Lurasidone Pediatric Bipolar Study

Bipolar I Depression Clinical Trial

— Illuminate  

Official title:

A Randomized, 6-Week, Double-blind, Placebo-Controlled, Flexible Dose, Parallel-Group Study to Evaluate the Efficacy and Safety of Lurasidone in Children and Adolescent Subjects With Bipolar I Depression

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02046369
• Other study ID #: D1050326
• Secondary ID: 2013-004903-37
• Status: Completed
• Phase: Phase 3
• First received: January 23, 2014
• Last updated: November 20, 2017
• Start date: March 2014
• Est. completion date: October 2016

Study information

• Verified date: November 2017
• Source: Sunovion
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

A study to evaluate efficacy and safety of flexibly dosed Lurasidone in children and adolescents with bipolar I depression

Description:

This is a randomized, parallel, double-blind, placebo-controlled study designed to evaluate the efficacy and safety of flexibly dosed lurasidone (20 - 80 mg/day) for 6 weeks compared with placebo in children and adolescent subjects with depression associated with Bipolar I Disorder (bipolar depression).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 350
• Est. completion date: October 2016
• Est. primary completion date: October 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 10 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. If emancipated, subjects must provide written informed consent. In accordance with Institutional Review Board (IRB) requirements, the subject will complete an informed assent prior to study participation.

• Male or female subjects 10 to 17 years of age, inclusive with bipolar I disorder, most recent episode depressed, with or without rapid cycling disease course (= 4 episodes of mood disturbance but < 8 episodes in the previous 12 months) and without psychotic features (diagnosed by DSM-V criteria, and confirmation of the bipolar I disorder 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]). Note: The current episode of major depression associated with bipolar I disorder must be confirmed by the investigator and noted in the source records.

• Subject has a lifetime history of at least one manic episode. A reliable informant (eg, family member or caregiver) or medical records must be able to confirm this history.

• Subject's current major depressive episode is = 4 weeks and less than 12 months in duration.

• CDRS-R score = 45 at screening and Baseline.

• YMRS score = 15 (with YMRS Item 1 [elevated mood] score = 2) at screening and Baseline.

• Within 3rd to 97th percentile for gender specific BMI-for-age growth charts from the World Health Organization (WHO) growth charts

• 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 7 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 (eg, 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 7 days after the last dose of study drug has been taken.

• 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.

• Subjects may have a lifetime diagnosis of ADHD. If a subject is taking psychostimulants for ADHD, they must have been on a stable treatment regimen of these medication(s) for 30 days prior to screening and the treatment regimen is expected to remain stable throughout the study. This must be confirmed by the investigator and noted in the source records.

Exclusion Criteria:

• Has an Axis I or Axis II (DSM-IV or any DSM-5) diagnosis other than bipolar I disorder that has been the primary focus of treatment within 3 months of screening.

• Subject has been hospitalized for a bipolar manic or mixed episode within the 30 days prior to randomization.

• Has a history or current diagnosis of intellectual disability, autism spectrum disorder, 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.

• CDRS-R total score > 85 at screening or Baseline

• Demonstrates a decrease (improvement) of = 25% in the CDRS-R adjusted total score between Screening and Baseline visits, or the CDRS-R is below 45 at 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 prior adequate trials (ie, adequate dose and duration) of an antipsychotic agent within the current episode of depression, or subject has a history of non-response to an adequate (6-week) trial of three or more antidepressants (with or without mood stabilizers) during the current episode.

• 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.

• 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.

• 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 substance abuse disorder (with the exception of caffeine or tobacco) based on DSM-5 criteria within the last 6 months prior to screening.

• Positive test results at screening or Baseline for:

1. Urine drugs of abuse (including amphetamines/methamphetamines, barbiturates, benzodiazepines, cocaine, opioids, phencyclidine, and cannabinoids). A positive test for amphetamines/methamphetamines, barbiturates, opioids, or benzodiazepines 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), 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 screening.

• 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, atomoxetine or alpha 2 agonists (eg, guanfacine) 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 all psychotropic medications prior to randomization with the exception of those medications explicitly permitted within 3 days prior to randomization (7 days prior to randomization for aripiprazole).

• 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 or has a score of 7 on item 13, Suicidal Ideation, on the CDRS-R.

• 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.

