NCT02606214

A Multiple Ascending Dose Study With a Dose Formulation Comparison Cohort to Evaluate the Safety, Tolerability, and Pharmacokinetics of TBA-354 in Healthy Adult Subjects

A Phase I, Double-Blind, Placebo Controlled, Randomized, Multiple Ascending Dose Study With a Dose Formulation Comparison Cohort to Evaluate the Safety, Tolerability, and Pharmacokinetics of TBA-354 in Healthy Adult Subjects

• Status: Terminated
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 18 (actual)
• Sponsor: Global Alliance for TB Drug Development · Academic / Other
• Sex: All
• Age: 19 Years – 50 Years
• Healthy volunteers: Accepted

Summary

The objective of the study is to evaluate the safety and tolerability of multiple doses of TBA-354 in healthy subjects.

Detailed description

This is a randomized, double-blind, placebo-controlled, multiple ascending dose study conducted at one study center in the United States. Three (3) multiple ascending dose cohorts are planned with twelve (12) healthy subjects (9 active and 3 placebo) in each cohort. There will also be a dose formulation comparison cohort, enrollment of six (6) subjects is planned. An additional multiple dose cohort of twelve (12) subjects may be enrolled. Safety will be assessed throughout the study; serial ECGs and serial blood samples will be collected for the safety and pharmacokinetics (PK) assessment of TBA-354. 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. Upon review of cohort data, the Sponsor, in conjunction with the Principal Investigator, may decide to: 1. Escalate the dose as planned. 2. Evaluate an intermediate dose level prior to proceeding to the next planned dose level if concerns arise from PK and safety that do not warrant in ceasing escalation. 3. Repeat a given dose level in a new cohort of subjects. 4. Increase the dose of the next cohort if the PK is lower than expected in the previous cohort. 5. Add a cohort if the PK is lower than expected after a cohort and there are no safety concerns. 6. Halt the study. During dose escalation, at no time will the projected Cmax of any individual exceed 7.6 µg/mL, which is the highest mean value at the no-observed-adverse-effect-level from the 3-month log toxicology study TBA 354 NCLN-103. The predicted median Cmax of the final cohort can exceed 3.2 µg/mL only if there have been no safety concerns. Subjects in the Multiple Ascending Dose (MAD) Cohorts will be housed in the Celerion clinic from check-in to Day 15. Subjects will return to the clinic each day from Day 16-Day 21 and have a final one-week follow up phone interview upon completion. Subjects in the Dose Formulation Cohort will be housed in the Clerion clinic from check-in to Day 3, visit the clinic each day for Days 4-7, and be housed in the clinic for Days 14-16. Then subjects will return for a daily visit for Days 17-20, and be contacted for a final one-week follow up phone interview upon completion on Day 28.

Conditions

• Tuberculosis

Interventions

Type	Name	Description
DRUG	TBA-354
DRUG	TBA-354 Placebo

Timeline

• Start date: 2015-11-01
• Primary completion: 2015-12-01
• Completion: 2016-12-01
• First posted: 2015-11-17
• Last updated: 2019-09-18