Evaluate Safety, Tolerability, PK of TBAJ-876 in Healthy Adults

• Status: Active, not recruiting
• Trial end date: 2022-03-01
• Target enrollment: 0
• Participant gender: All

Summary

A Phase 1, Partially Blind, Placebo Controlled, Randomized, Combined Single Ascending Dose with a Food Effect Cohort (Part 1) and Multiple Ascending Dose Study (Part 2) Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of TBAJ-876 in Healthy Adult Subjects

• Phase: Phase 1
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: Global Alliance for TB Drug Development

Criteria

Inclusion Criteria:

All volunteers must satisfy the following criteria to be considered for study participation:

1. Understands study procedures and voluntarily provides written informed consent prior to the start of any study-specific procedures.

2. Is a healthy adult male or female, 19 to 50 years of age (inclusive) at the time of screening.

3. Has a body mass index (BMI) ≥18.5 and ≤32.0 (kg/m2) and a body weight of no less than 50.0 kg.

4. Is medically healthy with no clinically significant screening results (e.g., laboratory profiles normal or up to Grade 1 per DMID Toxicity Tables), as deemed by the Investigator. Note: Lab results within the testing facility's normal range will not be considered AEs when referenced to the DMID assessment/grading scale. If exclusionary lab criteria are met, values may be confirmed by repeat evaluation.

5. Has not used tobacco- or nicotine-containing products (including smoking cessation products), for a minimum of 6 months before dosing.

6. If female of non-childbearing potential, she has undergone one of the following sterilization procedures at least 6 months before dosing:

• Hysteroscopic sterilization;

• Bilateral tubal ligation or bilateral salpingectomy;

• Hysterectomy; or

• Bilateral oophorectomy;

• Or is postmenopausal with amenorrhea for at least 1 year before the first dose with serum FSH levels consistent with postmenopausal status (i.e., greater than 40 mIU/mL) at screening.

7. If female of childbearing potential, must be using effective birth control methods, as defined below and is willing to continue practicing birth control methods and not planning to conceive throughout treatment and for 12 weeks (male participants) or 6 weeks (female participants) after the last dose of trial medication. The following are allowed birth control methods for this study:

• Double barrier method (e.g., diaphragm with spermicide; condoms with spermicide);

• Intrauterine device (IUD);

• Abstinence (and must agree to use a double barrier method if they become sexually active during the study);

• Vasectomized partner (at least 6 months before dosing);

• Non-surgical permanent sterilization (e.g., Essure® procedure) at least 3 months before dosing;

• Implanted or intrauterine hormonal contraceptives in use for at least 6 consecutive months before study dosing; and/or

8. If a non-vasectomized male (or male vasectomized less than 120 days prior to study start) he must agree to the following during study participation and for 90 days after the last administration of study drug:

• Use a condom with spermicide while engaging in sexual activity or be sexually abstinent; and

• Not donate sperm during this time. In the event the sexual partner is surgically sterile or postmenopausal, use of a condom with spermicide is not necessary. None of the birth control restrictions listed above are required for vasectomized males whose procedure was performed more than 120 days before study start.

9. Is willing to answer inclusion and exclusion criteria questionnaire at check-in.

10. Is able to comply with the protocol and the assessments therein, including all restrictions.

11. Is willing and able to remain in the study unit for the entire duration of the assigned confinement period and return for outpatient visits.

12. If assigned to receive study drug under fed conditions, is willing and able to consume the entire high-calorie, high-fat breakfast meal in the timeframe required.

Exclusion Criteria:

Volunteers will be excluded from study participation for any of the following:

1. History or presence of clinically significant cardiovascular (heart murmur), pulmonary, hepatic, renal, hematologic, gastrointestinal, endocrine, immunologic, dermatologic, neurologic, psychiatric disease or any other condition that, in the opinion of the Investigator, would jeopardize the safety of the subject or the validity of the study results.

2. Any presence of musculoskeletal toxicity (severe tenderness with marked impairment of activity, or frank necrosis).

3. Surgery within the past 90 days prior to dosing as determined by the Investigator to be clinically relevant.

4. History or presence of alcoholism or drug abuse within the past 2 years as determined by the Investigator to be clinically relevant.

5. Participation in another clinical trial within 30 days prior to dosing.

6. Female subjects who are pregnant or lactating.

7. Positive result on a urine drug/alcohol screen at screening or check-in.

8. Positive result on urine cotinine at screening.

9. Has the following laboratory abnormalities at screening:

1. ALT or AST Grade 2 or greater (> 2.0 times ULN)

2. Creatinine Grade 2 or greater (>1.6 times ULN)

3. Pancreatic lipase Grade 2 or greater (>1.6 times ULN)

4. Amylase Grade 2 or greater (>1.6 times ULN)

5. Total bilirubin Grade 2 or greater

6. CPK (> 1.25 times ULN) If exclusionary lab criteria are met, values may be confirmed by repeat evaluation.

10. Has a positive test for hepatitis B surface antigen, hepatitis C antibody, or HIV at screening.

11. Seated blood pressure (BP) is less than 90/40 mmHg or greater than 140/90 mmHg at screening, Day -1 (check-in) or predose. Out-of-range vital signs may be repeated once for confirmation. Out of range values will not be considered AEs if the repeat assessment is in range.

12. Seated heart rate is lower than 40 beat per minute (bpm) or higher than 99 bpm at screening, Day -1 (check-in) or predose. Out-of-range vital signs may be repeated once for confirmation. Out of range values will not be considered AEs if the repeat assessment is in range.

13. Any clinically significant ECG abnormality at screening (as deemed by decision of the Investigator and the Sponsor's Medical Monitor).

NOTE: The following may be considered not clinically significant without consulting the Sponsor's Medical Monitor:

• Mild first degree A-V block (P-R interval <0.23 sec)

• Right or left axis deviation

• Incomplete right bundle branch block

• Isolated left anterior fascicular block (left anterior hemiblock) in younger athletic subjects

14. QTcF interval >450 msec for males or >470 msec for females at screening, Day -1, or Day 1 (predose), or history of prolonged QT syndrome. For the triplicate ECGs taken at screening and on Day -1, the average QTcF interval of the 3 ECG recordings will be used to determine qualification.

15. 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).

16. Use of any prescription medication within 14 days prior to dosing.

17. Use of any over-the-counter (OTC) medication, including herbal products and vitamins, within 7 days prior to dosing, except acetaminophen. Up to 3 grams per day of acetaminophen is allowed only at occasional use and at the discretion of the Investigator prior to dosing.

18. Use of any drugs or substances known to be significant inhibitors of cytochrome P450 (CYP) enzymes and/or significant inhibitors or substrates of P-glycoprotein (P-gp) and/or organic anion transporting polypeptides (OATP) within 14 days prior to the first dose of study drug.

19. Use of any drugs or substances known to be inducers of CYP enzymes and/or Pgp, including St. John's Wort, within 30 days prior to the first dose of study drug.

20. Blood donation or significant blood loss within 56 days before the first dose of study medication until the end-of-study visit.

21. Plasma donation within 7 days before the first dose of study medication until the end-of-study visit.

22. Has been on a significantly abnormal diet during the 4 weeks preceding the first dose of study medication.

23. Unwilling to remove any artificial nails (e.g. acrylic, gel) or fingernail polish and not use such products for the duration of the study.

24. History or presence of allergic or adverse response to Listerine breath strips or aspartame.

25. If assigned to the fasted/fed cohort, is lactose intolerant.