A Phase 1 Study to Evaluate Safety, Tolerability, PK, and PK Interactions of TBA-7371
Condition: Tuberculosis; Tuberculosis, Pulmonary
MeSH terms: Tuberculosis; Tuberculosis, Pulmonary
Study type: Interventional
Phase: Phase 1

Summary: 
      The primary objective of the study is to evaluate the safety and tolerability of single and
      multiple doses of TBA-7371 in healthy subjects
    

Detailed description: 
      Three - part, partially-blinded, placebo controlled, combined single ascending dose with a
      food effect cohort and multiple ascending dose and a drug-drug interaction study to be
      conducted in one study center in the United States.

      Part 1 has a single ascending dose (SAD) design with up to 5 planned dose levels. Based on
      the interim PK for the dose escalation decisions, a dose cohort will be selected to return
      for an additional dose after a high calorie, high fat meal.

      Safety will be assessed throughout the study; serial ECGs and serial blood samples will be
      collected for the safety and PK assessment of TBA-7371. Dose escalation to the next cohort
      (i.e., dose level) will not take place until the Sponsor, in conjunction with the Principal
      Investigator, has determined that adequate safety, tolerability and PK from the previous
      cohort has been demonstrated to permit proceeding to the next cohort.

      Interim PK analyses will be performed for the dose escalation decisions, to select the
      intermediate dose for the food effect cohort, and to reconsider the sampling time points as
      the study progresses. All samples will be sent for analysis and the bioanalytical lab will be
      unblinded and only run the analysis on active treatment subjects. Data from the analysis used
      for the escalation meetings will only include active treatment subjects, and will be blinded
      by subject.

      Subjects will be housed in the WCT clinic from at least 24 hours prior (from Day -2), until
      48 hours after dosing. Subjects will return for subsequent follow up safety and PK
      assessments on Day 4 and will be contacted via a phone call for follow-up questioning about
      adverse events 7 days later (Study Day 11). One cohort will return after a washout of at
      least 7 days or five half-lives (whichever is longer) of their fasting dose to receive the
      same intermediate dose (TBD mg) under fed conditions.

      Part 2 has a multiple ascending dose design. The dose cohorts for Part 2 will be determined
      based on model predictions to determine the steady-state Cmax exposure, and safety from Part
      1.

      In this multiple ascending dose part, each subject will be administered TBA-7371 or matching
      placebo for 14 days with corresponding PK measurements. Three dose cohorts are planned. After
      each dose cohort, the Sponsor and Investigator will review the PK and safety data before
      proceeding to the next dose level.

      Part 3 has an open-label, multi-dose, fixed sequence drug-drug interaction study design. The
      dose of TBA-7371 to be studied will dependent on the interim PK analyses and safety from Part
      2.

      In this DDI part, each subject (n=14) will be administered midazolam (2 mg suspension) and
      bupropion (150 mg, tablet) together on Day 1, followed by a 7-day washout, followed by
      administration of TBA-7371 on Days 8 through 21, followed by administration of midazolam, and
      bupropion on Day 22. PK will be assessed for midazolam on Days 1 and 22, bupropion on Days 1
      - 5 and 22 - 26, and TBA-7371 on Days 8-21.

      At the end of Part 1 and at the end of Part 2, pharmacokinetic and safety data along with
      reasons for doses for the next part (Part 2 and Part 3, respectively) will be sent to the
      Food and Drug Administration (FDA) for review and approval. The study will not proceed to
      Part 2 or Part 3 until the FDA provides approval.
    

Intervention name(s): TBA-7371; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): The test product is TBA-7371 25 mg/ml oral suspension formulation and TBA-7371 matching placebo oral suspension.; The test product is TBA-7371 25 mg/ml oral suspension formulation and TBA-7371 matching placebo oral suspension.
Other intervention name(s): Midazolam (oral syrup); Bupropion; Matching Placebo for TBA-7371
Intervention MeSH terms: Midazolam; Bupropion
Allocation: Randomized
Intervention model: Sequential Assignment
Masking: Single (Participant)
Primary purpose: Treatment
Keywords: tuberculosis; TBA7371; TBA-7371; TB Alliance; TB; Pulmonary Tuberculosis