A Phase 1, Drug-Drug Interaction Study of TBAJ-876 in Healthy Adults

NCT ID: NCT05526911

Last Updated: 2024-10-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 28 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-06-30
• Study Completion Date: 2022-09-26

Brief Summary

A Phase 1, Drug-Drug Interaction Study to Evaluate the Safety, Tolerability, and the Induction Potential of TBAJ-876 on CYP3A4 and P-glycoprotein and the Inhibition Potential of TBAJ-876 on P-glycoprotein in Healthy Adult Subjects

Detailed Description

This study was a two-part, open-label drug-drug interaction study conducted in one study center in the United States. Two groups were planned, Group 1 and Group 2. Group 2 to be conducted based on the Group 1 results.

Group 1 to assess the induction potential of TBAJ-876 on the sensitive CYP3A4 substrate midazolam (M) and inhibition and induction potential of TBAJ-876 on the sensitive P-glycoprotein substrate Digoxin (D).

Group 2 was only to be conducted if the results of Group 1 show that TBAJ-876 is a moderate inducer of either CYP3A4 (geometric mean ratio [GMR] of midazolam area under the curve [AUC] <0.50 when co-administered with TBAJ-876) or P-glycoprotein (GMR of digoxin AUC <0.50 when co-administered with TBAJ-876) or a moderate inhibitor of P-glycoprotein (GMR of digoxin AUC ≥2.0 when co-administered with TBAJ-876). These results were used to decide that a second phase of the study was not needed.

If Group 1 concluded that TBAJ-876 is a moderate inducer or inhibitor, Group 2 had intended to quantify the magnitude of inhibition or induction of TBAJ-876 of the antiretroviral regimen TLD, a fixed dose combination of tenofovir disoproxil fumarate (TFD), lamivudine (3TC) and dolutegravir (DTG), a regimen likely to be used in future clinical studies of TBAJ-876 by subjects living with HIV

Safety was assessed throughout the study for all subjects. Safety assessments included physical examinations, vital signs, serial ECGs, adverse events (AEs), clinical and laboratory tests (including hematology, serum chemistry, coagulation, and urinalysis).

Conditions

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Group 1

The pharmacokinetics of midazolam, a CYP3A4 substrate, and digoxin, a P-gp substrate, will be studied before and after dosing with TBAJ-876.

Group Type: EXPERIMENTAL

TBAJ-876

Intervention Type: DRUG

• Day 6 to Day 13: 200 mg TBAJ-876 oral suspension, fed
• Day 14 to Day 19: 165 mg TBAJ-876 oral suspension, fed
• Day 20 and Day 21: 200 mg TBAJ-876 oral suspension, fasting
• Day 22 to Day 24: 150 mg TBAJ-876 oral suspension, fed

Midazolam

Intervention Type: DRUG

Day 1 and Day 20: Midazolam oral syrup: 2 mg, fasted

Digoxin

Intervention Type: DRUG

Day 2 and Day 21: Digoxin tablet: 0.25 mg, fasted

Interventions

TBAJ-876

• Day 6 to Day 13: 200 mg TBAJ-876 oral suspension, fed
• Day 14 to Day 19: 165 mg TBAJ-876 oral suspension, fed
• Day 20 and Day 21: 200 mg TBAJ-876 oral suspension, fasting
• Day 22 to Day 24: 150 mg TBAJ-876 oral suspension, fed

Intervention Type: DRUG

Midazolam

Day 1 and Day 20: Midazolam oral syrup: 2 mg, fasted

Intervention Type: DRUG

Digoxin

Day 2 and Day 21: Digoxin tablet: 0.25 mg, fasted

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Is a healthy adult male or female, 18 to 55 years of age (inclusive) at the time of screening.
• Has a body mass index (BMI) ≥18.5 and ≤32.0 (kg/m2) and a body weight of no less than 50.0 kg at the time of screening and check-in.
• Is medically healthy with no clinically significant screening results (e.g., laboratory profiles normal or up to Grade 1 per Division of Microbiology and Infectious Diseases (DMID) Toxicity Tables), as deemed by the Investigator.
• Has not used tobacco- or nicotine-containing products (including smoking cessation products), for a minimum of 6 months before dosing.
• Is willing and able to consume the entire high-calorie, high-fat breakfast meal in the timeframe required.

Exclusion Criteria

• History or presence of significant cardiovascular abnormalities, heart murmur, pulmonary, hepatic, renal, haematological, gastrointestinal, endocrine, immunologic, dermatologic, neurological, or psychiatric disease as determined by the Investigator to be clinically relevant.
• Any musculoskeletal abnormality (severe tenderness with marked impairment of activity) or musculoskeletal toxicity (frank necrosis).
• Positive results at screening for Human Immunodeficiency Virus (HIV), Hepatitis B Surface Antigen (HBsAg), or Hepatitis C antibodies (HCV).
• Positive Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) results within 6 days prior to Day 1.
• Current or history of prolonged QT syndrome.
• 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).
• Use of any drugs or substances known to be inducers of CYP enzymes and/or P-gp, including St. John's Wort, within 30 days prior to the first dose of study drug.
• Is lactose intolerant.
• History or presence of allergic, or adverse response to midazolam, digoxin, dolutegravir, tenofovir, lamivudine or any related drugs.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Global Alliance for TB Drug Development

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Antonio Lombardi, MD

Role: STUDY_CHAIR

Global Alliance for TB Drug Development

Locations

TKL Research, Inc.

Fair Lawn, New Jersey, United States

Countries

United States

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

TBAJ-876-CL002

Identifier Type: -

Identifier Source: org_study_id