A Study of Dopamine Type 2 (D2) Receptor Occupancy Following a Single Oral Dose of OROS Paliperidone

Open-label Positron Emission Tomography (PET) Study of Central D2-receptor Occupancy in Healthy Subjects Following a Single Oral Dose of OROS Paliperidone

The purposes of this study are to estimate the relationship of D2-receptor occupancy to plasma concentration and to assess the safety of OROS paliperidone.

Study Overview

• Status: Completed
• Conditions: Schizophrenia
• Intervention / Treatment: Drug: OROS paliperidone

Detailed Description

This is a single-center, single-dose, open-label, Phase-1 Positron Emission Tomography (PET) study in 4 healthy volunteers, 2 men and 2 women. After screening, healthy eligible volunteers will be hospitalized in the study unit from study Day 2 to Day 4. On Day 1 (the day before hospitalization), volunteers will enter the study unit from 5:00 p.m. to 8:00 p.m. for baseline prolactin blood sampling and sedation assessment. Each volunteer will have a control magnetic resonance imaging (at screening) and 3 PET measurements using the radioligand [11]C raclopride to measure central D2 receptor occupancy in the putamen. Blood samples to measure plasma concentrations of paliperidone will be collect immediately before and at scheduled time points after dose administration on Day 2, and immediately before, halfway through, and immediately after the PET-2 and PET-3 measurements. Serum prolactin levels will be measured immediately before and at several scheduled time points after dose administration, and immediately before and after each PET measurement. At scheduled time points, supine and standing blood pressures, pulse, sensorium changes, temperature, and degree of sedation will be recorded, volunteers will be questioned about adverse events, and they will be evaluated for extrapyramidal symptoms (EPS). Adverse events will be recorded and followed throughout the study. The rationale for the study design is based on previous PET studies with risperidone, which indicated that PET measurement of D2 receptor occupancy after a single dose of medication is useful in predicting an effective clinical dose range. Single oral dose (6 mg) of OROS paliperidone

• Study Type: Interventional
• Enrollment (Actual): 4
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 45 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Within 20% of ideal body weight
• If a woman, must be surgically sterile, or practicing an effective method of birth control (e.g., prescription oral contraceptives, contraceptive injections, intrauterine device, double-barrier method, male partner sterilization) before entry and throughout the study
• and must have a negative serum beta HCG test at screening
• Healthy on the basis of a pre-study physical examination, medical history, anamnesis, electrocardiogram, magnetic resonance imaging of the brain, and the results of blood biochemistry and hematology tests and a urinalysis carried out less than 2 weeks before the first dose. If the results of the biochemistry or hematology tests or the urinalysis testing are not within the laboratory's reference ranges the volunteer can be included only on condition that the investigator judges that the deviations are not clinically significant.

Exclusion Criteria:

• History or suspicion of alcohol, barbiturate, amphetamine or narcotic abuse
• History of cardiac arrhythmias, bronchospastic or respiratory disease, cardiovascular, neurologic, renal, hepatic, endocrine, or immunologic disease
• Drug allergy to raclopride, paliperidone, or risperidone or any of its excipients
• Use of concomitant medication, except for paracetamol and hormonal contraceptives. All other medication must have been stopped at least 14 days before the first PET examination
• Received an experimental drug or used an experimental medical device within 30 days before the planned start of treatment
• Previously used an antipsychotic medication
• Previously participated in a PET study or measurement
• Had a significant loss of blood <1 month before the first PET examination
• Pregnant as confirmed by a positive beta-HCG test at screening and before the first PET examination, or breastfeeding
• Claustrophobia.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: SINGLE_GROUP
• Masking: NONE

What is the study measuring?

Primary Outcome Measures

Outcome Measure
to evaluate D2 receptor occupancy and plasma concentration of paliperidone at defined times after intake of a single dose of OROS paliperidone 6 mg

Secondary Outcome Measures

Outcome Measure
to derive pharmacokinetic/pharmacodynamic relationships and the occurrence of adverse events

Collaborators and Investigators

• Sponsor: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.

Publications and helpful links

Helpful Links

• A study of dopamine type 2 (D2) receptor occupancy following a single oral dose of OROS paliperidone

Study record dates

Study Major Dates

• Study Start: March 1, 2003
• Study Completion (ACTUAL): June 1, 2003

Study Registration Dates

• First Submitted: November 20, 2008
• First Submitted That Met QC Criteria: November 20, 2008
• First Posted (ESTIMATE): November 24, 2008

Study Record Updates

• Last Update Posted (ESTIMATE): June 10, 2011
• Last Update Submitted That Met QC Criteria: June 8, 2011
• Last Verified: March 1, 2010

More Information

Terms related to this study

• Keywords: Schizophrenia; dopamine; mood disorders; antipsychotic drugs; receptor occupancy; OROS paliperidone
• Additional Relevant MeSH Terms: Mental Disorders; Schizophrenia Spectrum and Other Psychotic Disorders; Schizophrenia; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Antipsychotic Agents; Tranquilizing Agents; Psychotropic Drugs; Serotonin Agents; Dopamine Agents; Serotonin 5-HT2 Receptor Antagonists; Serotonin Antagonists; Dopamine D2 Receptor Antagonists; Dopamine Antagonists; Paliperidone Palmitate
• Other Study ID Numbers: CR004267