Early Clinical Evaluation of the Pharmacokinetics and Mechanism Based Pharmacodynamics of Haloperidol Using Positron Emission Tomography in Healthy Volunteers

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01193621
Recruitment Status : Completed
First Posted : September 2, 2010
Last Update Posted : July 11, 2013
Seoul National University Hospital
Information provided by (Responsible Party):
Kyun-Seop Bae, Asan Medical Center

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Healthy Drug: haloperidol, PET Phase 1

Detailed Description:
  1. Study Design

    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

  2. Measurement 2.1 The D2 receptor Occupancy of haloperidol.
  3. 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
  4. 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

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 12 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Official Title: Early Clinical Evaluation of the Pharmacokinetics and Mechanism Based Pharmacodynamics of Haloperidol Using Positron Emission Tomography in Healthy Volunteers
Study Start Date : January 2008
Actual Primary Completion Date : July 2010
Actual Study Completion Date : January 2012

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
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

  1. 0.5 mg 4
  2. 1 mg 4
  3. 5 mg 4
Drug: haloperidol, PET
  1. Biodistribution study Intravenous 18F haloperidol(10 mCi) Dose injection two times before whole body PET scan
  2. D2-receptor occupancy study Group Doses No. of subjects 1 0.5 mg 4 2 1 mg 4 3 3 mg 4

above doses will be administrated orally every 24 hours for 7 days.

Primary Outcome Measures :
  1. 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) ]

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Ages Eligible for Study:   19 Years to 45 Years   (Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes

Inclusion Criteria:

  • Overtly healthy males as determined by medical history and physical examination
  • Age from 19 to 45 years
  • Weight ≥ 45 kg and within ± 20% of IBW
  • Clinical laboratory test results within normal reference range for the National Cancer Center, Hospital or results with minor deviations which are judged to be not clinically significant by the investigator
  • Normal blood pressure and heart rate (supine and standing) as determined by the investigator
  • Are reliable and willing to make themselves available for the duration of the study, and who will abide by the study restrictions
  • Have given written informed consent

Exclusion Criteria:

  • History or presence of cardiovascular, respiratory, hepatic, renal, gastrointestinal, neurological disorders capable of altering the absorption, metabolism or elimination of drugs, or of constituting a risk factor when taking the study medication
  • An episode of febrile disease or infectious disease within the past 2 weeks
  • Evidence of significant active hematologic disease and/or blood donation in the last 2 months
  • Evidence of significant active neuropsychiatric disease
  • Regular use of drugs or abuse
  • History of drug hypersensitivity or clinically significant allergic reactions of any origin
  • Participation in a study involving administration of an investigational compound within the past 30 days
  • Have a regular alcohol intake greater than 21 units/week or subjects unwilling to stop alcohol for the duration of the study periods
  • Intend to use concomitant drug therapy, including non prescription medication on a regular basis apart from vitamin/mineral supplements
  • Smoking history for recent 3 months
  • Use of medication within 7 days prior to the study. If this situation arises inclusion of an otherwise suitable volunteer may be at the discretion of the investigator

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 identifier (NCT number): NCT01193621

Korea, Republic of
Asan Medical Center
Seoul, Korea, Republic of, 138-736
Sponsors and Collaborators
Asan Medical Center
Seoul National University Hospital

Responsible Party: Kyun-Seop Bae, Associate Professor, Asan Medical Center Identifier: NCT01193621     History of Changes
Other Study ID Numbers: 2009-0692
First Posted: September 2, 2010    Key Record Dates
Last Update Posted: July 11, 2013
Last Verified: July 2013

Keywords provided by Kyun-Seop Bae, Asan Medical Center:
early evaluation
D2-receptor occupancy

Additional relevant MeSH terms:
Haloperidol decanoate
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Antipsychotic Agents
Tranquilizing Agents
Central Nervous System Depressants
Psychotropic Drugs
Dopamine Antagonists
Dopamine Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Anti-Dyskinesia Agents