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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
February 10, 2014
June 14, 2017
March 2014
March 2015   (Final data collection date for primary outcome measure)
  • 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
  • Peak Plasma Concentration (Cmax) for Active Moiety [ Time Frame: Pre-dose and 204 days Post-dose (32 time points will be carried out within). ]
  • Trough Plasma Concentration (Cmin) for Active Moiety [ Time Frame: Pre-dose and 204 days Post-dose (32 time points will be carried out within). ]
  • Area under the curve to the last quantified concentration (AUClast) and Area under the curve extrapolated to infinity (AUC∞) for Active Moiety [ Time Frame: Pre-dose and 204 days Post-dose (32 time points will be carried out within). ]
  • Terminal rate constant (λz), Terminal half-life (t1/2) and Time to peak concentration (tmax) for Active Moiety [ Time Frame: Pre-dose and 204 days Post-dose (32 time points will be carried out within). ]
Complete list of historical versions of study NCT02086786 on ClinicalTrials.gov Archive Site
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.
  • Peak Plasma Concentration (Cmax) for Risperidone and 9OH-Risperidone Moieties [ Time Frame: Pre-dose and 204 days Post-dose (32 time points will be carried out within). ]
  • Trough Plasma Concentration (Cmin) for Risperidone and 9OH-Risperidone Moieties [ Time Frame: Pre-dose and 204 days Post-dose (32 time points will be carried out within). ]
  • Occurrence, nature, onset time, duration, intensity, action taken, outcome and relationship to study drug of AEs as a Measure of Safety [ Time Frame: Pre-dose and 204 days Post-dose (32 time points will be carried out within). ]
  • Area under the curve to the last quantified concentration (AUClast) and Area under the curve extrapolated to infinity (AUC∞) for Risperidone and 9OH-Risperidone Moieties [ Time Frame: Pre-dose and 204 days Post-dose (32 time points will be carried out within). ]
  • Terminal rate constant (λz), Terminal half-life (t1/2) and Time to peak concentration (tmax) for Risperidone and 9OH-Risperidone Moieties [ Time Frame: Pre-dose and 204 days Post-dose (32 time points will be carried out within). ]
  • Area Under the Concentration-time Curve for To perform a descriptive comparison of the PK data between the gluteal and the deltoid muscle administration of the injectable ISM formulation [ Time Frame: Pre-dose and 204 days Post-dose (32 time points will be carried out within). ]
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

Change From Baseline in the Positive and Negative Syndrome Scale (PANSS) Total Score to Month 4 [ Time Frame: From Pre-dose to month 4; 3 timepoints Post-Dose 1, Pre-dose and 1 timepoint after Doses 2, 3 and 4 wtihin a timeframe of 28 days. ]
 
Pharmacokinetics and Tolerability Study of Risperidone ISM® in Schizophrenia
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
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.

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.
Interventional
Phase 2
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Schizophrenia
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: Gluteus (Risperidone ISM)
    Risperidone ISM (75 mg) injection in the gluteal muscle at 28-day intervals
    Intervention: Drug: Risperidone ISM
  • Experimental: Deltoid (Risperdione ISM)
    Risperidone ISM (75 mg) injection in the deltoid muscle at 28-day intervals
    Intervention: Drug: Risperidone ISM
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
70
March 2015
March 2015   (Final data collection date for primary outcome measure)

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.
Sexes Eligible for Study: All
18 Years to 65 Years   (Adult)
No
Contact information is only displayed when the study is recruiting subjects
United States
 
 
NCT02086786
ROV-RISP-2011-02
No
Not Provided
Plan to Share IPD: No
Rovi Pharmaceuticals Laboratories
Rovi Pharmaceuticals Laboratories
Not Provided
Study Chair: Jordi Llaudó, M.D Rovi Laboratorios Farmacéuticos
Rovi Pharmaceuticals Laboratories
May 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP