Pediatric Schizophrenia Efficacy and Safety Study

Schizophrenia Clinical Trial

Official title:

A 6-Week Randomized, Parallel, Double-Blind, Placebo-Controlled, Fixed-Dose, Multicenter Study To Evaluate The Efficacy and Safety of Lurasidone in Adolescent Subjects With Schizophrenia

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01911429
• Other study ID #: D1050301
• Secondary ID: 2013-001695-38
• Status: Completed
• Phase: Phase 3
• First received: July 22, 2013
• Last updated: January 7, 2016
• Start date: August 2013
• Est. completion date: December 2015

Study information

• Verified date: January 2016
• Source: Sunovion
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationUkraine: Ministry of HealthItaly: The Italian Medicines AgencySerbia: Medicines and Medical Devices AgencyBulgaria: Bulgarian Drug AgencyColombia: National Institutes of HealthChina: Ministry of HealthRomania: National Medicines AgencySpain: Spanish Agency of MedicinesKorea: Food and Drug AdministrationMalaysia: Ministry of HealthPhilippines : Food and Drug AdministrationMexico: Ministry of Health
• Study type: Interventional

Clinical Trial Summary

Efficacy and Safety study of Lurasidone in pediatric patients.

Description:

To evaluate the efficacy of lurasidone (40 mg/day and 80 mg/day) compared with placebo in adolescent subjects with schizophrenia (diagnosed by Diagnostic and Statistical Manual of Mental Disorders, 4th Ed., Text Revision [DSM-IV-TR] criteria) as measured by the change from Baseline in the Positive and Negative Syndrome Scale (PANSS) total score at Week 6.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 285
• Est. completion date: December 2015
• Est. primary completion date: December 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 13 Years to 17 Years

Eligibility

Inclusion Criteria:

• Written informed consent from parent(s) or legal guardian(s) with sufficient intellectual capacity to understand the study and support subjects' adherence to the study procedures must be obtained for subjects who are not emancipated. In accordance with Institutional Review Board (IRB) requirements, the subject will complete an informed assent prior to study participation.

• Male or female subjects 13 to 17 years of age, inclusive, at the time of consent.

• DSM-IV-TR axis I primary diagnosis of schizophrenia (including disorganized (295.10), paranoid (295.30), undifferentiated (295.90) subtypes) and confirmation of the schizophrenia diagnosis by an adequately trained clinician at the time of screening, by means of the Schedule for Affective Disorders and Schizophrenia for School-age Children (K-SADS-PL).

• PANSS total score = 70 at screening and Baseline.

• CGI-S = 4 at screening and Baseline.

• Within 5th to 95th percentile for gender specific weight-for-age and height-for-age Growth Charts from National Center for Health Statistics.

• In good physical health on the basis of medical history, physical examination, and laboratory screening.

• Females who participate in this study:

are unable to become pregnant (eg, premenarchal, surgically sterile, etc.); -OR-

practices true abstinence (consistent with lifestyle) and must agree to remain abstinent from signing informed consent to at least 30 days after the last dose of study drug has been taken;

-OR-

are sexually active and willing to use a medically effective method of birth control (e.g., male using condom and female using condom, diaphragm, contraceptive sponge, spermicide, contraceptive pill, or intrauterine device) from signing informed consent to at least 7 days after the last dose of study drug has been taken.

• Males must be willing to remain sexually abstinent (consistent with lifestyle) or use an effective method of birth control (eg, male using condom and female using condom, diaphragm, contraceptive sponge, spermicide, contraceptive pill, or intrauterine device) from signing informed consent to at least 30 days after the last dose of study drug has been taken.

• In the judgement of the clinician, the subject has an acute exacerbation of psychotic symptoms (no longer than 2 months in duration) and marked deterioration of function from baseline (by history) or, the subject has been hospitalized for the purpose of treating an acute psychotic exacerbation for 2 consecutive weeks or less immediately before screening.

• In the judgment of the investigator, the subject is able to swallow the size and number of study drug tablets specified per protocol.

• Willing and able to adhere to protocol-specified meal requirements during dosing.

