TuberculosisPhase 2NCT01225640
PNU-100480 In Newly Diagnosed, Drug Sensitive Patients With Pulmonary TB; Early Bactericidal Activity; Whole Blood Assay
A Phase 2 study testing PNU-100480 and RHZE in people with Tuberculosis, run by Sequella, Inc. at 2 sites in South Africa.
Trial summary
PNU-100480 is being developed for the treatment of both drug resistant and sensitive tuberculosis. This is an efficacy and safety study to characterize the effect of PNU-100480 when given for 14 days to treatment-naive patients with drug-sensitive pulmonary tuberculosis. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Tuberculosis
- What is being tested?
- PNU-100480 and RHZE
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 59 participants
- Where
- 2 sitesSouth Africa
- Study dates
- Aug 2011to Dec 2011
- Phase
- Phase 2
- 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 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Adult males or females between 18 and 65 years; women of childbearing potential must be willing to adhere to lifestyle requirements regarding contraception/pregnancy prevention.
- Newly diagnosed sputum smear-positive pulmonary TB confirmed with acid-fast bacillus (AFB) smear and chest x-ray. Patients with TB more than 5 years ago who completed treatment, are healthy, and meet other inclusion criteria may be included.
- Body weight between 40 and 90 kg, inclusive (in light clothing, no shoes).
- Reasonably normal hemoglobin (>=8 gm/dL), renal function (serum creatinine <2 mg/dL), hepatic function (serum AST <3xULN and total bilirubin <1.3 mg/dL), and random glucose <150 mg/dL.
Who cannot join
- HIV infection with helper/inducer T-lymphocytes (CD4 cell) count of <=350x10-6/L.
- Presence of significant hemoptysis. Subjects who cough up frank blood (more than blood streaked sputum) will not be eligible.
- Pregnant or nursing females; females of childbearing potential unwilling or unable to adhere to contraception guidelines.
- Significant respiratory impairment (respiratory rate >35/minute).
- Clinical suspicion of disseminated TB or tuberculosis meningitis.
- Subjects with diabetes mellitus on insulin and/or who have poorly controlled disease.
- Subjects with confirmed or suspected multi-drug resistant TB.
Trial locations and contacts
2 sites in 1 country.
South Africa2 sites
Pfizer Investigational Site
Bellville, Cape Town, 7530
Pfizer Investigational Site
Cape Town, 7700
About this study
Official title: A Phase 2a, Open-Label, Randomized Study In Treatment-Naive, Sputum Smear Positive Subjects With Drug-Sensitive Pulmonary Tuberculosis To Assess Early Bactericidal Activity (EBA) And Whole Blood Activity (WBA) Of PNU-100480 (PF-02341272)
PNU-100480 is being developed for the treatment of both drug resistant and sensitive tuberculosis. This is an efficacy and safety study to characterize the effect of PNU-100480 when given for 14 days to treatment-naive patients with drug-sensitive pulmonary tuberculosis.
- Conditions
- Tuberculosis
- Being tested
- PNU-100480, RHZE
- Keywords
- Tuberculosis, EBA, WBA
- 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
600 mg twice daily (BID) for 14 days
PNU-100480Drug
1200 mg once daily (QD) for 14 days
RHZEDrug
Also called Rifafour, Rimstar
Combination tablet (RHZE) dosed by weight. Dosage strength per tablet is 150 mg Rifampicin (R)/75 mg Isoniazid (H)/400 mg Pyrazinamide (Z)/275 mg Ethambutol (E)
| Study group | Role | What they receive |
|---|---|---|
| PNU-100480 600 mg BID | Experimental | Not described Receives: Drug: PNU-100480 |
| PNU-100480 1200 mg QD | Experimental | Not described Receives: Drug: PNU-100480 |
| RHZE | Active comparator | conjugated tablet with 4 drug combination of RHZE, Rifafour® e275 will be used in countries where can be sourced locally Receives: Drug: RHZE |
What is being measured
The primary outcome is the main question the study is designed to answer.
The primary endpoint is rate of change in sputum log CFU/mL count (EBA) from Days 0-2.
Measured: Days 0-2
Secondary outcomes (10)
Rate of change in sputum log CFU/mL count (extended EBA).
Measured: Days 2-14
Rate of change in sputum log CFU/mL count (extended EBA).
Measured: Days 0-14
Rate of change in culture time to positivity (TTP) measured by MGIT and in log transformed TTP
Measured: Days 02-; 2-14; 0-14
Cumulative whole blood bactericidal activity (measured as log reduction in CFU) against intracellular M. tuberculosis relative to administered dose and drug PK
Measured: Day 1
Cumulative whole blood bactericidal activity (measured as log reduction in CFU) against intracellular M. tuberculosis relative to administered dose and drug PK
Measured: Day 13-14
Plasma concentrations of PNU-100480 and PNU-101603 will be used to determine PK parameters (AUCtau, AUC tau,ss, Cmax, Tmax, terminal half-life t1/2, Cavg, Rac) as data permit
Measured: Day 1
Plasma concentrations of PNU-100480 and PNU-101603 will be used to determine PK parameters (AUCtau, AUC tau,ss, Cmax, Tmax, terminal half-life t1/2, Cavg, Rac) as data permit
Measured: Day 13-14
Safety assessments including physical exams, AEs, laboratory tests, ECGs, and vital signs.
