A Trial of Single- and Multiple-doses of Aripiprazole in Adult Subjects With Schizophrenia or Bipolar I Disorder

NCT03854409 | Completed Phase 1 FDA Drug

• 1 other identifier: 031-201-00279
• Study Type: interventional
• Target: 72
• Locations: 1 country
• Sites: 4

Brief Summary

The primary objective of this trial is to evaluate the pharmacokinetics (PK) of aripiprazole long-acting injectable (LAI) (420 mg) following deltoid or gluteal muscle administration in adult subjects with schizophrenia or bipolar I disorder.

Conditions

Schizophrenia; Bipolar I Disorder

Outcome Measures

Primary Outcomes (31)

• Part A - Single Dose Group: Maximum Observed Plasma Concentration (Cmax) for Aripiprazole and Dehydro-Aripiprazole

  Day 1 to Day 126

• Part B - Group 1: Maximum Observed Plasma Concentration (Cmax) for Aripiprazole and Dehydro-Aripiprazole

  Day 1 to Day 57

• Part B - Group 2: Maximum Observed Plasma Concentration (Cmax) for Aripiprazole and Dehydro-Aripiprazole

  Day 1 to Day 57

• Part A - Single Dose Group: Plasma Concentration at 28 Days Postdose (C28) for Aripiprazole and Dehydro-Aripiprazole

  Day 28

• Part B - Group 1: Plasma Concentration at 28 Days Postdose (C28) for Aripiprazole and Dehydro-Aripiprazole

  Day 28

• Part B - Group 2: Plasma Concentration at 28 Days Postdose (C28) for Aripiprazole and Dehydro-Aripiprazole

  Day 28

• Part A - Single Dose Group: Time to Reach the Maximum Plasma Concentration (Tmax) for Aripiprazole and Dehydro-Aripiprazole

  Day 1 to Day 126

• Part B - Group 1: Time to Reach the Maximum Plasma Concentration (Tmax) for Aripiprazole and Dehydro-Aripiprazole

  Day 1 to Day 57

• Part B - Group 2: Time to Reach the Maximum Plasma Concentration (Tmax) for Aripiprazole and Dehydro-Aripiprazole

  Day 1 to Day 57

• Part A - Single Dose Group: Area Under the Concentration-Time Curve from time Zero to Time t (the Last Observable Concentration; AUCt) for Aripiprazole and Dehydro-Aripiprazole

  Day 1 to Day 126

• Part B - Group 1: Area Under the Concentration-Time Curve from time Zero to Time t (the Last Observable Concentration; AUCt) for Aripiprazole and Dehydro-Aripiprazole

  Day 1 to Day 57

• Part B - Group 2: Area Under the Concentration-Time Curve from time Zero to Time t (the Last Observable Concentration; AUCt) for Aripiprazole and Dehydro-Aripiprazole

  Day 1 to Day 57

• Part A - Single Dose Group: Area Under the Concentration-Time Curve from Time Zero to 28 Days Postdose (AUC0-28) for Aripiprazole and Dehydro-Aripiprazole

  Day 1 to Day 28

• Part B - Group 1: Area Under the Concentration-Time Curve from Time Zero to 28 Days Postdose (AUC0-28) for Aripiprazole and Dehydro-Aripiprazole

  Day 1 to Day 28

• Part B - Group 2: Area Under the Concentration-Time Curve from Time Zero to 28 Days Postdose (AUC0-28) for Aripiprazole and Dehydro-Aripiprazole

  Day 1 to Day 28

• Part A - Single Dose Group: Area Under the Plasma Concentration-time Curve from Time 0 to Infinity for Aripiprazole (AUC∞) for Aripiprazole and Dehydro-Aripiprazole

  Day 1 to Day 126

• Part B - Group 1: Area Under the Plasma Concentration-time Curve from Time 0 to Infinity for Aripiprazole (AUC∞) for Aripiprazole and Dehydro-Aripiprazole

  Day 1 to Day 57

• Part B - Group 2: Area Under the Plasma Concentration-time Curve from Time 0 to Infinity for Aripiprazole (AUC∞) for Aripiprazole and Dehydro-Aripiprazole

  Day 1 to Day 57

• Part A - Single Dose Group: Terminal Phase Elimination Half-life (T1/2) for Aripiprazole and Dehydro-Aripiprazole

  Day 1 to Day 126

• Part B - Group 1: Terminal Phase Elimination Half-life (T1/2) for Aripiprazole and Dehydro-Aripiprazole

  Day 1 to Day 57

• Part B - Group 2: Terminal Phase Elimination Half-life (T1/2) for Aripiprazole and Dehydro-Aripiprazole

  Day 1 to Day 57

• Part A - Single Dose Group: Oral Clearance (CL/F) for Aripiprazole Only

  Apparent clearance of the drug from plasma after extravascular administration (CL/F).

  Day 1 to Day 126

• Part B - Group 1: Oral Clearance (CL/F) for Aripiprazole Only

  Apparent clearance of the drug from plasma after extravascular administration (CL/F).

  Day 1 to Day 57

• Part B - Group 2: Oral Clearance (CL/F) for Aripiprazole Only

  Apparent clearance of the drug from plasma after extravascular administration (CL/F).

  Day 1 to Day 57

• Part A - Multiple Dose Group: Maximum Observed Plasma Concentration (Cmax) for Aripiprazole and Dehydro-Aripiprazole (Following the Fifth Dose Only)

  Fifth dose will be administered on Day 113.

  Day 113 to Day 169

• Part A - Multiple Dose Group: Plasma Concentration at 28 Days Postdose (C28) for Aripiprazole and Dehydro-Aripiprazole

  Day 29, Day 57, Day 84, Day 113, Day 141 (All post-dose)

• Part A - Multiple Dose Group: Time to Reach the Maximum Plasma Concentration (Tmax) (Following the Fifth Dose Only) for Aripiprazole and Dehydro-Aripiprazole

  Participants will receive their 5th dose on Day 113.

  Day 113 to Day 169

• Part A - Multiple Dose Group: Area Under the Concentration-Time Curve from Time Zero to 28 Days Postdose (AUC0-28) (Following the Fifth Dose Only) for Aripiprazole and Dehydro-Aripiprazole

  Participants will receive their 5th dose on Day 113.

  Day 113 to Day 169

• Part A - Multiple Dose Group: Terminal Phase Elimination Half-life (T1/2) (Following the Fifth Dose Only) for Aripiprazole and Dehydro-Aripiprazole

  Participants will receive their 5th dose on Day 113.

  Day 113 to Day 169

• Part A - Multiple Dose Group: Oral Clearance (CL/F) (Following the Fifth Dose Only; for Aripiprazole Only)

  Participants will receive their 5th dose on Day 113.

  Day 113 to Day 169

• Part A - Multiple Dose Group: Ratio of Dehydro-Aripiprazole to Aripiprazole C28 and AUC0-28 (Following the Fifth Dose Only)

  Participants will receive their 5th dose on Day 113.

  Day 113 (following fifth dose) to Day 141

Secondary Outcomes (48)

• Part A - Single Dose: Number of Participants with an Adverse Event (AE)

  Day 1 to End of Trial (Maximum 126 Days from First Dose)

• Part A - Multiple Dose: Number of Participants with an Adverse Event (AE)

  Day 1 to End of Trial (Maximum 169 Days from First Dose)

• Part B: Number of Participants with an Adverse Event (AE)

  Day 1 to End of Trial (Maximum 57 Days from First Dose)

• Part A - Single Dose: Number of Participants with Markedly Abnormal Vital Sign Measurements

  Baseline to End of Trial (Maximum 126 Days from First Dose)

• Part A - Multiple Dose: Number of Participants with Markedly Abnormal Vital Sign Measurements

  Baseline to End of Trial (Maximum 169 Days from First Dose)

Study Arms (7)

Part A - Deltoid Site: Single Dose Group

EXPERIMENTAL

Participants will receive a single dose of aripiprazole LAI.

Drug: Aripiprazole

Part A - Gluteal Site: Single Dose Group

EXPERIMENTAL

Participants will receive a single dose of aripiprazole LAI.

Drug: Aripiprazole

Part A - Deltoid Site: Multiple Dose Group

EXPERIMENTAL

Participants will receive five injections of aripiprazole LAI, administered at monthly intervals.

