PEARL Schizophrenia Maintenance

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Sunovion
ClinicalTrials.gov Identifier:
NCT01435928
First received: September 15, 2011
Last updated: April 7, 2014
Last verified: April 2014
  Purpose

Lurasidone HCI is a compound that is FDA-approved for the treatment of schizophrenia. This clinical study is designed to test the hypothesis that Lurasidone is effective in the long term maintenance treatment of schizophrenia.


Condition Intervention Phase
Schizophrenia
Drug: Lurasidone
Drug: Matching Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Double-Blind, Placebo-Controlled, Randomized Withdrawal Study Of Lurasidone For The Maintenance Treatment Of Subjects With Schizophrenia

Resource links provided by NLM:


Further study details as provided by Sunovion:

Primary Outcome Measures:
  • Time to the first relapse event within 28 weeks [ Time Frame: 28 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Time to all-cause discontinuation [ Time Frame: 28 weeks ] [ Designated as safety issue: Yes ]
  • Positive and Negative Syndrome Scale (PANSS) Total score and PANSS subscores [ Time Frame: 28 Weeks ] [ Designated as safety issue: No ]
  • Clinical Global Impression - Severity of Illness Scale (CGI-S) score [ Time Frame: 28 Weeks ] [ Designated as safety issue: No ]
  • Montgomery-Asberg Depression Rating Scale (MADRS) total score [ Time Frame: 28 Weeks ] [ Designated as safety issue: No ]
  • Short Form-12v2 Health Survey (SF-12v2) [ Time Frame: 28 Weeks ] [ Designated as safety issue: No ]
  • Modified Specific Levels of Functioning (SLOF) total score and SLOF subscale scores (social functioning and community living skills) [ Time Frame: 28 Weeks ] [ Designated as safety issue: No ]
  • Brief Adherence Rating Scale [ Time Frame: 28 Weeks ] [ Designated as safety issue: No ]
  • Smoking questionnaire [ Time Frame: 28 Weeks ] [ Designated as safety issue: No ]
  • Intent to attend questionnaire [ Time Frame: 28 Weeks ] [ Designated as safety issue: No ]
  • Adverse events (AEs), discontinuations due to AEs, and serious AEs (SAEs) [ Time Frame: 28 Weeks ] [ Designated as safety issue: Yes ]
  • Weight, laboratory measures, vital signs, physical examinations and electrocardiograms (ECGs) [ Time Frame: 28 Weeks ] [ Designated as safety issue: Yes ]
  • Movement disorders, as assessed by Abnormal Involuntary Movement Scale (AIMS), Barnes Akathisia Rating Scale (BAS), and the Simpson-Angus Scale (SAS) [ Time Frame: 28 Weeks ] [ Designated as safety issue: Yes ]
  • Columbia-Suicide Severity Rating Scale (C-SSRS) [ Time Frame: 28 Weeks ] [ Designated as safety issue: Yes ]

Other Outcome Measures:
  • EuroQol (EQ-5D) [ Time Frame: 28 Weeks ] [ Designated as safety issue: No ]
  • Health Service Utilization Questionnaire (HSUQ) [ Time Frame: 28 Weeks ] [ Designated as safety issue: No ]
  • Health Economics Exit Questionnaire [ Time Frame: 28 Weeks ] [ Designated as safety issue: No ]

Enrollment: 285
Study Start Date: September 2011
Study Completion Date: August 2013
Primary Completion Date: August 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Lurasidone
Lurasidone 40 and 80 mg, once daily in the evening with a meal or 30 minutes after eating
Drug: Lurasidone
Lurasidone 40 and 80 mg, once daily in the evening with a meal or 30 minutes after eating
Other Name: Latuda
Placebo Comparator: Placebo
Matching placebo once daily in the evening with a meal or 30 minutes after eating
Drug: Matching Placebo
Matching placebo once daily in the evening with a meal or 30 minutes after eating

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Open Label:

Subject provides written informed consent and is willing and able to comply with the protocol in the opinion of the Investigator.

Subject is ≥ 18 and ≤ 75 years of age, on the day of signing the informed consent.

Subject meets DSM-IV-TR criteria for a primary diagnosis of schizophrenia [including disorganized (295.10), paranoid (295.30), undifferentiated (295.90) subtypes as established by clinical interview (using the DSM-IV-TR as a reference and confirmed using the SCID-CT)]. The duration of the subject's illness whether treated or untreated must be ≥ 1 year.

Subject has had at least one prior episode of psychotic exacerbation as judged by the Investigator in the two years preceding screening.

