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Study to Evaluate the Efficacy and Safety of Adjunctive Pimavanserin in Major Depressive Disorder (CLARITY)

Phase 2
Completed
Conditions
Adjunctive Treatment of Major Depressive Disorder
Interventions
Other: Placebo
Registration Number
NCT03018340
Lead Sponsor
ACADIA Pharmaceuticals Inc.
Brief Summary

To assess the efficacy of pimavanserin compared to placebo when given adjunctively to a selective serotonin reuptake inhibitor (SSRI)/serotonin-norepinephrine reuptake inhibitor (SNRI) antidepressant as treatment of patients with Major Depressive Disorder (MDD) and an inadequate response to antidepressant therapy

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
207
Inclusion Criteria
  1. Adult patients, aged 18 years and above

  2. A clinical diagnosis of major depressive disorder (MDD)

  3. Is being treated with one of the following SSRI or SNRI antidepressants as monotherapy:

    • Citalopram
    • Escitalopram
    • Paroxetine
    • Fluoxetine
    • Sertraline
    • Duloxetine
    • Venlafaxine
    • Desvenlafaxine
    • Venlafaxine XR
  4. Has a history of inadequate response to antidepressant treatments

Exclusion Criteria
  1. Patient has a psychotic disorder other than MDD
  2. Patient has current evidence of a serious and/or unstable neurologic, cardiovascular, respiratory, gastrointestinal, renal, hepatic, hematologic, or other medical disorder, including cancer or malignancies, which would affect the patient's ability to participate in the program
  3. Patient has a history or symptoms of long QT syndrome

Patients will be evaluated at screening to ensure that all criteria for study participation are met. Patients may be excluded from the study based on these assessments (and specifically if it is determined that their baseline health and psychiatric condition do not meet all pre-specified entry criteria).

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Placebo + SSRI/SNRIPlaceboPlacebo, taken as two tablets, once daily by mouth All patients continued to receive selective serotonin reuptake inhibitor/serotonin norepinephrine reuptake inhibitor (SSRI/SNRI) antidepressants at a stable dose for the duration of the study.
Pimavanserin 34 mg + SSRI/SNRIPimavanserinDrug- pimavanserin, 34 mg, taken as two 17 mg tablets, once daily by mouth All patients continued to receive selective serotonin reuptake inhibitor/serotonin norepinephrine reuptake inhibitor (SSRI/SNRI) antidepressants at a stable dose for the duration of the study.
Primary Outcome Measures
NameTimeMethod
Change From Baseline to Week 5 in the HAMD-17 Total ScoreBaseline, 5 weeks and 10 weeks during Stage 1 and Stage 2, respectively

The Hamilton Rating Scale for Depression (HAMD-17) is a 17-item scale to assess depression. The HAMD-17 consists of 8 items with a score on a 3 point scale and 9 items with a score on a 5 point scale. Each item is rated from least (0) to most frequent or most severe, as applicable, with highest scores of 2 to 4, depending on the item. Items are summed up to calculate the HAMD-17 total score. The total score ranges from 0 to 52. A higher total score indicates more severe depression.

Secondary Outcome Measures
NameTimeMethod
Change From Baseline to Week 5 in SF-12 ScoreBaseline, 5 weeks and 10 weeks during Stage 1 and Stage 2, respectively

The 12-Item Short Form Health Survey is a patient-reported outcome measure that addresses 8 domains of physical functioning, role - physical, bodily pain, general health perceptions, vitality, social functioning, role - emotional, and mental health. Composite scores were obtained representing physical health and mental health composite summaries, Physical Component Summary (PCS) and Mental Component Summary (MCS), respectively. An algorithm was used to generate PCS and MCS for comparison to normative data. In normative data, the mean score was set to 50; thus, scores \>50 indicate better physical or mental health than the mean and scores \<50 indicate worse health. A higher score is indicative of a better health state.

Change From Baseline to Week 5 in DAI-10 ScoreBaseline, 5 weeks and 10 weeks during Stage 1 and Stage 2, respectively

The Drug Attitude Inventory-10 is a 6-item patient-facing questionnaire to evaluate a patient's perceptions and experiences of treatment. It contains 6 items that a patient who is fully adherent to prescribed medication would answer as "True," and 4 items that a patient who is fully adherent would rate as "False." Scores are allocated to each answer and the total score is calculated as the sum. A correct answer is scored +1 and an incorrect answer is scored -1. The total score ranges from -10 to 10 and is the sum of pluses and minuses. A positive total score indicates a positive subjective response (adherent) and a negative total score indicates a negative subjective response (nonadherent). Higher scores denoted better adherence.

Change From Baseline to Week 5 in the SDS Total ScoreBaseline, 5 weeks and 10 weeks during Stage 1 and Stage 2, respectively

The Sheehan Disability Scale is a 3-item patient-facing 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 scale from 0 (no impairment) to 10 (most severe). The total SDS score ranges from 0 to 10. It is calculated as the arithmetic mean of the scores for all 3 items. A higher score indicates greater disability.

Treatment Response and Remission Rates at the End of 5-week Treatment PeriodBaseline, 5 weeks and 10 weeks during Stage 1 and Stage 2, respectively

The Hamilton Rating Scale for Depression (HAMD-17) is a 17-item scale to assess depression. Each item is rated from least (0) to most frequent or most severe, as applicable, with highest scores of 2 to 4 depending on the item. Items are summed up to calculate the HAMD-17 total score. A higher total score indicates more severe depression.

Treatment response was defined as a reduction from Baseline in HAMD-17 total score of \>=50%.

Remission was defined as a HAMD-17 total score \<=7.

