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

Global Alliance for TB Drug Development

Status and phase: Completed; Phase 1

Conditions: Tuberculosis; Mycobacterium Tuberculosis Infection; Multi Drug Resistant Tuberculosis; Drug-resistant Tuberculosis; Drug Sensitive Tuberculosis; Tuberculosis, Pulmonary; Pulmonary Disease

Treatments: Drug: TBAJ-876 100 mg tablet; Drug: Placebo suspension; Drug: TBAJ-876 suspension; Drug: TBAJ-876 25 mg tablet

Study type: Interventional

Funder types: Other

Identifiers

NCT04493671

TBAJ-876-CL-001

Details and patient eligibility

About

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

Full description

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).

Enrollment: 137 patients

Sex: All

Ages: 19 to 50 years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion criteria

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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137 participants in 16 patient groups, including a placebo group

TBAJ-876 10mg SAD

Active Comparator group

Description:

Cohort 1 single dose of 10 mg TBAJ-876 (n=6) under fasted conditions

Treatment:

Drug: TBAJ-876 suspension

TBAJ-876 25mg SAD

Active Comparator group

Description:

Cohort 2, Single dose of 25 mg TBAJ-876 (n=6) under fasted conditions

Treatment:

Drug: TBAJ-876 suspension

TBAJ-876 50mg SAD

Active Comparator group

Description:

Cohort 3 single dose of 50 mg TBAJ-876 (n=6) under fasted conditions

Treatment:

Drug: TBAJ-876 suspension

TBAJ-876 100mg fasted SAD

Active Comparator group

Description:

Cohort 4, single dose of 100 mg TBAJ-876 (n=9) under fasted conditions

Treatment:

Drug: TBAJ-876 suspension

TBAJ-876 100mg fed SAD

Active Comparator group

Description:

Cohort 4, dose of 100 mg TBAJ-876 (n=10) under fed conditions

Treatment:

Drug: TBAJ-876 suspension

TBAJ-876 200mg SAD

Active Comparator group

Description:

Cohort 5 single dose of 200 mg TBAJ-876 (n=6) under fasted conditions

Treatment:

Drug: TBAJ-876 suspension

TBAJ-876 400mg SAD

Active Comparator group

Description:

Cohort 6, single dose of 400 mg TBAJ-876) (n=6) under fasted conditions

Treatment:

Drug: TBAJ-876 suspension

TBAJ-876 800mg SAD

Active Comparator group

Description:

Cohort 7, Single dose of 800 mg TBAJ-876 (n=6) under fasted conditions

Treatment:

Drug: TBAJ-876 suspension

TBAJ-876 Placebo SAD

Placebo Comparator group

Description:

Single dose matching placebo for TBAJ-876 under fasted conditions (n=13)

Treatment:

Drug: Placebo suspension

TBAJ-876 25mg MAD

Active Comparator group

Description:

25 mg TBAJ-876 (n=9) for 14 days under fed conditions

Treatment:

Drug: TBAJ-876 suspension

TBAJ-876 75mg MAD

Active Comparator group

Description:

75 mg TBAJ-876) (n=9) for 14 days under fed conditions

Treatment:

Drug: TBAJ-876 suspension

TBAJ-876 200mg MAD

Active Comparator group

Description:

200 mg TBAJ-876 (n=9) for 14 days under fed conditions

Treatment:

Drug: TBAJ-876 suspension

TBAJ-876 Placebo MAD

Placebo Comparator group

Description:

Matching placebo for TBAJ-876 for 14 days under fed conditions (n=12)

Treatment:

Drug: Placebo suspension

TBAJ-876 1x100 mg rBA fasted

Active Comparator group

Description:

Single dose TBAJ-876 of 100 mg (1 x 100 mg tablet) (n=10) under fasted conditions

Treatment:

Drug: TBAJ-876 100 mg tablet

TBAJ-876 1x100 mg rBA fed

Active Comparator group

Description:

Single dose TBAJ-876 of 100 mg (1 x 100 mg tablet) (n=10) under fed conditions

Treatment:

Drug: TBAJ-876 100 mg tablet

TBAJ-876 4x25 mg rBA fasted

Active Comparator group

Description:

Single dose TBAJ-876 of 100 mg (4 x 25 mg tablets) (n=10) under fasted conditions

Treatment:

Drug: TBAJ-876 25 mg tablet