Single Ascending Dose Study of RBP-7000

NCT02768649 | Completed Phase 1

• 1 other identifier: RB-US-09-0008
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study was to assess the safety and tolerability of injections of RBP-7000 in subjects with stable schizophrenia

Conditions

Schizophrenia

Outcome Measures

Primary Outcomes (1)

• Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] after a subcutaneous injection of a single 60 mg, 90 mg, and 120 mg dose of risperidone in RBP-7000 in subjects with clinically stable schizophrenia

  Adverse events, serious adverse events, and discontinuations due to AEs related to treatment.

  Day 1 through Day 85

Secondary Outcomes (5)

• Maximum plasma concentration (Cmax) of risperidone and total risperidone

  Day 0 through Day 85

• Time of occurrence of Cmax (Tmax) of risperidone and total risperidone

  Day 0 through time of last quantifiable concentration

• Area under the plasma concentration versus time curve (AUC)

  Day 0 through Day 85

• Observed terminal rate constant of risperidone and total risperidone (λz)

  Day 0 through Day 85

• Terminal half-life of risperidone and total risperidone (T1/2)

  Day 0 through Day 85

Study Arms (3)

Cohort 1

EXPERIMENTAL

Eligible subjects received a test dose of 0.25 risperidone prior to dosing with RBP-7000. Fifteen eligible subjects then received low dose RBP-7000

Drug: RBP-7000; Drug: risperidone

Cohort 2

EXPERIMENTAL

After safety and tolerability review of the data from Day 1 to Day 15 of the low dose arm, 3 subjects were dosed in Cohort 2 with a higher dose of RBP-7000. A safety and tolerability review of the data from Day 1 to Day 15 was completed for the 3 subjects before the remaining 12 were dosed.

Drug: RBP-7000; Drug: risperidone

Cohort 3

EXPERIMENTAL

After safety and tolerability review of the data from Day 1 to Day 15 of the medium dose arm, 3 subjects were dosed in Cohort 3 with a higher dose of RBP-7000. A safety and tolerability review of the data from Day 1 to Day 15 was completed for the 3 subjects before the remaining 12 were dosed.

Drug: RBP-7000; Drug: risperidone

Interventions

RBP-7000 DRUG

Sequential dosing of each cohort

Cohort 1; Cohort 2; Cohort 3

risperidone DRUG

All eligible subjects received a test dose of risperidone to ensure tolerability prior to dosing with RBP-7000.

Also known as: test dose

Cohort 1; Cohort 2; Cohort 3

Eligibility Criteria

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

You may qualify if:

• Subjects with confirmed diagnosis of paranoid, residual, or undifferentiated schizophrenia in a documented letter from the subject's psychiatrist or primary care provider.
• Clinically stable subjects (subjects whom the PI established by medical record or by history from the subject and at least 1 reliable informant, that the subject had been clinically stable for at least 60 days without hospitalization).
• Subjects with body mass index (BMI) between 18 and 33 kg/m2 and weight of at least 49.9 kg.
• Subjects who gave written informed consent.

You may not qualify if:

• Subjects taking any risperidone product within the last 60 days prior to study screening.
• Subjects with a history of cancer (excluding resected basal cell or squamous cell carcinoma of the skin) unless they had been disease free for ≥ 5 years.
• Subjects with another active medical condition or organ disease that could have either compromised subject safety or interfered with the safety and/or outcome evaluation of the study drug. This included, but was not limited to the following abnormalities: total bilirubin \> 2.5 mg/dL (51 μmol/L), alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \> 3 × the upper limit of normal (ULN) or clinically significant serum creatinine \> 2 x ULN, international normalized ratio (INR) ≥ 2.0. Other excluded medical conditions included, but were not limited to: history of heart attack, brain injury, low blood pressure, and clinically significant irregular heartbeat as interpreted by the PI.
• Subjects who were known to have acquired immune deficiency syndrome or to be human immunodeficiency virus (HIV) positive.
• Subjects with evidence or history of significant hepatic disorder, including acute or chronic hepatitis B and acute hepatitis C. Subjects with hepatitis C antibody and liver functions ≤ 1.5 times the ULN could be included in the study.
• Subjects with known diagnosis of type 1 or 2 diabetes or subjects with a clinically significant abnormal hemoglobin A1c (HbA1c) at screening as interpreted by the PI.
• Subjects with clinically significant comorbidities that could affect near-term survival.
• Subjects treated with any investigational drug within the last 30 days prior to study screening.
• Subjects with significant traumatic injury, major surgery, or open biopsy within the last 4 weeks prior to study screening.
• Subjects receiving opioid or opioid-containing analgesics within the last 30 days prior to study screening.
• Subjects consuming \> 1 alcoholic drink per day within the last 30 days prior to study screening (defined as 1 oz. of 80 proof spirits, 12 oz. of beer, or 4 oz. of wine).
• Subjects with prior allergic reactions, sensitivities, or other known contraindications to any component of RBP-7000 (i.e., risperidone, poly \[DL-lactide-co-glycolide\], or N-methylpyrrolidone).
• Subjects with other concurrent uncontrolled illness that may have interfered with the ability to participate in the study.
• Women with a positive pregnancy test at screening. Women of childbearing potential, who were pregnant or lactating, seeking pregnancy, or failing to take adequate contraceptive precautions (e.g., an oral or injectable contraceptive, an approved hormonal implant or topical patch, or an intrauterine device). Should a female subject become sexually active, she must have agreed to use a double-barrier method or barrier plus spermicide. A woman of childbearing potential was defined as any female who was less than 2 years post-menopausal or had not undergone a hysterectomy or surgical sterilization, e.g., bilateral tubal ligation or bilateral ovariectomy (oophorectomy). Females who were post-menopausal were confirmed by the follicle stimulating hormone (FSH) test at initial screening.
• Subjects with a positive urine drug screen for opioids, cocaine, amphetamines, methadone, marijuana, barbiturates, benzodiazepines, methamphetamine, phencyclidine, or tricyclic antidepressants unless the positive screen was determined to be secondary to an allowable concomitant medication.

Sponsors & Collaborators

• Indivior Inc.: lead

Study Sites (1)

CRI Worldwide

Willingboro, New Jersey, 08046, 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 Design

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

Study Record Dates

• First Submitted: May 3, 2016
• First Posted: May 11, 2016
• Study Start: April 1, 2011
• Primary Completion: February 1, 2012
• Study Completion: February 1, 2012
• Last Updated: May 11, 2016

Record last verified: 2016-05

Locations

US (1)