Efficacy and Safety of Adjunctive Pimavanserin for the Treatment of Schizophrenia (ENHANCE-1)

May 29, 2020 updated by: ACADIA Pharmaceuticals Inc.

A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Adjunctive Pimavanserin for the Treatment of Schizophrenia

To evaluate the efficacy and safety of adjunctive pimavanserin compared with adjunctive placebo in the treatment of schizophrenia

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

396

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Bulgaria
      • Burgas, Bulgaria, 8000
      • Pazardzhik, Bulgaria, 4400
      • Plovdiv, Bulgaria, 4000
      • Sofia, Bulgaria, 1431
      • Sofia, Bulgaria, 1606
      • Sofia, Bulgaria, 1202
      • Sofia, Bulgaria, 1408
      • Sofia, Bulgaria, 1680
      • Targovishte, Bulgaria, 7700
      • Tserova Koria, Bulgaria, 5047
      • Varna, Bulgaria, 9020
      • Veliko Tarnovo, Bulgaria, 5000
      • Veliko Tarnovo, Bulgaria, 5047
      • Vratsa, Bulgaria, 3000
  • Canada
      • Toronto, Canada, M6J 1H4
    • Ontario
      • Chatham, Ontario, Canada, N7L1C1
    • Quebec
      • Montréal, Quebec, Canada, H3A 1A1
  • Czechia
      • Hradec Králové, Czechia, 503 41
      • Plzen, Czechia, 312 00
      • Praha 10, Czechia, 100 00
      • Praha 10, Czechia, 106 00
      • Praha 6, Czechia, 160 00
      • Říčany, Czechia, 251 01
  • Hungary
      • Debrecen, Hungary, 4032
      • Pecs, Hungary, 7633
    • Bács-Kiskun Megya
      • Kalocsa, Bács-Kiskun Megya, Hungary, 6300
    • Pest Megye
      • Budapest, Pest Megye, Hungary, 1036
      • Budapest, Pest Megye, Hungary, 1083
  • Lithuania
      • Kaunas, Lithuania, 48259
      • Kaunas, Lithuania, 44279
      • Kaunas, Lithuania, 50185
      • Silute, Lithuania, 99142
      • Vilnius, Lithuania, 09112
  • Poland
      • Białystok, Poland, 15 756
      • Bydgoszcz, Poland, 85 080
      • Lublin, Poland, 20 080
      • Lublin, Poland, 20 582
      • Pruszcz Gdański, Poland, 83 000
  • Russian Federation
      • Arkhangelsk, Russian Federation, 163530
      • Moscow, Russian Federation, 115522
      • Saint Petersburg, Russian Federation, 197341
      • Saint Petersburg, Russian Federation, 192019
      • Saint-Petersburg, Russian Federation, 192019
      • Saint-Petersburg, Russian Federation, 193167
      • Saint-Petersburg, Russian Federation, 195112
      • Saint-Petersburg, Russian Federation, 190121
      • Samara, Russian Federation, 443016
      • Smolensk, Russian Federation, 214019
      • Stavropol', Russian Federation, 355038
      • Voronezh, Russian Federation, 394024
      • Yaroslavl, Russian Federation, 150003
    • Leningrad
      • Roshchino, Leningrad, Russian Federation, 188820
    • Lipetsk
      • Plekhanovo, Lipetsk, Russian Federation, 399313
    • Stavropol
      • Tonnel'nyy, Stavropol, Russian Federation, 357034
  • Serbia
      • Belgrade, Serbia, 11000
      • Belgrade, Serbia, 11 000
      • Kovin, Serbia, 26 220
      • Kragujevac, Serbia, 34 000
      • Nis, Serbia, 18 000
  • Ukraine
      • Dnipro, Ukraine, 49005
      • Hlevakha, Ukraine, 08631
      • Kharkiv, Ukraine, 61068
      • Kyiv, Ukraine, 04080
      • Kyiv, Ukraine, 01133
      • Kyiv, Ukraine, 02192
      • Kyiv, Ukraine, 08631
      • Odesa, Ukraine, 65014
      • Oleksandrivka, Ukraine, 67513
      • Poltava, Ukraine, 36013
      • Smila, Ukraine, 20708
      • Smila, Ukraine, 08631
      • Vinnytsia, Ukraine, 21005
    • Vil. Stepanivka
      • Kherson, Vil. Stepanivka, Ukraine, 73488
  • United States
    • Arizona
      • Phoenix, Arizona, United States, 85012
    • Arkansas
      • Little Rock, Arkansas, United States, 72211
      • Rogers, Arkansas, United States, 72758
    • California
      • Bellflower, California, United States, 90706
      • Cerritos, California, United States, 90703
      • Culver City, California, United States, 90230
      • Lemon Grove, California, United States, 91945
      • Long Beach, California, United States, 90822
      • San Diego, California, United States, 92103
      • San Diego, California, United States, 92123
      • Santa Ana, California, United States, 92705
      • Torrance, California, United States, 90502
    • Florida
      • Boca Raton, Florida, United States, 33431
      • Lauderhill, Florida, United States, 33319
      • Miami, Florida, United States, 33122
    • Georgia
      • Atlanta, Georgia, United States, 30328
      • Atlanta, Georgia, United States, 30331
    • Illinois
      • Chicago, Illinois, United States, 60611
      • Chicago, Illinois, United States, 60612
      • Hoffman Estates, Illinois, United States, 60169
    • Louisiana
      • Lake Charles, Louisiana, United States, 70629
    • Maryland
      • Catonsville, Maryland, United States, 21228
    • Michigan
      • Ann Arbor, Michigan, United States, 48105
    • Nevada
      • Las Vegas, Nevada, United States, 89102
    • New Jersey
      • Berlin, New Jersey, United States, 08009
    • New York
      • Cedarhurst, New York, United States, 11516
      • Jamaica, New York, United States, 11432
      • Rochester, New York, United States, 14618
    • North Carolina
      • Charlotte, North Carolina, United States, 28211
    • Ohio
      • Dayton, Ohio, United States, 45417
    • South Carolina
      • Charleston, South Carolina, United States, 29407
    • Texas
      • Richardson, Texas, United States, 75080
    • Utah
      • Salt Lake City, Utah, United States, 84105

