Clinical trial NCT04493671: Evaluate Safety, Tolerability, PK of TBAJ-876 in Healthy Adults
Official title: A Phase 1, Partially Blind, Placebo Controlled, Randomized, Combined Single Ascending Dose With a Food Effect Cohort, Multiple Ascending Dose, and Relative Bioavailability Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of TBAJ-876 in Healthy Adult Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Pulmonary Disease
Tuberculosis, Pulmonary
Tuberculosis
Multi Drug Resistant Tuberculosis
Drug Sensitive Tuberculosis
Drug-resistant Tuberculosis
Mycobacterium Tuberculosis Infection
Keywords: TBAJ-876
Diarylquinoline
DARQ
Lead sponsor: Global Alliance for TB Drug Development
Sponsor class: OTHER
First posted: 2020-07-30
Enrollment: 137
Sex: ALL
Minimum age (years): 19
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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

Detailed 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).

Eligibility 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.

Primary outcomes:
measure: Number of Participants with Treatment-Related Adverse Events in Part 1, Single Ascending Dose
timeFrame: Day 1 to Day 28
measure: Number of Participants with Treatment-Related Adverse Events in Part 2, Multiple Ascending Dose
timeFrame: Day 1 to Day 133
measure: Number of Participants with Treatment-Related Adverse Events in Part 3, Relative Bioavailability Study
timeFrame: Day 1 to Day 21
Secondary outcomes:
measure: AUCExtrap [Pharmacokinetic Analysis]
timeFrame: Days 1 - 28
measure: AUCinf [Pharmacokinetic Analysis]
timeFrame: Days 1 - 28
measure: AUClast [Pharmacokinetic Analysis]
timeFrame: Days 1 - 28
measure: AUCtau [Pharmacokinetic Analysis]
timeFrame: Days 1 - 28
measure: Cavg [Pharmacokinetic Analysis]
timeFrame: Days 1 - 28
measure: Clast [Pharmacokinetic Analysis]
timeFrame: Days 1 - 28
measure: CL/F [Pharmacokinetic Analysis]
timeFrame: Days 1 - 28
measure: CLss/F [Pharmacokinetic Analysis]
timeFrame: Days 1 - 28
measure: Cmax [Pharmacokinetic Analysis]
timeFrame: Days 1 - 28
measure: RAUC [Pharmacokinetic Analysis]
timeFrame: Days 1 - 28
measure: RCmax [Pharmacokinetic Analysis]
timeFrame: Days 1 - 28
measure: Tlast [Pharmacokinetic Analysis]
timeFrame: Days 1 - 28
measure: Tmax [Pharmacokinetic Analysis]
timeFrame: Days 1 - 28
measure: T1/2 [Pharmacokinetic Analysis]
timeFrame: Days 1 - 28
measure: Vz/F [Pharmacokinetic Analysis]
timeFrame: Days 1 - 28
measure: λz [Pharmacokinetic Analysis]
timeFrame: Days 1 - 28
Other outcomes:
Locations:
city: San Antonio
country: United States
facility: Worldwide Clinical Trials
state: Texas
Study officials:
affiliation: Global Alliance for TB Drug Development
name: Antonio Lombardi, MD
role: STUDY_CHAIR
References:
citation: Lombardi A, Pappas F, Nedelman J, Hickman D, Jaw-Tsai S, Olugbosi M, Bruinenberg P, Beumont M, Sun E. Pharmacokinetics and safety of TBAJ-876, a novel antimycobacterial diarylquinoline, in healthy subjects. Antimicrob Agents Chemother. 2024 Oct 8;68(10):e0061324. doi: 10.1128/aac.00613-24. Epub 2024 Aug 28.