TuberculosisPhase 1NCT00990990
Safety, Tolerability, Pharmacokinetics And Measurement Of Whole Blood Activity (WBA) Of PNU-100480 After Multiple Oral Doses In Healthy Adult Volunteers
A Phase 1 study testing PNU-100480 and Linezolid in people with Tuberculosis, run by Sequella, Inc. at 1 site in United States.
Trial summary
The purpose of this study is to assess the safety, tolerability and pharmacokinetics of multiple doses of PNU-100480 given for 14 or 28 days. Killing activity against the bacterium that causes tuberculosis (TB) will also be measured. Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Tuberculosis
- What is being tested?
- PNU-100480 and Linezolid
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 59 participants
- Where
- 1 siteUnited States
- Study dates
- Oct 2009to May 2010
- 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 18 to 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Healthy adult volunteers willing and able to be confined to the Clinical Research Unit and comply with study schedule.
- Women of non-childbearing potential only.
Who cannot join
- History of hypersensitivity to, or intolerance of, linezolid.
- Antibiotic treatment within 14 days prior to dosing, or any previous antibiotic use at the discretion of the investigator.
- Previous history of irritable bowel syndrome (IBS) or inflammatory bowel disease (IBD).
Trial locations and contacts
1 site in 1 country.
United States1 site
Pfizer Investigational Site
New Haven, Connecticut, 06511
About this study
Official title: A Phase 1, Double-Blind, Randomized, Placebo-Controlled Study To Evaluate The Safety, Tolerability, Pharmacokinetics And Pharmacodynamics Of PNU-100480 (PF-02341272) After Administration Of Multiple Escalating Oral Doses To Healthy Adult Subjects
The purpose of this study is to assess the safety, tolerability and pharmacokinetics of multiple doses of PNU-100480 given for 14 or 28 days. Killing activity against the bacterium that causes tuberculosis (TB) will also be measured. The effect of adding an additional tuberculosis (TB) agent (given for 2 days) in addition to PNU-100480 will be evaluated. Linezolid open label to determine activity in whole blood assay (WBA).
Read the detailed description
Evaluate safety, tolerability, pharmacokinetics and whole blood activity (WBA) of PNU-100480 given for 14 or 28 days; evaluate WBA of PNU with pyrazinamide; evaluate WBA of linezolid
- Conditions
- Tuberculosis
- Being tested
- PNU-100480, Placebo, Linezolid
- Keywords
- Safety tolerability pharmacokinetics (PK) pharmacodynamics whole blood activity (WBA) PNU-100480 linezolid pyrazinamide multiple dose
- Medical subject headings
- Tuberculosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PNU-100480Drug
100 mg BID for 14 days
PlaceboDrug
to match 100 mg BID for 14 days
PNU-100480Drug
300 mg BID for 14 days
PlaceboDrug
to match 300 mg BID for 14 days
PNU-100480Drug
600 mg BID for 14 days
PlaceboDrug
to match 600 mg BID for 14 days
PNU-100480Drug
1200 mg QD for 14 days
PlaceboDrug
to match 1200 mg QD for 14 days
PNU-100480Drug
600 mg BID for 28 days with pyrazinamide (25 mg/kg up to 2 g) QD on Days 27-28
PlaceboDrug
placebo to match 600 mg BID for 28 days with pyrazinamide (25 mg/kg up to 2 g) QD on Days 27-28
PNU-100480Drug
PNU-100480 dose up to total of 1200 mg daily for 28 days with pyrazinamide (25 mg/kg up to 2 g) QD on Days 27-28
PlaceboDrug
placebo to match dose up to total of 1200 mg daily for 28 days with pyrazinamide (25 mg/kg up to 2 g) QD on Days 27-28
LinezolidDrug
300 mg QD for 4 days (open label)
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1 | Experimental | Not described Receives: Drug: PNU-100480; Drug: Placebo |
| Cohort 2 | Experimental | Not described Receives: Drug: PNU-100480; Drug: Placebo |
| Cohort 3 | Experimental | Not described Receives: Drug: PNU-100480; Drug: Placebo |
| Cohort 4 | Experimental | Not described Receives: Drug: PNU-100480; Drug: Placebo |
| Cohort 5 | Experimental | Not described Receives: Drug: PNU-100480; Drug: Placebo |
| Cohort 6 (optional) | Experimental | Not described Receives: Drug: PNU-100480; Drug: Placebo |
| Linezolid Cohort | Experimental | Not described Receives: Drug: Linezolid |
What is being measured
The primary outcome is the main question the study is designed to answer.
