Study Assessing Pharmacokinetics and Bioavailability of Three Novel Triazine Compounds
Condition: Malaria
MeSH terms: Malaria
Study type: Interventional
Phase: Early Phase 1

Summary: 
      Open-label, randomized, microdose study
    

Detailed description: 
      This is an open-label, randomized, fixed-sequence, microdose study of three Carbon-14 radio
      labeled (14C) triazine compounds WR826647, WR909388, WR909390 designed in accordance with ICH
      Guidance for Industry M3(R2) (ICH 2009). Subjects will be randomized to one of three groups
      to receive 100 mcg WR826647, WR909388, or WR909390 at an exposure no greater than 250 nCi per
      dose, administered both IV (bolus) and PO with a six half-life wash-out period between IV and
      PO administration. Interim analyses will be done at Day 14 following the IV dosing groups in
      order to assess half-lives of the three compounds to ensure the wash-out period between IV
      and PO dosing is at least six half-lives long.

      Pharmacokinetic parameters of the 3 compounds will be calculated from the plasma-time data
      using Phoenix WinNonlin version 6.3 or higher, and descriptive statistics assessed using SAS
      version 9.3 or higher. No statistical significance inferences will be made. An analysis of
      variance (ANOVA) will be performed on the natural logarithm (ln) transformed dose-adjusted
      AUCinf to estimate the bioavailability. The sample size of 6 subjects per group is considered
      adequate to obtain useful data to compute descriptive statistics. Interim analyses will be
      done after the IV dosing groups in order to assess half-lives of the 3 compounds to ensure
      the wash-out period between IV bolus and oral dosing is at least 6 half-lives long.
    

Intervention name(s): WR826647; WR909388; WR909390
Intervention type(s): Drug; Drug; Drug
Intervention description(s): 100 mcg Carbon-14 radio labeled WR826647 at an exposure no greater than 250 nCi per dose, administered both IV (bolus) and PO with a six half-life wash-out period between IV and PO administration. Interim analyses will be done at Day 14 following the IV dosing groups in order to assess half-lives of the three compounds to ensure the wash-out period between IV and PO dosing is at least six half-lives long.; 100 mcg Carbon-14 radio labeled WR909388 at an exposure no greater than 250 nCi per dose, administered both IV (bolus) and PO with a six half-life wash-out period between IV and PO administration. Interim analyses will be done at Day 14 following the IV dosing groups in order to assess half-lives of the three compounds to ensure the wash-out period between IV and PO dosing is at least six half-lives long.; 100 mcg Carbon-14 radio labeled WR909309 at an exposure no greater than 250 nCi per dose, administered both IV (bolus) and PO with a six half-life wash-out period between IV and PO administration. Interim analyses will be done at Day 14 following the IV dosing groups in order to assess half-lives of the three compounds to ensure the wash-out period between IV and PO dosing is at least six half-lives long.
Other intervention name(s): Triazine WR826647; Triazine WR909388; Triazine WR909390
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Subjects will be randomized to one of three groups to receive 100 mcg Carbon-14 radio labeled WR826647, WR909388, or WR909390
Masking: None (Open Label)
Primary purpose: Diagnostic