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Trial record 14 of 730 for:    Area Under Curve AND Bioavailability

Comparative Bioavailability of Risperidone

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ClinicalTrials.gov Identifier: NCT03527186
Recruitment Status : Completed
First Posted : May 17, 2018
Last Update Posted : July 1, 2019
Sponsor:
Information provided by (Responsible Party):
Rovi Pharmaceuticals Laboratories

Brief Summary:
This is an open-label, one sequence study to evaluate the steady-state comparative bioavailability of 100 mg Risperidone ISM® injectable every 4 weeks compared to once daily 4 mg oral risperidone in subjects with schizophrenia stabilized on oral risperidone treatment.

Condition or disease Intervention/treatment Phase
Schizophrenia Drug: Risperidone ISM® 100 mg Phase 1

Detailed Description:

This is an open-label, 1-sequence study in subjects who are on stable oral risperidone treatment. The study consists of a screening visit, 1 treatment period with inpatient and outpatient visits, and a follow-up visit.

Subjects who are on existing oral risperidone treatment (4 mg) will continue the oral regimen for 1 week to achieve steady-state concentrations of risperidone. Following the oral risperidone treatment, a single intramuscular (IM) dose of 100 mg risperidone ISM® will be administered deeply into the gluteal muscle. A total of 4 IM doses will be given that will be separated by 4 weeks.

Safety assessments and pharmacokinetic (PK) sampling will be performed on each dosing day and each outpatient visit. A final follow-up visit will take place to assess each subject for safety and to obtain PK samples.

Approximately 58 subjects will be enrolled, with the intent to complete 41 subjects. Fifty-eight subjects were estimated for enrollment based on 41 completers assuming an approximate drop-out rate of 30%.

The primary objective of this study is to evaluate the steady-state comparative bioavailability of 100 mg risperidone ISM® injectable every 4 weeks compared to once daily 4 mg oral risperidone in subjects with schizophrenia stabilized on oral risperidone treatment.

The secondary objective of this study is to evaluate the safety and tolerability of 100 mg risperidone ISM® injectable every 4 weeks compared to once daily 4 mg oral risperidone in subjects with schizophrenia stabilized on oral risperidone treatment.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 81 participants
Intervention Model: Sequential Assignment
Intervention Model Description: This is an open-label, 1-sequence study to evaluate the PK, safety, and tolerability of risperidone ISM® in subjects with schizophrenia who are on stable oral risperidone treatment. The study consists of a screening visit, 1 treatment period with inpatient and outpatient visits, and a follow-up visit.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open-Label, One-Sequence Study to Evaluate the Steady-State Comparative Bioavailability of Intramuscular Risperidone ISM® and Oral Risperidone
Actual Study Start Date : July 9, 2018
Actual Primary Completion Date : March 23, 2019
Actual Study Completion Date : April 6, 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Schizophrenia
Drug Information available for: Risperidone

Arm Intervention/treatment
Experimental: Risperidone ISM 100 mg
A single intramuscular (IM) dose of 100 mg risperidone ISM® will be administered deeply into the gluteal muscle. A total of 4 IM doses will be given; each dose will be separated by 4 weeks
Drug: Risperidone ISM® 100 mg
100 mg of risperidone ISM® administered every 4 weeks
Other Name: DORIA




Primary Outcome Measures :
  1. Area under the curve during the dosing interval (AUCtau) [ Time Frame: 28-day period following administration of the fourth dose of risperidone ISM® ]
    mean steady-state area under the curve during the dosing interval for the active moiety



Information from the National Library of Medicine

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

Subjects will be considered eligible to participate in this study if each one of the following inclusion criteria is satisfied at screening (or at baseline when specified):

  1. Male or female aged ≥18 and <65 years with a body mass index (BMI) of ≥17 kg/m2 but ≤35 kg/m2
  2. Current diagnosis of schizophrenia, according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria
  3. Outpatient; not hospitalized for worsening of schizophrenia within the last 3 months (hospitalization for social management within this time period is acceptable)
  4. Medically stable over the last month and psychiatrically stable without significant symptom exacerbation over the last 3 months based on the investigator's judgement
  5. On oral risperidone 4 mg daily as maintenance therapy for at least the last 4 weeks prior to screening and on 4 mg oral risperidone once daily (QD) for at least one week prior baseline (Day1, Visit 2)
  6. Agrees to taper off all prohibited medications prior to baseline
  7. On a stable dosage of all permitted medications (with the exception of medication to be used on an as-needed basis) for at least 2 weeks prior to the baseline visit and for the duration of the study
  8. Clinical Global Impression - Severity (CGI-S) score of ≤4 (moderately ill)
  9. A female subject of childbearing potential who is sexually active and using a medically accepted contraceptive method. Acceptable methods include condoms (male or female) with or without spermicidal agent, diaphragm or cervical cap with spermicide, medically prescribed intrauterine device, and hormonal contraceptives. A female subject of childbearing potential who is not currently sexually active must agree that should she be so while participating in the trial, she will use a medically accepted method of contraception for the remainder of the study and for 1 month afterward. Female patients who have had a hysterectomy, bilateral tubal ligation, or bilateral salpingooophorectomy are considered surgically sterile and are thus are exempt from the requirement to use contraception. Female patients who are postmenopausal are considered not of childbearing potential and thus exempt from the contraception requirement; for the purpose of this study, postmenopausal is defined as the permanent cessation of menstruation for at least 12 months prior to screening in women ≥ 45 years of age.
  10. Female subjects must have a negative pregnancy test at screening (serum test) and baseline (urine test)
  11. Psychotherapy should not be started or changed during a patient's participation in the study. It is acceptable for a patient already receiving psychotherapy to participate in the study
  12. Able to speak, read, and understand sufficiently to allow completion of all study assessments
  13. Must provide written informed consent prior to the initiation of any protocol-specific procedures

