TuberculosisPhase 1NCT03199313
Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Sutezolid
A Phase 1 study testing Sutezolid in people with Tuberculosis and Tuberculosis, Pulmonary, run by Global Alliance for TB Drug Development at 1 site in United States.
Trial summary
This is a randomized, double-blind, placebo-controlled, single ascending dose study conducted at one study center in the United States. Four (4) cohorts of 8 subjects each (6 active and 2 placebo). Subjects will participate in only one cohort. 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?
- Sutezolid
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 32 participants
- Where
- 1 siteUnited States
- Study dates
- 26 Sep 2017to 16 Dec 2017
- 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
- Subject understands study procedures and provides written, informed consent prior to all trial-related procedures.
- 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, as determined by the Investigator, screening results (e.g., laboratory profiles are normal or up to Grade 1 per Division of Microbiology and Infectious Diseases [DMID] Toxicity Tables) medical history, vital signs, ECGs, physical examination findings. Laboratory results within the testing facility's normal range will not be considered AEs when referenced to the DMID assessment/grading scale. If exclusionary laboratory criteria are met, values may be confirmed by repeat evaluation.
- 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:
Show all 18Show fewer
- 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.
- 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.
- 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 receive a phone call for follow-up questioning about AEs.
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.
- Medical History
- 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.
Show all 43Show fewer
- History of sensitivity or contraindication to use of linezolid or any study investigational products.
- Female subjects who are pregnant or lactating.
- 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 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)
- 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 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
- Brain surgery.
- History of head injury in the last five years
- Any serious disorder of the CNS or related neurological system, particularly one that may lower the seizure threshold.
- History of seizures Specific Treatments
- 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 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.
- 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 Laboratory Abnormalities
- 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. If exclusionary lab criteria are met, values may be confirmed by repeat evaluation.
- Positive results at screening for Human Immunodeficiency Virus (HIV), Hepatitis B Surface Antigen (HBsAg), or Hepatitis C antibodies (HCV).
- Is 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 receiving any of the following medications: monoamine oxidase (MAO) inhibitors (phenelzine, tranylcypromine), tricyclic antidepressants (amitriptyline, nortriptyline, protriptyline, doxepin, amoxapine, etc.), antipsychotics such as chlorpromazine and buspirone, serotonin re-uptake inhibitors (fluoxetine, paroxetine, sertraline, etc.), buproprion, agents known to prolong the QTc interval (erythromycin, clarithromycin, astemizole, type Ia [quinidine, procainamide, disopyramide] and III [amiodarone, sotalol] anti-arrhythmics, carbamazepine, sulfonylureas, and meperidine), within 30 days before the first dose of study drug or during the study drug treatment period.
- Use of any adrenergic/serotonergic agonists, such as pseudoephedrine and phenylpropanolamine (frequently found in cold and cough remedies), within 7 days before the first dose of study drug or during the study drug treatment period.
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 to Evaluate the Safety, Tolerability, and Pharmacokinetics of Sutezolid in Healthy Adult Subjects
This is a randomized, double-blind, placebo-controlled, single ascending dose study conducted at one study center in the United States. Four (4) cohorts of 8 subjects each (6 active and 2 placebo). 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 sutezolid.
Read more
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 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 clinic from at least 24 hours prior (from Day -2), until 48 hours (Day 3) after dosing. Subjects will be contacted via a phone call for follow-up questioning about adverse events 7 days later (Study Day 10).
- Conditions
- Tuberculosis, Tuberculosis, Pulmonary
- Being tested
- Sutezolid, Placebo
- Keywords
- tuberculosis, TB, Sutezolid, 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.
SutezolidDrug
Also called PNU-100480
Sutezolid supplied as tablets and matching placebo for oral administration.
PlaceboDrug
Also called Placebo Oral Tablet
Matching Sutezolid placebo
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1 Sentinel Group 1 - Active | Active comparator | N = 2, Initial dosing of Cohort 1 with 300 mg sutezolid or matching placebo, dosed 24 hours before the rest of Cohort 1 Group 2 Receives: Drug: Sutezolid |
| Cohort 1 Sentinel Group 1 - Placebo | Placebo comparator | N = 1, Initial dosing of Cohort 1 with 300 mg sutezolid or matching placebo, dosed 24 hours before the rest of Cohort 1 Group 2 Receives: Drug: Placebo |
| Cohort 1 Sentinel Group 2 - Active | Active comparator | N = 4, Secondary dosing of Cohort 1 with 300 mg sutezolid or matching placebo, dosed 24 hours after the rest of Cohort 1 Group 1 Receives: Drug: Sutezolid |
| Cohort 1 Sentinel Group 2 - Placebo | Placebo comparator | N = 1, Secondary dosing of Cohort 1 with 300 mg sutezolid or matching placebo, dosed 24 hours after the rest of Cohort 1 Group 1 Receives: Drug: Placebo |
| Cohort 2 - Active | Active comparator | N = 6, 600mg sutezolid or matching placebo Receives: Drug: Sutezolid |
| Cohort 2 - Placebo | Placebo comparator | N = 2, 600mg sutezolid or matching placebo Receives: Drug: Placebo |
| Cohort 3 - Active | Active comparator | N = 6, 1200 mg sutezolid or matching placebo Receives: Drug: Sutezolid |
| Cohort 3 - Placebo | Placebo comparator | N = 2, 1200 mg sutezolid or matching placebo Receives: Drug: Placebo |
| Cohort 4 - Active | Active comparator | N = 6, 1800 mg sutezolid or matching placebo Receives: Drug: Sutezolid |
| Cohort 4 - Placebo | Placebo comparator | N = 2, 1800 mg sutezolid or matching placebo Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety and tolerability of single oral doses of sutezolid in healthy adult subjects evaluated by Treatment Emergent Adverse Events (TEAEs)
Safety will be evaluated by Treatment Emergent Adverse Events (TEAEs) following doses of sutezolid or placebo
Measured: Days 0-10
Secondary outcomes (3)
Pharmacokinetics (PK) of single oral doses of sutezolid using Cmax
This will be measured through PK parameters like Cmax; Cmax = maximum observed concentration
Measured: Days 0-10
Pharmacokinetics (PK) of single oral doses of sutezolid using AUC
This will be measured through PK parameters like AUC; AUC = Area under the curve,
Measured: Days 0-10
Pharmacokinetics (PK) of single oral doses of sutezolid using Tmax
This will be measured through PK parameters like Tmax; Tmax = Time of the maximum drug concentration (obtained without interpolation)
Measured: Days 0-10
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 start26 Sep 2017
- Primary completion16 Dec 2017
- Study completion16 Dec 2017
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
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 32 participants (actual)
Sponsor and investigators
- Lead sponsor
- Global Alliance for TB Drug Development
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Paul Bruinenberg, MD, Study director, Global Alliance for TB Drug Development
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03199313
- Sponsor's protocol ID
- Sutezolid - CL001
- Status last verified
- Feb 2018
- First submitted
- 23 Jun 2017
- Last updated
- 8 Feb 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 8 Feb 2018. 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 to Evaluate the Safety, Tolerability, and Pharmacokinetics of Sutezolid in Healthy Adult Subjects
- ClinicalTrials.gov ID
- NCT03199313
- Acronym / sponsor ID
- Sutezolid - CL001
- Conditions
- Tuberculosis, Tuberculosis, Pulmonary
- Keywords
- tuberculosis, TB, Sutezolid, pulmonary tuberculosis
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 32 participants (actual)
- Lead sponsor
- Global Alliance for TB Drug DevelopmentUniversity, hospital or other
- Study start
- 26 Sep 2017 (actual)
- Primary completion
- 16 Dec 2017 (actual)
- Study completion
- 16 Dec 2017 (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.
This is a randomized, double-blind, placebo-controlled, single ascending dose study conducted at one study center in the United States. Four (4) cohorts of 8 subjects each (6 active and 2 placebo). 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 sutezolid.
