TuberculosisPhase 1NCT03199339
A Phase 1 Study to Evaluate Safety, Tolerability, PK, and PK Interactions of TBA-7371
A Phase 1 study testing TBA-7371 in people with Tuberculosis and Tuberculosis, Pulmonary, run by Global Alliance for TB Drug Development at 1 site in United States.
Trial 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 Read more about this study
- Who is it for?
- Ages 19 to 50 yearsHealthy volunteers can take part
- Conditions the study is for
- Tuberculosis, Tuberculosis, Pulmonary
- What is being tested?
- TBA-7371
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 74 participants
- Where
- 1 siteUnited States
- Study dates
- 29 Aug 2017to 8 Jul 2018
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 19 to 50 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Subjects must fulfill all of the following inclusion criteria and none of the exclusion criteria to be eligible for participation in the study, unless otherwise specified.
- 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:
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- 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.
- Willing to answer inclusion and exclusion criteria questionnaire at check-in.
- 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.
Who cannot join
- 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.
- 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, or any history of cholecystectomy.
- History or presence of alcoholism or drug abuse within the past 2 years as determined by the Investigator to be clinically relevant.
- Female subjects who are pregnant or lactating.
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- Positive results for the urine drug/alcohol screen at screening or check-in.
- Positive urine cotinine at screening or check in.
- 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, Day -2 (check-in), Day -1, or predose. Out-of-range vital signs may be repeated once for confirmation.
- Seated heart rate is lower than 40 bpm or higher than 99 bpm at screening, Day -2 (check-in), Day -1, or predose. Out-of-range vital signs may be repeated once for confirmation.
- Any electrocardiogram abnormality at Screening (as deemed by decision of the Investigator and the Sponsor's Medical Monitor).
- NOTE: The following can be considered not clinically significant without consulting the Sponsor's Medical Monitor:
- Mild first degree A-V block (P-R interval <0.23 sec) ii. Right or left axis deviation iii. Incomplete right bundle branch block iv. Isolated left anterior fascicular block (left anterior hemiblock) in younger athletic subjects
- QTcF interval >450 msec for males or >470 msec for females at screening, Day -2, Day -1, or Day 1 (pre-dose), 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).
- History of one or any combination of, the following:
- Seizures or seizure disorders ii. Brain surgery. iii. History of head injury in the last five years iv. Any serious disorder of the CNS or related neurological system, particularly one that may lower the seizure threshold.
- History of seizures
- Use of any prescription medication within 14 days prior to dosing.
- Use of any over-the-counter (OTC) medication, including herbal products and vitamins, within the 7 days prior to dosing, except acetaminophen. Up to 3 grams per day of acetaminophen is allowed at the discretion of the Investigator prior to dosing.
- 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.
- 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.
- Use of any drugs or substance known to lower the seizure threshold.
- Blood donation or significant blood loss within 56 days prior to dosing.
- Plasma donation within 7 days prior to dosing.
- Participation in another clinical trial within 28 days prior to dosing. Consumption of foods and beverages containing the following substances will be prohibited
- Has been on a significantly abnormal diet during the 4 weeks preceding the first dose of study medication.
- Unwilling to remove any artificial nails (e.g. acrylic, gel) or fingernail polish and not use such products for the duration of the study.
- Is colorblind (assessed using the Ishihara Color Vision Test)
- Additionally, the following exclusion applies only to subjects in Part 1, the SAD study:
- Is lactose intolerant.
- Additionally, the following exclusion applies only to subjects in Part 1 and 2, the SAD and MAD studies:
- History or presence of allergic or adverse response to Listerine breath strips or aspartame.
- Additionally, the following exclusions apply only to subjects in Part 3, the DDI study:
- History or presence of allergic or adverse response to midazolam, bupropion, or related drugs.
- History of presence of acute narrow-angle or untreated open-angle glaucoma
- Current or prior diagnosis of bulimia or anorexia nervosa
- Abrupt discontinuation of alcohol, benzodiazepines, barbiturates, or anti-epileptic drugs within 14 days prior to the first dose of study treatment
- Discontinued the use of monoamine oxidase inhibitors (MAOs) within 14 days prior to the first dose of study treatment
- History or presence of suicidal ideation or suicidal behavior as assessed by the Columbia-Suicide Severity Rating Scale (C-SSRS, Baseline/Screening Version) at the Screening Visit.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Phase 1, Partially-Blind, Placebo Controlled Randomized, Combined SAD With Food Effect Cohort and MAD and DDI Study to Evaluate Safety, Tolerability, PK and PK Interaction Between TBA-7371 With Midazolam and Bupropion in Healthy Subjects.
The primary objective of the study is to evaluate the safety and tolerability of single and multiple doses of TBA-7371 in healthy subjects
Read the detailed description
Three - part, partially-blinded, placebo controlled, combined single ascending dose with a food effect cohort and multiple ascending dose and a drug-drug interaction study to be conducted in one study center in the United States.
Part 1 has a single ascending dose (SAD) design with up to 5 planned dose levels. Based on the interim PK for the dose escalation decisions, a dose cohort will be selected to return for an additional dose after a high calorie, high fat meal.
Safety will be assessed throughout the study; serial ECGs and serial blood samples will be collected for the safety and PK assessment of TBA-7371. Dose escalation to the next cohort (i.e., dose level) will not take place until the Sponsor, in conjunction with the Principal Investigator, has determined that adequate safety, tolerability and PK from the previous cohort has been demonstrated to permit proceeding to the next cohort.
Interim PK analyses will be performed for the dose escalation decisions, to select the intermediate dose for the food effect cohort, and to reconsider the sampling time points as the study progresses. All samples will be sent for analysis and the bioanalytical lab will be unblinded and only run the analysis on active treatment subjects. Data from the analysis used for the escalation meetings will only include active treatment subjects, and will be blinded by subject.
Subjects will be housed in the WCT clinic from at least 24 hours prior (from Day -2), until 48 hours after dosing. Subjects will return for subsequent follow up safety and PK assessments on Day 4 and will be contacted via a phone call for follow-up questioning about adverse events 7 days later (Study Day 11). One cohort will return after a washout of at least 7 days or five half-lives (whichever is longer) of their fasting dose to receive the same intermediate dose (TBD mg) under fed conditions.
Part 2 has a multiple ascending dose design. The dose cohorts for Part 2 will be determined based on model predictions to determine the steady-state Cmax exposure, and safety from Part 1.
In this multiple ascending dose part, each subject will be administered TBA-7371 or matching placebo for 14 days with corresponding PK measurements. Three dose cohorts are planned. After each dose cohort, the Sponsor and Investigator will review the PK and safety data before proceeding to the next dose level.
Part 3 has an open-label, multi-dose, fixed sequence drug-drug interaction study design. The dose of TBA-7371 to be studied will dependent on the interim PK analyses and safety from Part 2.
In this DDI part, each subject (n=14) will be administered midazolam (2 mg suspension) and bupropion (150 mg, tablet) together on Day 1, followed by a 7-day washout, followed by administration of TBA-7371 on Days 8 through 21, followed by administration of midazolam, and bupropion on Day 22. PK will be assessed for midazolam on Days 1 and 22, bupropion on Days 1 - 5 and 22 - 26, and TBA-7371 on Days 8-21.
At the end of Part 1 and at the end of Part 2, pharmacokinetic and safety data along with reasons for doses for the next part (Part 2 and Part 3, respectively) will be sent to the Food and Drug Administration (FDA) for review and approval. The study will not proceed to Part 2 or Part 3 until the FDA provides approval.
- Conditions
- Tuberculosis, Tuberculosis, Pulmonary
- Being tested
- TBA-7371, Placebo
- Keywords
- tuberculosis, TBA7371, TBA-7371, TB Alliance, TB, Pulmonary Tuberculosis
- Medical subject headings
- Tuberculosis, Tuberculosis, Pulmonary
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TBA-7371Drug
Also called Midazolam (oral syrup), Bupropion
The test product is TBA-7371 25 mg/ml oral suspension formulation and TBA-7371 matching placebo oral suspension.
