Early Clinical Evaluation of the Pharmacokinetics and Mechanism Based Pharmacodynamics of Haloperidol Using Positron Emission Tomography in Healthy Volunteers
In the present study, the investigators will establish the clinical trial technology for early evaluation of drug characteristics in terms of pharmacokinetics and pharmacodynamics for haloperidol as a model drug, using positron emission tomography.
|Study Design:||Allocation: Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Parallel Assignment
Masking: Open Label
|Official Title:||Early Clinical Evaluation of the Pharmacokinetics and Mechanism Based Pharmacodynamics of Haloperidol Using Positron Emission Tomography in Healthy Volunteers|
- plasma haloperidol concentration [ Time Frame: day 1 0h (predose), day 1 6h, day 2 0h, day 3 0h (predose), day 5 0h (predose), and day 7 0h (predose), 0.5, 1, 2, 4, 6, 8, 12, 24(day 8 0h), 48(day 9 0h), 72h (day 10h) ] [ Designated as safety issue: No ]
|Study Start Date:||January 2008|
|Study Completion Date:||January 2012|
|Primary Completion Date:||July 2010 (Final data collection date for primary outcome measure)|
Active Comparator: haloperidol
0.5, 1, 3 mg of haloperidol will be administered orally every 24 hours for 7 days to 4 healthy subjects in each dose level (a total of 12 subjects).
Dose groups are as follows; D2-receptor occupancy study Group Single Oral Dose No. of subjects
Drug: haloperidol, PET
above doses will be administrated orally every 24 hours for 7 days.
This study will consist of two parts. One is "biodistribution study of haloperidol" in 12 subjects, and the other is "receptor occupancy study of haloperidol" in 12 subjects. In the biodistribution study, 18F-haloperidol (10 mCi) will be injected intravenously two times into each of the 12 subjects (cross-over design). Whole body PET will be conducted after the first haloperidol injection and local brain PET after the 2nd haloperidol injection after the 7 day washout period.
1.1 D2-receptor occupancy study Group Doses No. of subjects 1 0.5 mg 4 2 1 mg 4 3 3 mg 4
- Measurement 2.1 The D2 receptor Occupancy of haloperidol.
Test schedule 3.1 Biodistribution study
- Whole body PET (day 1)
- Brain local PET (day 8) 3.2 Receptor occupancy study
- Baseline PET before drug administration (day 1 0h), 6h (day 1 6h), 24h (day 2 0h), after the first haloperidol administration (day 1 0h), and 24 h (day 8), 72 h (day 10), and 168 h (day 14) after the last dosing of haloperidol (day 7 0h).
- Drug administration from day 1 through day 7 every 24 hours PK blood sampling (6 ml, each) prior to the first haloperidol administration (day 1 0h) and 6h (1 day 6h), 24h (2 day 0h), 48 h (3 day 0h), 96 h (5 day 0h), 144 h (7 day 0h) and, 0.5, 1, 2, 4, 6, 8, 12, 24 h (8day 0h), 48h (9day 0h), 72h (10 day 0h) after taking the last oral dose of haloperidol
- Analytic Methods 4.1 Pharmacokinetics: Noncompartmental Analysis Using Winnonlin Compartment model using NONMEM VII 4.2 Pharmacodynamics in the brain: Emax or linear model using NONMEM VII