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 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 clinic from at least 24 hours prior (from Day -2), until 48 hours (Day 3) after dosing. Subjects will be contacted via a phone call for follow-up questioning about adverse events 7 days later (Study Day 10).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 10
| Arm | Type | Receives |
|---|---|---|
| Cohort 1 Sentinel Group 1 - Active | Active comparator | Drug: SutezolidN = 2, Initial dosing of Cohort 1 with 300 mg sutezolid or matching placebo, dosed 24 hours before the rest of Cohort 1 Group 2 |
| Cohort 1 Sentinel Group 1 - Placebo | Placebo comparator | Drug: PlaceboN = 1, Initial dosing of Cohort 1 with 300 mg sutezolid or matching placebo, dosed 24 hours before the rest of Cohort 1 Group 2 |
| Cohort 1 Sentinel Group 2 - Active | Active comparator | Drug: SutezolidN = 4, Secondary dosing of Cohort 1 with 300 mg sutezolid or matching placebo, dosed 24 hours after the rest of Cohort 1 Group 1 |
| Cohort 1 Sentinel Group 2 - Placebo | Placebo comparator | Drug: PlaceboN = 1, Secondary dosing of Cohort 1 with 300 mg sutezolid or matching placebo, dosed 24 hours after the rest of Cohort 1 Group 1 |
| Cohort 2 - Active | Active comparator | Drug: SutezolidN = 6, 600mg sutezolid or matching placebo |
| Cohort 2 - Placebo | Placebo comparator | Drug: PlaceboN = 2, 600mg sutezolid or matching placebo |
| Cohort 3 - Active | Active comparator | Drug: SutezolidN = 6, 1200 mg sutezolid or matching placebo |
| Cohort 3 - Placebo | Placebo comparator | Drug: PlaceboN = 2, 1200 mg sutezolid or matching placebo |
| Cohort 4 - Active | Active comparator | Drug: SutezolidN = 6, 1800 mg sutezolid or matching placebo |
| Cohort 4 - Placebo | Placebo comparator | Drug: PlaceboN = 2, 1800 mg sutezolid or matching placebo |
Who may qualify
- Ages
- 19 to 50 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (18 listed)
- Subject understands study procedures and provides written, informed consent prior to all trial-related procedures.
- 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, as determined by the Investigator, screening results (e.g., laboratory profiles are normal or up to Grade 1 per Division of Microbiology and Infectious Diseases [DMID] Toxicity Tables) medical history, vital signs, ECGs, physical examination findings. Laboratory results within the testing facility's normal range will not be considered AEs when referenced to the DMID assessment/grading scale. If exclusionary laboratory criteria are met, values may be confirmed by repeat evaluation.
- No use of tobacco or nicotine containing products (including smoking cessation products), for a minimum of 6 months prior to dosing.
Key exclusion criteria (43 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.
- Medical History
- 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.
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 |
|---|---|---|
| SutezolidAlso: PNU-100480Sutezolid supplied as tablets and matching placebo for oral administration. | Drug | Cohort 1 Sentinel Group 1 - Active, Cohort 1 Sentinel Group 2 - Active, Cohort 2 - Active, Cohort 3 - Active, Cohort 4 - Active |
| PlaceboAlso: Placebo Oral TabletMatching Sutezolid placebo | Drug | Cohort 1 Sentinel Group 1 - Placebo, Cohort 1 Sentinel Group 2 - Placebo, Cohort 2 - Placebo, Cohort 3 - Placebo, Cohort 4 - Placebo |
Primary outcome
Safety and tolerability of single oral doses of sutezolid in healthy adult subjects evaluated by Treatment Emergent Adverse Events (TEAEs)
Time frame: Days 0-10
Safety will be evaluated by Treatment Emergent Adverse Events (TEAEs) following doses of sutezolid or placebo
3 secondary outcomes
Pharmacokinetics (PK) of single oral doses of sutezolid using Cmax
Time frame: Days 0-10
Pharmacokinetics (PK) of single oral doses of sutezolid using AUC
Time frame: Days 0-10
Pharmacokinetics (PK) of single oral doses of sutezolid using Tmax
Time frame: Days 0-10
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 8 Feb 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.
Paul Bruinenberg, 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 Sutezolid 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 18 inclusion and 43 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 8 Feb 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 oral doses of sutezolid in healthy adult subjects evaluated by Treatment Emergent Adverse Events (TEAEs) (time frame: Days 0-10). 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 8 Feb 2018.