Exclusion Criteria:

• Has an Axis I or Axis II diagnosis other than schizophrenia that has been the primary focus of treatment within 3 months of screening.

• Has a history or current diagnosis of mental retardation, neuroleptic malignant syndrome, or any neurologic disorder, or severe head trauma.

• Lifetime history of human immunodeficiency virus (HIV) positive or acquired immune deficiency syndrome (AIDS), or history of Hepatitis B or C.

• Any of the following:

Documented history of chromosomal disorder with developmental impairment (ie, trisomy chromosome 21; 22q11 deletion syndrome).

Evidence of any chronic organic disease of the CNS such as tumors, inflammation, active seizure disorder, vascular disorder, potential CNS related disorders that might occur in childhood- eg, Duchenne Muscular dystrophy, myasthenia gravis, or other neurologic or serious neuromuscular disorders. In addition, subjects must not have a history of persistent neurological symptoms attributable to serious head injury. Past history of febrile seizure, drug-induced seizure, or alcohol withdrawal seizure is not exclusionary.

• PANSS total scores = 120 at screening or Baseline.

• Exhibits evidence of moderate or severe extrapyramidal symptoms, dystonia, tardive dyskinesia, or any other moderate or severe movement disorder. Severity to be determined by the investigator.

• Lifetime history of electroconvulsive therapy (ECT).

• Resistant to antipsychotic treatment based on at least two different prior adequate trials (ie, adequate dose and duration) of an antipsychotic agent within the current episode of schizophrenia.

• Clinically significant neurological, metabolic (including type 1 diabetes), hepatic, renal, hematological, pulmonary, cardiovascular, gastrointestinal, carcinoma, and/or urological disorder that would pose a risk to the subjects if they were to participate in the study or that might confound the results of the study.

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 during screening.

• Has a history of malignancy < 5 years prior to signing the informed consent.

• Clinically significant finding(s) on physical examination determined by the investigator to pose a health concern to the subject while on study.

• Clinically relevant abnormal laboratory values or abnormal vital sign values/findings.

Note: If any laboratory results are outside the normal range, the site may have the subject retested. If upon retesting the value remains outside the normal range, the significance of this value must be discussed with the Medical Monitor for enrollment consideration.

• A history or presence of abnormal ECG, which in the investigator's opinion is clinically significant. Abnormal screening ECGs will be centrally over-read, and eligibility will be determined based on the over-read.

• Presence or history (within the last year) of a medical or surgical condition (eg, gastrointestinal disease) that might interfere with the absorption, metabolism, or excretion of orally administered lurasidone.

• Clinically significant alcohol abuse/dependence or drug abuse/dependence based on DSM-IV-TR criteria within the last 6 months prior to screening.

• Positive test results at screening or Baseline for:

1. Urine drugs of abuse (amphetamines, barbiturates, benzodiazepines, cocaine, opiates, phencyclidine, cannabinoids, and methadone). A positive test for amphetamines, barbiturates, opiates, benzodiazepines or methadone may not result in exclusion of subjects if the investigator determines that the positive test is as a result of taking prescription medicine(s) as prescribed. In the event a subject tests positive for cannabinoids (tetrahydrocannabinol) or alcohol, the investigator will evaluate the subject's ability to abstain from prohibited substances during the study. If in the investigator's clinical judgment the subject will abstain, the subject may be enrolled after consultation with the Medical Monitor.

2. Pregnancy test.

• Females who are pregnant, lactating, or likely to become pregnant during the study.

• Participated in another interventional clinical trial or receiving an investigational product within 30 days prior to randomization.

• Donation of whole blood within 60 days prior to randomization.

• Known history or presence of clinically significant intolerance to any antipsychotic medications including but not limited to angioedema, serotonin or neuroleptic malignant syndromes.

• Clinically relevant history of drug hypersensitivity to lurasidone or any components in the formulation.

• Use of concomitant medications that consistently prolong the QT/QTc interval within 28 days prior to randomization.

• Received depot neuroleptics unless the last injection was at least 1 month or 1 treatment cycle prior to screening, whichever is longer.