To evaluate the safety and tolerability of ascending oral doses of PNU-100480 administered as extemporaneously prepared suspension (EPS) over 14 and 28 days in healthy adult volunteers.
Measured: Monitor adverse events daily; safety eval pre-dose, specified times , discharge, follow-up/as needed
Secondary outcomes (4)
To characterize the single dose and steady state pharmacokinetics of ascending oral doses of PNU-100480 administered over 14 and 28 days in healthy adult volunteers with regard to the parent drug and its metabolites.
Measured: Full and sparse PK sampling from Day 1 through final day of dosing
To characterize the bactericidal activity in blood of orally administered PNU-100480 against intracellular M. tuberculosis in relation to blood concentrations ofPNU-100480 and its metabolites.
Measured: Full and sparse sampling from Day 1 through final day of dosing
To characterize the effect of once a day administration of pyrazinamide for 2 days on the pharmacokinetics and bactericidal activity in blood of orally administered PNU-100480 against intracellular M. tuberculosis (Cohorts 5 and 6, Days 27-28 only).
Measured: Days 27-28 as applicable
To characterize pharmacokinetics and bactericidal activity in blood of orally administered linezolid against intracellular M. tuberculosis following 4 days of QD dosing.
Measured: As applicable up to Day 4
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Oct 2009 (estimated)
- Study startOct 2009
- Primary completionMay 2010
- Study completionMay 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- 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
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 59 participants (actual)
Sponsor and investigators
- Lead sponsor
- Sequella, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Lisa Beth Ferstenberg, M.D., Study director, Sequella, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00990990
- Sponsor's protocol ID
- B1171002
- Status last verified
- Aug 2013
- First submitted
- 6 Oct 2009
- Last updated
- 28 Aug 2013
- Results posted
- No
- Data monitoring committee
- No
Publications
Wallis RS, Jakubiec WM, Kumar V, Silvia AM, Paige D, Dimitrova D, Li X, Ladutko L, Campbell S, Friedland G, Mitton-Fry M, Miller PF. Pharmacokinetics and whole-blood bactericidal activity against Mycobacterium tuberculosis of single doses of PNU-100480 in healthy volunteers. J Infect Dis. 2010 Sep 1;202(5):745-51. doi: 10.1086/655471.
PubMed 20629533
Study at a glance
From the registry record, last updated by the sponsor on 28 Aug 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1, Double-Blind, Randomized, Placebo-Controlled Study To Evaluate The Safety, Tolerability, Pharmacokinetics And Pharmacodynamics Of PNU-100480 (PF-02341272) After Administration Of Multiple Escalating Oral Doses To Healthy Adult Subjects
- ClinicalTrials.gov ID
- NCT00990990
- Acronym / sponsor ID
- B1171002
- Conditions
- Tuberculosis
- Keywords
- Safety tolerability pharmacokinetics (PK) pharmacodynamics whole blood activity (WBA) PNU-100480 linezolid pyrazinamide multiple dose
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 59 participants (actual)
- Lead sponsor
- Sequella, Inc.Industry (pharma, biotech, devices)
- Study start
- Oct 2009
- Primary completion
- May 2010 (actual)
- Study completion
- May 2010 (actual)
- First posted
- 7 Oct 2009 (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 purpose of this study is to assess the safety, tolerability and pharmacokinetics of multiple doses of PNU-100480 given for 14 or 28 days. Killing activity against the bacterium that causes tuberculosis (TB) will also be measured. The effect of adding an additional tuberculosis (TB) agent (given for 2 days) in addition to PNU-100480 will be evaluated. Linezolid open label to determine activity in whole blood assay (WBA).
Detailed description
Evaluate safety, tolerability, pharmacokinetics and whole blood activity (WBA) of PNU-100480 given for 14 or 28 days; evaluate WBA of PNU with pyrazinamide; evaluate WBA of linezolid
Study design
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 7
| Arm | Type | Receives |
|---|---|---|
| Cohort 1 | Experimental | Drug: PNU-100480, Drug: Placebo |
| Cohort 2 | Experimental | Drug: PNU-100480, Drug: Placebo |
| Cohort 3 | Experimental | Drug: PNU-100480, Drug: Placebo |
| Cohort 4 | Experimental | Drug: PNU-100480, Drug: Placebo |
| Cohort 5 | Experimental | Drug: PNU-100480, Drug: Placebo |
| Cohort 6 (optional) | Experimental | Drug: PNU-100480, Drug: Placebo |
| Linezolid Cohort | Experimental | Drug: Linezolid |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (2 listed)
- Healthy adult volunteers willing and able to be confined to the Clinical Research Unit and comply with study schedule.
