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Pharmacokinetics and Tolerability Study of Risperidone ISM® in Schizophrenia (PRISMA-2)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Rovi Pharmaceuticals Laboratories
ClinicalTrials.gov Identifier:
NCT02086786
First received: February 10, 2014
Last updated: June 14, 2017
Last verified: May 2015
  Purpose
To characterize the pharmacokinetics (PK) of the injectable intramuscular (IM) long-acting formulation (in situ microparticle, ISM) of risperidone over four IM injections in the gluteal and deltoid muscle at 28-day intervals and at one dose strength (75 mg) in patients with schizophrenia.

Condition Intervention Phase
Schizophrenia Drug: Risperidone ISM Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: No masking
Primary Purpose: Treatment
Official Title: Multicenter, Open-label, Two-arm, Parallel-design, Repeat-dose Clinical Trial to Evaluate the PK, Safety, and Tolerability of Four Intramuscular Injections of Risperidone ISM® 75 mg, at 28 Day Intervals in Patients With Schizophrenia

Resource links provided by NLM:


Further study details as provided by Rovi Pharmaceuticals Laboratories:

Primary Outcome Measures:
  • Peak Plasma Concentration (Cmax) for Active Moiety [ Time Frame: Dose 1, 2 and 3: Pre-dose; at 2, 8, 12, 24 and 48 hours post-dose; 5, 7, 10, 14, 18, and 21 days post-dose. Dose 4: Pre dose; at 2, 8, 12, 24, and 48 hours post-dose; at 5, 7, 10, 14, 18, 21, 25, 28, 32, 37, 42, 60, 75, 90, 105, and 120 days post-dose. ]
  • Trough Plasma Concentration (Cmin) for Active Moiety [ Time Frame: Dose 1, 2 and 3: Pre-dose; at 2, 8, 12, 24 and 48 hours post-dose; 5, 7, 10, 14, 18, and 21 days post-dose. Dose 4: Pre dose; at 2, 8, 12, 24, and 48 hours post-dose; at 5, 7, 10, 14, 18, 21, 25, 28, 32, 37, 42, 60, 75, 90, 105, and 120 days post-dose. ]
  • Area Under the Curve to the Last Quantified Concentration (AUClast) for Active Moiety [ Time Frame: Dose 1, 2 and 3: Pre-dose; at 2, 8, 12, 24 and 48 hours post-dose; 5, 7, 10, 14, 18, and 21 days post-dose. Dose 4: Pre dose; at 2, 8, 12, 24, and 48 hours post-dose; at 5, 7, 10, 14, 18, 21, 25, 28, 32, 37, 42, 60, 75, 90, 105, and 120 days post-dose. ]
  • Area Under the Curve Extrapolated to Infinity (AUC∞) for Active Moiety [ Time Frame: Dose 1, 2 and 3: Pre-dose; at 2, 8, 12, 24 and 48 hours post-dose; 5, 7, 10, 14, 18, and 21 days post-dose. Dose 4: Pre dose; at 2, 8, 12, 24, and 48 hours post-dose; at 5, 7, 10, 14, 18, 21, 25, 28, 32, 37, 42, 60, 75, 90, 105, and 120 days post-dose. ]
  • AUCτ for Active Moiety [ Time Frame: Dose 1, 2 and 3: Pre-dose; at 2, 8, 12, 24 and 48 hours post-dose; 5, 7, 10, 14, 18, and 21 days post-dose. Dose 4: Pre dose; at 2, 8, 12, 24, and 48 hours post-dose; at 5, 7, 10, 14, 18, 21, 25, 28, 32, 37, 42, 60, 75, 90, 105, and 120 days post-dose. ]
    AUCτ is the area under the curve over the dosing interval (τ), where the dosing interval is 28 days