Subject has a PANSS Total score ≥ 80 with a score ≥ 4 on 1 or more of any PANSS Positive subscale items at screening and open-label baseline (Visit 2).

Subject has a CGI-S score of ≥ 4 at screening and open-label baseline (Visit 2).

Subject is not pregnant (must have a negative serum pregnancy test at screening) or nursing (must not be lactating) and is not planning pregnancy within the projected duration of the study.

Female subject of reproductive potential agrees to remain abstinent or use adequate and reliable contraception throughout the study and for at least 30 days after the last dose of lurasidone has been taken. In the Investigator's judgment, the subject will adhere to this requirement.

Adequate contraception is defined as continuous use of either two barrier methods (e.g., condom and spermicide or diaphragm with spermicide) or a hormonal contraceptive. Acceptable hormonal contraceptives include the following: a) contraceptive implant (such as Norplant®) implanted at least 90 days prior to screening; b) injectable contraception (such as medroxyprogesterone acetate injection) given at least 14 days prior to screening; or c) oral contraception taken as directed for at least 30 days prior to screening.

Subjects who are of non-reproductive potential, i.e., subject who is surgically sterile, has undergone tubal ligation, or is postmenopausal (defined as at least 12 months of spontaneous amenorrhea or between 6 and 12 months of spontaneous amenorrhea with follicle stimulating hormone (FSH) concentrations within postmenopausal range as determined by laboratory analysis) are not required to remain abstinent or use adequate contraception.

Subject is able and agrees to remain off prior antipsychotic medication for the duration of the study.

Subject has had a stable living arrangement at the time of screening and agrees to return to a similar living arrangement after discharge, if hospitalized. This criterion is not meant to exclude subjects who have temporarily left a stable living arrangement (e.g., due to psychosis). Such subjects remain eligible to participate in this protocol. Chronically homeless subjects should not be enrolled.

Subject is in good physical health on the basis of medical history, physical examination, and laboratory screening.

Subject who requires concomitant medication treatment with the following agents may be included if they have been on stable doses (i.e., minor adjustments only) for the specified times: 1) antidepressant agents (except fluvoxamine) and/or mood stabilizers (except carbamazepine or oxcarbazepine) must be stable for at least 30 days prior to open-label baseline, 2) oral hypoglycemics must be stable for at least 30 days prior to screening, 3) antihypertensive agents must be stable for at least 30 days prior to screening, and 4) thyroid hormone replacement must be stable for at least 90 days prior to screening. (Note: CYP3A4 inducers and inhibitors will not be allowed).

Subject is willing and able to comply with the protocol assessments and visits, in the opinion of the study nurse/coordinator and the Investigator.

Double-blind -

Subject must achieve and maintain clinical stability for a total of at least 12 weeks in the open label phase, defined as:

  1. a PANSS Total score ≤ 70, a CGI-S score < 4 and a PANSS item score of ≤ 4 (moderate or less) on all PANSS Positive subscale items over at least 12 weeks with the allowance of two excursions (except during the last 4 weeks of the open-label phase) assessed at weekly study visits:

    • An excursion is defined as a PANSS total score up to a maximum of 80 and/or a CGI-S score up to a maximum of 4 and/or a PANSS Positive subscale item score up to a maximum of 5.

  2. a PANSS item score of ≤ 4 (moderate or less) on item G8 (uncooperativeness)
  3. taking a stable dose of lurasidone for the last 4 weeks of the open-label phase.

Exclusion Criteria:

Open Label - Subject has a DSM-IV Axis I or Axis II diagnosis other than schizophrenia that has been the primary focus of treatment within 3 months of screening.

Subject answers "yes" to "Suicidal Ideation" item 4 (active suicidal ideation with some intent to act, without specific plan) or item 5 (active suicidal ideation with specific plan and intent) on the C-SSRS assessment at screening (in the past month) or baseline.

Subject has attempted suicide within 3 months prior to the screening phase. Subject currently has a clinically significant medical condition including the following: neurological, metabolic (including Type 1 diabetes), hepatic, renal, hematological, pulmonary, cardiovascular, gastrointestinal, and/or urological disorder such as unstable angina, congestive heart failure (uncontrolled), or central nervous system (CNS) infection that would pose a risk to the subject if they were to participate in the study or that might confound the results of the study. Subjects with human immunodeficiency virus (HIV) seropositivity (or history of seropositivity) will be excluded.

Note: Active medical conditions that are minor or well-controlled are not exclusionary if they do not affect risk to the subject or the study results. In cases in which the impact of the condition upon risk to the subject or study results is unclear, the Medical Monitor should be consulted. Any subject with a known cardiovascular disease or condition (even if controlled) must be discussed with the Medical Monitor before being screened.