PlaceboDrug
Also called Matching Placebo for TBA-7371
The test product is TBA-7371 25 mg/ml oral suspension formulation and TBA-7371 matching placebo oral suspension.
| Study group | Role | What they receive |
|---|---|---|
| SAD Part 1 Cohort 1 First Dose - Active | Active comparator | N = 2, 100 mg TBA-7371 or matching placebo Receives: Drug: TBA-7371 |
| SAD Part 1 Cohort 1 First Dose - Placebo | Placebo comparator | N = 1, 100 mg TBA-7371 or matching placebo Receives: Drug: Placebo |
| SAD Part 1 Cohort 1 Second Dose - Active | Active comparator | N = 4, 100 mg TBA-7371 or matching placebo Receives: Drug: TBA-7371 |
| SAD Part 1 Cohort 1 Second Dose -Placebo | Placebo comparator | N = 1, 100 mg TBA-7371 or matching placebo Receives: Drug: Placebo |
| SAD Part 1 Cohort 2 - Active | Active comparator | N= 6, 250 mg TBA-7371 or matching placebo Receives: Drug: TBA-7371 |
| SAD Part 1 Cohort 2 - Placebo | Placebo comparator | N = 2, 250 mg TBA-7371 or matching placebo Receives: Drug: Placebo |
| SAD Part 1 Cohort 3 - Active | Active comparator | N = 6, 500 mg TBA-7371 or matching placebo Receives: Drug: TBA-7371 |
| SAD Part 1 Cohort 3 - Placebo | Placebo comparator | N = 2, 500 mg TBA-7371 or matching placebo Receives: Drug: Placebo |
| SAD Part 1 Cohort 4 - Active | Active comparator | N = 6, 1000 mg TBA-7371 or matching placebo Receives: Drug: TBA-7371 |
| SAD Part 1 Cohort 4 - Placebo | Placebo comparator | N = 2, 1000 mg TBA-7371 or matching placebo Receives: Drug: Placebo |
| SAD Part 1 Cohort 5 - Active | Active comparator | N = 6, 1500 mg TBA-7371 or matching placebo Receives: Drug: TBA-7371 |
| SAD Part 1 Cohort 5 - Placebo | Placebo comparator | N = 2, 1500 mg TBA-7371 or matching placebo Receives: Drug: Placebo |
| MAD Part 2 Cohort 1 - Active | Active comparator | N = 9, 100 mg TBA-7371 or matching placebo Receives: Drug: TBA-7371 |
| MAD Part 2 Cohort 1 - Placebo | Placebo comparator | N = 3, 100 mg TBA-7371 or matching placebo for 14 days Receives: Drug: Placebo |
| MAD Part 2 Cohort 2 - Active | Active comparator | N = 9, 200 mg TBA-7371 or matching placebo for 14 days Receives: Drug: TBA-7371 |
| MAD Part 2 Cohort 2 - Placebo | Placebo comparator | N = 3, 200 mg TBA-7371 or matching placebo for 14 days Receives: Drug: Placebo |
| MAD Part 2 Cohort 3 - Active | Active comparator | N = 9, 400 mg TBA-7371 or matching placebo for 14 days Receives: Drug: TBA-7371 |
| MAD Part 2 Cohort 3 - Placebo | Placebo comparator | N = 3, 400 mg TBA-7371 or matching placebo for 14 days Receives: 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 Receives: Drug: TBA-7371 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: Days 0-28 (depending on dosing schedule)
Secondary outcomes (10)
Pharmacokinetics (PK) of single and multiple doses of TBA-7371 AUC(0-t)
This will be measured through AUC(0-t). AUC = Area under the curve, t = determined time point
Measured: Days 0-28 (depending on dosing schedule)
Pharmacokinetics (PK) of single and multiple doses of TBA-7371 using Cmax
This will be measured through Cmax. , Cmax = maximum observed concentration
Measured: Days 0-28 (depending on dosing schedule)
Pharmacokinetics (PK) of single and multiple doses of TBA-7371 using Tmax
This will be measured through Tmax, Tmax = Time of the maximum drug concentration (obtained without interpolation)
Measured: 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
This will be measured through PK parameters like AUC; AUC = Area under the curve
Measured: 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
This will be measured through PK parameters like Cmax; Cmax = maximum observed concentration
Measured: Days 0-28 (depending on dosing schedule)
Compare the rate and extent of absorption of a single oral dose of TBA-7371 using Tmax, when administered after a high-calorie, high-fat meal versus when it's administered fasting in healthy adult subjects
This will be measured through PK parameters like Tmax; Tmax = Time of the maximum drug concentration (obtained without interpolation)
Measured: Days 0-28 (depending on dosing schedule)
