- Change From Baseline on the 30-item Geriatric Depression Scale (GDS) [ Time Frame: baseline (Week 1), Week 13, Week 25 ] [ Designated as safety issue: No ]
The 30-item Geriatric Depression Scale (GDS) is a self-administered test of 30 questions to measure the severity of depression. The yes/no questions result in a range of scores from 0 (normal) to 30 (severe depression).
- Change From Baseline in the HAMD-17 Total Score, Subscales, and Individual Items [ Time Frame: baseline (Week 1), Week 13, Week 25 ] [ Designated as safety issue: No ]
Total Score assess depression severity (scores 0-52). Core, Maier and Bech subscales assess symptoms of depression (scores:0-20=Core; 0-24=Maier; 0-22=Bech). Anxiety/Somatization subscale assesses severity of anxiety (0-18). Retardation subscale assesses dysfunction in mood and work (0-14). Sleep subscale assesses insomnia (0-6). Individual item scores may range from 0-4 or 0-2. Higher numbers indicate more severe symptoms.
- Change From Baseline in the Brief Pain Inventory (BPI) Severity and Interference Scores [ Time Frame: baseline (Week 1), Week 13, Week 25 ] [ Designated as safety issue: No ]
The Brief Pain Inventory (severity and interference scales) (BPI) is a self-reported scale that measures the severity of pain and the interference of pain on function. Severity scores: 0 (no pain) to 10 (severe pain) on each question assessing worst pain, least pain, and average pain in past 24 hours, and pain right now. Interference scores: 0 (does not interfere) to 10 (completely interferes) on each question assessing interference of pain in past 24 hours for general activity, mood, walking ability, normal work, relations with other people, sleep, and enjoyment of life.
- Change From Baseline in the Numeric Rating Scales (NRS) for Pain Item Scores [ Time Frame: baseline (Week 1), Week 13, Week 25 ] [ Designated as safety issue: No ]
Numeric Rating Scales (Semantic Differential Scales) for Pain are 6 self-administered scales that assesses experience of overall pain, back pain, headache, shoulder pain, time in pain while awake, and pain interference with daily activities, during the past week. Each item is scored on a numeric 11-point semantic differential scale (0-10) from 0 = no pain to 10 = pain as severe as you can imagine; or 0 = none of the time to 10 = all of the time; or 0 = no interference to 10 = unable to do any activities at all.
- Patient's Global Impression of Improvement (PGI-I) at 13 Weeks and 25 Weeks [ Time Frame: Week 13, Week 25 ] [ Designated as safety issue: No ]
The PGI-Improvement scale is a patient-rated instrument that measures perceived improvement in symptoms. It is a 7-point scale where a score of 1 indicates that the patient is "very much improved," a score of 4 indicates that the patient has experienced "no change," and a score of 7 indicates that the patient is "very much worse."
- Change From Baseline in the Clinical Global Impression-Severity (CGI-S) [ Time Frame: baseline (Week 1), Week 13, Week 25 ] [ Designated as safety issue: No ]
Measures severity of illness at the time of assessment. Scores range from 1 (normal, not at all ill) to 7 (among the most extremely ill patients).
- Change From Baseline in the Mini-Mental State Exam (MMSE) [ Time Frame: baseline (Week 1), Week 9, Week 25 ] [ Designated as safety issue: No ]
Mini-Mental State Examination (MMSE)is a widely used rating measure of cognitive ability. Scores range from 0 to 30. The MMSE will be used to categorize patients as with or without dementia. Higher number indicates better cognitive ability. Patients with a MMSE score of 20 to 23 will be categorized as having mild dementia, while those with a score of ≥ 24 will be categorized as having no dementia.
- Change From Baseline in the Quality of Life, Enjoyment, and Satisfaction Questionnaire (Q-LES-Q-SF) [ Time Frame: baseline (Week 1), Week 13, Week 25 ] [ Designated as safety issue: No ]
The Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q-SF) measures the degree of enjoyment and satisfaction experienced in various areas of daily life. The short version is a self-administered 16 item scale evaluating satisfaction of general activities on a 5-point Likert scale that indicates the degree of enjoyment or satisfaction achieved during the past week (1 = very poor and 5 = very good).
