TuberculosisPhase 1NCT02288481
A Phase 1 Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of TBA-354 in Healthy Adult Subjects
A Phase 1 study testing TBA-354 in people with Tuberculosis, run by Global Alliance for TB Drug Development at 1 site in United States.
Trial summary
The objective of this study is to evaluate the safety and tolerability of single oral doses of TBA-354 when administered to healthy adult 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
- What is being tested?
- TBA-354
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 48 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2015to Jun 2015
- 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. Subjects must continue to meet all inclusion criteria to be able to participate in the Food Effect study.
- 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 kg.
- Medically healthy with no clinically significant screening results (e.g., laboratory profiles, medical histories, vital signs, electrocardiograms (ECGs), physical examination) as deemed by the Principal 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 have undergone one of the following sterilization procedures at least 6 months prior to dosing:
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- 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 serumfollicle-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.
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. Subjects must continue to meet none of the Exclusion Criteria in order to participate in the Food Effect study.
- History or presence of significant cardiovascular, pulmonary, hepatic, renal, hematological, gastrointestinal, endocrine, immunologic, dermatologic, neurological, or psychiatric disease.
- History of any illness that, in the opinion of the Principal 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 Principal Investigator to be clinically relevant.
- History or presence of alcoholism or drug abuse within the past 2 years.
- Hypersensitive or idiosyncratic reactions to compounds related to TBA-354 (e.g., nitroimidazoles such as metronidazole, etc.).
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- 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.
- 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 clinically significant ECG abnormality at Screening (as deemed by the Principal Investigator and the Sponsor's Medical Monitor).
- NOTE: The following can be considered not clinically significant without consulting 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
- QTcF interval >450 msec for males or >470 msec for females (the average value for the replicate ECG at screening and Check-In), 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, (excluding febrile seizures of childhood).
- Brain trauma or brain surgery.
- Any serious disorder of the CNS or related neurological system, particularly one that may lower the seizure threshold.
- 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. Up to 2 grams per day of acetaminophen is allowed at the discretion of the Principal Investigator.
- Use of any drugs or substances known to be significant inhibitors of CYP enzymes and/or significant inhibitors or substrates of P-gp and/or 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 28 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.
- Prior treatment with investigational products PA-824 or OPC-67683.
- Consumption of the following prior to dosing period:
- Alcohol 48 hours prior to dosing
- Grapefruit/Mandarin Oranges 10 days prior to dosing
- Caffeine/Xanthine 24 hours prior to dosing
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase 1, Randomized, Double-Blind, Placebo-Controlled, Single Ascending Dose Study With a Food Effect Cohort to Evaluate the Safety, Tolerability, and Pharmacokinetics of TBA-354 in Healthy Adult Subjects
The objective of this study is to evaluate the safety and tolerability of single oral doses of TBA-354 when administered to healthy adult subjects.
Read the detailed description
This is a randomized, double-blind, placebo-controlled, single ascending dose study conducted at one study center in the United States. Six (6) cohorts of 8 subjects each (6 active and 2 placebo), with one cohort crossing over to assess food effect, are planned for evaluation. Subjects will participate in only one cohort.
Safety will be assessed throughout the study; serial ECGs and serial blood samples will be collected for the safety and PK assessment of TBA-354.
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. Upon review of cohort data, the Sponsor, in conjunction with the Principal Investigator, may decide to:
- Escalate dose as planned.
- Evaluate an intermediate dose level prior to proceeding to the next planned dose level if concerns arise from signs and symptoms that do not warrant ceasing escalation as described above.
- Repeat a given dose level in a new cohort of subjects.
- Halt the study.
Blinded 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.
Subjects will be housed in the Celerion 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 Days 4 to 7 and will be contacted via a phone call for follow-up questioning about adverse events 7 days later (Study Day 14). One cohort will return after a washout of at least 14 days or five half-lives (whichever is longer) of their fasting dose to receive the same intermediate dose (TBD mg) under fed conditions.
- Conditions
- Tuberculosis
- Being tested
- TBA-354, Placebo
- Keywords
- Tuberculosis, TBA-354, Pulmonary Tuberculosis, TB
- 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-354Drug
TBA-354 supplied as a 20 mg /mL suspension and matching placebo suspension for oral administration.
PlaceboOther
Placebo Suspension
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1 10 mg TBA-354 | Experimental | Not described Receives: Drug: TBA-354 |
| Cohort 1 placebo | Placebo comparator | Placebo Suspension Receives: Other: Placebo |
| Cohort 2 25 mg TBA-354 | Experimental | Not described Receives: Drug: TBA-354 |
| Cohort 2 placebo | Placebo comparator | Placebo Suspension Receives: Other: Placebo |
| Cohort 3 60 mg TBA-354 | Experimental | Not described Receives: Drug: TBA-354 |
| Cohort 3 placebo | Placebo comparator | Placebo Suspension Receives: Other: Placebo |
| Cohort 4 150 mg TBA-354 | Experimental | Not described Receives: Drug: TBA-354 |
| Cohort 4 placebo | Placebo comparator | Placebo Suspension Receives: Other: Placebo |
| Cohort 5 400 mg TBA-354 | Experimental | Not described Receives: Drug: TBA-354 |
| Cohort 5 placebo | Placebo comparator | Placebo Suspension Receives: Other: Placebo |
| Cohort 6 1000 mg TBA-354 | Experimental | Not described Receives: Drug: TBA-354 |
| Cohort 6 placebo | Placebo comparator | Placebo Suspension Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
The primary endpoint of the study will be the number and severity of treatment emergent adverse events (TEAEs) following single doses of TBA-354 and placebo.
Measured: Day 1, 2, 4, 5, 6, 7, 14
Secondary outcomes (4)
Pharmacokinetics of TBA-354 in plasma following single oral doses. Cmax, AUC0-24
Tmax: Time of the maximum drug concentration (obtained without interpolation). Cmax: Maximum observed drug concentration. AUC0-24: Area under concentration time curve 0 to 24 hours
Measured: Day 1 (Hour 0, 1, 2, 4, 6, 7, 8, 12, 16), Day 2 (Hour 20, 24, 30, 36, 42), Follow up (Hour 72, 96, 120, 144)
Effect of food on the Pharmacokinetics parameters of TBA-354 in plasma following an intermediate single oral dose. Cmax, AUC0-24
Tmax: Time of the maximum drug concentration (obtained without interpolation). Cmax: Maximum observed drug concentration. AUC0-24: Area under concentration time curve 0 to 24 hours
Measured: Day 1 (Hour 0, 1, 2, 4, 6, 7, 8, 12, 16), Day 2 (Hour 20, 24, 30, 36, 42), Follow up (Hour 72, 96, 120, 144)
Number of subjects/time points with abnormal findings in safety electrocardiogram
Calculated in terms of QT corrected for heart rate according to Fridericia's corrected formula (QTcF) outliers (QTcF > 450, > 480, and > 500 msec; and change-from-baseline QTcF > 30 and > 60 msec).
Measured: Screening; Day 1 (Hour 0, 1, 2, 4, 6, 8, 12, 16); Day 2 Hour 20, 24, 30, 36 and 48; Follow up Hour 144
Placebo-corrected safety electrocardiogram Change-from-baseline heart rate
Change-from-baseline heart rate, QT corrected for heart rate according to Fridericia's corrected formula (QTcF), PR, QRS, QT, and incidence of abnormal T-wave morphology from cardiodynamic electrocardiograms extracted from the pre-specified time points.
Measured: Screening; Day 1 (Hour 0, 1, 2, 4, 6, 8, 12, 16); Day 2 Hour 20, 24, 30, 36 and 48; Follow up Hour 144
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Nov 2014 (estimated)
- Study startJan 2015
- Primary completionJun 2015
- Study completionJun 2015
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
- Single group
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 48 participants (actual)
Sponsor and investigators
- Lead sponsor
- Global Alliance for TB Drug Development
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Michael Gartner, MD, Principal investigator, Celerion
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02288481
- Sponsor's protocol ID
- TBA-354-CL-001
- Status last verified
- Sep 2019
- First submitted
- 7 Nov 2014
- Last updated
- 6 Sep 2019
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 6 Sep 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1, Randomized, Double-Blind, Placebo-Controlled, Single Ascending Dose Study With a Food Effect Cohort to Evaluate the Safety, Tolerability, and Pharmacokinetics of TBA-354 in Healthy Adult Subjects
- ClinicalTrials.gov ID
- NCT02288481
- Acronym / sponsor ID
- TBA-354-CL-001
- Conditions
- Tuberculosis
- Keywords
- Tuberculosis, TBA-354, Pulmonary Tuberculosis, TB
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 48 participants (actual)
- Lead sponsor
- Global Alliance for TB Drug DevelopmentUniversity, hospital or other
- Study start
- Jan 2015
- Primary completion
- Jun 2015 (actual)
- Study completion
- Jun 2015 (actual)
- First posted
- 11 Nov 2014 (estimated)
- 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 objective of this study is to evaluate the safety and tolerability of single oral doses of TBA-354 when administered to healthy adult subjects.
Detailed description
This is a randomized, double-blind, placebo-controlled, single ascending dose study conducted at one study center in the United States. Six (6) cohorts of 8 subjects each (6 active and 2 placebo), with one cohort crossing over to assess food effect, are planned for evaluation. Subjects will participate in only one cohort.
Safety will be assessed throughout the study; serial ECGs and serial blood samples will be collected for the safety and PK assessment of TBA-354.
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. Upon review of cohort data, the Sponsor, in conjunction with the Principal Investigator, may decide to:
- Escalate dose as planned.
- Evaluate an intermediate dose level prior to proceeding to the next planned dose level if concerns arise from signs and symptoms that do not warrant ceasing escalation as described above.
