NCT05526911

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

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

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 28 (actual)
• Sponsor: Global Alliance for TB Drug Development · Academic / Other
• Sex: All
• Age: 18 Years – 55 Years
• Healthy volunteers: Accepted

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

Interventions

Type	Name	Description
DRUG	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
DRUG	Midazolam	Day 1 and Day 20: Midazolam oral syrup: 2 mg, fasted
DRUG	Digoxin	Day 2 and Day 21: Digoxin tablet: 0.25 mg, fasted

Timeline

• Start date: 2022-06-30
• Primary completion: 2022-09-26
• Completion: 2022-09-26
• First posted: 2022-09-02
• Last updated: 2024-10-08
• Results posted: 2024-10-08

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study