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

NCT05526911 | Completed Phase 1 Results FDA Drug

• 1 other identifier: TBAJ-876-CL002
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

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

Conditions

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

Keywords

TBAJ-876; Diarylquinoline; DARQ

Outcome Measures

Primary Outcomes (6)

• TBAJ-876 Effect on the Pharmacokinetics of the CYP-3A4 Substrate Midazolam in Healthy Adult Subjects: Pharmacokinetic Parameters AUC

  Geometric mean and range of midazolam's area under the (plasma concentration vs. time) curve when co-administered with TBAJ-876 versus when administered alone.

  Day 1: pre-dose, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 24 hours; Day 20: pre-dose, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 24 hours

• TBAJ-876 Effect on the Pharmacokinetics of the CYP-3A4 Substrate Midazolam in Healthy Adult Subjects: Pharmacokinetic Parameters CMAX

  Geometric mean and range of midazolam's maximum concentration when co-administered with TBAJ-876 versus when administered alone.

  Day 1: pre-dose, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 24 hours; Day 20: pre-dose, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 24 hours

• TBAJ-876 Effect on the Pharmacokinetics of the CYP-3A4 Substrate Midazolam in Healthy Adult Subjects: Geometric Mean Ratios

  Geometric mean ratio of midazolam's area under the (plasma concentration vs. time) curve and Cmax when co-administered with TBAJ-876 versus when administered alone. Inference will be based on analysis of variance applied to log-transformed parameters.

  Day 1: pre-dose, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 24 hours; Day 20: pre-dose, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 24 hours

• TBAJ-876 Effect on the Pharmacokinetics of the P-gp Substrate Digoxin: Pharmacokinetic Parameters AUC

  Geometric mean of digoxin's area under the (plasma concentration vs. time) curve when co-administered with TBAJ-876 versus when administered alone, and similarly for the maximum concentration.

  Day 2: pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96 hours; Day 21: pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96 hours

• TBAJ-876 Effect on the Pharmacokinetics of the P-gp Substrate Digoxin: Pharmacokinetic Parameters CMAX

  Geometric mean of digoxin's Cmax when co-administered with TBAJ-876 versus when administered alone, and similarly for the maximum concentration.

  Day 2: pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96 hours; Day 21: pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96 hours

• TBAJ-876 Effect on the Pharmacokinetics of the P-gp Substrate Digoxin: Geometric Mean Ratio

  Geometric mean ratio of digoxin's area under the (plasma concentration vs. time) curve and Cmax when co-administered with TBAJ-876 versus when administered alone, and similarly for the maximum concentration. Inference will be based on analysis of variance applied to log-transformed parameters.

  Day 2: pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96 hours; Day 21: pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96 hours

Secondary Outcomes (1)

• Number of Participants With Treatment-Related Adverse Events (TEAE) in Group 1 Population

  from date of the start of treatment to the end of study at 25 days

Study Arms (1)

Group 1

EXPERIMENTAL

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

Drug: TBAJ-876; Drug: Midazolam; Drug: Digoxin

Interventions

TBAJ-876 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

Group 1

Midazolam DRUG

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

Group 1

Digoxin DRUG

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

Group 1

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Global Alliance for TB Drug Development: lead

Study Sites (1)

TKL Research, Inc.

Fair Lawn, New Jersey, 07410, United States

Location

MeSH Terms

Conditions

Lung Diseases; Tuberculosis, Pulmonary; Tuberculosis; Tuberculosis, Multidrug-Resistant

Interventions

TBAJ-876; Midazolam; Digoxin

Condition Hierarchy (Ancestors)

Respiratory Tract Diseases; Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Respiratory Tract Infections

Intervention Hierarchy (Ancestors)

Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Digitalis Glycosides; Cardenolides; Cardiac Glycosides; Cardanolides; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Glycosides; Carbohydrates

Results Point of Contact

• Title: Antonio Lombardi
• Organization: TB Alliance

antonio.lombardi-consultant@tballiance.org

917.601.0024

Study Officials

• Antonio Lombardi, MD

  Global Alliance for TB Drug Development

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 31, 2022
• First Posted: September 2, 2022
• Study Start: June 30, 2022
• Primary Completion: September 26, 2022
• Study Completion: September 26, 2022
• Last Updated: October 8, 2024
• Results First Posted: October 8, 2024

Record last verified: 2024-07

Locations

US (1)