  • Time to Peak Concentration (Tmax) for Active Moiety [ Time Frame: Dose 1, 2 and 3: Pre-dose; at 2, 8, 12, 24 and 48 hours post-dose; 5, 7, 10, 14, 18, and 21 days post-dose. Dose 4: Pre dose; at 2, 8, 12, 24, and 48 hours post-dose; at 5, 7, 10, 14, 18, 21, 25, 28, 32, 37, 42, 60, 75, 90, 105, and 120 days post-dose. ]
  • Terminal Half-life (t1/2) for Active Moiety [ Time Frame: Dose 1, 2 and 3: Pre-dose; at 2, 8, 12, 24 and 48 hours post-dose; 5, 7, 10, 14, 18, and 21 days post-dose. Dose 4: Pre dose; at 2, 8, 12, 24, and 48 hours post-dose; at 5, 7, 10, 14, 18, 21, 25, 28, 32, 37, 42, 60, 75, 90, 105, and 120 days post-dose. ]
  • PTF for Active Moiety [ Time Frame: Dose 1, 2 and 3: Pre-dose; at 2, 8, 12, 24 and 48 hours post-dose; 5, 7, 10, 14, 18, and 21 days post-dose. Dose 4: Pre dose; at 2, 8, 12, 24, and 48 hours post-dose; at 5, 7, 10, 14, 18, 21, 25, 28, 32, 37, 42, 60, 75, 90, 105, and 120 days post-dose. ]
    Peak to Trough Fluctuation ratio for the Active Moiety


Secondary Outcome Measures:
  • Accumulation Ratio (RA) for Active Moiety [ Time Frame: Dose 1, 2 and 3: Pre-dose; at 2, 8, 12, 24 and 48 hours post-dose; 5, 7, 10, 14, 18, and 21 days post-dose. Dose 4: Pre dose; at 2, 8, 12, 24, and 48 hours post-dose; at 5, 7, 10, 14, 18, 21, 25, 28, 32, 37, 42, 60, 75, 90, 105, and 120 days post-dose. ]
    Defined as AUC (0-28 days) after the 4th dose divided by the AUC (0-28 days) of the first dose.


Other Outcome Measures:
  • Positive and Negative Syndrome Scale (PANSS) Total Score [ Time Frame: Baseline, Days 5, 7, 10, 14, 18, and 21 post Dose 1; Dose 2, 3 and 4 post dose; Days 5, 7, 10, 14, 18, and 21 post Dose 2, 3, and 4; Days 25, 28, 32, 37, 42, 60, 75, 90, and 105 post Dose 4; Day 120 post Dose 4 or early termination. ]

    The change in PANSS score from Baseline by visit 48.

    The PANSS combines 3 subscales: The positive scale (7 items), the negative scale (7 items) and the general psychopathology scale (16 items).

    PANSS Items Scores: 1 = Absent, 2 = Minimal, 3 = Mild, 4 = Moderate, 5 = Moderate Severe, 6 = Severe, 7 = Extreme.

    Subscales are summed to compute a total score Range for each of the subscales: Positive scale (7-49); Negative scale (7-49); General psychopathology scale (16-112) Range for the PANSS total scale: 30-210 PANSS total score ≤70: stable schizophrenia PANSS total score between >70: decompensated schizophrenia



Enrollment: 70
Study Start Date: March 2014
Study Completion Date: March 2015
Primary Completion Date: March 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Gluteus (Risperidone ISM)
Risperidone ISM (75 mg) injection in the gluteal muscle at 28-day intervals
Drug: Risperidone ISM

Four doses of 75 mg of Risperidone ISM as intramuscular (IM) injection into the deltoid muscle at 28-day intervals.

Four doses of 75 mg of Risperidone ISM as intramuscular injections into the gluteal muscle at 28-day intervals.

Other Name: No other names
Experimental: Deltoid (Risperdione ISM)
Risperidone ISM (75 mg) injection in the deltoid muscle at 28-day intervals
Drug: Risperidone ISM

Four doses of 75 mg of Risperidone ISM as intramuscular (IM) injection into the deltoid muscle at 28-day intervals.

Four doses of 75 mg of Risperidone ISM as intramuscular injections into the gluteal muscle at 28-day intervals.

Other Name: No other names

Detailed Description:

This was a multicenter, open-label, two-arm, parallel-design, repeat-dose clinical study designed to evaluate the PK, safety, and tolerability of Risperidone ISM®, a new long-acting injectable formulation of the licensed drug risperidone, administered in the gluteal muscle or the deltoid muscle. Participants were patients with a diagnosis of schizophrenia capable of understanding, signing, and consenting to study participation on their own.

