Study to Evaluate Safety, Tolerability, and the PK Profile of TBI-223 in Healthy Subjects
Condition: Tuberculosis; Tuberculosis, Pulmonary
MeSH terms: Tuberculosis; Tuberculosis, Pulmonary
Study type: Interventional
Phase: Phase 1

Summary: 
      A Phase 1, Partially-Blinded, Placebo-Controlled, Randomized, Multiple Ascending Dose Study
      to Include A Single Dose Food-Effect Study to Evaluate the Safety, Tolerability, and the PK
      Profile of TBI-223 in Healthy Subjects
    

Detailed description: 
      This is a partially-blinded, placebo-controlled, randomized multiple ascending dose (MAD)
      study to be conducted at one study center. Thirty-six (36) subjects will be enrolled in 3
      cohorts with 12 subjects per cohort. Within each cohort, 9 subjects will be assigned to
      receive active treatment and 3 subjects will receive placebo. Each subject will participate
      in one dose level. The first 2 cohorts (food-effect cohorts) will begin dosing of TBI-223 on
      Day 1 under fasted conditions, followed by a 3 day washout period and then by multiple doses
      of TBI-223 administered after a high-calorie, high-fat meal from Day 4 through Day 17 (total
      of 14 days). The third cohort (nonfood- effect cohort) will begin dosing of TBI-223 on Day 1
      and continue through Day 14, all doses administered after a high-calorie, high-fat meal. Each
      subject will be administered TBI-223 tablets (SR1 or IR or a combination of both
      formulations) or placebo once daily for 14 days with corresponding pharmacokinetic
      measurements. After each dose cohort, the Sponsor and Investigator will review the
      pharmacokinetic and safety data before proceeding to the next dose level. Dose escalation to
      the next cohort (i.e., dose level) or decisions regarding changed or additional cohorts will
      not take place until the Sponsor, in conjunction with the Principal Investigator and dose
      escalating committee, has determined that adequate safety, tolerability, and pharmacokinetics
      from the previous cohort(s) have been demonstrated to permit proceeding to the next cohort.
      Additional cohorts (up to 12 subjects per cohort) may be enrolled if deemed appropriate by
      the Sponsor to study other dose levels, change proposed cohorts, or to study a different
      dosage formulation The Institutional Review Board (IRB) should be immediately notified of the
      dose escalation or any revised approach for review and approval. Safety will be assessed
      throughout the study for all subjects. Safety assessments will include physical and detailed
      neurological examinations, vital signs (blood pressure, pulse rate, respiration rate,
      temperature and pulse oximetry), electrocardiograms (ECGs), cardiac monitoring, adverse
      events (AEs), and clinical laboratory tests (including hematology, serology, serum chemistry,
      coagulation, and urinalysis). Blood and urine will be collected for clinical laboratory
      evaluations. The Principal Investigator, in conjunction with the Sponsor may collect
      additional blood if necessary, for repeat laboratory or safety evaluations including AE
      follow up. Female subjects will have blood collected for serum pregnancy testing. Females
      claiming postmenopausal status will have blood collected to measure follicle stimulating
      hormone (FSH) levels.

      During each cohort, blood samples (trough samples) will be obtained before each dose of study
      drug, and at the time points on the events schedule. Plasma pharmacokinetic samples will be
      analyzed for TBI-223 and M2 using validated analytical methods. Appropriate pharmacokinetic
      parameters will be calculated using non compartmental methods.
    

Intervention name(s): 1800 mg TBI-223; 2400mg TBI-223; 3000mg TBI-223; TBI-223 Placebo; TBI-223 Placebo; TBI-223 Placebo
Intervention type(s): Drug; Drug; Drug; Drug; Drug; Drug
Intervention description(s): 3 x 600 mg SR1 tablets; 3 x 600 mg SR1 tablets and 1 x 600 mg IR tablets; 4 x 600 mg SR1 tablets and 1 x 600 mg IR tablets; 3 x Placebo tablets; 4 x Placebo tablets; 5 x Placebo tablets
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Treatment
Keywords: TB; Tuberculosis; TBI-223; Pulmonary Tuberculosis