Lofexidine Mass Balance in Volunteers
Condition: Normal Healthy Volunteers
Study type: Interventional
Phase: Phase 1

Summary: 
      The purpose of this study is to see how lofexidine (investigational study formulation drug)
      is absorbed, broken down, and removed from the body. To do this, a special form of the study
      drug will be used that has a radioactive carbon atom attached. Blood, urine, and feces
      samples will be collected at different times to measure the amount of the study drug and
      radioactivity they contain. The amount of radioactivity you will be exposed to is less than
      the amount of radiation from a regular X-ray.
    

Detailed description: 
      The purpose of this study is to determine the mass balance of a single oral dose of 14C
      labeled lofexidine. Study US WorldMeds Reference Number USWM-LX1-1003, conducted in July and
      August of 2011, was a single-center, open-label, two-period, two-treatment, randomized
      sequence study to determine the mass balance and absolute bioavailability of a single oral
      dose of 14C-labeled lofexidine compared to a single intravenous dose of lofexidine. During
      the conduct of the study, deficiencies occurred in the collection and processing of urine
      samples from subjects administered the oral dose of 14C-labeled lofexidine. In study
      USWM-LX1-1003-1, six male subjects will be dosed with 14C labeled lofexidine oral solution in
      order to provide accurate data for the mass balance portion of the study. Male subjects who
      successfully participated in and completed study USWM-LX1-1003 will be enrolled first.
      Additional male subjects will be enrolled as needed to provide a cohort of 6 subjects.
      Additional provisions to ensure adequate urine collections have now been implemented at the
      site and will be utilized in USWM-LX1-1003-1. All blood draws for pharmacokinetic analysis
      and radioanalysis, and all urine and fecal collection intervals, will occur at the same time
      points in USWM-LX1-1003-1 as they did in USWM-LX1-1003.

      To study the absorption, distribution, metabolism, and elimination (ADME), trace amounts of
      14C compounds are quantified using accelerator mass spectrometry (AMS). As a form of an
      isotope ratio atom counter that achieves the lowest detection limits of any type of mass
      spectrometry, AMS provides quantitative sensitivity towards 14C labeled compounds to low
      attomole (10-18) levels. This high degree of sensitivity enables the detection of compounds
      in very small specimens and/or tissues after administration of doses that can be both
      chemically and radiochemically small (microdose levels).

      At the radioactive dose to be given (approximately 280 nCi; 10.36 kBq) the total radiation
      exposure to the participant is within the level of background radiation exposure that occurs
      naturally and orders of magnitude (1000 fold reduction on average) below the levels typical
      for human metabolism studies using 14C tracers.
    

Intervention name(s): Lofexidine hydrochloride
Intervention type(s): Drug
Intervention description(s): Single Dose = Solution containing 400 μg lofexidine HCl and a tracer amount of 14C lofexidine
Intervention MeSH terms: Lofexidine
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Basic Science
Keywords: Phase 1; Normal healthy volunteers; Mass Balance