• Received treatment with antidepressants, stimulants, or atomoxetine within 3 days prior to randomization, fluoxetine hydrochloride within 21 days of randomization, monoamine oxidase (MAO) inhibitor within 28 days of randomization, or clozapine within 120 days of randomization.

• Use of any antipsychotic medication (other than study drug), carbamazepine, oxcarbazepine, eslicarbazepine acetate, or fluvoxamine, within 3 days prior to randomization (7 days prior to randomization for aripiprazole) and until follow-up.

• Has a prolactin concentration = 100 ng/mL at screening, or has a history of pituitary adenoma.

• At screening or Baseline the subject answers "yes" to "Suicidal Ideation" Items 4 or 5 on the C-SSRS.

• Subject is considered by the investigator to be at imminent risk of suicide or injury to self, others, or property during the study. Subject has a history of one or more serious suicide attempts (based on the investigator's judgment) in the 3 months prior to screening. Subjects determined to be at risk of suicide or injury, as assessed by the investigator at screening, will be referred for further psychiatric evaluation.

• Adhering to a special diet for the 28 days prior to drug administration (eg, liquid, protein, raw food diet).

• Subject is planning to move during the study, is chronically homeless, or is unable to attend all planned study visits. The Medical Monitor will be consulted for individual cases, as needed.

• Demonstrates a decrease (improvement) of > 25% in the PANSS score between screening and Baseline visits.

• Subject with newly diagnosed Type 2 diabetes during screening. A subject with Type 2 diabetes is eligible for study inclusion if considered clinically stable, which is defined as:

Random (non-fasting) screening glucose is < 200 mg/dl (11.1 mmol/L); and If = 200 mg/dL (11.1 mmol/L) must be retested in a fasted state. Retested fasted value cannot be = 126 mg/dL.

HbA1c = 6.5%; and 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 required hospitalization for diabetes or related complications in the past 12 months.

• Subject requires use of concomitant medications that are potent inducers or inhibitors of the cytochrome P450 (CYP) 3A4 enzyme system (Appendix C) from signing informed consent until follow-up.

• Clinically significant orthostatic hypotension (ie., a drop in systolic blood pressure of 20 mmHg or more and/or drop in diastolic blood pressure of 10 mmHg or more within 4 minutes of standing up).

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Schizophrenia

Intervention

Drug:
• Lurasidone 40 mg
Lurasidone 40 mg once daily
• Lurasidone 80 mg
Lurasidone 80 mg once daily
• Placebo 40 or 80 mg
Placebo 40 or 80 mg once daily