Subject has evidence of any chronic organic disease of the CNS such as tumors, inflammation, and active seizure disorder, vascular disorder, Parkinson's disease, Alzheimer's disease or other forms of dementia, myasthenia gravis, or other degenerative processes. In addition, subject must not have a history of mental retardation or persistent neurological symptoms attributable to serious head injury. Note: Past history of febrile seizures, drug-induced seizures, or alcohol withdrawal seizures is not exclusionary.

Note: Past history of febrile seizures, drug-induced seizures, or alcohol withdrawal seizures is not exclusionary.

Subject demonstrates evidence of acute hepatitis, clinically significant chronic hepatitis, or evidence of clinically significant impaired hepatic function through clinical and laboratory evaluation.

Note: Subjects with serum alanine transaminase (ALT) or aspartate transaminase (AST) levels ≥ 3 times the upper limit of the reference ranges provided by the central laboratory require retesting. If on retesting, the laboratory value remains ≥ 3 times the upper limit, such subjects will be discussed with the Medical Monitor for enrollment consideration.

Subject has a history of stomach or intestinal surgery or any other condition that could interfere with or is judged by the Investigator to interfere with absorption, distribution, metabolism, or excretion of study drug.

Subject with Type 1 or Type 2 insulin-dependent diabetes.

Subject with newly diagnosed Type 2 diabetes during screening. Subject with Type 2 diabetes is eligible for study inclusion if the following condition is met at screening:

if a subject is currently being treated with oral anti-diabetic medication(s), the dose must have been stable for at least 4 weeks prior to screening. Such medication may be adjusted or discontinued during the study, as clinically indicated.

Subject has any abnormal laboratory parameter at screening that indicates a clinically significant medical condition as determined by the Investigator. Subjects with a fasting blood glucose at screening ≥ 126 mg/dL (7.0 mmol/L) or HbA1c ≥ 7.0% will be excluded.

Note: Subjects with random (non-fasting) blood glucose at screening ≥ 200 mg/dL (11.1 mmol/L) must be retested in a fasted state.

Subject has a prolactin concentration > 100 ng/mL at screening or has a history of pituitary adenoma.

Subject has a history of malignancy < 5 years prior to signing the informed consent, except for adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer. Pituitary tumors of any duration are excluded.

Subject is judged to be resistant to antipsychotic treatment defined as any one of the following:

  1. failure to respond to > 2 marketed antipsychotic agents, given at an adequate dose and for an adequate duration (within the past 2 years)
  2. history of treatment with clozapine for refractory psychosis Subject is unlikely to achieve a stable condition for ≥ 12 weeks during the open-label lurasidone phase based on the totality of evidence from the psychiatric history and/or the current presentation.

Subject is receiving an antipsychotic medication above the maximum recommended (country-specific) dose at or prior to screening and, in the judgment of the Investigator, is unlikely to respond to standard doses of lurasidone.

Subject has received depot antipsychotics unless the last injection was at least one treatment cycle or at least 30 days (whichever is longer) prior to the screening phase.

Subject has received treatment with MAO inhibitors within 14 days prior to the screening phase.

Subject requires treatment with any potent CYP3A4 inhibitors or inducers during the study (see Appendix 3).

Subject has received electroconvulsive therapy treatment within the 3 months prior to screening or is expected to require electroconvulsive therapy (ECT) during the study.

Subject has a history of neuroleptic malignant syndrome. Subject exhibits evidence of severe tardive dyskinesia, severe dystonia, or any other severe movement disorder. Severity will be determined by the Investigator.

Subject has a history of alcohol or substance abuse (DSM-IV-TR criteria) within 3 months prior to screening or alcohol or substance dependence (DSM-IV-TR criteria) within 12 months prior to screening. The only exceptions include caffeine or nicotine abuse/dependence.

Subject tests positive for drugs of abuse at screening. In the event a subject tests positive for cannabinoids (tetrahydrocannabinol), the Investigator will evaluate the subject's ability to abstain from using this drug during the study. This information will be discussed with the Medical Monitor prior to study enrollment.

Subject had a history or presence of an abnormal electrocardiogram (ECG), which in the Investigator's opinion is clinically significant (Medical Monitor may be consulted to determine clinical significance).

Subject has poor peripheral venous access that will limit the ability to draw blood as judged by the Investigator.

Subject has a history of hypersensitivity to more than 2 distinct chemical classes of drug (e.g., sulfas and penicillins).

Subject was screened or washed out previously more than three times for this study.