Drug: Aripiprazole

Part A - Gluteal Site: Multiple Dose Group

EXPERIMENTAL

Participants will receive five injections of aripiprazole LAI, administered at monthly intervals.

Drug: Aripiprazole

Part B - Gluteal Site: Group 1 (X)

EXPERIMENTAL

Participants will receive a single dose of aripiprazole LAI.

Drug: Aripiprazole

Part B - Gluteal Site: Group 1 (Y)

EXPERIMENTAL

Participants will receive a single dose of aripiprazole LAI.

Drug: Aripiprazole

Part B - Gluteal Site: Group 2

EXPERIMENTAL

Participants will receive a single dose of aripiprazole LAI.

Drug: Aripiprazole

Interventions

Aripiprazole DRUG

Injection.

Also known as: (OPC-14597)

Part A - Deltoid Site: Multiple Dose Group; Part A - Deltoid Site: Single Dose Group; Part A - Gluteal Site: Multiple Dose Group; Part A - Gluteal Site: Single Dose Group; Part B - Gluteal Site: Group 1 (X); Part B - Gluteal Site: Group 1 (Y); Part B - Gluteal Site: Group 2

Eligibility Criteria

• Age: 18 Years - 64 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Male and female subjects between 18 and 64 years of age, inclusive.
• Body mass index of 18 to 35 kg/m2, inclusive.
• A current diagnosis of schizophrenia or a current diagnosis of bipolar I disorder as defined by DSM-5 criteria.
• Prior history of tolerating aripiprazole per investigator's judgment.

You may not qualify if:

• Subjects who have met DSM-5 criteria for substance dependence within the past 180 days
• Use of any psychotropic medications other than their current non-aripiprazole antipsychotic or mood stabilizer(s) medication or subjects who use more than one antipsychotic or mood stabilizer(s) medication at screening.
• Subjects may not receive varenicline beyond screening.
• Use of any prescription medication not specifically approved by the medical monitor.
• Females who are pregnant or lactating. A negative serum pregnancy test must be confirmed prior to the first dose of IMP for all female subjects.
• Subjects who had participated in any clinical trial involving a psychotropic medication within 1 month prior to enrollment; subjects who had participated in a previous aripiprazole LAI trial within the last 1 year (ie, enrolled but did not receive aripiprazole LAI); or who had previously enrolled and received IMP in an aripiprazole LAI clinical trial.
• Any major surgery within 30 days prior to enrollment or scheduled/elective surgery during the trial.
• Subjects currently in an acute relapse of schizophrenia.
• Subjects with a current DSM-5 diagnosis other than schizophrenia or bipolar I disorder
• Electroconvulsive therapy must not be conducted within 2 months prior to administration of the IMP
• Subjects with a history of neuroleptic malignant syndrome or clinically significant tardive dyskinesia as assessed by the investigator.
• History of or current hepatitis or acquired immunodeficiency syndrome or carriers of HBsAg, anti-HCV, and/or HIV antibodies.
• History of any significant drug allergy or known or suspected hypersensitivity, in particular to aripiprazole or other quinolinones.
• Subjects deemed intolerant of receiving injections.

Sponsors & Collaborators

• Otsuka Pharmaceutical Development & Commercialization, Inc.: lead
• PRA Health Sciences: collaborator
• H. Lundbeck A/S: collaborator

Study Sites (4)

Woodland International Research Group

Little Rock, Arkansas, 72211, United States

Location

Collaborative Neuroscience Network

Garden Grove, California, 92845, United States

Location

Hassman Research Institute

Berlin, New Jersey, 08009, United States

Location

Community Clinical Research

Austin, Texas, 78754, United States

Location

MeSH Terms

Conditions

Schizophrenia

Interventions

Aripiprazole

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Quinolones; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 12, 2019
• First Posted: February 26, 2019
• Study Start: January 31, 2019
• Primary Completion: April 5, 2019
• Study Completion: February 20, 2020
• Last Updated: September 2, 2020

Record last verified: 2019-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: Data will be available after marketing approval in global markets, or beginning 1-3 years following article publication. There is no end date to the availability of the data.
• Access Criteria: Otsuka will share data on an Otsuka-owned remotely accessible data sharing platform with Python and R analytical software. Research requests should be directed to clinicaltransparency@Otsuka-us.com

Locations

US (4)