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

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ClinicalTrials.gov Identifier: NCT03018340
Recruitment Status : Completed
First Posted : January 12, 2017
Results First Posted : November 14, 2019
Last Update Posted : November 14, 2019
Sponsor:
Information provided by (Responsible Party):
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

Condition or disease Intervention/treatment Phase
Adjunctive Treatment of Major Depressive Disorder Drug: Pimavanserin Other: Placebo Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 207 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase 2, Multicenter, Randomized, Double-blind, Placebo-controlled, Study to Evaluate the Efficacy and Safety of Adjunctive Pimavanserin in Major Depressive Disorder
Actual Study Start Date : December 2016
Actual Primary Completion Date : September 2018
Actual Study Completion Date : October 2018

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Pimavanserin 34 mg + SSRI/SNRI
Drug- 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.
Drug: Pimavanserin
Pimavanserin 34 mg, tablet, 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.

Placebo Comparator: Placebo + SSRI/SNRI
Placebo, 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.
Other: Placebo
Placebo, 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.




Primary Outcome Measures :
  1. Change From Baseline to Week 5 in the HAMD-17 Total Score [ Time Frame: Baseline, 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 :
  1. Change From Baseline to Week 5 in the SDS Total Score [ Time Frame: Baseline, 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.

  2. Treatment Response and Remission Rates at the End of 5-week Treatment Period [ Time Frame: Baseline, 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.


  3. Change From Baseline to Week 5 in CGI-S Total Score [ Time Frame: Baseline, 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.

  4. CGI-I Score at Week 5 [ Time Frame: Baseline, 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.

  5. Change From Baseline to Week 5 in SF-12 Score [ Time Frame: Baseline, 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.

  6. Change From Baseline to Week 5 in DAI-10 Score [ Time Frame: Baseline, 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.

  7. Change From Baseline to Week 5 in KSS Score [ Time Frame: Baseline, 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.

  8. Change From Baseline to Week 5 in MGH-SFI Score [ Time Frame: Baseline, 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.

  9. Change From Baseline to Week 5 in BIS-11 Score [ Time Frame: Baseline, 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.

  10. Change From Baseline to Week 5 in SIS Score [ Time Frame: Baseline, 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.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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).


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03018340


  Show 36 Study Locations
Sponsors and Collaborators
ACADIA Pharmaceuticals Inc.
  Study Documents (Full-Text)

Documents provided by ACADIA Pharmaceuticals Inc.:
Study Protocol  [PDF] April 26, 2017
Statistical Analysis Plan  [PDF] August 21, 2018


Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: ACADIA Pharmaceuticals Inc.
ClinicalTrials.gov Identifier: NCT03018340     History of Changes
Other Study ID Numbers: ACP-103-042
First Posted: January 12, 2017    Key Record Dates
Results First Posted: November 14, 2019
Last Update Posted: November 14, 2019
Last Verified: October 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Additional relevant MeSH terms:
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Depressive Disorder
Depression
Depressive Disorder, Major
Mood Disorders
Mental Disorders
Behavioral Symptoms
Norepinephrine
Pimavanserin
Antidepressive Agents
Serotonin
Serotonin Uptake Inhibitors
Psychotropic Drugs
Adrenergic alpha-Agonists
Adrenergic Agonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Sympathomimetics
Autonomic Agents
Peripheral Nervous System Agents
Vasoconstrictor Agents
Serotonin Receptor Agonists
Serotonin Agents
Neurotransmitter Uptake Inhibitors
Membrane Transport Modulators
Antiparkinson Agents
Anti-Dyskinesia Agents
Antipsychotic Agents
Tranquilizing Agents