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 55 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Adults patients, between 18 and 55 years of age
  2. A clinical diagnosis of schizophrenia with a minimum duration of 1 year

  3. The main background antipsychotic with which the subject is being treated must be one of the antipsychotics listed below:

    • Aripiprazole

    • Aripiprazole long-acting injectables:

      • Abilify Maintena®
      • Aristada®
    • Risperidone
    • Risperidone long-acting injection
    • Olanzapine
    • Lurasidone
    • Cariprazine
    • Brexpiprazole
    • Asenapine
  4. Has had a partial but inadequate response to antipsychotic treatment
  5. Has a history of response to antipsychotic treatment other than clozapine

Exclusion Criteria:

  1. Patient has a psychiatric disorder other than schizophrenia
  2. Patient has a history of resistance to antipsychotic treatment

  3. A urine drug screen (UDS) result at Baseline that indicates the presence of any tested prohibited substance of potential abuse, except marijuana

    a. Patients with a result indicating the presence of marijuana are permitted if they agree to abstain from marijuana use during the study and the medical monitor approves the subject's participation

  4. Patient has current evidence of a serious and/or unstable psychiatric, 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
  5. Patient has had a myocardial infarction in the last six months
  6. Patient is taking a medication or drug that prolongs the QT interval or has a family or personal 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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Pimavanserin
Drug- pimavanserin 34 mg, 20 mg, or 10 mg taken as two tablets + background antipsychotic, once daily by mouth
Drug: Pimavanserin
Pimavanserin 34 mg, 20 mg, or 10 mg , taken as two tablets once daily by mouth
Placebo Comparator: Placebo
Placebo + background antipsychotic, taken as two tablets, once daily by mouth
Drug: Placebo
Placebo, taken as two tablets, once daily by mouth

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change From Baseline to Week 6 in the Positive and Negative Syndrome Scale (PANSS) Total Score
Time Frame: From baseline to Week 6
The PANSS is a 30-item scale used to evaluate the presence, absence, and severity of schizophrenia symptoms. The 30 items are arranged as 7 positive symptom items (P1 to P7), 7 negative symptom items (N1 to N7), and 16 general psychopathology symptom items (G1 to G16). Items are scored over the past week (7 days) on a 7-point scale ranging from 1 (absent) to 7 (extreme). The PANSS total score can range from a minimum of 30 to a maximum of 210, where a higher score signifies greater severity of schizophrenia symptoms.
From baseline to Week 6