- Probability of Remission as Measured by the HAMD-17 Total Score ≤7 and ≤10 [ Time Frame: Week 13, Week 25 ] [ Designated as safety issue: No ]
Remission (visitwise binary outcome, yes/no) is defined as HAMD-17 Total Score ≤7 and ≤10. HAMD-17 measures depression severity. The total score can range from 0 (normal) to 52 (severe depression). The visitwise probability of patients meeting criteria for remission (either Total Score ≤7 or ≤10) was analyzed using a categorical, pseudo-likelihood-based repeated measures approach. This analysis included the fixed, categorical effects of treatment, investigator, visit, and treatment-by-visit interaction, as well as the continuous, fixed covariate of baseline score.
- Probability of Response at Endpoint as Measured by ≥50% Improvement in the HAMD-17 Total Score [ Time Frame: Week 13, Week 25 ] [ Designated as safety issue: No ]
Response (visitwise binary outcome, yes/no) is defined as ≥ 50% reduction from baseline in the HAMD-17 total score. HAMD-17 measures depression severity. The total score can range from 0 (normal) to 52 (severe depression). The visitwise probability of patients meeting criteria for response was analyzed using a categorical, pseudo-likelihood-based repeated measures approach. This analysis included the fixed, categorical effects of treatment, investigator, visit, and treatment-by-visit interaction, as well as the continuous, fixed covariate of baseline score.
- Probability of Remission as Measured by the HAMD-17 Total Score ≤7 and ≤10 by Medical Comorbidity Severity as Assessed by the Cumulative Illness Rating Scale-Geriatric Version (CIRS-G) [ Time Frame: Week 13, Week 25 ] [ Designated as safety issue: No ]
Remission defined as HAMD-17 Total Score ≤7 and ≤10. HAMD-17 measures depression severity. Total score ranges: 0 (normal) to 52 (severe depression). Visitwise probability of patients achieving remission was analyzed using a categorical, pseudo-likelihood-based repeated measures approach. CIRS-G evaluates 14 organ-specific categories using a rating strategy of 0=no problems; 1=current mild problem/past significant problem; 2=moderate disability/morbidity; 3=severe/constant significant disability; and 4=extremely severe/immediate treatment required/end organ failure. Total score ranges: 0 to 56.
- Probability of Efficacy Onset as Measured by at Least 20% Sustained Reduction From Baseline in the HAMD-17 Maier Subscale at Week 3 [ Time Frame: Week 3 ] [ Designated as safety issue: No ]
Patients are considered to have met onset (visitwise binary outcome, yes/no) criteria at a particular visit if they had at least 20% reduction from baseline in the HAMD-17 Maier subscale at that visit and at all subsequent visits in the acute phase. Maier subscale measures core symptoms of depression and scores range from 0 (normal) to 24 (severe). The visitwise probability of patients meeting onset criteria was analyzed using a categorical, pseudo-likelihood-based repeated measures approach.
- Change From Baseline in Supine Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) [ Time Frame: baseline (Week 1), Week 13, Week 25 ] [ Designated as safety issue: Yes ]
- Change From Baseline in Pulse Rate [ Time Frame: baseline (Week 1), Week 13, Week 25 ] [ Designated as safety issue: Yes ]
- Change From Baseline in Weight [ Time Frame: baseline (Week 1), Week 13, Week 25 ] [ Designated as safety issue: Yes ]
- Number of Participants With Abnormal Vital Signs and Weight at Any Time During the Study [ Time Frame: Baseline (Week 1) through Week 25 ] [ Designated as safety issue: Yes ]
A patient has a treatment-emergent elevated supine systolic blood pressure if the value is ≥140 with an increase ≥10 from baseline. A patient has a treatment-emergent elevated supine diastolic blood pressure if the value is ≥90 with an increase ≥10 from baseline. A patient has a treatment-emergent elevated supine pulse if the value is ≥100 with an increase ≥10 from baseline.
A patient has abnormal weight change if the gain or loss is ≥7% compared to baseline.
- Number of Participants Experiencing Sustained Hypertension (SH) or Orthostatic Hypotension (OH) [ Time Frame: baseline (Week 1) through Week 25 ] [ Designated as safety issue: Yes ]
Sustained Hypertension is defined as supine systolic BP >= 140 (or diastolic BP >= 90) mm Hg and increase from baseline (highest value in baseline visit interval) >= 10 mm Hg for 3 or more consecutive visits in postbaseline visit interval. Orthostatic Hypotension is defined as standing diastolic BP at least 10 mm Hg less than the supine diastolic BP or the standing systolic BP at least 20 mm Hg less than the supine systolic BP at any time in postbaseline visit interval and a patient does not meet this criterion at any visit in baseline interval.