- Repeat a given dose level in a new cohort of subjects.
- Halt the study.
Blinded 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.
Subjects will be housed in the Celerion 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 Days 4 to 7 and will be contacted via a phone call for follow-up questioning about adverse events 7 days later (Study Day 14). One cohort will return after a washout of at least 14 days or five half-lives (whichever is longer) of their fasting dose to receive the same intermediate dose (TBD mg) under fed conditions.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Double blind (participant, investigator)
- Number of arms
- 12
| Arm | Type | Receives |
|---|---|---|
| Cohort 1 10 mg TBA-354 | Experimental | Drug: TBA-354 |
| Cohort 1 placebo | Placebo comparator | Other: PlaceboPlacebo Suspension |
| Cohort 2 25 mg TBA-354 | Experimental | Drug: TBA-354 |
| Cohort 2 placebo | Placebo comparator | Other: PlaceboPlacebo Suspension |
| Cohort 3 60 mg TBA-354 | Experimental | Drug: TBA-354 |
| Cohort 3 placebo | Placebo comparator | Other: PlaceboPlacebo Suspension |
| Cohort 4 150 mg TBA-354 | Experimental | Drug: TBA-354 |
| Cohort 4 placebo | Placebo comparator | Other: PlaceboPlacebo Suspension |
| Cohort 5 400 mg TBA-354 | Experimental | Drug: TBA-354 |
| Cohort 5 placebo | Placebo comparator | Other: PlaceboPlacebo Suspension |
| Cohort 6 1000 mg TBA-354 | Experimental | Drug: TBA-354 |
| Cohort 6 placebo | Placebo comparator | Other: PlaceboPlacebo Suspension |
Who may qualify
- Ages
- 19 to 50 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (18 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. Subjects must continue to meet all inclusion criteria to be able to participate in the Food Effect study.
- 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 kg.
- Medically healthy with no clinically significant screening results (e.g., laboratory profiles, medical histories, vital signs, electrocardiograms (ECGs), physical examination) as deemed by the Principal 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 (37 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. Subjects must continue to meet none of the Exclusion Criteria in order to participate in the Food Effect study.
- History or presence of significant cardiovascular, pulmonary, hepatic, renal, hematological, gastrointestinal, endocrine, immunologic, dermatologic, neurological, or psychiatric disease.
- History of any illness that, in the opinion of the Principal 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 Principal Investigator to be clinically relevant.
- History or presence of alcoholism or drug abuse within the past 2 years.
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-354TBA-354 supplied as a 20 mg /mL suspension and matching placebo suspension for oral administration. | Drug | Cohort 1 10 mg TBA-354, Cohort 2 25 mg TBA-354, Cohort 3 60 mg TBA-354, Cohort 4 150 mg TBA-354, Cohort 5 400 mg TBA-354, Cohort 6 1000 mg TBA-354 |
| PlaceboPlacebo Suspension | Other | Cohort 1 placebo, Cohort 2 placebo, Cohort 3 placebo, Cohort 4 placebo, Cohort 5 placebo, Cohort 6 placebo |
Primary outcome
The primary endpoint of the study will be the number and severity of treatment emergent adverse events (TEAEs) following single doses of TBA-354 and placebo.
Time frame: Day 1, 2, 4, 5, 6, 7, 14
4 secondary outcomes
Pharmacokinetics of TBA-354 in plasma following single oral doses. Cmax, AUC0-24
Time frame: Day 1 (Hour 0, 1, 2, 4, 6, 7, 8, 12, 16), Day 2 (Hour 20, 24, 30, 36, 42), Follow up (Hour 72, 96, 120, 144)
Effect of food on the Pharmacokinetics parameters of TBA-354 in plasma following an intermediate single oral dose. Cmax, AUC0-24
Time frame: Day 1 (Hour 0, 1, 2, 4, 6, 7, 8, 12, 16), Day 2 (Hour 20, 24, 30, 36, 42), Follow up (Hour 72, 96, 120, 144)
Number of subjects/time points with abnormal findings in safety electrocardiogram
Time frame: Screening; Day 1 (Hour 0, 1, 2, 4, 6, 8, 12, 16); Day 2 Hour 20, 24, 30, 36 and 48; Follow up Hour 144
Placebo-corrected safety electrocardiogram Change-from-baseline heart rate
Time frame: Screening; Day 1 (Hour 0, 1, 2, 4, 6, 8, 12, 16); Day 2 Hour 20, 24, 30, 36 and 48; Follow up Hour 144
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 6 Sep 2019.
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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.
Michael Gartner, MD principal investigator
Celerion
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-354 in people with Tuberculosis, 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 18 inclusion and 37 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 6 Sep 2019. 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?
The primary endpoint of the study will be the number and severity of treatment emergent adverse events (TEAEs) following single doses of TBA-354 and placebo. (time frame: Day 1, 2, 4, 5, 6, 7, 14). 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 6 Sep 2019.