=Weight Gain, 36= Weight Loss. 2) Weight gain and weight loss AEs were determined by the following definitions: a. weight gain of \>7% from pre-morbid weight, b. weight loss of \>7% from pre-morbid weight in the RCT phase.
Skin and subcutaneous tissue disorders Hyperhidrosis	1.6% 1/64 • Number of events 1 • 36 Weeks of RCT Phase Are based on items of the Udvalg for Kliniske Undersogelser Side effect scale (UKU), based on the following system: 1) Items with an increase of ≥2 points from baseline and items rated as a 3 on the UKU that were rated \<3 at baseline. Exceptions include the following items: 35=Weight Gain, 36= Weight Loss. 2) Weight gain and weight loss AEs were determined by the following definitions: a. weight gain of \>7% from pre-morbid weight, b. weight loss of \>7% from pre-morbid weight in the RCT phase.	3.2% 2/62 • Number of events 2 • 36 Weeks of RCT Phase Are based on items of the Udvalg for Kliniske Undersogelser Side effect scale (UKU), based on the following system: 1) Items with an increase of ≥2 points from baseline and items rated as a 3 on the UKU that were rated \<3 at baseline. Exceptions include the following items: 35=Weight Gain, 36= Weight Loss. 2) Weight gain and weight loss AEs were determined by the following definitions: a. weight gain of \>7% from pre-morbid weight, b. weight loss of \>7% from pre-morbid weight in the RCT phase.
Nervous system disorders Hypersomnia	3.1% 2/64 • Number of events 2 • 36 Weeks of RCT Phase Are based on items of the Udvalg for Kliniske Undersogelser Side effect scale (UKU), based on the following system: 1) Items with an increase of ≥2 points from baseline and items rated as a 3 on the UKU that were rated \<3 at baseline. Exceptions include the following items: 35=Weight Gain, 36= Weight Loss. 2) Weight gain and weight loss AEs were determined by the following definitions: a. weight gain of \>7% from pre-morbid weight, b. weight loss of \>7% from pre-morbid weight in the RCT phase.	4.8% 3/62 • Number of events 3 • 36 Weeks of RCT Phase Are based on items of the Udvalg for Kliniske Undersogelser Side effect scale (UKU), based on the following system: 1) Items with an increase of ≥2 points from baseline and items rated as a 3 on the UKU that were rated \<3 at baseline. Exceptions include the following items: 35=Weight Gain, 36= Weight Loss. 2) Weight gain and weight loss AEs were determined by the following definitions: a. weight gain of \>7% from pre-morbid weight, b. weight loss of \>7% from pre-morbid weight in the RCT phase.
Psychiatric disorders Indifference	1.6% 1/64 • Number of events 1 • 36 Weeks of RCT Phase Are based on items of the Udvalg for Kliniske Undersogelser Side effect scale (UKU), based on the following system: 1) Items with an increase of ≥2 points from baseline and items rated as a 3 on the UKU that were rated \<3 at baseline. Exceptions include the following items: 35=Weight Gain, 36= Weight Loss. 2) Weight gain and weight loss AEs were determined by the following definitions: a. weight gain of \>7% from pre-morbid weight, b. weight loss of \>7% from pre-morbid weight in the RCT phase.	0.00% 0/62 • 36 Weeks of RCT Phase Are based on items of the Udvalg for Kliniske Undersogelser Side effect scale (UKU), based on the following system: 1) Items with an increase of ≥2 points from baseline and items rated as a 3 on the UKU that were rated \<3 at baseline. Exceptions include the following items: 35=Weight Gain, 36= Weight Loss. 2) Weight gain and weight loss AEs were determined by the following definitions: a. weight gain of \>7% from pre-morbid weight, b. weight loss of \>7% from pre-morbid weight in the RCT phase.
Psychiatric disorders Insomnia	3.1% 2/64 • Number of events 2 • 36 Weeks of RCT Phase Are based on items of the Udvalg for Kliniske Undersogelser Side effect scale (UKU), based on the following system: 1) Items with an increase of ≥2 points from baseline and items rated as a 3 on the UKU that were rated \<3 at baseline. Exceptions include the following items: 35=Weight Gain, 36= Weight Loss. 2) Weight gain and weight loss AEs were determined by the following definitions: a. weight gain of \>7% from pre-morbid weight, b. weight loss of \>7% from pre-morbid weight in the RCT phase.	6.5% 4/62 • Number of events 4 • 36 Weeks of RCT Phase Are based on items of the Udvalg for Kliniske Undersogelser Side effect scale (UKU), based on the following system: 1) Items with an increase of ≥2 points from baseline and items rated as a 3 on the UKU that were rated \<3 at baseline. Exceptions include the following items: 35=Weight Gain, 36= Weight Loss. 2) Weight gain and weight loss AEs were determined by the following definitions: a. weight gain of \>7% from pre-morbid weight, b. weight loss of \>7% from pre-morbid weight in the RCT phase.
