Clinical trial NCT01911429: Pediatric Schizophrenia Efficacy and Safety Study
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Schizophrenia
Keywords: schizophrenia
Lurasidone
Latuda
Lead sponsor: Sumitomo Pharma America, Inc.
Sponsor class: INDUSTRY
First posted: 2013-07-30
Enrollment: 327
Sex: ALL
Minimum age (years): 13
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Efficacy and Safety study of Lurasidone in pediatric patients.

Detailed 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.

Eligibility criteria: 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).

Primary outcomes:
measure: Change From Baseline in the Positive and Negative Syndrome Scale (PANSS) Total Score at Week 6.
timeFrame: Baseline to 6 weeks
Secondary outcomes:
measure: Change From Baseline in Clinical Global Impression Severity (CGI-S) Scale
timeFrame: baseline, week 6
measure: Change From Baseline in PANSS Positive Subscale Scores
timeFrame: baseline, week 6
measure: Change From Baseline in PANSS Positive, Negative Subscale Scores
timeFrame: baseline, week 6
measure: Proportion of Responders, Where Response is Based on ≥ 20% Improvement From Baseline in PANSS Total Score at Week 6
timeFrame: week 6
measure: Change From Baseline in Pediatric Quality of Life Enjoyment and Satisfaction Questionnaire (PQ-LES-Q)
timeFrame: baseline, week 6
measure: Change From Baseline in Clinician-rated Children's Global Assessment Scale (CGAS)
timeFrame: baseline, week 6
measure: Change From Baseline in PANSS General Psychopathology Subscale Scores
timeFrame: baseline, week 6
measure: Change From Baseline in PANSS Excitability Subscale Scores
timeFrame: baseline, week 6
Other outcomes:
Locations:
city: Dothan
country: United States
facility: Harmonex Neuroscience Research
state: Alabama
city: Anaheim
country: United States
facility: California Pharmaceutical Research Institute, Inc
state: California
city: Bakersfield
country: United States
facility: Central Valley Medical Research
state: California
city: Culver City
country: United States
facility: ProScience Research Group
state: California
city: Downey
country: United States
facility: Diligent Clinical Trials, Inc
state: California
city: Garden Grove
country: United States
facility: Collaborative Neuroscience Network, LLC
state: California
city: Irvine
country: United States
facility: Global Clinical Trials, LLC
state: California
city: Orange
country: United States
facility: Neuropsychiatric Research Center of Orange County
state: California
city: Panorama City
country: United States
facility: Asclepes Research
state: California
city: Riverside
country: United States
facility: CITrials, Inc. - Riverside & San Bernardino County
state: California
city: Hartford
country: United States
facility: Hartford Hospital
state: Connecticut
city: Washington
country: United States
facility: Children's National Medical Center
state: District of Columbia
city: Bradenton
country: United States
facility: Florida Clinical Research Center, LLC
state: Florida
city: Gainesville
country: United States
facility: Sarkis Clinical Trials - Parent
state: Florida
city: Orlando
country: United States
facility: APG Research, LLC
state: Florida
city: Sanford
country: United States
facility: Medical Research Group of Central Florida
state: Florida
city: Atlanta
country: United States
facility: Atlanta Center for Medical Research
state: Georgia
city: Smyrna
country: United States
facility: Institute for Behavioral Medicine, LLC
state: Georgia
city: Naperville
country: United States
facility: Baber Research Group
state: Illinois
city: Lake Charles
country: United States
facility: Lake Charles Clinical Trials, LLC
state: Louisiana
city: Baltimore
country: United States
facility: Kennedy Krieger Institute
state: Maryland
city: Bloomfield Hills
country: United States
facility: Neurobehavioral Medicine Group, PLLC
state: Michigan
city: Neptune
country: United States
facility: Jersey Shore University Medical Center
state: New Jersey
city: New York
country: United States
facility: Manhattan Behavioral Medicine, LLC
state: New York
city: Rochester
country: United States
facility: Finger Lakes Clinical Research
state: New York
city: Staten Island
country: United States
facility: Richmond Behavioral Associates
state: New York
city: Cincinnati
country: United States
facility: University of Cincinnati Medical Center
state: Ohio
city: Cleveland
country: United States
facility: University Hospitals Case Medical Center
state: Ohio
city: Oklahoma City
country: United States
facility: Cutting Edge Research Group
state: Oklahoma
city: Memphis
country: United States
facility: Research Strategies of Memphis, LLC
state: Tennessee
city: Austin
country: United States
facility: BioBehavioral Research of Austin
state: Texas
city: Dallas
country: United States
facility: Pillar Clinical Research, LLC
state: Texas
city: El Campo
country: United States
facility: BioBehavioral Research of Austin
state: Texas
city: The Woodlands
country: United States
facility: Family Psychiatry of The Woodlands, P.A.
state: Texas
city: Orem
country: United States
facility: Aspen Clinical Research
state: Utah
city: Charlottesville
country: United States