Subject is currently participating, or has participated in, a study with an investigational or marketed compound or device within 3 months prior to signing the informed consent, or has participated in 2 or more studies within 12 months prior to signing the informed consent.

Subject is homeless or did not have a stable residence for the 3 months prior to the screening phase.

Subject is unable to cooperate with any study procedures, unlikely to adhere to the study procedures and keep appointments, in the opinion of the Investigator, or was planning to relocate during the study.

Subject requires guardianship under the laws of his/her country.

Double-blind - Subjects who in the Investigator's judgment have not been compliant with study medication during the open-label stabilization phase.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01435928

  Hide Study Locations
Locations
United States, Arizona
Woodland Research Northwest
Springdale, Arizona, United States, 72764
United States, Arkansas
K&S Professional Research
Little Rock, Arkansas, United States, 72201
Woodland International Research Group
Little Rock, Arkansas, United States, 72211
United States, California
Comprehensive Clinical Development Inc.
Cerritos, California, United States, 90703
Diligent Clinical Trials
Downey, California, United States, 90241
Synergy Escondido
Escondido, California, United States, 92025
Collaborative Neuroscience Network, Inc.
Garden Grove, California, United States, 92845
Axis Clinical Trials
Los Angeles, California, United States, 90036
Synergy Clinical Research Center
National City, California, United States, 91950
Excell Clinical Trials
Oceanside, California, United States, 92056
CNRI - Los Angeles LLC,8309 Telegraph Road
Pico Rivera, California, United States, 90660
California Neuropsychopharmacology Clinical Research Instit
San Diego, California, United States, 92102
Neuropsychiatric Research Center of Orange County
Santa Ana, California, United States, 92701
Collaborative Neuroscience Network Inc.
Torrance, California, United States, 90502
United States, Florida
Florida Clinical Research Center, LLC
Bradenton, Florida, United States, 34208
Accurate Clinical Trials
Kissimme, Florida, United States, 34742
Florida Clinical Research Center, LLC
Maitland, Florida, United States, 32751
Galiz Research
Miami Springs, Florida, United States, 33166
Medical Research Group of Central Florida
Orange City, Florida, United States, 32763
United States, Georgia
Comprehensive NeuroScience, Inc.
Atlanta, Georgia, United States, 30328
Atlanta Center for Medical Research
Atlanta, Georgia, United States, 30308
United States, Louisiana
Lake Charles Clinical Trials
Lake Charles, Louisiana, United States, 70629
Lousiana Clinical Research, LLC
Shreveport, Louisiana, United States, 71104
United States, Maryland
CBH Health LLC
Rockville, Maryland, United States, 20850
United States, Missouri
Psychiatric Care and Research Center
O'Fallon, Missouri, United States, 63368
Psych Care Consultants Research
St. Louis, Missouri, United States, 63128
United States, Nevada
Center for Psychiatry and Behavioral Medicine, Inc.
Las Vegas, Nevada, United States, 89128
Horne Research
Las Vegas, Nevada, United States, 89102
United States, New Jersey
CRI Worldwide LLC
Willingboro, New Jersey, United States, 08046
United States, New York
University of New York, Dept. of Psychiatry
Buffalo, New York, United States, 14218
Neurobehavioral Research, Inc.
Cedarhurst, New York, United States, 11516
Comprehensive Clinical Development, Inc
Fresh Meadows, New York, United States, 11366
Finger Lakes Clinical Research
Rochester, New York, United States, 14618
Behavioral Medical Research of Staten Island
Staten Island, New York, United States, 10305
United States, Oklahoma
Oklahoma Clinical Research
Oklahoma City, Oklahoma, United States, 73116
Cutting Edge Research Group
Oklahoma City, Oklahoma, United States, 73116
United States, Pennsylvania
CRI Worldwide LLC at Kirkbride
Philadelphia, Pennsylvania, United States, 19139
United States, Rhode Island
Lincoln Research
Lincoln, Rhode Island, United States, 02865
United States, Texas
FutureSearch Clinical Trials LP
Austin, Texas, United States, 78756
Community Clinical Research, Inc.
Austin, Texas, United States, 78754
FutureSearch Clinical Trials, LP
