Study of Lurasidone in Treating Antipsychotic Naive or Quasi-Naive Children and Adolescents
Study Details
Study Description
Brief Summary
The overarching purpose of this pilot study is to collect preliminary data regarding the variability of weight gain associated with lurasidone (Latuda©) treatment of antipsychotic naive children and adolescents in order to inform decisions about including a lurasidone arm in a future large scale trial of different approaches to minimize antipsychotic associated weight gain in the pediatric population. In adults, lurasidone appears to cause minimal weight gain. The participants will be 6-19 years old with psychotic spectrum, mood spectrum, or autism spectrum disorders. They will have 4 weeks or less of lifetime antipsychotic exposure.
Detailed Description
This is a multi-site, 12-week, open-label study assessing the weight and metabolic changes associated with lurasidone treatment. Antipsychotic (AP) naive subjects will start open-label treatment by following a flexible titration schedule. Quasi-antipsychotic naive subjects (less than 4 weeks of total AP treatment) will be started on lurasidone and tapered off the other antipsychotic over an estimated 4 weeks depending on the dose and tolerability of the prior antipsychotic. Other psychoactive medications including antidepressants, benzodiazepines, stimulants, alpha-2 agonists, and mood stabilizers are allowed as long as the dose is not changed, unless it is clinically necessary. Assessments of weight, efficacy, and side effects are conducted at baseline, week 2, week 4, week 8, and week 12. The primary outcome is percent change in weight. The secondary outcomes include psychiatric efficacy measures and side effects.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Flexible Dose Latuda© Lurasidone (Latuda©)dose will be determined solely by the clinician in accordance with the best interests of each participant. |
Drug: Latuda©
All subjects will be started on 20-40mg of Latuda© at night (suggested intake with food). Subsequently, the dose may be increased as clinically indicated and based on tolerability every 7 days by 20-40mg to a maximum of 160mg per day with food which may be given as a single or twice daily dose depending on participant's preference. The maintenance dose will be determined solely by the clinician in accordance with the best interests of each participant.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Change in Weight [Baseline to 12 weeks]
Change in weight from Baseline to Week 12 will be assessed as the primary outcome measure. Subjects will be asked to step on a special scale called a tanita which will calculate weight, fat mass at each study visit.
Secondary Outcome Measures
- Proportion of Participants Completing Treatment [12 weeks]
Data will be collected on why participants terminated the study. If terminated early, the specific reason will be collected such as efficacy or tolerability.
- Changes in Efficacy Measures [Baseline to 12 weeks]
Efficacy measures included the Aberrant Behavior Checklist-Community (ABC-C) total score which focuses on problem behaviors in five subdomains, including irritability, attention, repetitive behaviors, unusual speech, and social withdrawal. Differences in subdomains were not assessed. The ABC-C total score is the sum of 58 items, each rated among 0 = Not at all; 1 = Slight in degree; 2 = Moderately serious; and 3 = Severe in degree. The ABC-C total score ranges from 0 to 174. Higher values of ABC-C total scores represent greater severity of illness.
- Number of Participants Experiencing Side Effects [Baseline to12 weeks]
Assessment of the medication side effects associated with lurasidone (Latuda©) in children and adolescents.
- Overall Clinical Improvement [Baseline to 12 weeks]
Overall psychiatric functioning will be assessed with the improvement (CGI-I) subscales of the CGI. CGI-I items are rated from 1 (very much improved) to 7 (very much worse).
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Male and female children and adolescents between 6 and 19 years of age of any race or ethnicity
-
Subject must meet Diagnostic Statistical Manual (DSM)-IV-Text Revision (TR) criteria for a psychotic spectrum, mood spectrum or autism spectrum disorder as defined by one of the following diagnoses:
-
schizophrenia (any type)
-
schizoaffective disorder
-
schizophreniform disorder
-
psychosis Not Otherwise Specified (NOS)
-
autistic disorder with significant irritability/aggression (Aberrant Behavioral Checklist-Community (ABC-C) Irritability subscale score of greater than or equal to 18)
-
Asperger syndrome with significant irritability/aggression (ABC-C Irritability subscale score of greater than or equal to 18)
-
pervasive developmental disorder NOS with significant irritability/aggression (ABC-C Irritability subscale score of greater than or equal to 18)
-
bipolar type I
-
bipolar type II
-
mood disorder NOS
-
major depression with psychotic features
-
major depression (unresponsive to 2 different antidepressants)
-
severe mood dysregulation (SMD) according to Leibenluft and colleagues broad spectrum bipolar disorder
-
Subjects must have ≤ 4 weeks of lifetime exposure to an antipsychotic medication at any dosage. These medications include olanzapine (Zyprexa©), quetiapine (Seroquel©), risperidone (Risperdal©), ziprasidone (Geodon©), aripiprazole (Abilify©), asenapine (Saphris©), iloperidone (Fanapt©), lurasidone (Latuda©), haloperidol, chlorpromazine, perphenazine, fluphenazine, thiothixene, or clozapine