- Summary of Adverse Events and Serious Adverse Events Leading to Discontinuation [ Time Frame: baseline (Week 1) through Week 25 ] [ Designated as safety issue: Yes ]
Adverse Events and Serious Adverse Events leading to study discontinuation.
- Change From Baseline in Laboratory Values - Platelet Count [ Time Frame: baseline (Week 1), Week 13, Week 25 ] [ Designated as safety issue: Yes ]
Results are reported for laboratory analytes that exhibited statistically significantly different changes from baseline to endpoint between treatment groups. Statistical significance was considered at the 0.05 level.
- Change From Baseline in Laboratory Values - Uric Acid [ Time Frame: baseline (Week 1), Week 13, Week 25 ] [ Designated as safety issue: Yes ]
Results are reported for laboratory analytes that exhibited statistically significantly different changes from baseline to endpoint between treatment groups. Statistical significance was considered at the 0.05 level.
- Change From Baseline in Laboratory Values - Erythrocyte Count [ Time Frame: baseline (Week 1), Week 25 ] [ Designated as safety issue: Yes ]
Results are reported for laboratory analytes that exhibited statistically significantly different changes from baseline to endpoint between treatment groups. Statistical significance was considered at the 0.05 level.
- Change From Baseline in Laboratory Values - Hemoglobin, Mean Cell Hemoglobin Concentration (MCHC) [ Time Frame: baseline (Week 1), Week 25 ] [ Designated as safety issue: Yes ]
Results are reported for laboratory analytes that exhibited statistically significantly different changes from baseline to endpoint between treatment groups. Statistical significance was considered at the 0.05 level.
- Change From Baseline in Laboratory Values - Chloride and Fasting Glucose [ Time Frame: baseline (Week 1), Week 25 ] [ Designated as safety issue: Yes ]
Results are reported for laboratory analytes that exhibited statistically significantly different changes from baseline to endpoint between treatment groups. Statistical significance was considered at the 0.05 level.
- Number of Participants With Abnormal Laboratory Values - Low Leukocyte Count [ Time Frame: baseline (Week 1) through Week 13 ] [ Designated as safety issue: Yes ]
The number of participants with abnormal laboratory values at any time during the study period. Results are reported for laboratory analytes that exhibited statistically significantly different proportions of participants who had abnormal values between treatment groups. Statistical significance was considered at the 0.05 level. The lower limit of normal for leukocyte count is 3.8 Billion/Liter. Participants who had a value below that number were considered to have abnormally low leukocyte count.
- Change From Baseline in Electrocardiograms [ Time Frame: baseline (Week 1), Week 25 ] [ Designated as safety issue: No ]
The Electrocardiogram measures include the following time intervals: QT interval, QT Interval Corrected for Heart Rate Using Fridericia's Formula (QTcF), QT Interval Corrected for Heart Rate Using Bazett's Formula (QTcB), PR interval and QRS interval.
- Number of Participants With Successful Treatment Outcome [ Time Frame: Baseline (Week 1) through Week 25 ] [ Designated as safety issue: No ]
Successful treatment outcome defined as: Participant completed the study and being in remission (HAMD-17 Total score ≤7 and ≤10) at least for the last two visits (4 weeks)of the study. The HAMD-17 is used to assess the severity of depression. The total score ranges from 0 (not at all depressed) to 52 (severely depressed).
- Change From Baseline on Cognitive Test Scores: Verbal Learning and Recall Test (VLRT), Symbol Digit Substitution Test (SDST), Trail Making Test (Part B), 2-Digit Cancellation Test (2DCT), and the Composite Cognitive Score Derived From the Above Scores [ Time Frame: baseline (Week 1), Week 9, Week 25 ] [ Designated as safety issue: No ]
The cognitive assessment battery is composed of four tests: Verbal Learning (score 0-15)and Delayed Recall(score 0-15) test, SDST(Score 0-133),2DCT(score 0-40),Trail Making(Part B)(score 0-180).They are designed to challenge the patient's abilities in the following areas: verbal learning and memory; attention to visually presented material; and working memory and executive function. Composite Cognitive score(0-51)is derived from normalized individual test scores. For Trail Making Test,lower number indicates better cognition. For all other test scores,higher number indicates better cognition.
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