A Phase 1 Study to Evaluate Safety, Tolerability, PK, and PK Interactions of TBA-7371

NCT03199339 | Completed Phase 1 FDA Drug

• 1 other identifier: TBA-7371-CL001
• Study Type: interventional
• Target: 74
• Locations: 1 country
• Sites: 1

Brief Summary

The primary objective of the study is to evaluate the safety and tolerability of single and multiple doses of TBA-7371 in healthy subjects

Conditions

Tuberculosis; Tuberculosis, Pulmonary

Keywords

tuberculosis; TBA7371; TBA-7371; TB Alliance; TB; Pulmonary Tuberculosis

Outcome Measures

Primary Outcomes (1)

• Safety and tolerability of single and multiple doses of TBA-7371 in healthy subjects by number and severity of treatment emergent adverse events (TEAEs)

  The primary endpoint of the study will be the number and severity of treatment emergent adverse events (TEAEs) following single doses of TBA-7371 and placebo

  Days 0-28 (depending on dosing schedule)

Secondary Outcomes (10)

• Pharmacokinetics (PK) of single and multiple doses of TBA-7371 AUC(0-t)

  Days 0-28 (depending on dosing schedule)

• Pharmacokinetics (PK) of single and multiple doses of TBA-7371 using Cmax

  Days 0-28 (depending on dosing schedule)

• Pharmacokinetics (PK) of single and multiple doses of TBA-7371 using Tmax

  Days 0-28 (depending on dosing schedule)

• Compare the rate and extent of absorption of a single oral dose of TBA-7371 using AUC, when administered after a high-calorie, high-fat meal versus when it's administered fasting in healthy adult subjects

  Days 0-28 (depending on dosing schedule)

• Compare the rate and extent of absorption of a single oral dose of TBA-7371 using Cmax, when administered after a high-calorie, high-fat meal versus when it's administered fasting in healthy adult subjects

  Days 0-28 (depending on dosing schedule)

Study Arms (19)

SAD Part 1 Cohort 1 First Dose - Active

ACTIVE COMPARATOR

N = 2, 100 mg TBA-7371 or matching placebo

Drug: TBA-7371

SAD Part 1 Cohort 1 First Dose - Placebo

PLACEBO COMPARATOR

N = 1, 100 mg TBA-7371 or matching placebo

Drug: Placebo

SAD Part 1 Cohort 1 Second Dose - Active

ACTIVE COMPARATOR

N = 4, 100 mg TBA-7371 or matching placebo

Drug: TBA-7371

SAD Part 1 Cohort 1 Second Dose -Placebo

PLACEBO COMPARATOR

N = 1, 100 mg TBA-7371 or matching placebo

Drug: Placebo

SAD Part 1 Cohort 2 - Active

ACTIVE COMPARATOR

N= 6, 250 mg TBA-7371 or matching placebo

Drug: TBA-7371

SAD Part 1 Cohort 2 - Placebo

PLACEBO COMPARATOR

N = 2, 250 mg TBA-7371 or matching placebo

Drug: Placebo

SAD Part 1 Cohort 3 - Active

ACTIVE COMPARATOR

N = 6, 500 mg TBA-7371 or matching placebo

Drug: TBA-7371

SAD Part 1 Cohort 3 - Placebo

PLACEBO COMPARATOR

N = 2, 500 mg TBA-7371 or matching placebo

Drug: Placebo

SAD Part 1 Cohort 4 - Active

ACTIVE COMPARATOR

N = 6, 1000 mg TBA-7371 or matching placebo

Drug: TBA-7371

SAD Part 1 Cohort 4 - Placebo

PLACEBO COMPARATOR

N = 2, 1000 mg TBA-7371 or matching placebo

Drug: Placebo

SAD Part 1 Cohort 5 - Active

ACTIVE COMPARATOR

N = 6, 1500 mg TBA-7371 or matching placebo

Drug: TBA-7371

SAD Part 1 Cohort 5 - Placebo

PLACEBO COMPARATOR

N = 2, 1500 mg TBA-7371 or matching placebo

Drug: Placebo

MAD Part 2 Cohort 1 - Active

ACTIVE COMPARATOR

N = 9, 100 mg TBA-7371 or matching placebo

Drug: TBA-7371

MAD Part 2 Cohort 1 - Placebo

PLACEBO COMPARATOR

N = 3, 100 mg TBA-7371 or matching placebo for 14 days

Drug: Placebo

MAD Part 2 Cohort 2 - Active

ACTIVE COMPARATOR

N = 9, 200 mg TBA-7371 or matching placebo for 14 days

Drug: TBA-7371

MAD Part 2 Cohort 2 - Placebo

PLACEBO COMPARATOR

N = 3, 200 mg TBA-7371 or matching placebo for 14 days

Drug: Placebo

MAD Part 2 Cohort 3 - Active

ACTIVE COMPARATOR

N = 9, 400 mg TBA-7371 or matching placebo for 14 days

Drug: TBA-7371

MAD Part 2 Cohort 3 - Placebo

PLACEBO COMPARATOR

N = 3, 400 mg TBA-7371 or matching placebo for 14 days

Drug: Placebo

DDI Part 3 Cohort 1

ACTIVE COMPARATOR

14 subjects to receive midazolam and bupropion before and after orally giving 200mg of TBA-7371, 1 per day for 14 days

Drug: TBA-7371

Interventions

TBA-7371 DRUG

The test product is TBA-7371 25 mg/ml oral suspension formulation and TBA-7371 matching placebo oral suspension.

Also known as: Midazolam (oral syrup), Bupropion

DDI Part 3 Cohort 1; MAD Part 2 Cohort 1 - Active; MAD Part 2 Cohort 2 - Active; MAD Part 2 Cohort 3 - Active; SAD Part 1 Cohort 1 First Dose - Active; SAD Part 1 Cohort 1 Second Dose - Active; SAD Part 1 Cohort 2 - Active; SAD Part 1 Cohort 3 - Active; SAD Part 1 Cohort 4 - Active; SAD Part 1 Cohort 5 - Active

Placebo DRUG

The test product is TBA-7371 25 mg/ml oral suspension formulation and TBA-7371 matching placebo oral suspension.

Also known as: Matching Placebo for TBA-7371

MAD Part 2 Cohort 1 - Placebo; MAD Part 2 Cohort 2 - Placebo; MAD Part 2 Cohort 3 - Placebo; SAD Part 1 Cohort 1 First Dose - Placebo; SAD Part 1 Cohort 1 Second Dose -Placebo; SAD Part 1 Cohort 2 - Placebo; SAD Part 1 Cohort 3 - Placebo; SAD Part 1 Cohort 4 - Placebo; SAD Part 1 Cohort 5 - Placebo

Eligibility Criteria

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

You may not 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:
• i. Hysteroscopic sterilization ii. Bilateral tubal ligation or bilateral salpingectomy iii. Hysterectomy iv. Bilateral oophorectomy v. 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.
• 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.
• Is willing and able to remain in the study unit for the entire duration of the assigned confinement period and return for outpatient visits.
• If enrolled in Part 1 and assigned to the fasted/fed cohort, is willing and able to consume the entire high-calorie, high-fat breakfast meal in the timeframe required.
• Subjects will be excluded from the study if there is evidence of any of the following criteria at screening or check-in, as appropriate.
• 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.

Sponsors & Collaborators

• Global Alliance for TB Drug Development: lead

Study Sites (1)

Worldwide Clinical Trials

San Antonio, Texas, 78217, United States

Location

MeSH Terms

Conditions

Tuberculosis; Tuberculosis, Pulmonary

Interventions

Midazolam; Bupropion

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

Intervention Hierarchy (Ancestors)

Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Propiophenones; Ketones; Organic Chemicals

Study Officials

• Angelo Del Parigi, MD

  Global Alliance for TB Drug Development

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: Part 1 and Part 2 participants will be masked, Part 3 participants will not be masked.
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 23, 2017
• First Posted: June 26, 2017
• Study Start: August 29, 2017
• Primary Completion: July 8, 2018
• Study Completion: July 8, 2018
• Last Updated: October 17, 2018

Record last verified: 2018-02

Locations

US (1)