A Positron-Emission-Tomography (PET) Study to Measure the Blockade of Dopamine Receptors (D2) in Specific Areas of the Brain in Relation to the Plasma Concentrations of Paliperidone Extended Release (ER) and Oral Risperidone in Schizophrenia Patients and Healthy Controls
Information source: Janssen-Cilag G.m.b.H
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Schizophrenia
Intervention: Paliperidone ER (Drug); Oral risperidone (Drug); PET Scan (Other); Oral risperidone (Drug); Oral risperidone (Drug); Paliperidone ER (Drug); Paliperidone ER (Drug); Oral risperidone (Drug); Paliperidone ER (Drug)
Phase: Phase 4
Status: Terminated
Sponsored by: Janssen-Cilag G.m.b.H Official(s) and/or principal investigator(s): Janssen-Cilag G.m.b.H. Clinical Trial, Study Director, Affiliation: Janssen-Cilag G.m.b.H
Summary
The primary objective of this study is to compare the effect of two different antipsychotic
compounds which are used in the treatment of schizophrenia (paliperidone ER and risperidone)
at their target sites in two specific areas of the brain in patients with schizophrenia. A
specialized X-ray known as Positron Emission Tomography (PET) Imaging is used to assess the
areas of the brain targeted by both compounds.
Clinical Details
Official title: The "Therapeutic Window" of the "Atypical" Antipsychotic Paliperidone Extended Release (ER)-A Positron Emission Tomography Study With [18F]Fallypride as the Radiotracer
Study design: Allocation: Non-Randomized, Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary outcome: Percentage of Paliperidone or Risperidone Dopamine D2 Receptor Occupancies
Secondary outcome: Plasma Concentrations of Paliperidone and RisperidoneAssessment of the Ratio of Dopamine D2-receptor Occupancies in Two Different Areas of the Brain
Detailed description:
This is an open-label (all people involved know the identity of the intervention),
non-randomized (patients are assigned to treatment groups), phase IV, monocentric (at one
single study site) interventional study evaluating the blocking effects two different doses
of paliperidone ER and oral risperidone have on the dopamine D2 receptors in the brain of
subchronic patients with schizophrenia. Dopamine is a substance produced and released in the
brain. Research indicates that dopamine levels are elevated in some areas of the brain in
acute schizophrenia psychosis. Antipsychotic medications like risperidone and paliperidone
ER are used to treat psychosis by blocking the dopamine receptors. Fallypride is a
radioactive tracer (a drug that emits radioactivity) that binds to the dopamine receptors in
the brain much the same as antipsychotic medications. It competes with the antipsychotic
compounds at the binding sites and is used when performing a specialized x-ray known as
Positron Emission Tomography (PET) Imaging. After a patient receives Fallypride, it
temporally binds to specific target areas in the brain and emits a brief and harmless
radioactive signal that is detected by the PET Scanner. Since paliperidone ER and
risperidone compete with Fallypride at the same target sites, the signal will differ
according to the binding effect of the compound. This technique provides an image showing
the direct effect medication has on the human brain and allows for comparisons of the
effects of different medications to be made. As this effect will fluctuate depending on the
concentration of the drug in the blood, during this study, PET measurements will be
correlated with the blood levels sampled. Patients will receive either paliperidone ER (6
patients with 6 mg per day, 6 patients with 9 mg per day) or oral risperidone (6 patients
with 4 mg per day, 6 patients with 6 mg per day). The primary objective of this study is to
compare the blocking effects each medication has on the dopamine D2 receptors at different
time points (shortly after taking medication and 24 hours after taking medication)
correlated with blood levels of the medication. The study consists of 3 visits on 3
consecutive days. Blood levels will be assessed for treatment groups 1 to 4 on day 2 and
day 3 and for groups 5 to 8 on day 3 (according to the last intake of study medication).
PET-Scans will be assessed for every group on day 3. Group 1 to 4 consists of patients whose
PET Scan will be assessed approximately 2 hours after taking medication (group 1 receives
paliperidone ER 6 mg, group 2 receives paliperidone ER 9 mg, group 3 receives risperidone 4
mg, group 4 receives risperidone 6 mg). Group 5 to 8 consists of patients whose PET Scan
will be assessed approximately 24 hours after taking medication (group 5 receives
paliperidone ER 6 mg, group 6 receives paliperidone ER 9 mg, group 7 receives risperidone 4
mg, group 8 receives risperidone 6 mg). Adverse Events (AE's) will be assessed as reported
spontaneously throughout the trial. The dose of antipsychotic medication will represent the
most frequent dose used in post acute treatment of schizophrenia. A group of healthy
volunteers (group 9) will serve as a control group to measure fallypride dopamine D2-
receptor occupancies under normal circumstances, in patients not affected by schizophrenia.
Patients will receive the same dosage throughout the study as prescribed prior to the start
of the study either paliperidone ER 6 mg tablet once daily or 9 mg tablet once daily or
risperidone 4 mg tablet once daily or 6 mg daily (two 3 mg tablets).
Eligibility
Minimum age: 18 Years.
Maximum age: 50 Years.
Gender(s): Both.
Criteria:
Inclusion Criteria:
- Patients with a diagnosis of schizophrenia according to Diagnostic and Statistical
Manual of Mental Disorders (DSM-IV) criteria
- Patients with a specified severity of the disease (Clinical Global Impression Scale
of Severity (CGI-S) range of > 2 < 5)
- Patients must be on antipsychotic medication with either paliperidone ER or oral
risperidone in monotherapy for at least two weeks and must be at least five days on a
stable dose of either paliperidone ER 6 mg or 9 mg or oral risperidone 4 mg or 6 mg
once daily
- Female patients of childbearing potential must have a negative human chorionic
gonadotropin urine pregnancy test (ß-HCG) at visit 1 or must be postmenopausal for at
least 1 year, surgically sterile, abstinent, or, if sexually active, agree to
practice an effective method of birth control before entry, throughout the study and
at least one month after study end
- Healthy control volunteers must be off all standard prescription drug therapy, over
the counter compounds (OTC) and recreational substances/drugs for at least one week
prior to participation in the study
- Female volunteers of childbearing potential must have a negative ß -HCG pregnancy
test at visit 1 or be postmenopausal for at least 1 year, surgically sterile,
abstinent, or, if sexually active, agree to practice an effective method of birth
control before entry, throughout the study and at least one month after the study end
- Patients and volunteers must be able to read, understand and sign the Institutional
Review Board approved informed consent form
Exclusion Criteria:
- Patients: Any depot neuroleptic medication (long acting injectables) in the last
three months
- Any antipsychotic compound, antidepressant, antiepileptic ("mood stabilizers"),
lithium, anticholinergic within 2 weeks prior to study
- Any psychopharmacologically active medication (except benzodiazepines, paracetamol
and zopiclone as rescue medication) taken within the trial
- Physical and psychological conditions that interfere with the study procedures, or
could influence the study results, or could endanger the patient during the study
- Alcohol and/or drug abuse four weeks prior to study start (patients with alcohol or
drug abuse as defined by the DSM-IV criteria can participate if free of their of
abuse for at least four weeks)
- Clinically relevant laboratory abnormality
- Pregnant or breast feeding patients
Locations and Contacts
Aachen, Germany
Additional Information
Starting date: September 2009
Last updated: January 14, 2014
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