Dallas, Texas, United States, 75231
Pillar Clinical Research LLC
Dallas, Texas, United States, 75243
Family Psychiatry of the Woodlands
The Woodlands, Texas, United States, 77381
United States, Utah
Department of Psychiatry, University of Utah Health Sciences Center
Salt Lake City, Utah, United States, 84132
United States, Washington
Frontier Institute
Spokane, Washington, United States, 99204
France
CHU Clermont-Ferrand - CMP B
Clermont-Ferrand Cedex 1, France, 63003
Centre Hospitalier Specialise du Jura - Centre Medico Psychiatric
Dole, France, 39100
Centre Hospitalier Guillaume Regnier
Rennes Cedex, France, 35703
Hopital Chalucet, Centre hospitalier intercommunal de toulon la Seyne sur mer (CHITS)
Toulon, France, 83000
Cabinet Medical
Toulouse, France, 31200
Italy
SC SPDC-Edificio n. 7, Ospedale S. Andrea
La Spezia, Italy, 19123
Dipartimento Salute Mentale ASL 1
Massa, Italy, 54100
A.O.U. Santa Chiara, U.O di Psichiatria 1 building n.4
Pisa, Italy, 56100
Russian Federation
Regional Government Institution Kipetsk Regional Psychoneurology Hospital
Lipetsk, Russian Federation, 399083
Limited Liability Company (LLC) Research Center for Treatment and rehabilitation "Phoenix"
Rostov-on-Don, Russian Federation, 344000
City Psychoneurological Dispensary #7 (with Hospital)
St-Petersburg, Russian Federation, 190005
St. Petersburg State Healthcare Institution (SPbSH) "City Psychiatric Hospital #6"
St. Petersburg, Russian Federation, 191167
St. Petersburg State Budgetary Healthcare Institution City Psychoneurology Dispensary #7 (with in-patient dept.) (SPb SBHI CPNDD-7), at daycare facility #1
St. Petersburg, Russian Federation, 19005
St. Petersburg State Government Healthcare Institution City Psychiatric Hospital #4 (St. Petersburg Insane Asylum Distributor)
St. Petersburg, Russian Federation, 19119
Serbia
Military Medical Academy, Clinic for Psychiatry
Belgrade, Serbia, 11000
Institute of Mental Health
Belgrade, Serbia, 11000
Clinical Centre Kragujevac, Clinic for Psychiatry
Kragujevac, Serbia, 34000
Clinical Centre Nis, Clinic for mental health protection
Nis, Serbia, 18000
Specialized Hospital for psychiatric diseases "Sveti Vracevi"
Novi Knezevac, Serbia, 23330`
Clinical Centre Vojvodina, Clinic for Psychiatry
Novi Sad, Serbia, 21000
Slovakia
Nemonnica s poliklinikou v Prievidzi so sidlom v Bojniciach, Psychiatricke oddelenie
Bojnice, Slovakia, 972 01
Psychiatricka ambulancia Mentum, s.r.o.
Bratislava, Slovakia, 82007
Psychiatricka nemocnica Michalovce
Michalovce, Slovakia, 071 01
PsychoLine s.r.o. Psychiatricka ambulancia
Rimavska Sobota, Slovakia, 97901
Psychiaticke oddelenie Vseobecna nemocnica Riimavska Sobota, NaP n.o.
Rimavska Sobota, Slovakia, 97912
Psychiatricke oddelenie, Nemocnica s poliklinikou sv. Barbory Roznava, a.s.
Roznava, Slovakia, 048 01
Centrum zdravia R. B.K. s.r.o. Psychiatricka ambulancia
Svidnik, Slovakia, 08901
South Africa
Research Unit, Department of Psychiatry Free State Psychiatric Complex
Bloemfontein, South Africa, 9300
Cape Trial Centre
Cape Town, W. Cape, South Africa, 7530
Denmar Hospital Consulting Rooms
Pretoria, South Africa, 0081
Sponsors and Collaborators
Sunovion
Investigators
Study Director: Medical Director, MD Sunovion
  More Information

No publications provided

Responsible Party: Sunovion
ClinicalTrials.gov Identifier: NCT01435928     History of Changes
Other Study ID Numbers: D1050238
Study First Received: September 15, 2011
Last Updated: April 7, 2014
Health Authority: United States: Food and Drug Administration
Bulgaria: Bulgarian Drug Agency
Croatia: Ministry of Health and Social Care
Czech Republic: State Institute for Drug Control
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
India: Drugs Controller General of India
Italy: The Italian Medicines Agency
Poland: The Central Register of Clinical Trials
Russia: Ministry of Health of the Russian Federation
Serbia and Montenegro: Agency for Drugs and Medicinal Devices
Slovakia: State Institute for Drug Control
South Africa: Medicines Control Council
Ukraine: Ministry of Health

Keywords provided by Sunovion:
Schizophrenia
Lurasidone
Latuda

Additional relevant MeSH terms:
Schizophrenia
Schizophrenia and Disorders with Psychotic Features
Mental Disorders

ClinicalTrials.gov processed this record on July 28, 2014