- Women of non-childbearing potential only.
Key exclusion criteria (3 listed)
- History of hypersensitivity to, or intolerance of, linezolid.
- Antibiotic treatment within 14 days prior to dosing, or any previous antibiotic use at the discretion of the investigator.
- Previous history of irritable bowel syndrome (IBS) or inflammatory bowel disease (IBD).
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 |
|---|---|---|
| PNU-100480100 mg BID for 14 days | Drug | Cohort 1 |
| Placeboto match 100 mg BID for 14 days | Drug | Cohort 1 |
| PNU-100480300 mg BID for 14 days | Drug | Cohort 2 |
| Placeboto match 300 mg BID for 14 days | Drug | Cohort 2 |
| PNU-100480600 mg BID for 14 days | Drug | Cohort 3 |
| Placeboto match 600 mg BID for 14 days | Drug | Cohort 3 |
| PNU-1004801200 mg QD for 14 days | Drug | Cohort 4 |
| Placeboto match 1200 mg QD for 14 days | Drug | Cohort 4 |
| PNU-100480600 mg BID for 28 days with pyrazinamide (25 mg/kg up to 2 g) QD on Days 27-28 | Drug | Cohort 5 |
| Placeboplacebo to match 600 mg BID for 28 days with pyrazinamide (25 mg/kg up to 2 g) QD on Days 27-28 | Drug | Cohort 5 |
| PNU-100480PNU-100480 dose up to total of 1200 mg daily for 28 days with pyrazinamide (25 mg/kg up to 2 g) QD on Days 27-28 | Drug | Cohort 6 (optional) |
| Placeboplacebo to match dose up to total of 1200 mg daily for 28 days with pyrazinamide (25 mg/kg up to 2 g) QD on Days 27-28 | Drug | Cohort 6 (optional) |
| Linezolid300 mg QD for 4 days (open label) | Drug | Linezolid Cohort |
Primary outcome
To evaluate the safety and tolerability of ascending oral doses of PNU-100480 administered as extemporaneously prepared suspension (EPS) over 14 and 28 days in healthy adult volunteers.
Time frame: Monitor adverse events daily; safety eval pre-dose, specified times , discharge, follow-up/as needed
4 secondary outcomes
To characterize the single dose and steady state pharmacokinetics of ascending oral doses of PNU-100480 administered over 14 and 28 days in healthy adult volunteers with regard to the parent drug and its metabolites.
Time frame: Full and sparse PK sampling from Day 1 through final day of dosing
To characterize the bactericidal activity in blood of orally administered PNU-100480 against intracellular M. tuberculosis in relation to blood concentrations ofPNU-100480 and its metabolites.
Time frame: Full and sparse sampling from Day 1 through final day of dosing
To characterize the effect of once a day administration of pyrazinamide for 2 days on the pharmacokinetics and bactericidal activity in blood of orally administered PNU-100480 against intracellular M. tuberculosis (Cohorts 5 and 6, Days 27-28 only).
Time frame: Days 27-28 as applicable
To characterize pharmacokinetics and bactericidal activity in blood of orally administered linezolid against intracellular M. tuberculosis following 4 days of QD dosing.
Time frame: As applicable up to Day 4
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 28 Aug 2013.
- Derived from this study: PubMed 20629533Wallis RS, Jakubiec WM, Kumar V, Silvia AM, Paige D, Dimitrova D, Li X, Ladutko L, Campbell S, Friedland G, Mitton-Fry M, Miller PF. Pharmacokinetics and whole-blood bactericidal activity against Mycobacterium tuberculosis of single doses of PNU-100480 in healthy volunteers. J Infect Dis. 2010 Sep 1;202(5):745-51. doi: 10.1086/655471.
- To obtain contact information for a study center near you, click here.Link provided by the sponsor.
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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.
Lisa Beth Ferstenberg, M.D. study director
Sequella, Inc.
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 PNU-100480 and Linezolid in people with Tuberculosis, run by Sequella, Inc. 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 2 inclusion and 3 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 28 Aug 2013. 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. 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?
To evaluate the safety and tolerability of ascending oral doses of PNU-100480 administered as extemporaneously prepared suspension (EPS) over 14 and 28 days in healthy adult volunteers. (time frame: Monitor adverse events daily; safety eval pre-dose, specified times , discharge, follow-up/as needed). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00990990, which also lists 1 linked publication.
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 28 Aug 2013.