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

This study is enrolling participants by invitation only.
Sponsor:
Information provided by:
Asan Medical Center
ClinicalTrials.gov Identifier:
NCT01193621
First received: September 1, 2010
Last updated: NA
Last verified: July 2009
History: No changes posted
  Purpose

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 Intervention Phase
Healthy
 Drug: haloperidol, PET
 Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Crossover 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

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by Asan Medical Center:

Primary Outcome Measures:
  • 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 ]

Estimated Enrollment: 24
Arms Assigned Interventions
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.

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

    1.2 Biodistribution study Intravenous Dose No. of Subjects 10 mCi 12

  2. Measurement 2.1 Pharmacokinetics/pharmacodynamics of haloperidol 2.2 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
  Eligibility

Ages Eligible for Study:   19 Years to 45 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01193621

Locations
Korea, Republic of
Asan Medical Center
Seoul, Korea, Republic of, 138-736
Sponsors and Collaborators
Asan Medical Center
  More Information

No publications provided

ClinicalTrials.gov Identifier: NCT01193621     History of Changes
Other Study ID Numbers: 2009-0692
Study First Received: September 1, 2010
Last Updated: September 1, 2010
Health Authority: Korea: Institutional Review Board
Korea: Food and Drug Administration

Keywords provided by Asan Medical Center:
early evaluation
pharmacokinetics
pharmacodynamics
Biodistribution
D2-receptor occupancy

Additional relevant MeSH terms:
Haloperidol
Haloperidol decanoate
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
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

ClinicalTrials.gov processed this record on May 23, 2013