PK, Safety, and Tolerability Study of RBP-7000 of Different Molecular Weight Polymer in Subjects With Schizophrenia

NCT02687984 | Completed Phase 1

• 1 other identifier: RB-US-15-0001
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 2

Brief Summary

Primary Objective: To assess the relative bioavailability of RBP-7000 formulated with 2 different molecular weights (MW) (low and high MW as test treatments) of poly (DL-lactide-co-glycolide) with a carboxylic acid end group (PLGH) polymer compared to intermediate MW PLGH polymer following single subcutaneous (SC) injection of RBP-7000 in subjects with stable schizophrenia. Secondary Objective: To evaluate the safety and tolerability of single SC injections of RBP-7000 using a PLGH polymer of 2 different MW (low and high MW as test treatments) compared to intermediate MW polymer in subjects with stable schizophrenia.

Conditions

Schizophrenia

Keywords

Schizophrenia; Long-acting Risperidone; Atrigel

Outcome Measures

Primary Outcomes (6)

• Initial Burst Parameters: Cmax of risperidone

  Maximum observed plasma concentration

  approximately 0-24 hours; Day 1 to Day 2

• Initial Burst Parameters: AUC0-24h of risperidone

  Area under the plasma concentration-time curve from time 0 to 24 hours post-dose; calculated using the linear trapezoidal rule.

  approximately 0-24 hours; Day 1 to Day 2

• Secondary Peak Parameters: Cmax of risperidone

  Maximum observed plasma concentration

  approximately 24-672 hours; Day 2 to Day 29

• Secondary Peak Parameters: AUCD2-D29 of risperidone

  Area under the plasma concentration-time curve from 24 hours post-dose (Day 2) to 672 hours post-dose (Day 29); calculated using the linear trapezoidal rule.

  approximately 24-672 hours; Day 2 to Day 29

• Overall Parameters: Cmax of risperidone

  Maximum observed plasma concentration

  Day 1 to Day 29

• Overall Parameters: AUCD1-D29 of risperidone

  Area under the plasma concentration-time curve from time 0 (Day 1) to 672 hours post-dose (Day 29); calculated using the linear trapezoidal rule.

  Day 1 to Day 29

Secondary Outcomes (7)

• Initial Burst Parameters: Cmax of 9-hydroxyrisperidone

  approximately 0-24 hours; Day 1 to Day 2

• Initial Burst Parameters: AUC0-24h of 9-hydroxyrisperidone

  approximately 0-24 hours; Day 1 to Day 2

• Secondary Peak Parameters: Cmax of 9-hydroxyrisperidone

  approximately 24-672 hours; Day 2 to Day 29

• Secondary Peak Parameters: AUCD2-D29 of 9-hydroxyrisperidone

  approximately 24-672 hours; Day 2 to Day 29

• Overall Parameters: Cmax of 9-hydroxyrisperidone

  Day 1 to Day 29

Study Arms (3)

RBP-7000 PLGH A

EXPERIMENTAL

A single subcutaneous injection of RBP-7000 containing 120 mg risperidone in the ATRIGEL® Delivery System formulated with 21 kDa PLGH polymer.

Drug: RBP-7000

RBP-7000 PLGH B

EXPERIMENTAL

A single subcutaneous injection of RBP-7000 containing 120 mg risperidone in the ATRIGEL® Delivery System formulated with 29 kDa PLGH polymer.

Drug: RBP-7000

RBP-7000 PLGH C

ACTIVE COMPARATOR

A single subcutaneous injection of RBP-7000 containing 120 mg risperidone in the ATRIGEL® Delivery System formulated with 26 kDa PLGH polymer. This intermediate molecular weight treatment serves as the reference treatment.

Drug: RBP-7000

Interventions

RBP-7000 DRUG

A single subcutaneous injection with doses of RBP-7000 containing 120 mg risperidone and either a low, high, or intermediate molecular weight PLGH polymer.

Also known as: Risperdal

RBP-7000 PLGH A; RBP-7000 PLGH B; RBP-7000 PLGH C

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 as defined by DSM-5 criteria.
• Clinically stable schizophrenia, as evidenced by the investigator evaluation, outpatient status for at least 30 days prior to screening, and confirmation of stability by a caregiver who has regular supportive contact with the subject.
• Otherwise healthy on the basis of physical examination.
• Body mass index (BMI) between 18 and 35 kg/m\^2 and weight of at least 49.9 kg at screening.

You may not qualify if:

• Subjects taking any oral risperidone product (except the test doses of 0.25 mg of risperidone); or subjects taking any risperidone or 9-hydroxyrisperidone sustained-release or depot formulation within 120 days prior to study screening; or subjects who have received the 3-month depot formulation of 9-hydroxyrisperidone within 2 years of study screening.
• Subjects taking a clinically relevant inducer or inhibitor of cytochrome P450 (CYP) 2D6, or CYP3A4, who have not undergone proper washout (minimum of 5 half-lives of the medication) of this prohibited medication prior to Day 1.
• Medications, which in the opinion of the Investigator in conjunction with the medical monitor, may be expected to significantly interfere with metabolism or excretion of risperidone and/or 9-hydroxyrisperidone; may be associated with a significant drug interaction with risperidone; or may pose a significant risk to a subject's participation in the study.
• Any natural products or herbal preparations including all vitamins and supplements throughout the study.
• Subjects with a history of cancer unless disease-free for ≥5 years (with the exception of resected basal cell or squamous cell carcinoma of the skin).
• Subjects with any other active medical condition/disorder/disease that may either compromise subject safety or interfere with the safety and/or outcome evaluation of the study drug.
• Subjects that had an exacerbation of schizophrenia in the last 30 days.
• Subjects with evidence or history (in the past 6 months prior to screening) of a significant hepatic disorder that may either compromise subject safety or interfere with the safety and/or outcome evaluation of the study drug, including:
• Acute or chronic hepatitis, including but not limited to hepatitis B or C.
• Total bilirubin \>1.5 x the upper limit of normal (ULN), or
• Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \>2x ULN.
• Subjects with a history of severe renal disease, or creatinine clearance \<60 mL/min
• Subjects with evidence or history of orthostatic hypotension within 6 months of screening.
• Subjects with absolute neutrophil count \<1.5x 10\^9/L (African and African/American \<1.2x 10\^9/L).
• Subjects with a history of drug-induced leucopenia.

Sponsors & Collaborators

• Indivior Inc.: lead

Study Sites (2)

Collaborative Neuroscience Network, LLC

Garden Grove, California, 92845, United States

Location

Collaborative Neuroscience Network

Torrance, California, 90502, United States

Location

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

Study Officials

• Study Director

  Indivior Inc.

  STUDY DIRECTOR

Study Design

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

Study Record Dates

• First Submitted: February 17, 2016
• First Posted: February 23, 2016
• Study Start: February 1, 2016
• Primary Completion: May 1, 2016
• Study Completion: May 1, 2016
• Last Updated: January 31, 2017

Record last verified: 2017-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)