facility: University of Virginia
state: Virginia
city: Bruxelles
country: Belgium
facility: Universitair Ziekenhuis Brussel
city: Ruse
country: Bulgaria
facility: MHC - Ruse, EOOD
city: Sofia
country: Bulgaria
facility: UMHAT "Alexandrovska" EAD
city: Targovishte
country: Bulgaria
facility: MHAT-Targovishte, AD
city: Varna
country: Bulgaria
facility: MHAT 'Sv. Marina', EAD
city: Barranquilla
country: Colombia
facility: Centro de Investigaciones y Proyectos en Neurociencias CIPNA
city: Bello
country: Colombia
facility: E.S.E. Hospital Mental de Antioquia
city: Bogota
country: Colombia
facility: Centro de Investigaciones del Sistema Nervioso Limitada - Grupo CISNE Ltda
city: Nantes Cedex 1
country: France
facility: CHU Nantes - Hôpital Mère-Enfant
state: Loire Atlantique
city: Nice
country: France
facility: Hôpitaux Pédiatriques de Nice CHU-Lenval
city: Budapest
country: Hungary
facility: Vadaskert Alapitvany a Gyermekek Lelki Egeszsegeert
city: Gyula
country: Hungary
facility: Bekes Megyei Pandy Kalman Korhaz
city: Incheon
country: Korea, Republic of
facility: Inha University Hospital
city: Jeonju-si
country: Korea, Republic of
facility: Chonbuk National University Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital, Yonsei University Health System
city: Lembah Pantai
country: Malaysia
facility: University Malaya Medical Centre
state: Kuala Lumpur
city: Culiacan
country: Mexico
facility: Centro para el Desarrollo de la Medicina y de Asistencia Medica Especializada S.C.
city: Monterrey
country: Mexico
facility: Accelerium S. de R.L. de C.V.
city: Monterrey
country: Mexico
facility: Instituto de Informacion de Investigacion en Salud Mental
city: Daveo City
country: Philippines
facility: Alexian Brothers Health and Wellness Center
city: Iloilo City
country: Philippines
facility: West Visayas State University Medical Center
city: Mandaluyong City
country: Philippines
facility: National Center for Mental Health
city: Quezon City
country: Philippines
facility: Veterans Memorial Medical Center
city: Torun
country: Poland
facility: Wojewodzki Szpital Zespolony im. L. Rydygiera w Toruniu
city: Tyniec Maly
country: Poland
facility: NZOZ Poradnia Zdrowia Psychicznego
city: Warszawa
country: Poland
facility: Instytut Psychiatrii i Neurologii
city: Caguas
country: Puerto Rico
facility: Centro de Investigacion Clinica Psiquiatrica
city: Ponce
country: Puerto Rico
facility: Centro de Investigacion Clinica Psiquiatrica
city: San Juan
country: Puerto Rico
facility: INSPIRA Clinical Research
city: Bucuresti
country: Romania
facility: Spitalul Clinic de Psihiatrie Prof. Dr. Alexandru Obregia
city: Iasi
country: Romania
facility: Spitalul Clinic de Psihiatrie Socola
city: Timisoara
country: Romania
facility: Spitalul Clinic de Urgenta pentru Copii "Louis Turcanu" Timisoara
city: Ekaterinburg
country: Russian Federation
facility: Sverdlov regional Psychiatric Clinical Hospital
city: Lipetsk
country: Russian Federation
facility: Regional Government Institution Kipetsk Regional Psychoneurology Hospital
city: Novgorod
country: Russian Federation
facility: Nizhny Novgorod Regional State Institution of Healthcare
city: Saratov
country: Russian Federation
facility: SHI Regional Clinical Psychiatry Hospital of St. Sofia
city: St. Petersburg
country: Russian Federation
facility: St. Petersburg State Healthcare Institution (SPSHI)
city: St. Petersburg
country: Russian Federation
facility: FSBI "Bekhterev Psychoneurological Research Institute SPb Russia"
city: Tomsk
country: Russian Federation
facility: FSBSI "Scientific Research Institute of Mental Health"
city: Torremolinos
country: Spain
facility: Hospital Marítimo de Torremolinos
state: Málaga
city: Barcelona
country: Spain
facility: Hospital Sant Joan de Deu
city: Ivano Frankivsk
country: Ukraine
facility: RPsH #3 Сhildren Dept SHEI Ivano-Frankivsk SMU
city: Kharkiv
country: Ukraine
facility: SI Institute of Neurology, Psychiatry and Narcology of NAMSU
city: Kharkiv
country: Ukraine
facility: SI Institute of Children and Adolescents Healthcare of NAMSU
city: Kherson,Vil. Stepanivka
country: Ukraine
facility: CI Kherson Regional Psychiatric Hospital of Kherson RC
city: Kyiv
country: Ukraine
facility: TMA Psychiatry in Kyiv Center of NT & Rehabilitation of Psychotic Conditions
city: Lviv
country: Ukraine
facility: CI Lviv Regional Clinical Psychiatric Hospital
city: Odesa
country: Ukraine
facility: CI Odesa Regional Medical Center of Mental Health
city: Poltava
country: Ukraine
facility: O.F. Maltcev Poltava RCPsH Children Dept Ukrainian Medical Stomatological Academy
city: Ternopil
country: Ukraine
facility: Ternopil RCCPH Dept of Psychiatry #9 (adolescent)& #8 (pediatric) Ternopil I.Ya. Gorbachevskyi SMU
city: Vinnytsia
country: Ukraine
facility: M.I. Pyrogov VNMU Ch of Psych&Nar BO CI O.I. Yuschenko VRPsH
city: Aberdeen
country: United Kingdom
facility: Royal Cornhill Hospital
state: Strathclyde
city: Birmingham
country: United Kingdom
facility: Northcroft
city: Edinburgh
country: United Kingdom
facility: Royal Edinburgh Hospital
Study officials:
affiliation: Sumitomo Pharma America, Inc.
name: Lurasidone Medical Director
role: STUDY_DIRECTOR
References: