Evaluate Safety, Tolerability, PK of TBAJ-876 in Healthy Adults

Global Alliance for TB Drug Development137 enrolled

Overview

A Phase 1, Partially Blind, Placebo Controlled, Randomized, Combined Single Ascending Dose (SAD) with a Food Effect Cohort (Part 1), Multiple Ascending Dose (MAD) (Part 2), and Relative Bioavailability (rBA) (Part 3) Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of TBAJ-876 in Healthy Adult Subjects

This study is a three-part, partially blinded, placebo controlled, combined single ascending dose with food-effect, multiple ascending dose study, and a single dose relative bioavailability study conducted at one study center in the United States. Safety will be assessed throughout the study for all subjects. Safety assessments will include physical examinations, vital signs, serial ECGs, cardiac monitoring, adverse events (AEs), and clinical laboratory tests (including hematology, serum chemistry, coagulation, and urinalysis).

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

TRIPLE

Enrollment

137

Conditions

Pulmonary Disease Tuberculosis, Pulmonary Tuberculosis

Interventions

TBAJ-876 suspensionDRUG

TBAJ-876 oral suspension, orally administered

Placebo suspensionDRUG

Placebo for TBAJ-876 oral Suspension; orally administered

TBAJ-876 100 mg tabletDRUG

TBAJ-876 100 mg tablets, orally administered

TBAJ-876 25 mg tabletDRUG

TBAJ-876 25 mg tablets, orally administered

Eligibility

Sex: ALLMin age: 19 YearsMax age: 50 YearsHealthy volunteers:

Medical Language ↔ Plain English

Key Inclusion Criteria: All volunteers must satisfy the following criteria to be considered for study participation: 1. Is a healthy adult male or female, 19 to 50 years of age (inclusive) at the time of screening. 2. Has a body mass index (BMI) ≥18.5 and ≤32.0 (kg/m2) and a body weight of no less than 50.0 kg. 3. Is medically healthy with no clinically significant screening results (e.g., laboratory profiles normal or up to Grade 1 per DMID Toxicity Tables), as deemed by the Investigator. 4. Has not used tobacco- or nicotine-containing products (including smoking cessation products), for a minimum of 6 months before dosing. 5. If assigned to receive study drug under fed conditions, is willing and able to consume the entire high-calorie, high-fat breakfast meal in the timeframe required. Key Exclusion Criteria: 1. History or presence of clinically significant cardiovascular (heart murmur), pulmonary, hepatic, renal, hematologic, gastrointestinal, endocrine, immunologic, dermatologic, neurologic, psychiatric disease or any other condition that, in the opinion of the Investigator, would jeopardize the safety of the subject or the validity of the study results. 2. Any presence of musculoskeletal toxicity (severe tenderness with marked impairment of activity, or frank necrosis). 3. Has a positive test for hepatitis B surface antigen, hepatitis C antibody, or HIV at screening. 4. Current or history of prolonged QT syndrome15. Family history of long-QT syndrome or sudden death without a preceding diagnosis of a condition that could be causative of sudden death (such as known coronary artery disease, congestive heart failure, or terminal cancer). 5. If assigned to the fasted/fed cohort, is lactose intolerant.

Outcomes

Primary Outcomes

Number of Participants with Treatment-Related Adverse Events in Part 1, Single Ascending Dose

Subjects will be monitored for any adverse events from the signing of the consent form until the end-of-study visit. The Investigator or a Sub-Investigator will assess its relationship to the study drug.

Time frame: Day 1 to Day 28

Number of Participants with Treatment-Related Adverse Events in Part 2, Multiple Ascending Dose

Time frame: Day 1 to Day 133

Number of Participants with Treatment-Related Adverse Events in Part 3, Relative Bioavailability Study

Time frame: Day 1 to Day 21

Secondary Outcomes

AUCExtrap [Pharmacokinetic Analysis]

PK parameters will be calculated from plasma concentrations of TBAJ-876 TBAJ-876, M2, and M3. AUCExtrap is the percentage of AUCinf based on extrapolation.

