A Phase 1, Drug-Drug Interaction Study of TBAJ-876 in Healthy Adults
Condition: Pulmonary Disease; Tuberculosis, Pulmonary; Tuberculosis; Multi Drug Resistant Tuberculosis; Drug Sensitive Tuberculosis; Drug-resistant Tuberculosis; Mycobacterium Tuberculosis Infection
MeSH terms: Tuberculosis; Latent Tuberculosis; Tuberculosis, Pulmonary; Tuberculosis, Multidrug-Resistant
Study type: Interventional
Phase: Phase 1

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 is a two-part, open-label drug-drug interaction study conducted in one study
      center in the United States. Two groups are planned, Group 1 and Group 2. Group 2 will be
      conducted based on the Group 1 results.

      Group 1 will 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 will only be conducted if the results of Group 1 show that TBAJ-876 is a moderate
      inducer of either CYP3A4 (midazolam AUC <0.50 when co-administered with TBAJ-876) or
      P-glycoprotein (digoxin AUC <0.50 when co-administered with TBAJ-876) or a moderate inhibitor
      of P-glycoprotein (digoxin AUC ≥2.0 when co-administered with TBAJ-876.

      This group will quantify the magnitude of inhibition or induction of TBAJ-876 on 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 will be assessed throughout the study for all subjects. Safety assessments will
      include physical examinations, vital signs, serial ECGs, adverse events (AEs), clinical and
      laboratory tests (including hematology, serum chemistry, coagulation, and urinalysis).
    

Intervention name(s): TBAJ-876; TBAJ-876; Midazolam; Digoxin; TLD
Intervention type(s): Drug; Drug; Drug; Drug; Drug
Intervention description(s): 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; 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: 200 mg TBAJ-876 oral suspension, fasting
Day 21 to Day 24: 150 mg TBAJ-876 oral suspension, fed; Day 1 and Day 20: Midazolam oral syrup: 2 mg, fasted; Day 2 and Day 21: Digoxin tablet: 0.25 mg, fasted; Day 1 and Day 20: fixed dose combination of dolutegravir 50 mg + tenofovir disoproxil fumarate 300 mg + lamivudine 300 mg, fasted
Other intervention name(s): tenofovir disoproxil fumarate (TDF), lamivudine (3TC), dolutegravir (DTG)
Intervention MeSH terms: Tenofovir; Lamivudine; Dolutegravir; Digoxin; Midazolam
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: TBAJ-876; Diarylquinoline; DARQ