A Multiple Ascending Dose Study With a Dose Formulation Comparison Cohort to Evaluate the Safety, Tolerability, and Pharmacokinetics of TBA-354 in Healthy Adult Subjects

NCT02606214 | Terminated Phase 1

• 1 other identifier: TBA-354-CL-002
• Study Type: interventional
• Target: 18
• Locations: 0 countries
• Sites: N/A

Brief Summary

The objective of the study is to evaluate the safety and tolerability of multiple doses of TBA-354 in healthy subjects.

Conditions

Tuberculosis

Keywords

Tuberculosis; TBA-354; Pulmonary Tuberculosis; TB

Outcome Measures

Primary Outcomes (2)

• The comparison of the percentage of subjects per dose cohort with treatment emergent adverse events (TEAEs) from Days 1 to 28 compared to placebo

  Multiple Ascending Dose Cohorts: Days 1-28, Dose Formulation Cohort: Days 1-28

• The percent of subjects per cohort with safety electrocardiogram change-from-baseline QTcF intervals of >30 milliseconds and =>60 milliseconds.

  QTcF = QT interval correct by Fridericia's method, percent = number of events/number of subjects

  Multiple Ascending Dose Data Time Point Days 1-3, 8, 12, 14-15, 21; Dose Formulation Cohort Data Time Point Days 1-3,7,14-16, 20

Secondary Outcomes (3)

• The mean Tmax of TBA-354 per dose cohort in plasma following dosing

  Multiple Ascending Dose Cohort: Days 1-14, Dose Formulation Cohort: Days 1-20

• The mean Cmax of TBA-354 per dose cohort in plasma following dosing

  Multiple Ascending Dose Cohort: Days 1-14, Dose Formulation Cohort: Days 1-20

• The mean AUC0-24 of TBA-354 per dose cohort in plasma following dosing

  Multiple Ascending Dose Cohort: Days 1-14, Dose Formulation Cohort: Days 1-20

Study Arms (7)

Dose Level 1: 50 mg TBA-354

EXPERIMENTAL

50 mg TBA-354 for 14 days (two 25 mg once daily)

Drug: TBA-354

Dose Level 1: Placebo

PLACEBO COMPARATOR

Placebo cohort for Dose Level 1

Drug: TBA-354 Placebo

Dose Level 2: 100 mg TBA-354

EXPERIMENTAL

100 mg TBA-354 for 14 days (one 100 mg tablet once daily)

Drug: TBA-354

Dose Level 2: Placebo

PLACEBO COMPARATOR

Placebo cohort for Dose Level 2

Drug: TBA-354 Placebo

Dose Level 3: 200 mg TBA-354

EXPERIMENTAL

200 mg TBA-354 for 14 days (two 100 mg once daily)

Drug: TBA-354

Dose Level 3: Placebo

PLACEBO COMPARATOR

Placebo cohort for Dose Level 3

Drug: TBA-354 Placebo

Dose Formulation Comparison Cohort

EXPERIMENTAL

All subjects in this cohort will receive two doses of the active drug. The first dose in three subjects will be a 100 mg TBA-354 tablet, followed 14 days later by a 100 mg dose of the TBA-354 suspension formulation. The first dose in the other three subjects will be 100 mgs of the TBA-354 suspension formulation, followed 14 days later by a 100 mg TBA-354 tablet dose. Placebo formulations will not be used in the dose formulation comparison cohort. Each dose will be administered orally with 200 ml of water after a minimum 8 hour overnight fast. Food will be given two hours after each dose.

Drug: TBA-354

Interventions

TBA-354 DRUG

Dose Formulation Comparison Cohort; Dose Level 1: 50 mg TBA-354; Dose Level 2: 100 mg TBA-354; Dose Level 3: 200 mg TBA-354

TBA-354 Placebo DRUG

Dose Level 1: Placebo; Dose Level 2: Placebo; Dose Level 3: Placebo

Eligibility Criteria

• Age: 19 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy adult male and females of non-childbearing potential, 19 to 50 years of age (inclusive) at the time of screening.
• Body mass index (BMI) ≥ 18.5 and ≤ 32.0 (kg/m2) and a body weight of no less than 50.0 kg.
• Medically healthy with no clinically significant screening results (e.g., laboratory profiles, medical histories, vital signs, ECGs, physical examination) as deemed by the Investigator.
• No use of tobacco or nicotine containing products (including smoking cessation products), for a minimum of 6 months prior to dosing.
• Females of non-childbearing potential, having undergone one of the following sterilization procedures at least 6 months prior to dosing:
• Hysteroscopic sterilization
• Bilateral tubal ligation or bilateral salpingectomy
• Hysterectomy
• Bilateral oophorectomy
• or be postmenopausal with amenorrhea for at least 1 year prior to the first dose with serum follicle stimulating hormone (FSH) levels consistent with postmenopausal status at screening.
• Non-vasectomized males (or males vasectomized less than 120 days prior to study start), must agree to the following during study participation and for 90 days following the last administration of study drug:
• use a condom with spermicide while engaging in sexual activity or be sexually abstinent
• not donate sperm during this time.
• In the event the sexual partner is surgically sterile, use of a condom with spermicide is not necessary. None of the restrictions listed above are required for vasectomized males whose procedure was performed more than 120 days prior to study start.

You may not qualify if:

• Subject understands study procedures and provides written informed consent for the trial.
• Be able to comply with the protocol and the assessments therein, including all restrictions.
• History or presence of significant cardiovascular, pulmonary, hepatic, renal, hematological, gastrointestinal, endocrine, immunologic, dermatologic, neurological, or psychiatric disease as determined by the Investigator to be clinically relevant.
• History of any illness that, in the opinion of the Investigator, might confound the results of the study or poses an additional risk to the subject by their participation in the study.
• Surgery within the past 90 days prior to dosing as determined by the Investigator to be clinically relevant.
• History or presence of alcoholism or drug abuse within the past 2 years as determined by the Investigator to be clinically relevant.
• Hypersensitive or idiosyncratic reactions to compounds related to TBA-354 (e.g., nitroimidazoles such as metronidazole, etc.).
• Female subjects who are pregnant or lactating.
• Positive results for the urine drug/alcohol screen at screening or check-in.
• Positive urine cotinine at screening.
• Serum magnesium potassium, or calcium laboratory values outside of the normal range at screening.
• Positive results at screening for Human Immunodeficiency Virus (HIV), Hepatitis B Surface Antigen (HBsAg), or Hepatitis C antibodies (HCV).
• Seated blood pressure is less than 90/40 mmHg or greater than 140/90 mmHg at screening.
• Heart rate is lower than 40 bpm or higher than 99 bpm at screening.
• Any electrocardiogram abnormality at Screening (as deemed by decision of the Investigator and the Sponsor's Medical Monitor).

Sponsors & Collaborators

• Global Alliance for TB Drug Development: lead

MeSH Terms

Conditions

Tuberculosis; Tuberculosis, Pulmonary

Interventions

TBA-354

Condition Hierarchy (Ancestors)

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

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 5, 2015
• First Posted: November 17, 2015
• Study Start: November 1, 2015
• Primary Completion: December 1, 2015
• Study Completion: December 1, 2016
• Last Updated: September 18, 2019

Record last verified: 2019-09