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change From Baseline to Week 6 in the Clinical Global Impression-Severity (CGI-S) Score
Time Frame: From baseline to Week 6
The CGI-S 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-S score denotes greater severity of the disorder.
From baseline to Week 6
Change From Baseline (CFBL) to Week 6 in PANSS Subscale Scores, i.e. PANSS Positive Subscale Score, PANSS Negative Subscale Score and PANSS General Psychopathological Scale Score
Time Frame: From baseline to Week 6

The PANSS is a 30-item scale used to evaluate the presence, absence, and severity of schizophrenia symptoms. The 30 items are arranged as 7 positive symptom items (P1 to P7), 7 negative symptom items (N1 to N7), and 16 general psychopathology symptom items (G1 to G16). Items are scored over the past week (7 days) on a 7-point scale ranging from 1 (absent) to 7 (extreme).

The PANSS positive subscale score can range from 7 to 49; the PANSS negative subscale score can range from 7 to 49; the PANSS general psychopathology scale score can range from 16 to 112.

For each of the subscale scores, a higher score signifies greater severity of schizophrenia symptoms.
From baseline to Week 6
PANSS Responders
Time Frame: From baseline to Week 6
Porportion of patients showing a PANSS response of >=20% or >=30% reduction in PANSS total score PANSS total score reduction signifies improvement.
From baseline to Week 6
Clinical Global Impression-Improvement (CGI-I) Response
Time Frame: From baseline to Week 6

The CGI-I is a 1-item scale, used to rate the improvement from 1 (very much improved) to 7 (very much worse). Higher scores denote less improvement.

A CGI-I score of 1 or 2 was counted as response. The Analysis was performed twice; once including missing values as non-responders (MN) and once including only observed cases (OC).
From baseline to Week 6
Clinical Global Impression-Improvement (CGI-I) Score at Week 6
Time Frame: From baseline to Week 6
The CGI-I is a 1-item scale, used to rate the improvement from 1 (very much improved) to 7 (very much worse). Higher scores denote less improvement.
From baseline to Week 6
Change From Baseline to Week 6 in Personal and Social Performance (PSP) Scale Score
Time Frame: From baseline to Week 6
The PSP is a validated 100-point (1 to100) single-item rating scale to assess the psychosocial functioning of patients with schizophrenia. The maximum score is 100. Higher scores denote better psychosocial functioning.
From baseline to Week 6
Drug Attitude Inventory (DAI-10)
Time Frame: From baseline to Week 6
The DAI-10 contains 6 items (1, 3, 4, 7, 9, and 10) that a patient who is fully adherent to study medication would answer as "True" and 4 items (2, 5, 6, and 8) that a patient who is fully adherent to study medication would answer as "False." A correct answer is scored +1 and an incorrect answer is scored -1; the total score is derived as overall sum. The score can range from -10 to 10. Positive total scores indicate adherence and negative total scores indicate non-adherence. Higher scores denote better adherence.
From baseline to Week 6
Change From Baseline to Week 6 in Karolinska Sleepiness Scale (KSS) Score
Time Frame: From baseline to Week 6
The KSS is a self-reported measure of a patient's level of drowsiness. In this study, drowsiness was to be rated during the last week (7 days). Scoring is based on a 9-point verbally anchored scale ranging from 1 (extremely alert) to 9 (very sleepy, great effort to keep awake, fighting sleep). The maximum score is 9. Higher scores denote more drowsiness.
From baseline to Week 6

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

ACADIA Pharmaceuticals Inc.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 26, 2016

Primary Completion (Actual)

May 28, 2019

Study Completion (Actual)

June 25, 2019

Study Registration Dates

First Submitted

November 18, 2016

First Submitted That Met QC Criteria

November 18, 2016

First Posted (Estimate)

November 22, 2016

Study Record Updates

Last Update Posted (Actual)

June 17, 2020

Last Update Submitted That Met QC Criteria

May 29, 2020

Last Verified

May 1, 2020

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ACP-103-034
  • 2016-003434-24 (EudraCT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Subscribe