Locations

Country	Name	City	State
Belgium	Universitair Ziekenhuis Brussel	Bruxelles
Bulgaria	MHC - Ruse, EOOD	Ruse
Bulgaria	UMHAT "Alexandrovska" EAD	Sofia
Bulgaria	MHAT-Targovishte, AD	Targovishte
Bulgaria	MHAT 'Sv. Marina', EAD	Varna
Colombia	Centro de Investigaciones y Proyectos en Neurociencias CIPNA	Barranquilla
Colombia	E.S.E. Hospital Mental de Antioquia	Bello
Colombia	Centro de Investigaciones del Sistema Nervioso Limitada - Grupo CISNE Ltda	Bogota
France	CHU Nantes - Hôpital Mère-Enfant	Nantes Cedex 1	Loire Atlantique
France	Hôpitaux Pédiatriques de Nice CHU-Lenval	Nice
Hungary	Vadaskert Alapitvany a Gyermekek Lelki Egeszsegeert	Budapest
Hungary	Bekes Megyei Pandy Kalman Korhaz	Gyula
Korea, Republic of	Inha University Hospital	Incheon
Korea, Republic of	Chonbuk National University Hospital	Jeonju-si
Korea, Republic of	Severance Hospital, Yonsei University Health System	Seoul
Malaysia	University Malaya Medical Centre	Lembah Pantai	Kuala Lumpur
Mexico	Centro para el Desarrollo de la Medicina y de Asistencia Medica Especializada S.C.	Culiacan
Mexico	Accelerium S. de R.L. de C.V.	Monterrey
Mexico	Instituto de Informacion de Investigacion en Salud Mental	Monterrey
Philippines	Alexian Brothers Health and Wellness Center	Daveo City
Philippines	West Visayas State University Medical Center	Iloilo City
Philippines	National Center for Mental Health	Mandaluyong City
Philippines	Veterans Memorial Medical Center	Quezon City
Poland	Wojewodzki Szpital Zespolony im. L. Rydygiera w Toruniu	Torun
Poland	NZOZ Poradnia Zdrowia Psychicznego	Tyniec Maly
Poland	Instytut Psychiatrii i Neurologii	Warszawa
Puerto Rico	Centro de Investigacion Clinica Psiquiatrica	Caguas
Puerto Rico	Centro de Investigacion Clinica Psiquiatrica	Ponce
Puerto Rico	INSPIRA Clinical Research	San Juan
Romania	Spitalul Clinic de Psihiatrie Prof. Dr. Alexandru Obregia	Bucuresti
Romania	Spitalul Clinic de Psihiatrie Socola	Iasi
Romania	Spitalul Clinic de Urgenta pentru Copii "Louis Turcanu" Timisoara	Timisoara
Russian Federation	Sverdlov regional Psychiatric Clinical Hospital	Ekaterinburg
Russian Federation	Regional Government Institution Kipetsk Regional Psychoneurology Hospital	Lipetsk
Russian Federation	Nizhny Novgorod Regional State Institution of Healthcare	Novgorod
Russian Federation	SHI Regional Clinical Psychiatry Hospital of St. Sofia	Saratov
Russian Federation	FSBI "Bekhterev Psychoneurological Research Institute SPb Russia"	St. Petersburg
Russian Federation	St. Petersburg State Healthcare Institution (SPSHI)	St. Petersburg
Russian Federation	FSBSI "Scientific Research Institute of Mental Health"	Tomsk
Spain	Hospital Sant Joan de Deu	Barcelona
Spain	Hospital Marítimo de Torremolinos	Torremolinos	Málaga
Ukraine	RPsH #3 ?hildren Dept SHEI Ivano-Frankivsk SMU	Ivano Frankivsk
Ukraine	SI Institute of Children and Adolescents Healthcare of NAMSU	Kharkiv
Ukraine	SI Institute of Neurology, Psychiatry and Narcology of NAMSU	Kharkiv
Ukraine	CI Kherson Regional Psychiatric Hospital of Kherson RC	Kherson,Vil. Stepanivka
Ukraine	TMA Psychiatry in Kyiv Center of NT & Rehabilitation of Psychotic Conditions	Kyiv
Ukraine	CI Lviv Regional Clinical Psychiatric Hospital	Lviv
Ukraine	CI Odesa Regional Medical Center of Mental Health	Odesa
Ukraine	O.F. Maltcev Poltava RCPsH Children Dept Ukrainian Medical Stomatological Academy	Poltava
Ukraine	Ternopil RCCPH Dept of Psychiatry #9 (adolescent)& #8 (pediatric) Ternopil I.Ya. Gorbachevskyi SMU	Ternopil
Ukraine	M.I. Pyrogov VNMU Ch of Psych&Nar BO CI O.I. Yuschenko VRPsH	Vinnytsia
United Kingdom	Royal Cornhill Hospital	Aberdeen	Strathclyde
United Kingdom	Northcroft	Birmingham
United Kingdom	Royal Edinburgh Hospital	Edinburgh
United States	California Pharmaceutical Research Institute, Inc	Anaheim	California
United States	Atlanta Center for Medical Research	Atlanta	Georgia
United States	BioBehavioral Research of Austin	Austin	Texas
United States	Central Valley Medical Research	Bakersfield	California
United States	Kennedy Krieger Institute	Baltimore	Maryland
United States	Neurobehavioral Medicine Group, PLLC	Bloomfield Hills	Michigan
United States	Florida Clinical Research Center, LLC	Bradenton	Florida
United States	University of Virginia	Charlottesville	Virginia
United States	University of Cincinnati Medical Center	Cincinnati	Ohio
United States	University Hospitals Case Medical Center	Cleveland	Ohio
United States	ProScience Research Group	Culver City	California
United States	Pillar Clinical Research, LLC	Dallas	Texas
United States	Harmonex Neuroscience Research	Dothan	Alabama
United States	Diligent Clinical Trials, Inc	Downey	California
United States	BioBehavioral Research of Austin	El Campo	Texas
United States	Sarkis Clinical Trials - Parent	Gainesville	Florida
United States	Collaborative Neuroscience Network, LLC	Garden Grove	California
United States	Hartford Hospital	Hartford	Connecticut
United States	Global Clinical Trials, LLC	Irvine	California
United States	Lake Charles Clinical Trials, LLC	Lake Charles	Louisiana
United States	Research Strategies of Memphis, LLC	Memphis	Tennessee
United States	Baber Research Group	Naperville	Illinois
United States	Jersey Shore University Medical Center	Neptune	New Jersey
United States	Manhattan Behavioral Medicine, LLC	New York	New York
United States	Cutting Edge Research Group	Oklahoma City	Oklahoma
United States	Neuropsychiatric Research Center of Orange County	Orange	California
United States	Aspen Clinical Research	Orem	Utah
United States	APG Research, LLC	Orlando	Florida
United States	Asclepes Research	Panorama City	California
United States	CITrials, Inc. - Riverside & San Bernardino County	Riverside	California
United States	Finger Lakes Clinical Research	Rochester	New York
United States	Medical Research Group of Central Florida	Sanford	Florida
United States	Institute for Behavioral Medicine, LLC	Smyrna	Georgia
United States	Richmond Behavioral Associates	Staten Island	New York
United States	Family Psychiatry of The Woodlands, P.A.	The Woodlands	Texas
United States	Children's National Medical Center	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Sunovion

