Study to Evaluate Safety, Tolerability, and the PK Profile of TBI-223 in Healthy Subjects

Summary

Participation Requirements

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 s...

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.

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