Time frame: Days 1 - 28

AUCinf [Pharmacokinetic Analysis]

PK parameters will be calculated from plasma concentrations of TBAJ-876 TBAJ-876, M2, and M3. AUCinf is area under the concentration-time curve from time-zero extrapolated to infinity.

Time frame: Days 1 - 28

AUClast [Pharmacokinetic Analysis]

PK parameters will be calculated from plasma concentrations of TBAJ-876 TBAJ-876, M2, and M3. AUClast area under the concentration-time curve from time-zero to the time of the last quantifiable concentration; calculated using the linear trapezoidal rule.

Time frame: Days 1 - 28

AUCtau [Pharmacokinetic Analysis]

PK parameters will be calculated from plasma concentrations of TBAJ-876 TBAJ-876, M2, and M3. AUCtau is area under the concentration-time curve during the dosing interval; calculated using the linear trapezoidal rule.

Time frame: Days 1 - 28

Cavg [Pharmacokinetic Analysis]

PK parameters will be calculated from plasma concentrations of TBAJ-876 TBAJ-876, M2, and M3. Cavg is average concentration during the dosing interval.

Time frame: Days 1 - 28

Clast [Pharmacokinetic Analysis]

PK parameters will be calculated from plasma concentrations of TBAJ-876 TBAJ-876, M2, and M3. Clast is the last quantifiable concentration determined directly from individual concentration-time data.

Time frame: Days 1 - 28

CL/F [Pharmacokinetic Analysis]

PK parameters will be calculated from plasma concentrations of TBAJ-876 TBAJ-876, M2, and M3. CL/F is apparent total clearance after single administration.

Time frame: Days 1 - 28

CLss/F [Pharmacokinetic Analysis]

PK parameters will be calculated from plasma concentrations of TBAJ-876 TBAJ-876, M2, and M3. CLss/F is apparent total clearance after multiple administration.

Time frame: Days 1 - 28

Cmax [Pharmacokinetic Analysis]

PK parameters will be calculated from plasma concentrations of TBAJ-876 TBAJ-876, M2, and M3. Cmax is maximum concentration, determined directly from individual concentration-time data.

Time frame: Days 1 - 28

RAUC [Pharmacokinetic Analysis]

PK parameters will be calculated from plasma concentrations of TBAJ-876 TBAJ-876, M2, and M3. RAUC is accumulation factor during multiple dosing, based on AUCtau.

Time frame: Days 1 - 28

RCmax [Pharmacokinetic Analysis]

PK parameters will be calculated from plasma concentrations of TBAJ-876 TBAJ-876, M2, and M3. RCmax is accumulation factor during multiple dosing, based on Cmax.

Time frame: Days 1 - 28

Tlast [Pharmacokinetic Analysis]

PK parameters will be calculated from plasma concentrations of TBAJ-876 TBAJ-876, M2, and M3. Tlast is time of the last quantifiable concentration.

Time frame: Days 1 - 28

Tmax [Pharmacokinetic Analysis]

PK parameters will be calculated from plasma concentrations of TBAJ-876 TBAJ-876, M2, and M3. Tmax is time of the maximum concentration.

Time frame: Days 1 - 28

T1/2 [Pharmacokinetic Analysis]

PK parameters will be calculated from plasma concentrations of TBAJ-876 TBAJ-876, M2, and M3. T1/2 is the observed terminal half-life.

Time frame: Days 1 - 28

Vz/F [Pharmacokinetic Analysis]

PK parameters will be calculated from plasma concentrations of TBAJ-876 TBAJ-876, M2, and M3. Vz/F is apparent volume of distribution in the terminal phase.

Time frame: Days 1 - 28

λz [Pharmacokinetic Analysis]

PK parameters will be calculated from plasma concentrations of TBAJ-876 TBAJ-876, M2, and M3. λz is the observed terminal rate constant; estimated by linear regression through at least 3 data points in the terminal phase of the log concentration-time profile.

Time frame: Days 1 - 28

Evaluate Safety, Tolerability, PK of TBAJ-876 in Healthy Adults

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes