Absorption, Metabolism, and Excretion Study of [14C]-TNP-2092
Condition: Healthy
Study type: Interventional
Phase: Phase 1

Summary: 
      This is an open-label, single dose, Phase 1 study conducted at a single study center in the
      United States (USA). This study will evaluate the absorption, metabolism and elimination
      (AME), mass balance, safety and tolerability of a single dose of intravenously administered
      [14C]-TNP-2092.

      Healthy men aged 18 to 55, will be screened, and subjects who meet all eligibility criteria
      and provide written informed consent will be enrolled into the study within 28 days of
      Screening.

      Subjects will be admitted to the clinical unit on the day prior to dosing (Day -1). Subjects
      will fast overnight and then given a standard breakfast 30 min prior to dosing.

      Six subjects will be enrolled in the study and each will receive a single intravenous (IV)
      dose of 300 mg/3 μCi [14C]-TNP-2092 administered over 60 minutes (±10 minutes).
    

Detailed description: 
      This is an open-label, single dose, Phase 1 study conducted at a single study center in the
      United States (USA). This study will evaluate the absorption, metabolism and elimination
      (AME), mass balance, safety and tolerability of a single dose of intravenously administered
      [14C]-TNP-2092 Healthy men aged 18 to 55, will be screened, and subjects who meet all
      eligibility criteria and provide written informed consent will be enrolled into the study
      within 28 days of Screening.

      Subjects will be admitted to the clinical unit on the day prior to dosing (Day 1). Subjects
      will fast overnight and then given a standard breakfast 30 min prior to dosing.

      Six subjects will be enrolled in the study and each will receive a single intravenous (IV)
      dose of 300 mg/3 µCi [14C]-TNP-2092 administered over 60 minutes (±10 minutes).

      Subjects will remain in the unit for 7 days after dosing (until morning of Day 8) for
      observation and collection of whole blood, urine and fecal samples.

      Whole blood samples will be collected at pre-dose (-30 minutes) and at 15 minutes, 30
      minutes, 45 minutes, 1 h (end of infusion), and at 1 h 5 minutes, 1 h 10 minutes, 1 h 15
      minutes, 1 h 30 minutes, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours
      after initiation of the [14C]-TNP-2092 infusion (n=25 timepoints per subject). Depending on
      14C radiolabel recovery, an additional whole blood sample may be collected on Day 15 (336
      hours after initiation dosing) for a total of n=26 timepoints per subject. These samples will
      be used to determine concentrations of TNP-2092 (in plasma), metabolite profiling (in
      plasma), and total [14C] (whole blood and plasma).

      Urine will be continuously collected for [14C] recovery, and metabolite assessments from the
      time of admission until immediately prior to dosing (pre dose) and over the following
      collection intervals: 0-8, 8-16, 16-24, 24-48, 48-72, 72-96, 96-120, 120-144 and 144-168
      hours (Day 8) after initiation of the [14C]-TNP 2092 infusion (n=10 timepoints per subject).
      Depending on 14C radiolabel recovery, additional urine samples may be collected on Days 14
      and 15 (312-336 hours after dosing).

      Feces will be continuously collected for metabolite and [14C] recovery assessments from the
      time of admission until immediately prior to dosing (pre dose) and over the following
      collection intervals: 0-24, 24-48, 48-72, 72-96, 96-120, 120-144 and 144-168 hours (Day 8)
      after initiation of the [14C]-TNP-2092 infusion (n=8 timepoints per subject). Depending on
      14C radiolabel recovery, additional fecal samples may be collected on Days 14 and 15 (312-336
      hours after dosing).

      Safety will be assessed by physical examination, vital signs (VS), 12-lead
      electrocardiograms, clinical laboratory tests (serum chemistry panel, hematology,
      coagulation, and urinalysis), use of concomitant medications, collection of adverse events,
      and by unscheduled assessments as needed for management of adverse events.

      Subjects will be discharged from the CPC on Day 8 after completion of all 168h timepoint
      assessments. The Investigator will indicate whether ≥90% of the 14C radiolabel has been
      recovered in samples collected through 168h; if so, Day 8 will be the final study visit. If
      recovery of 14C in excreta is <90% by the time of discharge on Day 8, subjects will return to
      the site for an additional 24-hour PK confinement period on Days 14-15 (312-336h). The date
      of study completion for each subject will be defined as the last day that PK samples are
      collected. To avoid enrolling a participant with systemic 14C excess, samples of urine and/or
      blood (either whole blood or plasma) obtained at Screening must show no significant excess of
      14C over environmental background level.
    

Intervention name(s): [14C]-TNP-2092
Intervention type(s): Drug
Intervention description(s): Subjects will receive a single intravenous (IV) dose of 300 mg/3 µCi [14C]-TNP-2092 administered over 60 minutes (± 10 minutes).
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Other