Psychiatric disorders Libido decreased	6.2% 4/64 • Number of events 4 • 36 Weeks of RCT Phase Are based on items of the Udvalg for Kliniske Undersogelser Side effect scale (UKU), based on the following system: 1) Items with an increase of ≥2 points from baseline and items rated as a 3 on the UKU that were rated \<3 at baseline. Exceptions include the following items: 35=Weight Gain, 36= Weight Loss. 2) Weight gain and weight loss AEs were determined by the following definitions: a. weight gain of \>7% from pre-morbid weight, b. weight loss of \>7% from pre-morbid weight in the RCT phase.	0.00% 0/62 • 36 Weeks of RCT Phase Are based on items of the Udvalg for Kliniske Undersogelser Side effect scale (UKU), based on the following system: 1) Items with an increase of ≥2 points from baseline and items rated as a 3 on the UKU that were rated \<3 at baseline. Exceptions include the following items: 35=Weight Gain, 36= Weight Loss. 2) Weight gain and weight loss AEs were determined by the following definitions: a. weight gain of \>7% from pre-morbid weight, b. weight loss of \>7% from pre-morbid weight in the RCT phase.
Musculoskeletal and connective tissue disorders Musculoskeletal stiffness	1.6% 1/64 • Number of events 1 • 36 Weeks of RCT Phase Are based on items of the Udvalg for Kliniske Undersogelser Side effect scale (UKU), based on the following system: 1) Items with an increase of ≥2 points from baseline and items rated as a 3 on the UKU that were rated \<3 at baseline. Exceptions include the following items: 35=Weight Gain, 36= Weight Loss. 2) Weight gain and weight loss AEs were determined by the following definitions: a. weight gain of \>7% from pre-morbid weight, b. weight loss of \>7% from pre-morbid weight in the RCT phase.	0.00% 0/62 • 36 Weeks of RCT Phase Are based on items of the Udvalg for Kliniske Undersogelser Side effect scale (UKU), based on the following system: 1) Items with an increase of ≥2 points from baseline and items rated as a 3 on the UKU that were rated \<3 at baseline. Exceptions include the following items: 35=Weight Gain, 36= Weight Loss. 2) Weight gain and weight loss AEs were determined by the following definitions: a. weight gain of \>7% from pre-morbid weight, b. weight loss of \>7% from pre-morbid weight in the RCT phase.
Gastrointestinal disorders Nausea	3.1% 2/64 • Number of events 2 • 36 Weeks of RCT Phase Are based on items of the Udvalg for Kliniske Undersogelser Side effect scale (UKU), based on the following system: 1) Items with an increase of ≥2 points from baseline and items rated as a 3 on the UKU that were rated \<3 at baseline. Exceptions include the following items: 35=Weight Gain, 36= Weight Loss. 2) Weight gain and weight loss AEs were determined by the following definitions: a. weight gain of \>7% from pre-morbid weight, b. weight loss of \>7% from pre-morbid weight in the RCT phase.	6.5% 4/62 • Number of events 5 • 36 Weeks of RCT Phase Are based on items of the Udvalg for Kliniske Undersogelser Side effect scale (UKU), based on the following system: 1) Items with an increase of ≥2 points from baseline and items rated as a 3 on the UKU that were rated \<3 at baseline. Exceptions include the following items: 35=Weight Gain, 36= Weight Loss. 2) Weight gain and weight loss AEs were determined by the following definitions: a. weight gain of \>7% from pre-morbid weight, b. weight loss of \>7% from pre-morbid weight in the RCT phase.
Renal and urinary disorders Polyuria	1.6% 1/64 • Number of events 1 • 36 Weeks of RCT Phase Are based on items of the Udvalg for Kliniske Undersogelser Side effect scale (UKU), based on the following system: 1) Items with an increase of ≥2 points from baseline and items rated as a 3 on the UKU that were rated \<3 at baseline. Exceptions include the following items: 35=Weight Gain, 36= Weight Loss. 2) Weight gain and weight loss AEs were determined by the following definitions: a. weight gain of \>7% from pre-morbid weight, b. weight loss of \>7% from pre-morbid weight in the RCT phase.	0.00% 0/62 • 36 Weeks of RCT Phase Are based on items of the Udvalg for Kliniske Undersogelser Side effect scale (UKU), based on the following system: 1) Items with an increase of ≥2 points from baseline and items rated as a 3 on the UKU that were rated \<3 at baseline. Exceptions include the following items: 35=Weight Gain, 36= Weight Loss. 2) Weight gain and weight loss AEs were determined by the following definitions: a. weight gain of \>7% from pre-morbid weight, b. weight loss of \>7% from pre-morbid weight in the RCT phase.
