Biodistribution and Safety of a Radiopharmaceutical in Healthy Subjects - Full Text View

Purpose

The initial study of [123I] INER will be completed in two parts. Once Part A (Preliminary whole body biodistribution) is completed, Part B (Serial dynamic SPECT assessment of regional brain uptake and washout and plasma metabolite analysis to determine the brain penetrance and regional distribution and washout counts following 123-I INER injection) will commence. All study procedures will be conducted at the Institute for Neurodegenerative Disorders (IND) and Molecular NeuroImaging (MNI) in New Haven, CT. All subjects will undergo written informed consent and a screening evaluation including baseline clinical laboratory testing, and a baseline physical and neurological evaluation.

Condition	Intervention	Phase
Biodistribution and Metabolic Rate of 123-I INER	Drug: 123-I INER	Phase 1

Study Type:	Interventional
Study Design:	Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Diagnostic
Official Title:	Phase 1 Assessment of the Biodistribution and Safety of 123-I INER in Healthy Subjects

Resource links provided by NLM:

MedlinePlus related topics: Degenerative Nerve Diseases

U.S. FDA Resources

Further study details as provided by Institute for Neurodegenerative Disorders:

Primary Outcome Measures:

Assess the biodistribution and metabolic rate of 123-I INER for determination of radiation absorbed dose estimates. [ Time Frame: 2 yrs ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Assess of regional brain uptake and washout and plasma metabolite analysis to determine the brain penetrance and regional distribution and washout counts following 123-I INER injection. [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	10
Study Start Date:	April 2006
Estimated Study Completion Date:	April 2012
Estimated Primary Completion Date:	April 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: 123-I INER	Drug: 123-I INER Serial whole body planar imaging in the anterior and posterior projection will be performed at 1 min, 30 min, 1 h, 2h, 3h, 4h, 5h, 6h, 7h, 8h, and 18-24h following injection of 5 mCi of 123-I INER. Venous blood data will be acquired at each imaging time point. In addition a 24 hour urine collection will commence following radiotracer injection and urine sampled in five collections every 4 hours collection for first sixteen hours (4 collections), then one collection from 16 to 24 h. Whole body and source organs uptake will be analyzed on anterior and posterior images for calculating the radiation absorbed doses to organs using the MIRD method as described previously (Seibyl, et al, 1993). Plasma and urine metabolites will be characterized and safety assessments obtained.

Arms

Assigned Interventions

Experimental: 123-I INER

Drug: 123-I INER

Serial whole body planar imaging in the anterior and posterior projection will be performed at 1 min, 30 min, 1 h, 2h, 3h, 4h, 5h, 6h, 7h, 8h, and 18-24h following injection of 5 mCi of 123-I INER. Venous blood data will be acquired at each imaging time point. In addition a 24 hour urine collection will commence following radiotracer injection and urine sampled in five collections every 4 hours collection for first sixteen hours (4 collections), then one collection from 16 to 24 h. Whole body and source organs uptake will be analyzed on anterior and posterior images for calculating the radiation absorbed doses to organs using the MIRD method as described previously (Seibyl, et al, 1993). Plasma and urine metabolites will be characterized and safety assessments obtained.

Detailed Description:

All subjects will receive a full physical examination at IND to determine study eligibility. Written informed consent will be obtained prior to any study procedures. The screening procedures will include: review of medical and psychiatric history, review of medications, physical examination including height and body weight, vital sign measurements, review of inclusion/exclusion criteria, clinical laboratory testing (serum chemistries, CBC, urinalysis, urinary drug screen), urine pregnancy test for females of childbearing potential and electrocardiogram in preparation for the imaging study.

Part A: Four healthy subjects will each receive one injection of 123-I INER. Serial whole body planar imaging in the anterior and posterior projection will be performed over the 8-9 hour period following injection of 5 mCi of 123-I INER and again at 18-24 hours following injection. Venous blood data will be acquired at each imaging time point. In addition a 24 hour urine collection will commence following radiotracer injection. Whole body and source organs uptake will be analyzed on anterior and posterior images for calculating the radiation absorbed doses to organs. Plasma and urine metabolites will be characterized and safety assessments obtained. Serial safety assessments will include vital signs, serum chemistries, CBC, urinalysis, and EKGs.

