Phase I Study of the Safety, Distribution, and Radiation Dosimetry of Ultratrace Iobenguane 123I-mIBG (mIBG)

Phase I Study of the Safety, Distribution, and Radiation Dosimetry of Ultratrace Iobenguane 123I-mIBG-Nanodosing: the Path to Higher Sensitivity and Lower Toxicity Radiopharmaceuticals

The goal of this proposal is to produce and test high specific activity Ultratrace iobenguane I 123 in normal human volunteers.

Study Overview

• Status: Completed
• Conditions: Heart Failure; Neuroendocrine Tumors
• Intervention / Treatment: Drug: no carrier added metaiodobenzylguanidine

Detailed Description

The goal of this proposal is to produce and test high specific activity Ultratrace iobenguane I 123 in normal human volunteers. The low specific activity iobenguane I 123 has been shown to be useful for the detection and staging of neuroendocrine tumors in adults and children and imaging neuronal activity in the heart. The innovation in this proposal is through the use of patented solid phase technology to produce a proven diagnostic agent at extremely high specific activity to increase sensitivity and specificity and lower radiation exposure to normal organs without the pharmacologically active cold carrier compound. The FDA considers iobenguane labeled with two different isotopes of iodine [I-131 and I-123] as two distinct drugs requiring distinct regulatory applications.

To meet the required quality standards for the chemistry, manufacturing and controls component of an IND application, GMP quality polymer drug precursor is used to generate the Ultratrace diagnostic iodine-123 agent. Analytical methods were validated with the proposed final drug formulation to demonstrate the final drug does not interfere with tests used to define the identity, purity, and strength of the agent. The drug product was verified for apyrogenicity and sterility before human testing. The IND application was written and submitted to the FDA and the Duke Medical Center IRB. MIP produces clinical trial material, and will conduct human testing of the radioactive drug substance for safety and superiority compared to conventional iobenguane I 123 in normal healthy volunteers.

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• normal healthy volunteers with written informed consent who understand and are willing to comply with protocol requirements
• at least 21 years of age
• if female, then not of childbearing potential as documented by history (e.g., tubal ligation or hysterectomy) or is post menopausal with a minimum 1 year without menses
• if female of childbearing potential, a negative serum beta HCG pregnancy test within 24 hours prior to receiving iobenguane I 123
• if female of childbearing potential, agrees to use an acceptable form of birth control, defined as abstinence or use of IUD, oral contraceptive, barrier and spermicide, or hormonal implant, throughout the study period
• No existing predisposition to administration of thyroid blocking potassium iodide

Exclusion Criteria:

• females who are nursing
• documented history of significant allergy that required medical intervention to shellfish, X-ray contrast media, iodine/iodides, or iobenguane
• administered a radioisotope within 5 effective half-lives of that radioisotope prior to study enrollment
• abnormal screening laboratory studies (serum creatinine, SPOT, SGPT, total bilirubin as defined by standard laboratory reference ranges)
• those who have received an investigational compound and/or medical device within 30 days of entering this study
• pre-existing medical condition or circumstances which would significantly decrease the chances of obtaining reliable data, achieving study objectives, or completing the study, (e.g. cancer, heart disease, or other medical conditions which potentially alter normal biodistribution)
• is determined by the investigator that the patient is clinically unsuitable for the study
• are taking medication which inhibits uptake of iobenguane I 123 within 2 weeks of enrollment, or tricyclic antidepressants or related drugs within 6 weeks of enrollment. Categories of medications include sympathomimetics, antihypertensives and cardiovascular agents, opioids, antipsychotics, tricyclic antidepressants, and medications as previously published
• have participated in a clinical trial with an investigational drug in the past 30 days.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Radiation dosimetry; no carrier added metaiodobenzylguanidine	Drug: no carrier added metaiodobenzylguanidine; Sequential imaging was performed to determine radiation dosimetry of high specific activity 123I-mIBG; Other Names: Ultratrace

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Radiation dosimetry	Radiation dosimetry was measured by imaging at several time points. Blood and urine samples were also collected to correlate with imaging parameters. Side effects were also assessed after drug administration.	2 weeks

Collaborators and Investigators

• Sponsor: Bennett Chin
• Collaborators: National Cancer Institute (NCI); Molecular Insights Pharmaceuticals
• Investigators: Principal Investigator: Bennett B Chin, MD, Duke University

Publications and helpful links

General Publications

• Chin BB, Kronauge JF, Femia FJ, Chen J, Maresca KP, Hillier S, Petry NA, James OG, Oldan JD, Armor T, Stubbs JB, Stabin MG, Babich JW. Phase-1 clinical trial results of high-specific-activity carrier-free 123I-iobenguane. J Nucl Med. 2014 May;55(5):765-71. doi: 10.2967/jnumed.113.124057. Epub 2014 Mar 13.

Study record dates

Study Major Dates

• Study Start: November 1, 2009
• Primary Completion (Actual): June 1, 2011
• Study Completion (Actual): July 1, 2011

Study Registration Dates

• First Submitted: November 7, 2012
• First Submitted That Met QC Criteria: November 20, 2012
• First Posted (Estimate): November 21, 2012

Study Record Updates

• Last Update Posted (Estimate): November 21, 2012
• Last Update Submitted That Met QC Criteria: November 20, 2012
• Last Verified: November 1, 2012

More Information

Terms related to this study

• Keywords: Phase 1; no carrier added metaiodobenzylguanidine; radiation dosimetry
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Radiopharmaceuticals; 3-Iodobenzylguanidine
• Other Study ID Numbers: Pro00019124 (MIP-CA130394-01); 5R44CA130394-03 (U.S. NIH Grant/Contract)