Lurasidone Pediatric Bipolar Study (Illuminate)

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by Sunovion
Sponsor:
Information provided by (Responsible Party):
Sunovion
ClinicalTrials.gov Identifier:
NCT02046369
First received: January 23, 2014
Last updated: July 31, 2014
Last verified: July 2014
  Purpose

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


Condition Intervention Phase
Bipolar I Depression
Drug: Lurasidone
Drug: 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 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

Resource links provided by NLM:


Further study details as provided by Sunovion:

Primary Outcome Measures:
  • 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) [ Time Frame: 6 Weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Change from Baseline in Pediatric Anxiety Rating Scale (PARS) score as compared to placebo. [ Time Frame: 6 Weeks ] [ Designated as safety issue: No ]
  • Change from Baseline in Pediatric Quality of Life Enjoyment and Satisfaction Questionnaire (PQ-LES-Q) score as compared to placebo. [ Time Frame: 6 Weeks ] [ Designated as safety issue: No ]
  • Change from Baseline in Clinician-rated Children's Global Assessment Scale (CGAS) score as compared to placebo. [ Time Frame: 6 Weeks ] [ Designated as safety issue: No ]
  • Proportion of responders, where response is defined as ≥ 50% reduction from Baseline in adjusted CDRS-R total score at last observation carried forward (LOCF) Endpoint as compared to placebo. [ Time Frame: 6 Weeks ] [ Designated as safety issue: No ]
  • Proportion of subjects achieving remission, where remission is defined as post-baseline CDRS-R Total Score ≤ 28 and Young Mania Rating Scale (YMRS) total score ≤ 8 and Clinical Global Impressions-Bipolar Version Severity (CGI-BP-S) depression score ≤ 3. [ Time Frame: 6 Weeks ] [ Designated as safety issue: No ]
  • Change from Baseline in Attention-Deficit/Hyperactivity Disorder Rating Scale (ADHD-RS) score as compared to placebo. [ Time Frame: 6 Weeks ] [ Designated as safety issue: No ]
  • Proportions of subjects with adverse events (AEs), discontinuations due to AEs, and serious AEs (SAEs) [ Time Frame: 6 Weeks ] [ Designated as safety issue: Yes ]
  • Frequency and severity of suicidality using the Columbia Suicide Severity Rating Scale (C-SSRS) [ Time Frame: 6 Weeks ] [ Designated as safety issue: Yes ]
  • Vital signs and ECG measurements [ Time Frame: 6 Weeks ] [ Designated as safety issue: Yes ]
  • Movement disorders assessed by the Barnes Akathisia Rating Scale (BARS), the Abnormal Involuntary Movement Scale (AIMS), and the Simpson-Angus Scale (SAS) [ Time Frame: 6 Weeks ] [ Designated as safety issue: Yes ]
  • Weight, body mass index (BMI), and waist circumference [ Time Frame: 6 Weeks ] [ Designated as safety issue: Yes ]
  • Laboratory measures (including hormonal parameters), Tanner staging, menstrual cyclicity (female subjects), and physical examinations [ Time Frame: 6 Weeks ] [ Designated as safety issue: Yes ]
  • CogState Computerized Cognitive Test Battery [ Time Frame: 6 Weeks ] [ Designated as safety issue: Yes ]
  • Udvalg for Kliniske Undersogelser Side Effect Rating Scale (UKU) [ Time Frame: 6 Weeks ] [ Designated as safety issue: Yes ]
  • Proportion of subjects with treatment-emergent mania, defined as a YMRS score of ≥ 20 on any 2 consecutive visits or at the final assessment, or an AE of mania or hypomania. [ Time Frame: 6 Weeks ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 340
Study Start Date: March 2014
Estimated Study Completion Date: May 2016
Estimated Primary Completion Date: May 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Luradisone
Luradisone 20- 80 mg administered once daily
Drug: Lurasidone
Lurasidone flexibly dosed 20-80 mg once daily
Other Name: Latuda
Placebo Comparator: Placebo
Placebo administered once daily
Drug: Placebo
Placebo Comparator once daily

Detailed 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).

  Eligibility

Ages Eligible for Study:   10 Years to 17 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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. 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).
  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: NCT02046369

Contacts
Contact: Study Manager 1-866-503-6351

  Show 27 Study Locations
Sponsors and Collaborators
Sunovion
Investigators
Study Director: Medical Director, MD Sunovion
  More Information

No publications provided

Responsible Party: Sunovion
ClinicalTrials.gov Identifier: NCT02046369     History of Changes
Other Study ID Numbers: D1050326, 2013-004903-37
Study First Received: January 23, 2014
Last Updated: July 31, 2014
Health Authority: United States: Food and Drug Administration
Bulgaria: Bulgarian Drug Agency
China: Ministry of Health
Colombia: National Institutes of Health
Italy: The Italian Medicines Agency
Korea: Food and Drug Administration
Mexico: Ministry of Health
Philippines : Food and Drug Administration
Romania: National Medicines Agency
Serbia: Medicines and Medical Devices Agency
Spain: Ministry of Health
Ukraine: Ministry of Health

Keywords provided by Sunovion:
Lurasidone, Latuda, Bipolar Depression

Additional relevant MeSH terms:
Depression
Depressive Disorder
Behavioral Symptoms
Mood Disorders
Mental Disorders

ClinicalTrials.gov processed this record on August 21, 2014