Part B: Six healthy subjects will each receive one injection of 123-I INER. Following bolus intravenous injection of 5 mCi of 123-I INER over 15 seconds, serial dynamic SPECT brain acquisitions will be obtained to evaluate the regional brain uptake and washout of activity. Venous blood measures will be obtained with each acquisition and characterization of 123-I INER and metabolites will be assessed. Safety assessments will include vital signs, serum chemistries, CBC, urinalysis, and EKGs.

Eligibility

Ages Eligible for Study:	18 Years to 65 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	Yes

Criteria

Inclusion Criteria:

The subject is aged 18-65.
Written informed consent is obtained.
The subject has a negative history of neurological or psychiatric illness based on evaluation by a research physician.
For females, non-child bearing potential or negative urine pregnancy test on day of [123I] INER injection.

Exclusion Criteria:

The subject has a clinically significant clinical laboratory values abnormality, and/or medical or psychiatric illness.
The subject has any disorder that may interfere with drug absorption, distribution, metabolism, or excretion (including gastrointestinal surgery).
The subject has evidence of clinically significant gastrointestinal, cardiovascular, hepatic, renal, hematological, neoplastic, endocrine, neurological, immunodeficiency, pulmonary, or other disorder or disease.
Use of all prescription drugs or non-prescriptions drugs that may effect norepinephrine such as cold remedies (for 2 weeks prior to injection).
Pregnancy

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00316797

Locations

United States, Connecticut
Institute for Neurodegenerative Disorders
New Haven, Connecticut, United States, 06510

Sponsors and Collaborators

Institute for Neurodegenerative Disorders

Molecular NeuroImaging

Investigators

Principal Investigator:

John Seibyl, MD

Institute for Neurodegenerative Disorders

More Information

Additional Information:

Institute for Neurodegenerative Disorders This link exits the ClinicalTrials.gov site

Publications:

Abi-Dargham A, Innis RB, Wisniewski G, Baldwin RM, Neumeyer JL, Seibyl JP. Human biodistribution and dosimetry of iodine-123-fluoroalkyl analogs of beta-CIT. Eur J Nucl Med. 1997 Nov;24(11):1422-5.

Dey HM, Seibyl JP, Stubbs JB, Zoghbi SS, Baldwin RM, Smith EO, Zubal IG, Zea-Ponce Y, Olson C, Charney DS, et al. Human biodistribution and dosimetry of the SPECT benzodiazepine receptor radioligand iodine-123-iomazenil. J Nucl Med. 1994 Mar;35(3):399-404.

Fujita M, Seibyl JP, Vaupel DB, Tamagnan G, Early M, Zoghbi SS, Baldwin RM, Horti AG, KoreN AO, Mukhin AG, Khan S, Bozkurt A, Kimes AS, London ED, Innis RB. Whole-body biodistribution, radiation absorbed dose, and brain SPET imaging with [123i]5-i-A-85380 in healthy human subjects. Eur J Nucl Med Mol Imaging. 2002 Feb;29(2):183-90.

Seibyl JP, Wallace E, Smith EO, Stabin M, Baldwin RM, Zoghbi S, Zea-Ponce Y, Gao Y, Zhang WY, Neumeyer JL, et al. Whole-body biodistribution, radiation absorbed dose and brain SPECT imaging with iodine-123-beta-CIT in healthy human subjects. J Nucl Med. 1994 May;35(5):764-70.

Responsible Party:	John Seibyl, MD, Principal Investigator, Institute for Neurodegenerative Disorders
ClinicalTrials.gov Identifier:	NCT00316797 History of Changes
Other Study ID Numbers:	H01_INER_001/002
Study First Received:	April 19, 2006
Last Updated:	February 8, 2012
Health Authority:	United States: Food and Drug Administration

Keywords provided by Institute for Neurodegenerative Disorders:

SPECT
Nuclear Medicine

ClinicalTrials.gov processed this record on May 16, 2013