Skin and subcutaneous tissue disorders Pruritus	0.00% 0/64 • 36 Weeks of RCT Phase Are based on items of the Udvalg for Kliniske Undersogelser Side effect scale (UKU), based on the following system: 1) Items with an increase of ≥2 points from baseline and items rated as a 3 on the UKU that were rated \<3 at baseline. Exceptions include the following items: 35=Weight Gain, 36= Weight Loss. 2) Weight gain and weight loss AEs were determined by the following definitions: a. weight gain of \>7% from pre-morbid weight, b. weight loss of \>7% from pre-morbid weight in the RCT phase.	1.6% 1/62 • Number of events 1 • 36 Weeks of RCT Phase Are based on items of the Udvalg for Kliniske Undersogelser Side effect scale (UKU), based on the following system: 1) Items with an increase of ≥2 points from baseline and items rated as a 3 on the UKU that were rated \<3 at baseline. Exceptions include the following items: 35=Weight Gain, 36= Weight Loss. 2) Weight gain and weight loss AEs were determined by the following definitions: a. weight gain of \>7% from pre-morbid weight, b. weight loss of \>7% from pre-morbid weight in the RCT phase.
Skin and subcutaneous tissue disorders Rash	3.1% 2/64 • Number of events 2 • 36 Weeks of RCT Phase Are based on items of the Udvalg for Kliniske Undersogelser Side effect scale (UKU), based on the following system: 1) Items with an increase of ≥2 points from baseline and items rated as a 3 on the UKU that were rated \<3 at baseline. Exceptions include the following items: 35=Weight Gain, 36= Weight Loss. 2) Weight gain and weight loss AEs were determined by the following definitions: a. weight gain of \>7% from pre-morbid weight, b. weight loss of \>7% from pre-morbid weight in the RCT phase.	0.00% 0/62 • 36 Weeks of RCT Phase Are based on items of the Udvalg for Kliniske Undersogelser Side effect scale (UKU), based on the following system: 1) Items with an increase of ≥2 points from baseline and items rated as a 3 on the UKU that were rated \<3 at baseline. Exceptions include the following items: 35=Weight Gain, 36= Weight Loss. 2) Weight gain and weight loss AEs were determined by the following definitions: a. weight gain of \>7% from pre-morbid weight, b. weight loss of \>7% from pre-morbid weight in the RCT phase.
Nervous system disorders Somnolence	6.2% 4/64 • Number of events 5 • 36 Weeks of RCT Phase Are based on items of the Udvalg for Kliniske Undersogelser Side effect scale (UKU), based on the following system: 1) Items with an increase of ≥2 points from baseline and items rated as a 3 on the UKU that were rated \<3 at baseline. Exceptions include the following items: 35=Weight Gain, 36= Weight Loss. 2) Weight gain and weight loss AEs were determined by the following definitions: a. weight gain of \>7% from pre-morbid weight, b. weight loss of \>7% from pre-morbid weight in the RCT phase.	3.2% 2/62 • Number of events 2 • 36 Weeks of RCT Phase Are based on items of the Udvalg for Kliniske Undersogelser Side effect scale (UKU), based on the following system: 1) Items with an increase of ≥2 points from baseline and items rated as a 3 on the UKU that were rated \<3 at baseline. Exceptions include the following items: 35=Weight Gain, 36= Weight Loss. 2) Weight gain and weight loss AEs were determined by the following definitions: a. weight gain of \>7% from pre-morbid weight, b. weight loss of \>7% from pre-morbid weight in the RCT phase.
Psychiatric disorders Tension	4.7% 3/64 • Number of events 3 • 36 Weeks of RCT Phase Are based on items of the Udvalg for Kliniske Undersogelser Side effect scale (UKU), based on the following system: 1) Items with an increase of ≥2 points from baseline and items rated as a 3 on the UKU that were rated \<3 at baseline. Exceptions include the following items: 35=Weight Gain, 36= Weight Loss. 2) Weight gain and weight loss AEs were determined by the following definitions: a. weight gain of \>7% from pre-morbid weight, b. weight loss of \>7% from pre-morbid weight in the RCT phase.	0.00% 0/62 • 36 Weeks of RCT Phase Are based on items of the Udvalg for Kliniske Undersogelser Side effect scale (UKU), based on the following system: 1) Items with an increase of ≥2 points from baseline and items rated as a 3 on the UKU that were rated \<3 at baseline. Exceptions include the following items: 35=Weight Gain, 36= Weight Loss. 2) Weight gain and weight loss AEs were determined by the following definitions: a. weight gain of \>7% from pre-morbid weight, b. weight loss of \>7% from pre-morbid weight in the RCT phase.