Effects of multiple-dose administration of TBA-7371 on the pharmacokinetics of midazolam and bupropion using AUC
This will be measured through PK parameters like AUC; AUC = Area under the curve
Measured: Days 0-28 (depending on dosing schedule)
Effects of multiple-dose administration of TBA-7371 on the pharmacokinetics of midazolam and bupropion using Cmax
This will be measured through PK parameters like Cmax; Cmax = maximum observed concentration
Measured: Days 0-28 (depending on dosing schedule)
Effects of multiple-dose administration of TBA-7371 on the pharmacokinetics of midazolam and bupropion using Tmax
This will be measured through PK parameters like Tmax; Tmax = Time of the maximum drug concentration (obtained without interpolation)
Measured: Days 0-28 (depending on dosing schedule)
Safety and tolerability of the combination of TBA7371 with midazolam and bupropion by the 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
Measured: Days 0-28 (depending on dosing schedule)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Jun 2017
- Study start29 Aug 2017
- Primary completion8 Jul 2018
- Study completion8 Jul 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for TuberculosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 74 participants (actual)
Sponsor and investigators
- Lead sponsor
- Global Alliance for TB Drug Development
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Angelo Del Parigi, MD, Study director, Global Alliance for TB Drug Development
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03199339
- Sponsor's protocol ID
- TBA-7371-CL001
- Status last verified
- Feb 2018
- First submitted
- 23 Jun 2017
- Last updated
- 17 Oct 2018
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 17 Oct 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 1, Partially-Blind, Placebo Controlled Randomized, Combined SAD With Food Effect Cohort and MAD and DDI Study to Evaluate Safety, Tolerability, PK and PK Interaction Between TBA-7371 With Midazolam and Bupropion in Healthy Subjects.
- ClinicalTrials.gov ID
- NCT03199339
- Acronym / sponsor ID
- TBA-7371-CL001
- Conditions
- Tuberculosis, Tuberculosis, Pulmonary
- Keywords
- tuberculosis, TBA7371, TBA-7371, TB Alliance, TB, Pulmonary Tuberculosis
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 74 participants (actual)
- Lead sponsor
- Global Alliance for TB Drug DevelopmentUniversity, hospital or other
- Study start
- 29 Aug 2017 (actual)
- Primary completion
- 8 Jul 2018 (actual)
- Study completion
- 8 Jul 2018 (actual)
- First posted
- 26 Jun 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The primary objective of the study is to evaluate the safety and tolerability of single and multiple doses of TBA-7371 in healthy subjects
Detailed description
Three - part, partially-blinded, placebo controlled, combined single ascending dose with a food effect cohort and multiple ascending dose and a drug-drug interaction study to be conducted in one study center in the United States.
Part 1 has a single ascending dose (SAD) design with up to 5 planned dose levels. Based on the interim PK for the dose escalation decisions, a dose cohort will be selected to return for an additional dose after a high calorie, high fat meal.
Safety will be assessed throughout the study; serial ECGs and serial blood samples will be collected for the safety and PK assessment of TBA-7371. Dose escalation to the next cohort (i.e., dose level) will not take place until the Sponsor, in conjunction with the Principal Investigator, has determined that adequate safety, tolerability and PK from the previous cohort has been demonstrated to permit proceeding to the next cohort.
Interim PK analyses will be performed for the dose escalation decisions, to select the intermediate dose for the food effect cohort, and to reconsider the sampling time points as the study progresses. All samples will be sent for analysis and the bioanalytical lab will be unblinded and only run the analysis on active treatment subjects. Data from the analysis used for the escalation meetings will only include active treatment subjects, and will be blinded by subject.
Subjects will be housed in the WCT clinic from at least 24 hours prior (from Day -2), until 48 hours after dosing. Subjects will return for subsequent follow up safety and PK assessments on Day 4 and will be contacted via a phone call for follow-up questioning about adverse events 7 days later (Study Day 11). One cohort will return after a washout of at least 7 days or five half-lives (whichever is longer) of their fasting dose to receive the same intermediate dose (TBD mg) under fed conditions.
Part 2 has a multiple ascending dose design. The dose cohorts for Part 2 will be determined based on model predictions to determine the steady-state Cmax exposure, and safety from Part 1.
In this multiple ascending dose part, each subject will be administered TBA-7371 or matching placebo for 14 days with corresponding PK measurements. Three dose cohorts are planned. After each dose cohort, the Sponsor and Investigator will review the PK and safety data before proceeding to the next dose level.
Part 3 has an open-label, multi-dose, fixed sequence drug-drug interaction study design. The dose of TBA-7371 to be studied will dependent on the interim PK analyses and safety from Part 2.
In this DDI part, each subject (n=14) will be administered midazolam (2 mg suspension) and bupropion (150 mg, tablet) together on Day 1, followed by a 7-day washout, followed by administration of TBA-7371 on Days 8 through 21, followed by administration of midazolam, and bupropion on Day 22. PK will be assessed for midazolam on Days 1 and 22, bupropion on Days 1 - 5 and 22 - 26, and TBA-7371 on Days 8-21.
At the end of Part 1 and at the end of Part 2, pharmacokinetic and safety data along with reasons for doses for the next part (Part 2 and Part 3, respectively) will be sent to the Food and Drug Administration (FDA) for review and approval. The study will not proceed to Part 2 or Part 3 until the FDA provides approval.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Single blind (participant)
- Number of arms
- 19
| Arm | Type | Receives |
|---|---|---|
| SAD Part 1 Cohort 1 First Dose - Active | Active comparator | Drug: TBA-7371N = 2, 100 mg TBA-7371 or matching placebo |
| SAD Part 1 Cohort 1 First Dose - Placebo | Placebo comparator | Drug: PlaceboN = 1, 100 mg TBA-7371 or matching placebo |
| SAD Part 1 Cohort 1 Second Dose - Active | Active comparator | Drug: TBA-7371N = 4, 100 mg TBA-7371 or matching placebo |
| SAD Part 1 Cohort 1 Second Dose -Placebo | Placebo comparator | Drug: PlaceboN = 1, 100 mg TBA-7371 or matching placebo |
| SAD Part 1 Cohort 2 - Active | Active comparator | Drug: TBA-7371N= 6, 250 mg TBA-7371 or matching placebo |
| SAD Part 1 Cohort 2 - Placebo | Placebo comparator | Drug: PlaceboN = 2, 250 mg TBA-7371 or matching placebo |
| SAD Part 1 Cohort 3 - Active | Active comparator | Drug: TBA-7371N = 6, 500 mg TBA-7371 or matching placebo |
| SAD Part 1 Cohort 3 - Placebo | Placebo comparator | Drug: PlaceboN = 2, 500 mg TBA-7371 or matching placebo |
| SAD Part 1 Cohort 4 - Active | Active comparator | Drug: TBA-7371N = 6, 1000 mg TBA-7371 or matching placebo |
| SAD Part 1 Cohort 4 - Placebo | Placebo comparator | Drug: PlaceboN = 2, 1000 mg TBA-7371 or matching placebo |
| SAD Part 1 Cohort 5 - Active | Active comparator | Drug: TBA-7371N = 6, 1500 mg TBA-7371 or matching placebo |
| SAD Part 1 Cohort 5 - Placebo | Placebo comparator | Drug: PlaceboN = 2, 1500 mg TBA-7371 or matching placebo |
| MAD Part 2 Cohort 1 - Active | Active comparator | Drug: TBA-7371N = 9, 100 mg TBA-7371 or matching placebo |
| MAD Part 2 Cohort 1 - Placebo | Placebo comparator | Drug: PlaceboN = 3, 100 mg TBA-7371 or matching placebo for 14 days |
| MAD Part 2 Cohort 2 - Active | Active comparator | Drug: TBA-7371N = 9, 200 mg TBA-7371 or matching placebo for 14 days |
| MAD Part 2 Cohort 2 - Placebo | Placebo comparator | Drug: PlaceboN = 3, 200 mg TBA-7371 or matching placebo for 14 days |
| MAD Part 2 Cohort 3 - Active | Active comparator | Drug: TBA-7371N = 9, 400 mg TBA-7371 or matching placebo for 14 days |
