Safety, Tolerability, Pharmacokinetics and Efficacy of 180 mg Subcutaneous Risperidone From 6 mg Oral Risperidone

NCT03978832 | Completed Phase 4 Results FDA Drug

• 1 other identifier: INDV-7000-401
• Study Type: interventional
• Target: 69
• Locations: 1 country
• Sites: 1

Brief Summary

This study evaluates PERSERIS at a higher dose than what has been administered in previous clinical trials. Subjects with stable schizophrenia on a dose of 5-6 mg oral risperidone will be switched to PERSERIS at the higher dose, which is believed to be similar to the oral dose

Conditions

Schizophrenia

Outcome Measures

Primary Outcomes (1)

• Steady-state Average Plasma Concentration (Cavg,ss) of Risperidone and Total Active Moiety

  Cavg,ss for risperidone and total active moiety after oral and SC administration

  0-12 hours post-dose on Day -1, and 0-672 hours after Dose 3

Secondary Outcomes (18)

• Assessment of Local Injection Site Tolerability*

  First injection at Day 1 until last injection administered at Day 85

• The Number of Participants With TEAEs as Assessed by Local Injection Site*

  First injection at Day 1 until Day 120

• The Number of Participants With TEAEs as Assessed by Changes in Vital Signs

  Time subjects sign the informed consent form throughout the study until EOS (Day 113)

• The Number of Participants With TEAEs as Assessed by Changes in ECG

  Time participants sign the informed consent form throughout the study until EOS (Day 113)

• The Number of Participants With TEAEs as Assessed by Changes in Body Weight

  Time subjects sign the informed consent form throughout the study until EOS (Day 113)

Study Arms (1)

Oral Risperidone followed by PERSERIS

EXPERIMENTAL

All subjects will receive 2 SC injections of PERSERIS at each study visit every 28 days for a total of 4 visits of 2 injections each. The first 3 visit injections will be administered in the abdomen and the final visit injections will be administered in the back of the upper arm.

Drug: PERSERIS; Drug: Risperidone

Interventions

PERSERIS DRUG

PERSERIS is an extended-release SC injectable suspension administered once-monthly

Also known as: long acting risperidone

Oral Risperidone followed by PERSERIS

Risperidone DRUG

Oral risperidone

Also known as: Risperdal

Oral Risperidone followed by PERSERIS

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of schizophrenia
• Clinically stable as defined as no hospitalizations for acute exacerbations within 3 months of screening and Screening PANSS score ≤70
• Total body mass index (BMI) between 18 and 35 kg/m2
• Given written informed consent

You may not qualify if:

• Received a once-monthly long-acting injectable (LAI) antipsychotic within 60 days of screening and a once every 3 month LAI antipsychotic within 120 days of screening
• Taking the following concurrent or over the counter (OTC) products:
• Inducers or inhibitors of CYP2D6 within 14 days or 5 half-lives whichever is greater prior to study screening
• Bupropion, chlorpheniramine, cimetidine, clomipramine, doxepin or quinidine within 30 days prior to study screening
• Clozapine, phenothiazines, aripiprazole, haloperidol or any other antipsychotic other than oral risperidone within 14 days prior to study screening
• Selective serotonin reuptake inhibitors (SSRIs) or serotonin-norepinephrine reuptake inhibitors (SNRIs) within 30 days prior to study screening
• Opioids or opioid-containing analgesics within 14 days prior to study screening
• Medications, in the addition to those listed above which in the opinion of the Investigator in conjunction with the medical monitor, may be expected to significantly interfere with the metabolism or excretion of risperidone and/or 9-hydroxyrisperidone, that may be associated with a significant drug interaction with risperidone, or that may pose a significant risk to subjects' participation in the study. The medical monitor should be contacted with any questions regarding the use of CYP2D6 or 3A4 inducers or inhibitors in particular.
• History of cancer (with the exception of resected basal cell or squamous cell carcinoma of the skin) unless they have been disease free for ≥5 years.
• Another active medical condition or organ disease that may either compromise subject safety or interfere with the safety and/or outcome evaluation of the study drug.
• Evidence or history of a significant hepatic disorder that may either compromise subject safety or interfere with the safety and/or outcome evaluation of the study drug. Individuals with acute or chronic hepatitis (including but not limited to hepatitis B or C); or individuals with 1) total bilirubin \>1.5x the upper limit of normal (ULN) and/or 2) alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \>3x ULN will be excluded.
• A history of renal disease, or a creatinine clearance of less than 60 mL/min (as determined by the Cockcroft-Gault formula).
• A history of orthostatic hypotension, syncope, significant low white blood cell (WBC) count (i.e., based on absolute neutrophil count or drug-induced leukopenia or other medical conditions including, but not limited to, history of heart attack (i.e., myocardial infarction) or brain injury (i.e., traumatic with loss of consciousness and/or cardiovascular accident) within a year of Screening and clinically significant low blood pressure or arrhythmias as interpreted by the principal investigator (PI).
• Corrected QT interval \[Fridericia's calculation (QTcF)\] \>450 msec (male) or \>470 msec (female) at screening or prior to administration of the 1st dose of PERSERIS, or with a known history of Torsades de Points, or family member with sudden unexplained cardiac death.
• Known to have AIDS (acquired immunodeficiency syndrome) or to be HIV (human immunodeficiency virus) positive.

Sponsors & Collaborators

• Indivior Inc.: lead

Study Sites (1)

Collaborative Neuroscience Network

Garden Grove, California, 92845, United States

Location

Related Publications (1)

• Walling DP, Shinde SN, Pogoda JM, Kharidia J, Laffont CM. An Open-Label Study to Assess Monthly Risperidone Injections (180 mg) Following Switch from Daily Oral Risperidone (6 mg) in Stable Schizophrenic Patients. Clin Drug Investig. 2024 Apr;44(4):251-260. doi: 10.1007/s40261-024-01347-1. Epub 2024 Feb 22.

  PMID: 38388986 DERIVED

MeSH Terms

Conditions

Schizophrenia

Interventions

Risperidone

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: PERSERIS Medicines Development Lead and Head Global Clinical Operations and Development
• Organization: Indivior Inc

regan.fong@indivior.com

804 379-1090

Study Officials

• David Walling

  Collaborative Neuroscience Network

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: The study will enroll subjects currently on a stable dose of 5 or 6 mg of oral risperidone. After screening, eligible subjects will be admitted to the clinical unit and stabilized on 6 mg daily (3 mg oral risperidone twice a day) for 5 days, followed by an additional 3 days, during which the first injection of PERSERIS will be administered. Subjects will then return to the clinical unit every 28 days for an additional 3 admit periods for subsequent PERSERIS injections (2 injections per visit).

Study Record Dates

• First Submitted: May 30, 2019
• First Posted: June 7, 2019
• Study Start: June 28, 2019
• Primary Completion: May 12, 2020
• Study Completion: May 12, 2020
• Last Updated: July 7, 2021
• Results First Posted: July 7, 2021

Record last verified: 2021-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)