Infections and infestations Urinary tract infection	1.6% 1/64 • Number of events 1 • 36 Weeks of RCT Phase Are based on items of the Udvalg for Kliniske Undersogelser Side effect scale (UKU), based on the following system: 1) Items with an increase of ≥2 points from baseline and items rated as a 3 on the UKU that were rated \<3 at baseline. Exceptions include the following items: 35=Weight Gain, 36= Weight Loss. 2) Weight gain and weight loss AEs were determined by the following definitions: a. weight gain of \>7% from pre-morbid weight, b. weight loss of \>7% from pre-morbid weight in the RCT phase.	0.00% 0/62 • 36 Weeks of RCT Phase Are based on items of the Udvalg for Kliniske Undersogelser Side effect scale (UKU), based on the following system: 1) Items with an increase of ≥2 points from baseline and items rated as a 3 on the UKU that were rated \<3 at baseline. Exceptions include the following items: 35=Weight Gain, 36= Weight Loss. 2) Weight gain and weight loss AEs were determined by the following definitions: a. weight gain of \>7% from pre-morbid weight, b. weight loss of \>7% from pre-morbid weight in the RCT phase.
Investigations Weight decreased	4.7% 3/64 • Number of events 5 • 36 Weeks of RCT Phase Are based on items of the Udvalg for Kliniske Undersogelser Side effect scale (UKU), based on the following system: 1) Items with an increase of ≥2 points from baseline and items rated as a 3 on the UKU that were rated \<3 at baseline. Exceptions include the following items: 35=Weight Gain, 36= Weight Loss. 2) Weight gain and weight loss AEs were determined by the following definitions: a. weight gain of \>7% from pre-morbid weight, b. weight loss of \>7% from pre-morbid weight in the RCT phase.	4.8% 3/62 • Number of events 3 • 36 Weeks of RCT Phase Are based on items of the Udvalg for Kliniske Undersogelser Side effect scale (UKU), based on the following system: 1) Items with an increase of ≥2 points from baseline and items rated as a 3 on the UKU that were rated \<3 at baseline. Exceptions include the following items: 35=Weight Gain, 36= Weight Loss. 2) Weight gain and weight loss AEs were determined by the following definitions: a. weight gain of \>7% from pre-morbid weight, b. weight loss of \>7% from pre-morbid weight in the RCT phase.
Investigations Weight increased	14.1% 9/64 • Number of events 11 • 36 Weeks of RCT Phase Are based on items of the Udvalg for Kliniske Undersogelser Side effect scale (UKU), based on the following system: 1) Items with an increase of ≥2 points from baseline and items rated as a 3 on the UKU that were rated \<3 at baseline. Exceptions include the following items: 35=Weight Gain, 36= Weight Loss. 2) Weight gain and weight loss AEs were determined by the following definitions: a. weight gain of \>7% from pre-morbid weight, b. weight loss of \>7% from pre-morbid weight in the RCT phase.	4.8% 3/62 • Number of events 3 • 36 Weeks of RCT Phase Are based on items of the Udvalg for Kliniske Undersogelser Side effect scale (UKU), based on the following system: 1) Items with an increase of ≥2 points from baseline and items rated as a 3 on the UKU that were rated \<3 at baseline. Exceptions include the following items: 35=Weight Gain, 36= Weight Loss. 2) Weight gain and weight loss AEs were determined by the following definitions: a. weight gain of \>7% from pre-morbid weight, b. weight loss of \>7% from pre-morbid weight in the RCT phase.
Renal and urinary disorders Pollakiuria	1.6% 1/64 • Number of events 1 • 36 Weeks of RCT Phase Are based on items of the Udvalg for Kliniske Undersogelser Side effect scale (UKU), based on the following system: 1) Items with an increase of ≥2 points from baseline and items rated as a 3 on the UKU that were rated \<3 at baseline. Exceptions include the following items: 35=Weight Gain, 36= Weight Loss. 2) Weight gain and weight loss AEs were determined by the following definitions: a. weight gain of \>7% from pre-morbid weight, b. weight loss of \>7% from pre-morbid weight in the RCT phase.	0.00% 0/62 • 36 Weeks of RCT Phase Are based on items of the Udvalg for Kliniske Undersogelser Side effect scale (UKU), based on the following system: 1) Items with an increase of ≥2 points from baseline and items rated as a 3 on the UKU that were rated \<3 at baseline. Exceptions include the following items: 35=Weight Gain, 36= Weight Loss. 2) Weight gain and weight loss AEs were determined by the following definitions: a. weight gain of \>7% from pre-morbid weight, b. weight loss of \>7% from pre-morbid weight in the RCT phase.

Additional Information

Dr. George S. Alexopoulos

Weill Cornell Medicine

Phone: (914) 997-5767

Email: gsalexop@med.cornell.edu

Results disclosure agreements

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