| MAD Part 2 Cohort 3 - Placebo | Placebo comparator | Drug: PlaceboN = 3, 400 mg TBA-7371 or matching placebo for 14 days |
| DDI Part 3 Cohort 1 | Active comparator | Drug: TBA-737114 subjects to receive midazolam and bupropion before and after orally giving 200mg of TBA-7371, 1 per day for 14 days |
Who may qualify
- Ages
- 19 to 50 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (15 listed)
- Subjects must fulfill all of the following inclusion criteria and none of the exclusion criteria to be eligible for participation in the study, unless otherwise specified.
- 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.
Key exclusion criteria (42 listed)
- 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.
- 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, or any history of cholecystectomy.
- History or presence of alcoholism or drug abuse within the past 2 years as determined by the Investigator to be clinically relevant.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TBA-7371Also: Midazolam (oral syrup), BupropionThe test product is TBA-7371 25 mg/ml oral suspension formulation and TBA-7371 matching placebo oral suspension. | Drug | 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 |
| PlaceboAlso: Matching Placebo for TBA-7371The test product is TBA-7371 25 mg/ml oral suspension formulation and TBA-7371 matching placebo oral suspension. | Drug | 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 |
Primary outcome
Safety and tolerability of single and multiple doses of TBA-7371 in healthy subjects by number and severity of treatment emergent adverse events (TEAEs)
Time frame: Days 0-28 (depending on dosing schedule)
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
10 secondary outcomes
Pharmacokinetics (PK) of single and multiple doses of TBA-7371 AUC(0-t)
Time frame: Days 0-28 (depending on dosing schedule)
Pharmacokinetics (PK) of single and multiple doses of TBA-7371 using Cmax
Time frame: Days 0-28 (depending on dosing schedule)
Pharmacokinetics (PK) of single and multiple doses of TBA-7371 using Tmax
Time frame: 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
Time frame: 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
Time frame: Days 0-28 (depending on dosing schedule)
Compare the rate and extent of absorption of a single oral dose of TBA-7371 using Tmax, when administered after a high-calorie, high-fat meal versus when it's administered fasting in healthy adult subjects
Time frame: Days 0-28 (depending on dosing schedule)
Effects of multiple-dose administration of TBA-7371 on the pharmacokinetics of midazolam and bupropion using AUC
Time frame: Days 0-28 (depending on dosing schedule)
Effects of multiple-dose administration of TBA-7371 on the pharmacokinetics of midazolam and bupropion using Cmax
Time frame: Days 0-28 (depending on dosing schedule)
Effects of multiple-dose administration of TBA-7371 on the pharmacokinetics of midazolam and bupropion using Tmax
Time frame: Days 0-28 (depending on dosing schedule)
Safety and tolerability of the combination of TBA7371 with midazolam and bupropion by the number and severity of treatment emergent adverse events (TEAEs)
Time frame: Days 0-28 (depending on dosing schedule)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Oct 2018.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Angelo Del Parigi, MD study director
Global Alliance for TB Drug Development
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing TBA-7371 in people with Tuberculosis and Tuberculosis, Pulmonary, run by Global Alliance for TB Drug Development at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 15 inclusion and 42 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 17 Oct 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety and tolerability of single and multiple doses of TBA-7371 in healthy subjects by number and severity of treatment emergent adverse events (TEAEs) (time frame: Days 0-28 (depending on dosing schedule)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Oct 2018.