-
Subjects on other psychoactive medications are asked not to change dose of those medications during the course of the study unless clinically necessary
-
Sexually active girls must agree to use two effective forms of birth control (i.e. hormonal or spermicidal and barrier) or be abstinent)
-
Primary caretaker is able to participate in study appointments as is clinically indicated
-
Ability of child to participate in all aspects of the protocol per investigator's clinical judgment
-
After considering all aspects of study participation the subject (if an adult) or subject's parent or Legally Authorized Representative (LAR) must consent to participation
-
After considering all aspects of study participation, the subject must assent to participation if it is developmentally appropriate to obtain assent
Exclusion Criteria:
-
Based on current or lifetime DSM-IV-TR criteria, a diagnosis of Eating Disorder (Anorexia Nervosa or Bulimia Nervosa)
-
Based on DSM-IV-TR criteria, a diagnosis of Substance Dependence Disorder (other than tobacco dependence) within the past month
-
Treatment with the following concomitant medications: strong CYP3A4 inhibitors (ex: Ketoconazole), strong CYP3A4 inducers (ex: Rifampin)
-
Current or past treatment with lurasidone (Latuda©) that resulted in a non-response or intolerance
-
Females who are pregnant or breast-feeding
-
Ongoing or previously undisclosed child abuse requiring new department of social service intervention
-
Subjects who, in the Investigator's opinion, might not be suitable for the study
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | University of North Carolina | Chapel Hill | North Carolina | United States | 27517 |
Sponsors and Collaborators
- University of North Carolina, Chapel Hill
- Foundation of Hope, North Carolina
Investigators
- Principal Investigator: Linmarie Sikich, MD, University of North Carolina, Chapel Hill
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 12-2302
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Flexible Dose Latuda© |
|---|---|
| Arm/Group Description | Lurasidone (Latuda©)dose will be determined solely by the clinician in accordance with the best interests of each participant. Latuda©: All subjects will be started on 20-40mg of Latuda© at night (suggested intake with food). Subsequently, the dose may be increased as clinically indicated and based on tolerability every 7 days by 20-40mg to a maximum of 160mg per day with food which may be given as a single or twice daily dose depending on participant's preference. The maintenance dose will be determined solely by the clinician in accordance with the best interests of each participant. |
| Period Title: Overall Study | |
| STARTED | 9 |
| COMPLETED | 7 |
| NOT COMPLETED | 2 |
Baseline Characteristics
| Arm/Group Title | Flexible Dose Latuda© |
|---|---|
| Arm/Group Description | Lurasidone (Latuda©)dose will be determined solely by the clinician in accordance with the best interests of each participant. Latuda©: All subjects will be started on 20-40mg of Latuda© at night (suggested intake with food). Subsequently, the dose may be increased as clinically indicated and based on tolerability every 7 days by 20-40mg to a maximum of 160mg per day with food which may be given as a single or twice daily dose depending on participant's preference. The maintenance dose will be determined solely by the clinician in accordance with the best interests of each participant. |
| Overall Participants | 9 |
| Age (years) [Mean (Standard Deviation) ] | |
| Mean (Standard Deviation) [years] |
11.4
(3.2)
|
| Sex: Female, Male (Count of Participants) | |
| Female |
5
55.6%
|
| Male |
4
44.4%
|
| Race (NIH/OMB) (Count of Participants) | |
| American Indian or Alaska Native |
0
0%
|
| Asian |
0
0%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
| Black or African American |
0
0%
|
| White |
8
88.9%
|
| More than one race |
1
11.1%
|
| Unknown or Not Reported |
0
0%
|
| Region of Enrollment (participants) [Number] | |
| United States |
9
100%
|
Outcome Measures
| Title | Change in Weight |
|---|---|
| Description | Change in weight from Baseline to Week 12 will be assessed as the primary outcome measure. Subjects will be asked to step on a special scale called a tanita which will calculate weight, fat mass at each study visit. |
| Time Frame | Baseline to 12 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Flexible Dose Latuda© |
|---|---|
| Arm/Group Description | Lurasidone (Latuda©)dose will be determined solely by the clinician in accordance with the best interests of each participant. Latuda©: All subjects will be started on 20-40mg of Latuda© at night (suggested intake with food). Subsequently, the dose may be increased as clinically indicated and based on tolerability every 7 days by 20-40mg to a maximum of 160mg per day with food which may be given as a single or twice daily dose depending on participant's preference. The maintenance dose will be determined solely by the clinician in accordance with the best interests of each participant. |
| Measure Participants | 9 |
| Mean (95% Confidence Interval) [lbs] |
0.70
|
| Title | Proportion of Participants Completing Treatment |
|---|---|
| Description | Data will be collected on why participants terminated the study. If terminated early, the specific reason will be collected such as efficacy or tolerability. |
| Time Frame | 12 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Flexible Dose Latuda© |
|---|---|
