Multiple Ascending Dose Study of the Safety, Tolerability, Pharmacokinetic/Efficacy

NCT ID: NCT01677377

Last Updated: 2018-10-23

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 45 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-08-31
• Study Completion Date: 2013-04-30

Brief Summary

Evaluate the safety and tolerability of multiple subcutaneous injections of various dosages of risperidone with clinically stable schizophrenia

Detailed Description

This will be an open-label, Phase 2A, multiple ascending dose study in 1 to 3 sites, designed to evaluate the safety, tolerability, and pharmacokinetic (PK) profile of multiple subcutaneous injections of 60mg, 90mg, and 120mg doses of risperidone in the RBP-7000 formulation, in subjects with clinically-stable schizophrenia who are on a once daily stable dose of 2mg, 3mg, or 4mg of oral risperidone.

Conditions

Schizophrenia

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: FACTORIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Cohort 1, RBP-7000 60 mg

Participants who were stable on 2 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 60 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 2 mg oral daily risperidone on days 85-87.

Group Type: EXPERIMENTAL

Risperidone

Intervention Type: DRUG

Oral risperidone was supplied as 2, 3, or 4 mg tablets in blister packs or bottles and taken daily only during the oral dosing periods of the study, days -14 through -8 (if applicable), days -7 through -1, and days 85 through 87.

RBP-7000

Intervention Type: DRUG

RBP-7000 60 mg, 90 mg, and 120 mg were a mixture of the ATRIGEL® Delivery System and 60 mg, 90 mg, or 120 mg risperidone, respectively. Treatment was delivered as subcutaneous injections on study days 1, 29 and 57.

Cohort 2, RBP-7000 90 mg

Participants who were stable on 3 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 90 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 3 mg oral daily risperidone on days 85-87.

Group Type: EXPERIMENTAL

Risperidone

Intervention Type: DRUG

Oral risperidone was supplied as 2, 3, or 4 mg tablets in blister packs or bottles and taken daily only during the oral dosing periods of the study, days -14 through -8 (if applicable), days -7 through -1, and days 85 through 87.

RBP-7000

Intervention Type: DRUG

RBP-7000 60 mg, 90 mg, and 120 mg were a mixture of the ATRIGEL® Delivery System and 60 mg, 90 mg, or 120 mg risperidone, respectively. Treatment was delivered as subcutaneous injections on study days 1, 29 and 57.

Cohort 3, RBP-7000 120 mg

Participants who were stable on 4 mg oral daily risperidone during the run-in period received 3 single,unblinded, subcutaneous (SC) injection doses of 120 mg risperidone in RBP-7000 on study days 1, 29 and 57. Participants returned to 4 mg oral daily risperidone on days 85-87.

Group Type: EXPERIMENTAL

Risperidone

Intervention Type: DRUG

Oral risperidone was supplied as 2, 3, or 4 mg tablets in blister packs or bottles and taken daily only during the oral dosing periods of the study, days -14 through -8 (if applicable), days -7 through -1, and days 85 through 87.

RBP-7000

Intervention Type: DRUG

RBP-7000 60 mg, 90 mg, and 120 mg were a mixture of the ATRIGEL® Delivery System and 60 mg, 90 mg, or 120 mg risperidone, respectively. Treatment was delivered as subcutaneous injections on study days 1, 29 and 57.

Interventions

Risperidone

Oral risperidone was supplied as 2, 3, or 4 mg tablets in blister packs or bottles and taken daily only during the oral dosing periods of the study, days -14 through -8 (if applicable), days -7 through -1, and days 85 through 87.

Intervention Type: DRUG

RBP-7000

RBP-7000 60 mg, 90 mg, and 120 mg were a mixture of the ATRIGEL® Delivery System and 60 mg, 90 mg, or 120 mg risperidone, respectively. Treatment was delivered as subcutaneous injections on study days 1, 29 and 57.

Intervention Type: DRUG

Other Intervention Names

Risperdal; risperidone in Atrigel

Eligibility Criteria

Inclusion Criteria

• Male and female
• > 18 to < 65 years
• Diagnosis of paranoid, residual, or undifferentiated schizophrenia as defined by Diagnostic and Statistical Manual of Mental Disorders-IV-Text Revision (DSM-IV-TR) criteria

• Status: clinically stable subjects defined as subjects with no hospitalizations for acute exacerbations within 3 months of screening and screening total Positive and Negative Syndrome Scale (PANSS) score < 60
• Subjects who have given written informed consent

Exclusion Criteria

• Subjects taking any risperidone sustained release formulation within the 60 days prior to study screening
• Subjects taking the following concurrent medication/over-the-counter products:
• Inducers or inhibitors of cytochrome P450 2D6 (CYP-2D6) within 14 days or 7 half - lives (whichever occurs last) 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 (e.g., fluoxetine, paroxetine) or serotonin-norepinephrine reuptake inhibitors (e.g., venlafaxine, desvenlafaxine, duloxetine) within 30 days prior to study screening
• Opioids or opioid-containing analgesics within 14 days prior to study screening
• Medications, in addition to those listed above, which 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
• Subjects with a 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
• Subjects with another active medical condition or organ disease that may either compromise subject safety and/or outcome evaluation of the study drug
• Subjects with 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 hepatitis (including but not limited to B or C); or individuals with 1) total bilirubin >1.5x the upper limit of normal and/or 2) alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >2x upper limit of normal (ULN) will be excluded
• Subjects with hepatitis C antibody and AST, ALT, or alkaline phosphatase >2x and total bilirubin >1.3 mg/dL will be excluded
• Subjects with a history of renal disease, or a creatinine clearance of less than 80 mL/min (as determined by the Cockcroft Gault formula)
• Subjects with an international normalized ratio >2.0 at screening
• Subjects with corrected QT interval (Bazett's - QTcB) >450 msec (male) or >470 msec (female) at screening. Subjects with a QTc above these levels due to a benign right bundle branch block can be included in the study at the discretion of the PI
• Subjects who are known to have AIDS or to be HIV positive
• Subjects with suicidal ideation with intent and plan (Columbia-Suicide Severity Rating Scale (C-SSRS) affirmative answers to questions 4 and 5 of the ideation section) or suicide attempts within the last six months as noted on the C-SSRS, or subjects with uncontrolled depression in the opinion of the investigator
• Subjects with known diagnosis of type 1 or 2 diabetes or subjects with Hemoglobin A1c >7.0 at screening
• Subjects who have participated in a clinical trial within 30 days prior to study screening
• Subjects who meet the DSM-IV-TR criteria for alcohol abuse or dependence within the last six months of screening

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Indivior Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Philippa Whitelaw, Sr. Dir of Proj Deliver

Role: STUDY_DIRECTOR

Pharmaceutical Research Associates

Ashley Huston, PMP

Role: STUDY_DIRECTOR

Pharmaceutical Research Associates

Locations

Woodland International Research Group, Inc.

Little Rock, Alaska, United States

Ocean View Psychiatric Health Facility

Long Beach, California, United States

Countries

United States

Other Identifiers

RB-US-09-0009

Identifier Type: -

Identifier Source: org_study_id