Phase 1
N=28
A Phase 1, Drug-Drug Interaction Study of TBAJ-876 in Healthy Adults
Pulmonary Disease · Tuberculosis, Pulmonary · Tuberculosis · Multi Drug Resistant Tuberculosis · Drug Sensitive Tuberculosis
Bottom Line
View on ClinicalTrials.gov: NCT05526911 ↗Enrolled (actual)
28
Serious AEs
0.0%
Results posted
Oct 2024
Primary outcome: Primary: TBAJ-876 Effect on the Pharmacokinetics of the CYP-3A4 Substrate Midazolam in Healthy Adult Subjects: Pharmacokinetic Parameters AUC — 22.64; 25.22; 24.28; 25.68 ng.hr/mL
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 1
- Interventions
- TBAJ-876 (Drug); Midazolam (Drug); Digoxin (Drug)
- Age
- Adult · 18+ yrs
- Sex
- All
- Sponsor
- Global Alliance for TB Drug Development
- Primary completion
- Sep 2022
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY TBAJ-876 Effect on the Pharmacokinetics of the CYP-3A4 Substrate Midazolam in Healthy Adult Subjects: Pharmacokinetic Parameters AUC |
22.64; 25.22; 24.28; 25.68 | — |
| PRIMARY TBAJ-876 Effect on the Pharmacokinetics of the CYP-3A4 Substrate Midazolam in Healthy Adult Subjects: Pharmacokinetic Parameters CMAX |
7.26; 8.90 | — |
| PRIMARY TBAJ-876 Effect on the Pharmacokinetics of the CYP-3A4 Substrate Midazolam in Healthy Adult Subjects: Geometric Mean Ratios |
0.94; 1; .86 | — |
| PRIMARY TBAJ-876 Effect on the Pharmacokinetics of the P-gp Substrate Digoxin: Pharmacokinetic Parameters AUC |
11.57; 7.64; 24.57; 23.44 | — |
| PRIMARY TBAJ-876 Effect on the Pharmacokinetics of the P-gp Substrate Digoxin: Pharmacokinetic Parameters CMAX |
1.19; 1.01 | — |
| PRIMARY TBAJ-876 Effect on the Pharmacokinetics of the P-gp Substrate Digoxin: Geometric Mean Ratio |
1.51; 1.18 | — |
| SECONDARY Number of Participants With Treatment-Related Adverse Events (TEAE) in Group 1 Population |
5 | — |
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
Eligibility Criteria
Key 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.
Key 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.
Data sourced from ClinicalTrials.gov (NCT05526911). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.