Clinical trial NCT00934635
Conditions: Schizophrenia
Keywords: D2-receptor occupancy Antipsychotic drugs Paliperidone ER, Oral risperidone Dopamine Fallypride Plasma concentration Therapeutic window, Healthy controls
Sponsor: Janssen-Cilag G.m.b.H
Start date: 2009-09-01; Completion date: 2009-12-01
Enrollment: 2 participants; Allocation: NON_RANDOMIZED; Intervention model: PARALLEL

Brief 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.

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).

Arms: arm 1: Paliperidone ER 9 mg tablet once a day followed by PET scan in approximately 2 hours arm 2: Oral risperidone 4 mg tablet once a day followed by PET scan in approximately 2 hours arm 3: Oral risperidone 6 mg tablet once a day followed by PET scan in approximately 2 hours arm 4: Paliperidone ER 6 mg tablet once a day followed by PET scan in approximately 24 hours arm 5: Paliperidone ER 9 mg tablet once a day followed by PET scan in approximately 24 hours arm 6: Oral risperidone 4 mg tablet once a day followed by PET scan in approximately 24 hours arm 7: Oral risperidone 6 mg tablet once a day followed by PET scan in approximately 24 hours arm 8: PET Scan PET Scan arm 9: Paliperidone ER 6 mg tablet once a day followed by PET scan in approximately 2 hours
Interventions: intervention 1: Paliperidone ER intervention 2: Oral risperidone intervention 3: PET Scan intervention 4: Oral risperidone intervention 5: Oral risperidone intervention 6: Paliperidone ER intervention 7: Paliperidone ER intervention 8: Oral risperidone intervention 9: Paliperidone ER
Intervention descriptions: intervention 1: 9 mg tablet once a day followed by PET scan in approximately 2 hours intervention 2: 6 mg tablet once a day followed by PET scan in approximately 2 hours intervention 3: PET Scan intervention 4: 4 mg tablet once a day followed by PET scan in approximately 24 hours intervention 5: 4 mg tablet once a day followed by PET scan in approximately 2 hours intervention 6: 6 mg tablet once a day followed by PET scan in approximately 2 hours intervention 7: 6 mg tablet once a day followed by PET scan in approximately 24 hours intervention 8: 6 mg tablet once a day followed by PET scan in approximately 24 hours intervention 9: 9 mg tablet once a day followed by PET scan in approximately 24 hours

Protocol documents: