An Open Label Study of Aripiprazole Intramuscular Injection in Subjects With Schizophrenia

Schizophrenia Clinical Trial

Official title:

An Open-label, Randomized, Parallel Arm, Bioavailability Trial of Aripiprazole IM Depot Administered in the Deltoid or Gluteal Muscle in Adult Subjects With Schizophrenia

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01646827
• Other study ID #: 31-11-290
• Status: Completed
• Phase: Phase 1
• First received: June 18, 2012
• Last updated: July 1, 2014
• Start date: May 2012
• Est. completion date: April 2013

Study information

• Verified date: July 2014
• Source: Otsuka Pharmaceutical Development & Commercialization, Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to determine whether aripiprazole injection into the shoulder or the buttocks produces similar effects in the body

Description:

Extended-release gluteal intramuscular (IM) injection of aripiprazole has been tested in subjects with schizophrenia for safety and tolerability. This study will compare the gluteal IM aripiprazole injection with deltoid IM aripiprazole injection for safety and tolerability.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 37
• Est. completion date: April 2013
• Est. primary completion date: April 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 64 Years

Eligibility

Inclusion Criteria:

• Diagnosis of schizophrenia

• Stabilized on oral antipsychotic medication

• Good physical health

• BMI 18 to 35 kg/m2

• Prior history of tolerating aripiprazole

Exclusion Criteria:

• Sexually active males who will not commit to utilizing 2 of the approved birth control methods or who will not remain abstinent during the trial and for 180 days following the last dose of trial medication, or have not had an orchidectomy or sexually active females of childbearing potential who will not commit to utilizing 2 of the approved birth control methods or who will not remain abstinent during the trial and for 150 days following the last dose of trial medication. Abstinence will be permitted if it is confirmed and documented at every trial visit. If employing birth control, 2 of the following precautions must be used: vasectomy, tubal ligation, vaginal diaphragm, intrauterine device, birth control pill, birth control depot injections, implant, condom or sponge with spermicide.

• Subjects who have met DSM-IV-TR criteria for substance abuse or dependence within the past 180 days; including alcohol and benzodiazepines, but excluding caffeine and nicotine.

• Subjects with a positive drug screen for cocaine or other drugs of abuse (excluding stimulants and other prescribed medications and marijuana).

• Use of any psychotropic medications other than their current antipsychotic medication.

• Use of any CYP2D6 and CYP3A4 inhibitors, or CYP3A4 inducers within 14 days (fluoxetine 28 days) prior to dosing and for the duration of the trial.

• Females who are pregnant or lactating.

• Subjects who had participated in a previous IM depot trial within the last one year; or who had previously enrolled and received trial medication in an aripiprazole IM depot clinical trial.

• Any major surgery within 30 days prior to enrollment.

• Evidence of organ dysfunction or any clinically significant deviation from normal in physical, electrocardiographic, or clinical laboratory examinations.

• Subjects who have a significant risk of committing suicide based on history, routine psychiatric status examination, investigator's judgment, or who have an answer of "yes" on questions 4 or 5 (current or over the last 30 days) on the Baseline/Screening version of the Columbia Suicide Severity Rating Scale (C-SSRS).

• Subjects currently in an acute relapse of schizophrenia.

• Subjects with a current DSM-IV-TR diagnosis other than schizophrenia, including schizoaffective disorder, major depressive disorder, bipolar disorder, delirium, dementia, amnestic or other cognitive disorders. Also, subjects with borderline, paranoid, histrionic, schizotypal, schizoid or antisocial personality disorder.

• Subjects who were considered treatment-resistant to antipsychotic medication.

• Subjects who have had electroconvulsive therapy within 2 months of administration of trial drug.

• Subjects with a history of neuroleptic malignant syndrome or clinically significant tardive dyskinesia as assessed by the investigator.

• Any other sound medical reason not to be entered into the trial, as determined by the clinical investigator.

• Subjects who are known to be allergic, intolerant, or unresponsive to prior treatment with aripiprazole or other quinolinones.

Study Design

Allocation: Randomized, Endpoint Classification: Bio-availability Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Schizophrenia