• Subject with newly diagnosed Type 2 diabetes during screening or subject is on injectable medication for the treatment of Type 2 diabetes. 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.

• The use of concomitant medications that are potent inducers or inhibitors of the cytochrome P450 (CYP) 3A4 enzyme system during the trial (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).

Related Conditions & MeSH terms

• Bipolar I Depression
• Depression
• Depressive Disorder

Intervention

Drug:
• Lurasidone
Lurasidone flexibly dosed 20-80 mg once daily
• Placebo
Placebo Comparator once daily

Locations

Country	Name	City	State
Bulgaria	MHC - Ruse, EOOD	Ruse
Bulgaria	MHAT-Targovishte, AD	Targovishte
Bulgaria	DCC "Mladost M" - Varna, OOD	Varna
Colombia	Centro de Investigaciones y Proyectos en Neurociencias CIPNA	Barranquilla
Colombia	Centro de Investigaciones del Sistema Nervioso Limitada - Grupo CISNE Ltda	Bogota
France	CHU Nantes - Hôpital Mère-Enfant	Nantes Cedex 1
France	Hôpitaux Pédiatriques de Nice CHU-Lenval	Nice	Alpes Maritimes
Hungary	Vadaskert Alapitvany a Gyermekek Lelki Egeszsegeert	Budapest
Hungary	Bekes Megyei Pandy Kalman Korhaz	Gyula
Korea, Republic of	Chonnam National University Hospital	Gwangju	Jeollanam-do
Korea, Republic of	Inha University Hospital	Incheon
Korea, Republic of	Chonbuk National University Hospital	Jeonju	Jeollabuk-do
Korea, Republic of	Seoul National University Bundang Hospital	Seongnam-si
Korea, Republic of	Seoul National University Hospital	Seoul
Korea, Republic of	Severance Hospital, Yonsei University Health System	Seoul
Mexico	Centro para el Desarrollo de la Medicina y de Asistencia Medica Especializada S.C.	Culiacan
Mexico	Instituto de Investigaciones Aplicadas a la Neurociencia A.C.	Durango
Mexico	Accelerium S. de R.L. de C.V.	Monterrey	Nuevo León
Mexico	Instituto de Informacion de Investigacion en Salud Mental	Monterrey
Mexico	Consultorio Especializado Psiquiatría Infantil y Adolescentes	San Luis Potosí
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	NZOZ Poradnia Zdrowia Psychicznego	Kobierzyce
Poland	Wojewodzki Szpital Zespolony im. L. Rydygiera w Toruniu	Torun
Poland	Instytut Psychiatrii i Neurologii	Warsawa
Puerto Rico	INSPIRA Clinical Research	San Juan
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
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	Chair of Psychiatry and Narcology, Vinnytsia National Medical University, O.I. Yushchenko Regional Psychoneurological Hospital	Vinnytsia
United States	Atlanta Center for Medical Research	Atlanta	Georgia
United States	BioBehavioral Research of Austin	Austin	Texas
United States	Kennedy Krieger Institute	Baltimore	Maryland
United States	Neurobehavioral Medicine Group, PLLC	Bloomfield Hills	Michigan
United States	Pacific Institute Of Medical Sciences	Bothell	Washington
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	Ericksen Research & Development, LLC	Clinton	Utah
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	Sarkis Clinical Trials - Parent	Gainesville	Florida
United States	North Shore/Long Island Jewish PRIME	Glen Oaks	New York
United States	Hartford Hospital	Hartford	Connecticut
United States	Lake Charles Clinical Trials, LLC	Lake Charles	Louisiana
United States	Capstone Clinical Research, Inc.	Libertyville	Illinois
United States	Research Strategies of Memphis, LLC	Memphis	Tennessee
United States	Bioscience Research, LLC	Mount Kisco	New York
United States	Jersey Shore University Medical Center	Neptune	New Jersey
United States	Cutting Edge Research of Enid	Oklahoma City	Oklahoma
United States	Aspen Clinical Research	Orem	Utah
United States	APG Research, LLC	Orlando	Florida
United States	Psychiatric Associates	Overland Park	Kansas
United States	Clinical Research Partners, LLC	Petersburg	Virginia
United States	Finger Lakes Clinical Research	Rochester	New York
United States	St. Charles Psychiatric Associates	Saint Charles	Missouri
United States	Attalla Consultants, LLC	Smyrna	Georgia
United States	Richmond Behavioral Associates	Staten Island	New York
United States	Family Psychiatry of The Woodlands, P.A.	The Woodlands	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Sunovion