Countries where clinical trial is conducted

United States,  Belgium,  Bulgaria,  Colombia,  France,  Hungary,  Korea, Republic of,  Malaysia,  Mexico,  Philippines,  Poland,  Puerto Rico,  Romania,  Russian Federation,  Spain,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The primary efficacy variable is change from Baseline in the Positive and Negative Syndrome Scale (PANSS) total score at Week 6.		Baseline to 6 weeks	No
Secondary	Change from Baseline in Clinical Global Impression severity (CGI-S) scale at Day 4, Weeks 1, 2, 3, 4, 5, and 6		6 weeks	No
Secondary	Change from Baseline in PANSS total score at Day 4, Weeks 1, 2, 3, 4, and 5		5 weeks	No
Secondary	Change from Baseline in PANSS positive, negative, general psychopathology, and excitability subscale scores at Day 4, Weeks 1, 2, 3, 4, 5, and 6		6 weeks	No
Secondary	Proportion of responders, where response is based on = 20% improvement from Baseline in PANSS total score at Week 6		6 weeks	No
Secondary	Change from Baseline in Pediatric Quality of Life Enjoyment and Satisfaction Questionnaire (PQ-LES-Q) at Week 6		6 weeks	No
Secondary	Change from Baseline in Clinician-rated Children's Global Assessment Scale (CGAS) at Week 6		6 weeks	No
Secondary	Adverse Events		6 weeks	Yes
Secondary	Vital signs - will consist of supine systolic and diastolic blood pressures, respiration rate, heart rate, and oral body temperature		6 weeks	Yes
Secondary	Weight and Waist circumference		6 weeks	Yes
Secondary	CogState Computerized Cognitive Test Battery		6 weeks	Yes
Secondary	Barnes Akathisia Rating Scale (BARS)		6 weeks	Yes
Secondary	Abnormal Involuntary Movement Scale (AIMS)		6 weeks	Yes
Secondary	Simpson-Angus Scale (SAS)		6 weeks	Yes
Secondary	Columbia Suicide Severity Rating Scale (C-SSRS)		6 weeks	Yes
Secondary	Tanner Staging		6 weeks	Yes
Secondary	Menstrual Cyclicity - At Baseline, female subjects will be given a calendar to mark the beginning and end of each menses. History of menstrual cyclicity and irregularities will be collected at Visit 1.		6 weeks	Yes
Secondary	Proportion of remitters, defined as subjects who have score not exceeding 3(mild severity) for items P1, P3, N1, N4, N6, G5 and G9 of the PANSS at Week 6.		6 Weeks	No