Intervention

Drug:
• Aripiprazole IM Depot
One injection of 400 mg aripiprazole IM depot

Locations

Country	Name	City	State
United States	Community Clinical Research, Inc.	Austin	Texas
United States	Comprehensive Clinical Development, Inc.	Cerritos	California
United States	Collaborative Neuroscience Network, Inc.	Garden Grove	California
United States	CNRI - San Diego	San Diego	California
United States	Neuropsychiatric Research Center of Orange County	Santa Ana	California
United States	Comprehensive Clinical Development, Inc.	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Otsuka Pharmaceutical Development & Commercialization, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum Observed Plasma Concentration (Cmax) of Aripriprazole	Relative bioavailability (Frel) of aripiprazole intramuscular (IM) depot injected in the deltoid muscle compared to the gluteal muscle based on aripiprazole maximum (peak) plasma concentrations (Cmax) PK parameter.	Day 1: 4 hr, 8 hr, and 12 hr post dose, Days 2, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 25, 28, 35, 42, 49, 56, 63, 70, 77, 84, 98, 112 and 126/Early termination	No
Primary	Area Under the Concentration-Time Curve Infinity (AUC Infinity); Area Under the Concentration-Time Curve 28 (AUC 28), and Area Under the Concentration-Time Curve t (AUC t): Aripiprazole	Relative bioavailability (Frel) of aripiprazole IM depot injected in the deltoid muscle compared to the gluteal muscle based on area under the concentration-time curve (AUC) from time zero to the time of last measurable concentration (AUCt), AUC time curve 28, and AUC from time zero to infinity PK parameters.	Day 1: 4 hr, 8 hr, and 12 hr post dose, Days 2, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 25, 28, 35, 42, 49, 56, 63, 70, 77, 84, 98, 112 and 126/Early termination	No
Primary	Maximum Observed Plasma Concentration (Cmax) of Dehydro-Aripiprazole	Relative bioavailability (Frel) of aripiprazole intramuscular (IM) depot injected in the deltoid muscle compared to the gluteal muscle based on aripiprazole maximum (peak) plasma concentrations (Cmax) PK parameter.	Day 1: 4 hr, 8 hr, and 12 hr post dose, Days 2, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 25, 28, 35, 42, 49, 56, 63, 70, 77, 84, 98, 112 and 126/Early termination	No
Primary	Area Under the Concentration-Time Curve Infinity (AUC Infinity); Area Under the Concentration-Time Curve 28 (AUC 28), and Area Under the Concentration-Time Curve t (AUC t): Dehydro-Aripiprazole	Relative bioavailability (Frel) of aripiprazole IM depot injected in the deltoid muscle compared to the gluteal muscle based on area under the concentration-time curve (AUC) from time zero to the time of last measurable concentration (AUCt), AUC time curve 28 and AUC from time zero to infinity PK parameters.	Day 1: 4 hr, 8 hr, and 12 hr post dose, Days 2, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 25, 28, 35, 42, 49, 56, 63, 70, 77, 84, 98, 112 and 126/Early termination	No
Secondary	Number of Participants Reporting Treatment Emergent Adverse Events (TEAE).	Safety was measured according to standard adverse event collection as described in the adverse event section of the results.	Starting at the time the ICF was signed to Day 126/Early termination	Yes
Secondary	Number of Participants With Laboratory Values of Potential Clinical Relevance.	The laboratory tests were collected and processed in accordance with directions from the clinical chemistry laboratory. Based on criteria for identifying laboratory values of potential clinical relevance, the abnormal values were noted. Some of the criteria are as follows: For fasting triglycerides: men: = 160 mg/dL and women: = 120 mg/dL; Fasting glucose: = 115 mg/dL; Prolactin: > upper limit of normal (ULN); Neutrophils: = 1,500/mm3; and Creatine phosphokinase: = 3 x ULN.	Day 1, Day 28, Day 126/Early termination	Yes
Secondary	Number of Participants With Vital Signs of Potential Clinical Relevance-Blood Pressure	Vital sign assessment included orthostatic (supine and standing) blood pressure. Orthostatic assessments were made after participants had been in the supine position for at least 5 minutes and again after participants had been standing for 2 minutes, but not more than 3 minutes. Orthostatic hypotension defined as >/= 20 mm Hg decrease in systolic blood pressure and >/= 25 beats per minute increase in heart rate from supine to standing.	Day 1, Day 14, Day 28 and Day 126/Early termination	Yes
Secondary	Number of Participants With Vital Signs of Potential Clinical Relevance-Temperature	Vital sign assessment included body temperature measured in centigrade(C). Temperatures >=37.8°C and increase of >= 1.1°C were recorded.	Day 1, Day 14, Day 28 and Day 126/Early termination	Yes
Secondary	Number of Participants With Vital Signs of Potential Clinical Relevance-Heart Rate	Vital sign assessment included heart rate (supine and standing). Heart rate with increase or decrease of >/= 15 beats per minute were recorded.	Day 1, Day 14, Day 28 and Day 126/Early termination	Yes
Secondary	Number of Participants With Electrocardiogram (ECG) Measurements of Potential Clinical Relevance	Three 12 lead ECGs were performed approximately 5 minutes apart at each time point. The participant were supine and at rest (for at least 10 minutes) prior to the first ECG and will remain supine through the final ECG. Based on criteria for identifying ECG measurements of potential clinical relevance, the abnormal values were noted. Some of the criteria are as follows: For bradycardia: = 50 beats per minute (bpm); and for increase in QTc: QTc = 450msec.	Day 1, Day 14, Day 28 and Day 126/Early termination	Yes
Secondary	Visual Analog Scale (VAS) Score at Day 1, Day 14, Day 28 and Last Visit.	Injection site pain was assessed using a VAS, which was completed by the trial participant, and the investigator's assessment of most recent injection site, which was completed by the investigator. VAS is 100 mm line, 0=no pain, 100=unbearably painful.	Day 1, Day 14, Day 28 and last visit	Yes
Secondary	Number of Participants With Categorical Scores on the Columbia Suicide Severity Rating Scale.	This scale consists of a baseline evaluation that assesses the lifetime experience of the participant with suicide events and suicidal ideation and a post baseline evaluation that focuses on suicidality since the last trial visit.	Screening, Baseline, Week 1, Week 2, Week 8, Week 18 visit and Last visit.	Yes