Objectives:

Primary Objective

• To characterize the pharmacokinetics (PK) of the injectable intramuscular (IM) long-acting formulation of risperidone over four IM injections in the gluteal and deltoid muscle at 28 day intervals and at one dose strength (75 mg) in patients with schizophrenia.

Secondary Objectives

  • To document the attainment of steady-state exposure by the injectable formulation ISM® of risperidone over four IM injections in the gluteal and deltoid muscle at 28-day intervals and at one dose strength (75 mg) in patients with schizophrenia.
  • To perform a descriptive comparison of the PK data between the gluteal and the deltoid muscle administration of the injectable formulation ISM® of risperidone over four IM injections at 28-day intervals and at one dose strength (75 mg) in patients with schizophrenia.
  • To evaluate the safety and tolerability of the injectable formulation ISM® of risperidone after four IM injections in the gluteal muscle or deltoid muscle at 28-day intervals at one dose strength (75 mg) in patients with schizophrenia.

Exploratory Objectives

  • To explore the efficacy of once every four weeks of the injectable formulation ISM® of risperidone after four IM injections in the gluteal muscle or deltoid muscle at 28-day (± 1 day) intervals at one dose strength (75 mg) in patients with schizophrenia.
  • To characterize patients' metabolic phenotype (cytochrome P450 [CYP]2D6, CYP3A4) to explain any potential unexpected outlying PK value, and/or explore its relationship with any potential safety or tolerability issue.
  Eligibility

Ages Eligible for Study:   18 Years to 65 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Capable of providing informed consent.
  2. Male or female aged ≥18 years to ≤65 years.
  3. Current diagnosis of schizophrenia, according to Diagnostic and Statistical Manual
  4. Body mass index (BMI) ≥17 kg/m2 but ≤35 kg/m2.
  5. Medically stable over the last month, and psychiatrically stable
  6. On oral stable dosage of risperidone ≥4 mg daily as maintenance therapy.
  7. Total score ≤70 on the Positive and Negative Syndrome Scale.
  8. Using a medically accepted contraceptive method
  9. Agrees to washout all prohibited medications prior to baseline (day -1)

Exclusion Criteria:

  1. Informed consent obtained from a third party.
  2. Prisoners or patients who are compulsorily detained.
  3. Females who are breast-feeding and/or who have a positive pregnancy test.
  4. Presence of an uncontrolled, unstable clinically significant medical condition.
  5. Positive serology for Hepatitis B, Hepatitis C or anti-HIV 1 and 2 at screening.
  6. History of neuroleptic malignant syndrome.
  7. Current or past history of tardive dyskinesia.
  8. Positive urine drug or alcohol screen finding.
  9. Risk of committing self-harm or harm based on Columbia Suicidal Rating Scale.
  10. Taking more than one antidepressant.
  11. Use of depot antipsychotics within the last three months.
  12. Use of strong or moderate cytochrome P450 isoenzyme 3A4inducers
  13. Use of electroconvulsive therapy (ECT) within the last three months.
  14. Receipt of any investigational drugs within the last three months.
  15. Known or suspected allergy or hypersensitivity to risperidone
  16. Previous non-responder to risperidone treatment.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02086786

Locations
United States, Missouri
St Louis Clinical Trials, LC
Saint Louis, Missouri, United States, 63141
Sponsors and Collaborators
Rovi Pharmaceuticals Laboratories
Investigators
Study Chair: Jordi Llaudó, M.D Rovi Laboratorios Farmacéuticos
  More Information

Responsible Party: Rovi Pharmaceuticals Laboratories
ClinicalTrials.gov Identifier: NCT02086786     History of Changes
Other Study ID Numbers: ROV-RISP-2011-02
Study First Received: February 10, 2014
Results First Received: October 13, 2016
Last Updated: June 14, 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Additional relevant MeSH terms:
Schizophrenia
Schizophrenia Spectrum and Other Psychotic Disorders
Mental Disorders
Risperidone
Serotonin Antagonists
Serotonin Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Antipsychotic Agents
Tranquilizing Agents
Central Nervous System Depressants
Psychotropic Drugs
Dopamine Antagonists
Dopamine Agents

ClinicalTrials.gov processed this record on July 26, 2017