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

• Status: Completed
• Trial end date: 2016-05-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Indivior Inc.
• Treatments: Risperidone

Criteria

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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.

• Subjects who have acquired immune deficiency syndrome (AIDS) or to be human immunodeficiency virus (HIV)-positive.

• Subjects with other medical conditions including, but not limited to, history of heart attack (myocardial infarction) or brain injury (traumatic injury with loss of consciousness and/or cerebrovascular accident), or clinically significant low blood pressure or arrhythmias as interpreted by the Principal Investigator or medically qualified sub-investigator.

• Subjects with congenital long QT syndrome, history of prolonged QT in the 3 months prior to screening, or a corrected QT interval (Fridericia - QTcF) >450 msec (male) or >470 msec (female) at screening (Visit 1).

• Subjects with suicidal ideation with intent or plan

• Subjects with uncontrolled depression, in the opinion of the Investigator.

• Subjects with a diagnosis of insulin-dependent diabetes, or who have a hemoglobin A1c (HbA1c) ≥8.0% at screening, or have had changes in diabetic medication regimen in the 28 days prior to signing the informed consent document.

• Subjects with prior allergic reactions, sensitivities or other known contraindications to any component of RBP-7000 (e.g., risperidone, PLGH or NMP).

• Women of childbearing potential who are pregnant or breastfeeding, seeking pregnancy, or failing to use adequate contraceptive methods during the study.

• Subjects with the presence of opioids, cocaine, amphetamines, methadone, barbiturates, benzodiazepines, methamphetamines, cannabinoids, or phencyclidine in the urine as assessed by a urine drug screen.

• Subjects with epilepsy or other seizure disorders, Parkinson's disease or dementia.