Back to resultsA Phase 1, Drug-Drug Interaction Study of TBAJ-876 in Healthy Adults
Primary Purpose
Pulmonary Disease, Tuberculosis, Pulmonary, Tuberculosis
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
TBAJ-876
TBAJ-876
Midazolam
Digoxin
TLD
Sponsored by
About this trial
This is an interventional treatment trial for Pulmonary Disease focused on measuring TBAJ-876, Diarylquinoline, DARQ
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.
Sites / Locations
- TKL Research, Inc.
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Active Comparator
Arm Label
Group 1
Group 2
Arm Description
The pharmacokinetics of midazolam, a CYP3A4 substrate, and digoxin, a P-gp substrate, will be studied before and after dosing with TBAJ-876.
The pharmacokinetics of antiretroviral regimen TLD will be studied before and after dosing with TBAJ-876.
Outcomes
Primary Outcome Measures
TBAJ-876 effect on the pharmacokinetics of the CYP-3A4 substrate midazolam and the inhibition potential of TBAJ-876 on P-gp in healthy adult subjects
Geometric mean ratio of midazolam'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. Inference will be based on analysis of variance applied to log-transformed parameters.
TBAJ-876 effect on the pharmacokinetics of the P-gp substrate digoxin
Geometric mean ratio 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. Inference will be based on analysis of variance applied to log-transformed parameters.
Secondary Outcome Measures
Number of Participants with Treatment-Related Adverse Events in Group 1 Population
Subjects will be monitored for any adverse events from the signing of the consent form until the end-of-study visit. The Investigator or a Sub-Investigator will assess its relationship to the study drug.
Number of Participants with Treatment-Related Adverse Events in Group 2 Population
Subjects will be monitored for any adverse events from the signing of the consent form until the end-of-study visit. The Investigator or a Sub-Investigator will assess its relationship to the study drug.
Full Information
NCT ID
NCT05526911
First Posted
August 31, 2022
Last Updated
May 17, 2023
Sponsor
Global Alliance for TB Drug Development
1. Study Identification
Unique Protocol Identification Number
NCT05526911
Brief Title
A Phase 1, Drug-Drug Interaction Study of TBAJ-876 in Healthy Adults
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
May 2023
Overall Recruitment Status
Completed
Study Start Date
July 20, 2022 (Actual)
Primary Completion Date
August 28, 2022 (Actual)
Study Completion Date
August 28, 2022 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Global Alliance for TB Drug Development
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
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 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).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pulmonary Disease, Tuberculosis, Pulmonary, Tuberculosis, Multi Drug Resistant Tuberculosis, Drug Sensitive Tuberculosis, Drug-resistant Tuberculosis, Mycobacterium Tuberculosis Infection
Keywords
TBAJ-876, Diarylquinoline, DARQ
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
28 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Group 1
Arm Type
Active Comparator
Arm Description
The pharmacokinetics of midazolam, a CYP3A4 substrate, and digoxin, a P-gp substrate, will be studied before and after dosing with TBAJ-876.
Arm Title
Group 2
Arm Type
Active Comparator
Arm Description
The pharmacokinetics of antiretroviral regimen TLD will be studied before and after dosing with TBAJ-876.
Intervention Type
Drug
Intervention Name(s)
TBAJ-876
Intervention Description
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
Intervention Name(s)
TBAJ-876
Intervention Description
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
Intervention Type
Drug
Intervention Name(s)
Midazolam
Intervention Description
Day 1 and Day 20: Midazolam oral syrup: 2 mg, fasted
Intervention Type
Drug
Intervention Name(s)
Digoxin
Intervention Description
Day 2 and Day 21: Digoxin tablet: 0.25 mg, fasted
Intervention Type
Drug
Intervention Name(s)
TLD
Other Intervention Name(s)
tenofovir disoproxil fumarate (TDF), lamivudine (3TC), dolutegravir (DTG)
Intervention Description
Day 1 and Day 20: fixed dose combination of dolutegravir 50 mg + tenofovir disoproxil fumarate 300 mg + lamivudine 300 mg, fasted
Primary Outcome Measure Information:
Title
TBAJ-876 effect on the pharmacokinetics of the CYP-3A4 substrate midazolam and the inhibition potential of TBAJ-876 on P-gp in healthy adult subjects
Description
Geometric mean ratio of midazolam'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. Inference will be based on analysis of variance applied to log-transformed parameters.
Time Frame
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
Title
TBAJ-876 effect on the pharmacokinetics of the P-gp substrate digoxin
Description
Geometric mean ratio 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. Inference will be based on analysis of variance applied to log-transformed parameters.
Time Frame
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 Outcome Measure Information:
Title
Number of Participants with Treatment-Related Adverse Events in Group 1 Population
Description
Subjects will be monitored for any adverse events from the signing of the consent form until the end-of-study visit. The Investigator or a Sub-Investigator will assess its relationship to the study drug.
Time Frame
from date of the start of treatment to the end of study at 25 days
Title
Number of Participants with Treatment-Related Adverse Events in Group 2 Population
Description
Subjects will be monitored for any adverse events from the signing of the consent form until the end-of-study visit. The Investigator or a Sub-Investigator will assess its relationship to the study drug.
Time Frame
from date of the start of treatment to the end of the study at 25 days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
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.
Facility Information:
Facility Name
TKL Research, Inc.
City
Fair Lawn
State/Province
New Jersey
ZIP/Postal Code
07410
Country
United States
12. IPD Sharing Statement
Learn more about this trial
A Phase 1, Drug-Drug Interaction Study of TBAJ-876 in Healthy Adults
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