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Se-Methyl-Seleno-L- Cysteine (MSC) in Treating Healthy Patients

Phase 1
Completed
Conditions
Healthy, no Evidence of Disease
Interventions
Other: placebo
Other: pharmacological study
Other: laboratory biomarker analysis
Registration Number
NCT00489372
Lead Sponsor
National Cancer Institute (NCI)
Brief Summary

This randomized phase I trial is studying the side effects and best dose of Se-methyl-seleno-L-cysteine in healthy adult men. Studying samples of blood, urine, and toenail clippings in the laboratory from healthy men receiving Se-methyl-seleno-L-cysteine may help doctors learn more about how Se-methyl-seleno-L-cysteine works in the body.

Detailed Description

PRIMARY OBJECTIVES:

I. To evaluate the toxicity of MSC, given to healthy adult males as a single oral dose.

SECONDARY OBJECTIVES:

I. To characterize the pharmacokinetics of single oral doses of MSC in healthy adult male volunteers.

II. To evaluate the baseline selenium content of toenail clippings in healthy adult males.

OUTLINE: This is a multicenter, randomized, placebo controlled, double blind, dose escalation study. Participants are randomized to 1 of 2 arms.

Arm I: Participants receive oral placebo on day 1.

Arm II: Participants receive oral Se-methyl-seleno-l-cysteine (MSC) on day 1. Cohorts of 5 participants receive escalating doses of MSC until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 5 or 2 of 10 patients experience dose-limiting toxicity.

Participants undergo blood, urine, and toenail clipping collection for pharmacokinetic and correlative studies. Samples are analyzed for plasma protein levels of selenium for proteomic and gene expression, molecular fingerprinting by mass spectrometry, and RNA by gene array analysis.

After completion of study treatment, participants are followed at 7-14 days and at 30 days.

Recruitment & Eligibility

Status
COMPLETED
Sex
Male
Target Recruitment
36
Inclusion Criteria
  • Total body weight between 50 and 115 kg
  • Hgb > 12 gm/dl
  • Platelets > 100,000/μL
  • ANC > 1000/μL
  • Creatinine < 1.5 mg/dl
  • SGPT and SGOT < 3 X the institutional upper limit of normal (ULN)
  • Total bilirubin < 1.5 X the institutional ULN (subjects with a higher level of bilirubin due to a familial metabolism will be considered on an individual basis)
  • Life expectancy greater than 2 years
  • Male subjects must agree to use adequate contraception (barrier method of birth control; abstinence) prior to study entry and until study completion (i.e., at least two weeks after dose of study drug)
  • Ability to understand and the willingness to sign a written informed consent document
  • Agree to refrain from use of selenium supplements while on study
Exclusion Criteria
  • Not willing to remain at RPCI, and in follow up, as required
  • Presence of medical conditions, which in the opinion of the investigators, would compromise either the subject, or the integrity of the data
  • Individuals with a history of active liver or kidney disease within the past 6 months
  • Treatment with an investigational drug within 30 days prior to the dose of study drug
  • Use of prescription or nonprescription drugs, vitamins, or herbal supplements known to change gastric acidity (e.g., H2-antagonists, proton pump inhibitors, antacids) within 3 days of study drug administration
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to MSC (e.g. reaction to other selenium supplements)
  • Subjects who have donated 1 unit of blood within 30 days prior to the first dose of MSC
  • Subjects with a known history of heavy metal exposure, such as lead, mercury, of arsenic
  • ECOG performance status > 1
  • AUA total symptom score > 10 (or any individual symptom score of greater than or equal to 4 will exclude the participant)

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Arm I (placebo)laboratory biomarker analysisParticipants receive oral placebo on day 1.
Arm II (Se-methyl-seleno-L-cysteine)pharmacological studyParticipants receive oral Se-methyl-seleno-l-cysteine (MSC) on day 1. Cohorts of 5 participants receive escalating doses of MSC until the MTD is determined. The MTD is defined as the dose preceding that at which 2 of 5 or 2 of 10 patients experience dose-limiting toxicity.
Arm I (placebo)placeboParticipants receive oral placebo on day 1.
Arm I (placebo)pharmacological studyParticipants receive oral placebo on day 1.
Arm II (Se-methyl-seleno-L-cysteine)laboratory biomarker analysisParticipants receive oral Se-methyl-seleno-l-cysteine (MSC) on day 1. Cohorts of 5 participants receive escalating doses of MSC until the MTD is determined. The MTD is defined as the dose preceding that at which 2 of 5 or 2 of 10 patients experience dose-limiting toxicity.
Arm II (Se-methyl-seleno-L-cysteine)Se-methyl-seleno-L-cysteineParticipants receive oral Se-methyl-seleno-l-cysteine (MSC) on day 1. Cohorts of 5 participants receive escalating doses of MSC until the MTD is determined. The MTD is defined as the dose preceding that at which 2 of 5 or 2 of 10 patients experience dose-limiting toxicity.
Primary Outcome Measures
NameTimeMethod
Clinical toxicity in healthy adult male volunteers, graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) v3.0Up to 30 days

Summarized using descriptive statistics.

Secondary Outcome Measures
NameTimeMethod
Characterization of the pharmacokinetics of MSCUp to 24 hours post-dose

Descriptive statistics calculated for each cohort, using established pharmacokinetic analysis methods.

Selenium levels in toenail samplesUp to 24 hours post-dose

Summarized graphically.

Trial Locations

Locations (2)

Northwestern University

🇺🇸

Chicago, Illinois, United States

Roswell Park Cancer Institute

🇺🇸

Buffalo, New York, United States

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