Subjects will not be considered eligible to participate in this study if any one of the following exclusion criteria is satisfied at screening (or at baseline when specified):

  1. Presence of an uncontrolled, unstable, clinically significant medical condition (eg, renal, endocrine, hepatic, respiratory, cardiovascular, hematologic, immunologic or cerebrovascular disease, or malignancy) that in the opinion of the investigator could have interfered with the interpretation of safety and PK evaluations
  2. Presence of a clinically significant vital sign or physical examination finding that in the opinion of the investigator could potentially interfere with the ability to evaluate safety and tolerability of the trial medication or could impair the subject's ability to complete the trial
  3. Presence of a clinically significant abnormality on blood or urine safety tests, which do not improve on retesting. In particular, laboratory and/or clinical evidence of clinically significant hepatic conditions, such as:

    • alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 3 × upper limit of normal (ULN) and total bilirubin > 2 × ULN; or
    • ALT or AST > 3 × ULN with the appearance of jaundice, worsening of fatigue, nausea, vomiting, right upper quadrant pain or tenderness, fever, rash, or eosinophilia
  4. Corrected QT interval, Fridericia's correction (QTcF) interval greater than 450 msec for males and 470 msec for females, or other clinically significant ECG abnormality on screening or baseline
  5. If female, a positive serum pregnancy test, or planning to become pregnant between signing informed consent and 1 month after the last dose of trial medication, or is breastfeeding a child
  6. Uncontrolled or unstable diabetes, or a clinically significant abnormal Hba1c blood level
  7. Known or suspected (non-febrile) seizure disorder
  8. Known serological evidence of human immunodeficiency (HIV) antibody
  9. History of hepatitis B infection within the past year, or history of hepatitis C infection that has not been adequately treated and abnormal Liver Functional Tests (LFT) values
  10. History of neuroleptic malignant syndrome
  11. Current or past history of clinically significant tardive dyskinesia
  12. Primary diagnosis other than schizophrenia diagnosis that is primarily responsible for current symptoms and functional impairment
  13. Known or suspected diagnosis of mental retardation or organic brain disorder
  14. Positive urine drug/alcohol (ethanol breathalyzer is also acceptable) screen finding, unless the positive finding can be accounted for by documented prescription use. Individuals who have positive results for alcohol, cannabis, or other psychotropic substances but are not dependent on or abusing these substances may be included at the investigator's discretion, following a discussion between the investigator and the medical monitor
  15. Heavy smoker (consumption of >40 cigarettes daily)
  16. Fulfillment of the DSM-5 criteria for moderate or severe substance use disorder (excluding nicotine) within the past 6 months
  17. Diagnosis of a psychotic disorder or a behavioral disturbance that is thought to be substance-induced or due to substance abuse
  18. In the investigator's opinion, at imminent risk of committing self-harm or harm to others, based on clinical interview and responses provided on the Columbia-Suicide Severity Rating Scale (C-SSRS). Individuals will be excluded if they report having suicidal ideation of Type 4 or 5 in the past 2 months, or suicidal behavior in the past 6 months, as measured by the C-SSRS at screening or baseline
  19. On more than 1 antidepressant; or if on just one, a change in dose within the last 4 weeks prior to screen
  20. Use of depot antipsychotics within the last 6 to 9 months
  21. Use of electroconvulsive therapy (ECT) within the last 3 months
  22. Use of moderate or strong cytochrome P450 3A4 (CYP3A4)enzyme inducers and inhibitors (carbamazepine, phenytoin, rifampicin, phenobarbital) or moderate or strong cytochrome P450 2D6 (CYP2D6) inhibitors (fluoxetine, paroxetine) (see Appendix 11.2) within 3 days or a time period of 5 half lives of the concerning drug, whichever is longer, prior to baseline
  23. Unwilling to discontinue any of prohibited medications prior to the baseline visit; or, in the opinion of the investigator, is unable to safely taper off such medication without significant destabilization or increased risk of self-harm (suicide). Prohibited medications may include antipsychotics, phenobarbital, fluoxetine, fluoxetine combinations, paroxetine, benzodiazepines except lorazepam, diazepam, oxazepam, psychotropics, herbal drugs/dietary supplements for depression, anxiety, insomnia, rifampicin, and quinidine
  24. Receipt of any investigational drugs within the last 3 months
  25. Current participation in any other clinical trial
  26. In the investigator's opinion, medically non-compliant in the management of his or her disease
  27. Known or suspected allergy or hypersensitivity to risperidone or any of the ISM® excipients
  28. Previous non-responder to risperidone treatment
  29. Currently under involuntary in-patient commitment

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03527186


Locations
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United States, California
Collaborative Neuroscience Network
Long Beach, California, United States, 90806
United States, New Jersey
Hassman Research Institute
Berlin, New Jersey, United States, 08009
Sponsors and Collaborators
Rovi Pharmaceuticals Laboratories
Investigators
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Study Chair: Jordi Llaudó, MD Laboratorios Farmacéuticos Rovi

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Responsible Party: Rovi Pharmaceuticals Laboratories
ClinicalTrials.gov Identifier: NCT03527186     History of Changes
Other Study ID Numbers: RPV-RISP-2016-02
First Posted: May 17, 2018    Key Record Dates
Last Update Posted: July 1, 2019
Last Verified: March 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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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