Adjunctive Pimavanserin in Subjects With Major Depressive Disorder and Inadequate Response to Antidepressant Treatment

Phase 3, Multicenter, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of Adjunctive Pimavanserin in Subjects With Major Depressive Disorder and Inadequate Response to Antidepressant Treatment (ACP-103-054/059)

Status

Completed

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT03968159

Enrollment

298

Registered

2019-05-30

Start date

2019-04-25

Completion date

2020-05-29

Last updated

2021-11-17

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Adjunctive Treatment of Major Depressive Disorder

Brief summary

To evaluate the efficacy and safety of adjunctive pimavanserin compared to placebo in subjects with major depressive disorder who have an inadequate response to antidepressant therapy

Detailed description

Two separate studies, idential in design, were planned and initiated under 2 protocol IDs and NCTs, i.e. study ACP-103-54 (NCT03999918) and ACP-103-059 (NCT03968159). In March 2020, recruitment of new patients was paused due to the emerging coronavirus disease 2019 (COVID-19) pandemic. At that point in time, about half of the planned patients had been randomized. The Sponsor decided to combine the 2 identically designed trials, with a prespecified combined statistical analysis plan. As a result, both trials were closed and proceeded with database lock and statistical analysis of the combined data. No further patients were enrolled. This entry now includes the combined data of studies ACP-103-054 and ACP-103-059.

Interventions

DRUGPimavanserin

Pimavanserin 34 mg (provided as 2×17 mg tablets) administered orally as a single dose once daily

DRUGPlacebo

Placebo (2×placebo tablets \[size- and color-matched to pimavanserin\]) administered orally as a single dose once daily

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

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: 1. Citalopram 2. Escitalopram 3. Paroxetine 4. Fluoxetine 5. Sertraline 6. Duloxetine 7. Venlafaxine 8. Desvenlafaxine 9. Venlafaxine XR 4. Inadequate response to SSRI/SNRI antidepressant treatment is confirmed 5. If the subject is female, she must not be pregnant or breastfeeding. She must also be of non-childbearing potential OR must agree to use acceptable methods of contraception

Exclusion criteria

1. Has a history of psychotic disorder or is currently being treated or requires treatment for post-traumatic stress disorder, acute stress disorder, panic disorder, or obsessive compulsive disorder 2. Has current evidence of delirium or an unstable neurological, cardiovascular, respiratory, gastrointestinal, renal, hepatic, hematologic, or other medical disorder, including cancer or malignancies that would affect the patient's ability to participate in the program 3. Has a known history or symptoms of long QT syndrome 4. Is determined to be inappropriate for the study for any reason Additional inclusion/

Design outcomes

Primary

Measure	Time frame	Description
Change From Baseline to Week 5 in Hamilton Depression Scale (17 Items) (HAMD-17) Total Score	Baseline, Week 5	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. The total score ranging from 0 to 52 will be calculated as the sum of the scores for all 17 items. Higher total scores denote more severe depression.

Secondary

Measure	Time frame	Description
Change From Baseline to Week 5 in Sheehan Disability Scale (SDS) Score	Baseline, 5 weeks	The SDS is a 3-item subject-facing questionnaire used to evaluate impairments in the domains of work, social life/leisure, and family life/home responsibility. Subjects rate each item using an 11-point scale ranging from 0 (not at all) to 10 (extremely). Higher scores denote greater disability.
Change From Baseline to Week 5 in the Changes in Sexual Functioning Questionnaire Short Form	Baseline, 5 weeks	The CSFQ-14 is a 14-item version of the CSFQ. This is a patient-facing questionnaire, with a male version and a female version. The total score ranging from 14 to 70 will be calculated as the sum of the scores for all 14 items. Higher total scores denote better sexual functioning.
Change From Baseline to Week 5 in Karolinska Sleepiness Scale (KSS) Score	Baseline, 5 weeks	The KSS is a scale that measures the subject's drowsiness and is frequently used in studies measuring subjective sleepiness. Scoring is based on a 9-point verbally anchored scale going from 1 = extremely alert to 9 = very sleepy, great effort to keep awake, fighting sleep. Higher scores denote more drowsiness.
Change From Baseline to Week 1 in the HAMD-17 Total Score	Baseline, 1 week	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. The total score ranging from 0 to 52 will be calculated as the sum of the scores for all 17 items. Higher total scores denote more severe depression.
Change From Baseline to Week 5 in Clinical Global Impression-Severity (CGI-S) Score for Depressive Symptoms	Baseline, 5 weeks	The CGI-S rates the severity of a subject's depression over the past 7 days and the score ranges from 1 to 7. Higher CGI-S scores denote more severe depression.
Change From Baseline to Week 5 in the Hamilton Depression (HAMD) Anxiety/Somatization Factor Score	Baseline, 5 weeks	The Anxiety/Somatization factor of the HAMD-17 includes 6 items: psychic anxiety, somatic anxiety, gastrointestinal somatic symptoms, general somatic symptoms, hypochondriasis, and insight. The HAMD-17 Anxiety/Somatization factor score ranging from 0 to 18 will be calculated as the sum of the scores for the 6 items. Higher scores denote more severe anxiety/somatization condition.
Change From Baseline to Week 5 in the Barratt Impulsiveness Scale (BIS-11)	Baseline, 5 weeks	The BIS-11 is a questionnaire designed to assess the personality/behavioral construct of impulsiveness. It is composed of 30 items describing common impulsive or non-impulsive (reverse scored items: 1, 7, 8, 9, 10, 12, 13, 15, 20, 29, and 30) behaviors and preferences. Items are scored on the following 4-point scale: Rarely/Never = 1; Occasionally = 2; Often = 3; Almost Always/Always = 4. For reverse scored items, a response of 1 is recoded to 4; 2 is recoded to 3; 3 is recoded to 2; and 4 is recoded to 1. The BIS-11 score ranging from 30 to 120 will be calculated as the sum of the scores for all 30 items. Higher scores denote more impulsiveness.
Clinical Global Impression-Improvement (CGI-I) Score for Depressive Symptoms at Week 5	Baseline, 5 weeks	The CGI-I rates the change in a subject's depression over the past 7 days relative to the subject's symptoms at Baseline and the score ranges from 1 to 7. Higher CGI-I scores denote less improvement in Depression.
Treatment Responder and Treatment Remission Rates at Week 5	Baseline, 5 weeks	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. The total score ranging from 0 to 52 will be calculated as the sum of the scores for all 17 items. Treatment response is defined as a reduction from Baseline in HAMD-17 total score of 50% or more. Treatment remission is defined as a HAMD-17 total score ≤7.

Countries

Finland, Poland, Russia, Serbia, Slovakia, South Africa, Ukraine, United Kingdom, United States

Participant flow

Recruitment details

The study was performed in patients with with major depressive disorder who had an inadequate response to antidepressant treatment.

Pre-assignment details

During the screening period, patients were assessed for study eligibility, and prohibited medications were discontinued when medically appropriate.

Participants by arm

Arm	Count
Pimavanserin Pimavanserin 34 mg administered orally as a single dose once daily	148
Placebo Placebo tablets administered orally as a single dose once daily	150
Total	298

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Adverse Event	4	4
Overall Study	Lack of Efficacy	0	1
Overall Study	Lost to Follow-up	1	1
Overall Study	Not further specified	2	0
Overall Study	Protocol Violation	2	2
Overall Study	Use of prohibited medication	0	1
Overall Study	Withdrawal by Subject	4	6

Baseline characteristics

Characteristic	Pimavanserin	Placebo	Total
Age, Continuous	47.2 years STANDARD_DEVIATION 13.45	44.5 years STANDARD_DEVIATION 14.92	45.8 years STANDARD_DEVIATION 14.25
Race (NIH/OMB) American Indian or Alaska Native	1 Participants	0 Participants	1 Participants
Race (NIH/OMB) Asian	1 Participants	2 Participants	3 Participants
Race (NIH/OMB) Black or African American	6 Participants	8 Participants	14 Participants
Race (NIH/OMB) More than one race	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Unknown or Not Reported	3 Participants	3 Participants	6 Participants
Race (NIH/OMB) White	137 Participants	137 Participants	274 Participants
Region of Enrollment Finland	3 participants	9 participants	12 participants
Region of Enrollment Poland	12 participants	6 participants	18 participants
Region of Enrollment Russia	18 participants	12 participants	30 participants
Region of Enrollment Serbia	9 participants	8 participants	17 participants
Region of Enrollment Slovakia	4 participants	3 participants	7 participants
Region of Enrollment South Africa	1 participants	1 participants	2 participants
Region of Enrollment Ukraine	14 participants	16 participants	30 participants
Region of Enrollment United Kingdom	13 participants	21 participants	34 participants
Region of Enrollment United States	74 participants	74 participants	148 participants
Sex: Female, Male Female	96 Participants	112 Participants	208 Participants
Sex: Female, Male Male	52 Participants	38 Participants	90 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	0 / 148	0 / 150
other Total, other adverse events	54 / 148	43 / 150
serious Total, serious adverse events	2 / 148	2 / 150

Outcome results

Primary

Change From Baseline to Week 5 in Hamilton Depression Scale (17 Items) (HAMD-17) Total Score

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. The total score ranging from 0 to 52 will be calculated as the sum of the scores for all 17 items. Higher total scores denote more severe depression.

Time frame: Baseline, Week 5