Countries where clinical trial is conducted

United States,  Bulgaria,  Colombia,  France,  Hungary,  Korea, Republic of,  Mexico,  Philippines,  Poland,  Puerto Rico,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in the Children's Depression Rating Scale, Revised (CDRS-R) Total Score as Compared to Placebo From Double-Blind Baseline to Week 6 (Day 43) Baseline	CDRS-R total score: changes from baseline over time - mixed model for repeated measures. LS Mean and SE for change from baseline are based on Mixed Model for Repeated Measures.; The CDRS-R total score ranges from 17-113. In general, higher values of CDRS-R total score represent greater severity of illness.; The primary efficacy endpoint will be assessed between the placebo and treatment group.	baseline, Week 6
Secondary	Change From Baseline in Pediatric Anxiety Rating Scale (PARS) Score as Compared to Placebo.	PARS score: changes from baseline over time - mixed model for repeated measures-LS Mean and SE for change from baseline are based on Mixed Model for Repeated Measures.The PARS is a clinician-rated instrument for assessing over time the severity of anxiety symptoms associated with common DSM-IV anxiety disorders in children ages 6-17 years. The PARS is administered separately to the subject and to the caregiver. The instrument has 2 sections. The first section includes a 50-item symptom checklist, which the clinician rates as present or absent during the past week. The second section is comprised of 7 severity impairment items reflecting the severity/impairment of all symptoms endorsed in Section 1 of the PARS (during the past week). Each question is answered on a 0-5 Likert scale (0 for none, and 1-5 for minimal to extreme) with alternative responses of 8=Not Applicable and 9=Does Not Know. The PAR total score over all 7 questions ranges in value from 0 to 35.	baseline and week 6
Secondary	Change From Baseline in Pediatric Quality of Life Enjoyment and Satisfaction Questionnaire (PQ-LES-Q) Score as Compared to Placebo.	PQ-LES-Q percentage maximum possible score: changes from baseline over time - mixed model for repeated measures; LS Mean and SE for change from baseline are based on Mixed Model for Repeated Measures	baseline
Secondary	Change From Baseline in Clinician-rated Children's Global Assessment Scale (CGAS) Score as Compared to Placebo.	CGAS Score: changes from baseline over time - mixed model for repeated measures. LS Mean and SE for change from baseline are based on Mixed Model for Repeated Measures. LS Mean and SE for change from baseline are based on Mixed Model for Repeated Measures	baseline and week 6
Secondary	Change From Baseline in Attention-Deficit/Hyperactivity Disorder Rating Scale (ADHD-RS) Score as Compared to Placebo.	ADHD-RS total score: changes from baseline over time -ANCOVA-LS Mean and SE for change from baseline are based on ANCOVA. The Pediatric Quality of Life Enjoyment and Satisfaction Questionnaire (PQ-LES-Q is a 15-item self-report measure of the degree of enjoyment and satisfaction in various areas of daily living, based on the content of the Short From of the Q-LES-Q. Each item is rated on a 5-point scale, ranging from 1 (very poor) to 5 (very good). The first 14 items are the same as the General Activities section of the regular Q-LES-Q form and are used to compute the raw score. The PQ-LES-Q-SF percentage maximum possible score is calculated as follows:% Max = 100 × (Raw Score - Minimum Score) / (Maximum Score - Minimum Score),where the Minimum Score equals 14 and the Maximum Score equals 70, and the % maximum possible score can range from 0% to 100%. Higher scores indicate better quality of life.	baseline and week 6
Secondary	Change From Baseline in Clinical Global Impressions-Bipolar-Severity (CGI-BP-S) Depression Score	Change from baseline in Clinical Global Impressions-Bipolar-Severity (CGI-BP-S) depression score changes from baseline over time - mixed model for repeated measures. LS Mean and SE for change from baseline are based on Mixed Model for Repeated Measures.The CGI-BP-S is a three-question clinician-rated assessment of the subject's current illness state (depression, mania, and overall) using a 7-point scale (1(normal, not ill) to 7 (very severely ill)) for each question, where a higher score is associated with greater illness severity.	baseline and week 6