| Arm/Group Description | Lurasidone (Latuda©)dose will be determined solely by the clinician in accordance with the best interests of each participant. Latuda©: All subjects will be started on 20-40mg of Latuda© at night (suggested intake with food). Subsequently, the dose may be increased as clinically indicated and based on tolerability every 7 days by 20-40mg to a maximum of 160mg per day with food which may be given as a single or twice daily dose depending on participant's preference. The maintenance dose will be determined solely by the clinician in accordance with the best interests of each participant. |
| Measure Participants | 9 |
| Count of Participants [Participants] |
7
77.8%
|
| Title | Changes in Efficacy Measures |
|---|---|
| Description | Efficacy measures included the Aberrant Behavior Checklist-Community (ABC-C) total score which focuses on problem behaviors in five subdomains, including irritability, attention, repetitive behaviors, unusual speech, and social withdrawal. Differences in subdomains were not assessed. The ABC-C total score is the sum of 58 items, each rated among 0 = Not at all; 1 = Slight in degree; 2 = Moderately serious; and 3 = Severe in degree. The ABC-C total score ranges from 0 to 174. Higher values of ABC-C total scores represent greater severity of illness. |
| Time Frame | Baseline to 12 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Flexible Dose Latuda© |
|---|---|
| Arm/Group Description | Lurasidone (Latuda©)dose will be determined solely by the clinician in accordance with the best interests of each participant. Latuda©: All subjects will be started on 20-40mg of Latuda© at night (suggested intake with food). Subsequently, the dose may be increased as clinically indicated and based on tolerability every 7 days by 20-40mg to a maximum of 160mg per day with food which may be given as a single or twice daily dose depending on participant's preference. The maintenance dose will be determined solely by the clinician in accordance with the best interests of each participant. |
| Measure Participants | 9 |
| Mean (95% Confidence Interval) [units on a scale] |
-14
|
| Title | Number of Participants Experiencing Side Effects |
|---|---|
| Description | Assessment of the medication side effects associated with lurasidone (Latuda©) in children and adolescents. |
| Time Frame | Baseline to12 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Flexible Dose Latuda© |
|---|---|
| Arm/Group Description | Lurasidone (Latuda©)dose will be determined solely by the clinician in accordance with the best interests of each participant. Latuda©: All subjects will be started on 20-40mg of Latuda© at night (suggested intake with food). Subsequently, the dose may be increased as clinically indicated and based on tolerability every 7 days by 20-40mg to a maximum of 160mg per day with food which may be given as a single or twice daily dose depending on participant's preference. The maintenance dose will be determined solely by the clinician in accordance with the best interests of each participant. |
| Measure Participants | 9 |
| Count of Participants [Participants] |
3
33.3%
|
| Title | Overall Clinical Improvement |
|---|---|
| Description | Overall psychiatric functioning will be assessed with the improvement (CGI-I) subscales of the CGI. CGI-I items are rated from 1 (very much improved) to 7 (very much worse). |
| Time Frame | Baseline to 12 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Flexible Dose Latuda© |
|---|---|
| Arm/Group Description | Lurasidone (Latuda©)dose will be determined solely by the clinician in accordance with the best interests of each participant. Latuda©: All subjects will be started on 20-40mg of Latuda© at night (suggested intake with food). Subsequently, the dose may be increased as clinically indicated and based on tolerability every 7 days by 20-40mg to a maximum of 160mg per day with food which may be given as a single or twice daily dose depending on participant's preference. The maintenance dose will be determined solely by the clinician in accordance with the best interests of each participant. |
| Measure Participants | 9 |
| Mean (Standard Deviation) [units on a scale] |
2.67
(1.32)
|
Adverse Events
| Time Frame | ||
|---|---|---|
| Adverse Event Reporting Description | ||
| Arm/Group Title | Flexible Dose Latuda© | |
| Arm/Group Description | Lurasidone (Latuda©)dose will be determined solely by the clinician in accordance with the best interests of each participant. Latuda©: All subjects will be started on 20-40mg of Latuda© at night (suggested intake with food). Subsequently, the dose may be increased as clinically indicated and based on tolerability every 7 days by 20-40mg to a maximum of 160mg per day with food which may be given as a single or twice daily dose depending on participant's preference. The maintenance dose will be determined solely by the clinician in accordance with the best interests of each participant. | |
All Cause Mortality |
||
| Flexible Dose Latuda© | ||
| Affected / at Risk (%) | # Events | |
| Total | 0/9 (0%) | |
Serious Adverse Events |
||
| Flexible Dose Latuda© | ||
| Affected / at Risk (%) | # Events | |
| Total | 0/9 (0%) | |
Other (Not Including Serious) Adverse Events |
||
| Flexible Dose Latuda© | ||
| Affected / at Risk (%) | # Events | |
| Total | 3/9 (33.3%) | |
| Gastrointestinal disorders | ||
| Nausea | 3/9 (33.3%) | 3 |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Dr. Linmarie Sikich |
|---|---|
| Organization | UNC-Chapel Hill |
| Phone | |
| linmarie_sikich@med.unc.edu |
- 12-2302