Change From Baseline to Week 5 in CGI-S Total ScoreBaseline, 5 weeks and 10 weeks during Stage 1 and Stage 2, respectively

The Clinical Global Impression-Severity Scale is a 1-item scale, used to rate the severity of the disorder from 0 (not assessed) to 7 (among the most extremely ill patients). A higher CGI-I score denotes more severe depression.

CGI-I Score at Week 5Baseline, 5 weeks and 10 weeks during Stage 1 and Stage 2, respectively

The Clinical Global Impression- Improvement scale is a 1-item scale, used to rate the global improvement of the patient since beginning of the study from 0 (not assessed) to 7 (very much worse). A higher CGI-I score denotes less improvement in depression.

Change From Baseline to Week 5 in KSS ScoreBaseline, 5 weeks and 10 weeks during Stage 1 and Stage 2, respectively

The Karolinska Sleepiness Scale is a patient-facing 1-item scale that measures the patient's drowsiness. Scoring is based on a 9-point verbally anchored scale ranging from "extremely alert" (1) to "very sleepy, great effort to keep awake, fighting sleep" (9). Higher scores denote more drowsiness.

Change From Baseline to Week 5 in MGH-SFI ScoreBaseline, 5 weeks and 10 weeks during Stage 1 and Stage 2, respectively

The Massachusetts General Hospital Sexual Functioning Index is a patient-facing questionnaire that quantifies sexual dysfunction into 5 functional domains ("interest in sex," "sexual arousal," "ability to achieve orgasm," "ability to maintain erection" \[males only\], and "sexual satisfaction"). Patients rate each item using a 6-point scale ranging from 1 (good function) to 6 (poor function). The MGH-SFI score is calculated as the arithmetic mean of the item scores for the 5 domains. The mean MGH-SFI score ranges from a minimum value of 1 to a maximum value of 6. Higher scores denotes worse sexual dysfunction.

Change From Baseline to Week 5 in BIS-11 ScoreBaseline, 5 weeks and 10 weeks during Stage 1 and Stage 2, respectively

The Barratt Impulsiveness Scale-11 is a questionnaire for assessment of the personality/behavioral construct of impulsiveness. It is composed of 30 items describing common impulsive or non-impulsive (for reverse scored items) behaviors and preferences. Items are scored on a 4-point scale from Rarely/Never (1) to Almost Always/Always (4). Items are summed up to calculate the total score. The BIS-11 total score ranges from 30 to 120. Higher scores denotes more impulsiveness.

Change From Baseline to Week 5 in SIS ScoreBaseline, 5 weeks and 10 weeks during Stage 1 and Stage 2, respectively

The Sheehan Irritability Scale is a 7-item patient-reported outcome measure to measure the frequency, severity, and impairment associated with irritability in psychiatric patients. It includes items on: irritability, frustration, edginess/ impatience/ overreaction, moodiness, anger with self, anger with others, and temper. Items are answered on an 11-point rating scale where higher scores indicated greater severity (0=not at all, 10=extremely). Item responses are summed into a total score (range=0-70). Higher scores mean higher irritability.

Trial Locations

Locations (34)

Carolina Clinical Trials, Inc.

🇺🇸

Charleston, South Carolina, United States

Woodland Research Northwest

🇺🇸

Rogers, Arkansas, United States

Altea Research

🇺🇸

Las Vegas, Nevada, United States

Hassman Research Institute

🇺🇸

Berlin, New Jersey, United States

FutureSearch Trials of Dallas, L.P.

🇺🇸

Dallas, Texas, United States

UTSW

🇺🇸

Dallas, Texas, United States

Baylor College of Medicine

🇺🇸

Houston, Texas, United States

IPC Research

🇺🇸

Waukesha, Wisconsin, United States

Viking Clinical Research

🇺🇸

Temecula, California, United States

Synergy San Diego

🇺🇸

National City, California, United States

Schuster Medical Research Institute

🇺🇸

Sherman Oaks, California, United States

Collaborative Neuroscience Network, LLC

🇺🇸

Torrance, California, United States

Meridien Research

🇺🇸

Maitland, Florida, United States

Pacific Research Partners, LLC

🇺🇸

Oakland, California, United States

Pacific Clinical Research Medical Group

🇺🇸

Upland, California, United States

Emory University School of Medicine

🇺🇸

Atlanta, Georgia, United States

CNS Health care (Jacksonville)

🇺🇸

Jacksonville, Florida, United States

CNS Health care (Orlando)

🇺🇸

Orlando, Florida, United States

Alam Medical Research, INC

🇺🇸

Chicago, Illinois, United States

Alexian Brothers Center for Psychiatric Research

🇺🇸

Hoffman Estates, Illinois, United States

iResearch Atlanta

🇺🇸

Decatur, Georgia, United States

KUMC

🇺🇸

Wichita, Kansas, United States

St. Louis Clinical Trials

🇺🇸

Saint Louis, Missouri, United States

Finger Lakes Clinical Research

🇺🇸

Rochester, New York, United States

Manhattan Behavioral Medicine

🇺🇸

New York, New York, United States

Neuro-Behavioral Clinical Research

🇺🇸

Canton, Ohio, United States

UPenn

🇺🇸

Philadelphia, Pennsylvania, United States

BTC of Lincoln

🇺🇸

Lincoln, Rhode Island, United States

Pillar Clinical Research

🇺🇸

Richardson, Texas, United States

Ericksen Research & Development

🇺🇸

Clinton, Utah, United States

UAB

🇺🇸

Birmingham, Alabama, United States

IPS Research

🇺🇸

Oklahoma City, Oklahoma, United States

Rivus Wellness & Research Institute

🇺🇸

Oklahoma City, Oklahoma, United States

Summit Research Network (Oregon)

🇺🇸

Portland, Oregon, United States

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