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

Adjunctive Treatment of Major Depressive Disorder Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03018340
• Other study ID #: ACP-103-042
• Status: Completed
• Phase: Phase 2
• Start date: December 2016
• Est. completion date: October 2018

Study information

• Verified date: October 2019
• Source: ACADIA Pharmaceuticals Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 207
• Est. completion date: October 2018
• Est. primary completion date: September 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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).

Related Conditions & MeSH terms

• Adjunctive Treatment of Major Depressive Disorder
• Depression
• Depressive Disorder
• Depressive Disorder, Major
• Disease

Intervention

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.

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.

Locations

Country	Name	City	State
United States	Emory University School of Medicine	Atlanta	Georgia
United States	Hassman Research Institute	Berlin	New Jersey
United States	UAB	Birmingham	Alabama
United States	Meridien Research	Bradenton	Florida
United States	Neuro-Behavioral Clinical Research	Canton	Ohio
United States	Carolina Clinical Trials, Inc.	Charleston	South Carolina
United States	Alam Medical Research, INC	Chicago	Illinois
United States	Ericksen Research & Development	Clinton	Utah
United States	FutureSearch Trials of Dallas, L.P.	Dallas	Texas
United States	UTSW	Dallas	Texas
United States	iResearch Atlanta	Decatur	Georgia
United States	Collaborative Neuroscience Network, LLC	Garden Grove	California
United States	Alexian Brothers Center for Psychiatric Research	Hoffman Estates	Illinois
United States	Baylor College of Medicine	Houston	Texas
United States	CNS Health care (Jacksonville)	Jacksonville	Florida
United States	Altea Research	Las Vegas	Nevada
United States	BTC of Lincoln	Lincoln	Rhode Island
United States	Meridien Research	Maitland	Florida
United States	Synergy San Diego	National City	California
United States	Manhattan Behavioral Medicine	New York	New York
United States	Pacific Research Partners, LLC	Oakland	California
United States	IPS Research	Oklahoma City	Oklahoma
United States	Rivus Wellness & Research Institute	Oklahoma City	Oklahoma
United States	CNS Health care (Orlando)	Orlando	Florida
United States	UPenn	Philadelphia	Pennsylvania
United States	Summit Research Network (Oregon)	Portland	Oregon
United States	Pillar Clinical Research	Richardson	Texas
United States	Finger Lakes Clinical Research	Rochester	New York
United States	Woodland Research Northwest	Rogers	Arkansas
United States	St. Louis Clinical Trials	Saint Louis	Missouri
United States	Schuster Medical Research Institute	Sherman Oaks	California
United States	Viking Clinical Research	Temecula	California
United States	Collaborative Neuroscience Network, LLC	Torrance	California
United States	Pacific Clinical Research Medical Group	Upland	California
United States	IPC Research	Waukesha	Wisconsin
United States	KUMC	Wichita	Kansas

Sponsors (1)

Lead Sponsor	Collaborator
ACADIA Pharmaceuticals Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline to Week 5 in the HAMD-17 Total Score	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.	Baseline, 5 weeks and 10 weeks during Stage 1 and Stage 2, respectively
Secondary	Change From Baseline to Week 5 in the SDS Total Score	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.	Baseline, 5 weeks and 10 weeks during Stage 1 and Stage 2, respectively
Secondary	Treatment Response and Remission Rates at the End of 5-week Treatment Period	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.	Baseline, 5 weeks and 10 weeks during Stage 1 and Stage 2, respectively
Secondary	Change From Baseline to Week 5 in CGI-S Total Score	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.	Baseline, 5 weeks and 10 weeks during Stage 1 and Stage 2, respectively
Secondary	CGI-I Score at Week 5	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.	Baseline, 5 weeks and 10 weeks during Stage 1 and Stage 2, respectively
Secondary	Change From Baseline to Week 5 in SF-12 Score	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.	Baseline, 5 weeks and 10 weeks during Stage 1 and Stage 2, respectively
Secondary	Change From Baseline to Week 5 in DAI-10 Score	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.	Baseline, 5 weeks and 10 weeks during Stage 1 and Stage 2, respectively
Secondary	Change From Baseline to Week 5 in KSS Score	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.	Baseline, 5 weeks and 10 weeks during Stage 1 and Stage 2, respectively
Secondary	Change From Baseline to Week 5 in MGH-SFI Score	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.	Baseline, 5 weeks and 10 weeks during Stage 1 and Stage 2, respectively
Secondary	Change From Baseline to Week 5 in BIS-11 Score	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.	Baseline, 5 weeks and 10 weeks during Stage 1 and Stage 2, respectively
Secondary	Change From Baseline to Week 5 in SIS Score	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.	Baseline, 5 weeks and 10 weeks during Stage 1 and Stage 2, respectively