NCT03199339

A Phase 1 Study to Evaluate Safety, Tolerability, PK, and PK Interactions of TBA-7371

Phase 1, Partially-Blind, Placebo Controlled Randomized, Combined SAD With Food Effect Cohort and MAD and DDI Study to Evaluate Safety, Tolerability, PK and PK Interaction Between TBA-7371 With Midazolam and Bupropion in Healthy Subjects.

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 74 (actual)
• Sponsor: Global Alliance for TB Drug Development · Academic / Other
• Sex: All
• Age: 19 Years – 50 Years
• Healthy volunteers: Accepted

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.

Conditions

• Tuberculosis
• Tuberculosis, Pulmonary

Interventions

Type	Name	Description
DRUG	TBA-7371	The test product is TBA-7371 25 mg/ml oral suspension formulation and TBA-7371 matching placebo oral suspension.
DRUG	Placebo	The test product is TBA-7371 25 mg/ml oral suspension formulation and TBA-7371 matching placebo oral suspension.

Timeline

• Start date: 2017-08-29
• Primary completion: 2018-07-08
• Completion: 2018-07-08
• First posted: 2017-06-26
• Last updated: 2018-10-17

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study