Measured: Phys exam, AEs, and vitals are done at every visit (Screening through Day 15, Day 42/Follow-up)
Safety assessments including physical exams, AEs, laboratory tests, ECGs, and vital signs.
Measured: ECGs are done at Screening, Day 1, Day 14, 15 and 42/Follow-up
Safety assessments including physical exams, AEs, laboratory tests, ECGs, and vital signs.
Measured: Lab tests at Screening, Day 1, Day 15 and 42/Follow-up
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Oct 2010 (estimated)
- Study startAug 2011
- Primary completionDec 2011
- Study completionDec 2011
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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- 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
- NCT01225640
- Sponsor's protocol ID
- B1171003
- Status last verified
- Dec 2015
- First submitted
- 19 Oct 2010
- Last updated
- 14 Jan 2016
- Results posted
- No
- Data monitoring committee
- No
Publications
Wallis RS, Dawson R, Friedrich SO, Venter A, Paige D, Zhu T, Silvia A, Gobey J, Ellery C, Zhang Y, Eisenach K, Miller P, Diacon AH. Mycobactericidal activity of sutezolid (PNU-100480) in sputum (EBA) and blood (WBA) of patients with pulmonary tuberculosis. PLoS One. 2014 Apr 14;9(4):e94462. doi: 10.1371/journal.pone.0094462. eCollection 2014.
PubMed 24732289
Study at a glance
From the registry record, last updated by the sponsor on 14 Jan 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2a, Open-Label, Randomized Study In Treatment-Naive, Sputum Smear Positive Subjects With Drug-Sensitive Pulmonary Tuberculosis To Assess Early Bactericidal Activity (EBA) And Whole Blood Activity (WBA) Of PNU-100480 (PF-02341272)
- ClinicalTrials.gov ID
- NCT01225640
- Acronym / sponsor ID
- B1171003
- Conditions
- Tuberculosis
- Keywords
- Tuberculosis, EBA, WBA
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 59 participants (actual)
- Lead sponsor
- Sequella, Inc.Industry (pharma, biotech, devices)
- Study start
- Aug 2011
- Primary completion
- Dec 2011 (actual)
- Study completion
- Dec 2011 (actual)
- First posted
- 21 Oct 2010 (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.
PNU-100480 is being developed for the treatment of both drug resistant and sensitive tuberculosis. This is an efficacy and safety study to characterize the effect of PNU-100480 when given for 14 days to treatment-naive patients with drug-sensitive pulmonary tuberculosis.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| PNU-100480 600 mg BID | Experimental | Drug: PNU-100480 |
| PNU-100480 1200 mg QD | Experimental | Drug: PNU-100480 |
| RHZE | Active comparator | Drug: RHZEconjugated tablet with 4 drug combination of RHZE, Rifafour® e275 will be used in countries where can be sourced locally |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Adult males or females between 18 and 65 years; women of childbearing potential must be willing to adhere to lifestyle requirements regarding contraception/pregnancy prevention.
- Newly diagnosed sputum smear-positive pulmonary TB confirmed with acid-fast bacillus (AFB) smear and chest x-ray. Patients with TB more than 5 years ago who completed treatment, are healthy, and meet other inclusion criteria may be included.
- Body weight between 40 and 90 kg, inclusive (in light clothing, no shoes).
- Reasonably normal hemoglobin (>=8 gm/dL), renal function (serum creatinine <2 mg/dL), hepatic function (serum AST <3xULN and total bilirubin <1.3 mg/dL), and random glucose <150 mg/dL.
Key exclusion criteria (7 listed)
- HIV infection with helper/inducer T-lymphocytes (CD4 cell) count of <=350x10-6/L.
- Presence of significant hemoptysis. Subjects who cough up frank blood (more than blood streaked sputum) will not be eligible.
- Pregnant or nursing females; females of childbearing potential unwilling or unable to adhere to contraception guidelines.
- Significant respiratory impairment (respiratory rate >35/minute).
- Clinical suspicion of disseminated TB or tuberculosis meningitis.
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-100480600 mg twice daily (BID) for 14 days | Drug | PNU-100480 600 mg BID |
| PNU-1004801200 mg once daily (QD) for 14 days | Drug | PNU-100480 1200 mg QD |
| RHZEAlso: Rifafour, RimstarCombination tablet (RHZE) dosed by weight. Dosage strength per tablet is 150 mg Rifampicin (R)/75 mg Isoniazid (H)/400 mg Pyrazinamide (Z)/275 mg Ethambutol (E) | Drug | RHZE |
Primary outcome
The primary endpoint is rate of change in sputum log CFU/mL count (EBA) from Days 0-2.
Time frame: Days 0-2
10 secondary outcomes
Rate of change in sputum log CFU/mL count (extended EBA).
Time frame: Days 2-14
Rate of change in sputum log CFU/mL count (extended EBA).
Time frame: Days 0-14
Rate of change in culture time to positivity (TTP) measured by MGIT and in log transformed TTP
Time frame: Days 02-; 2-14; 0-14
Cumulative whole blood bactericidal activity (measured as log reduction in CFU) against intracellular M. tuberculosis relative to administered dose and drug PK
Time frame: Day 1
Cumulative whole blood bactericidal activity (measured as log reduction in CFU) against intracellular M. tuberculosis relative to administered dose and drug PK
Time frame: Day 13-14
Plasma concentrations of PNU-100480 and PNU-101603 will be used to determine PK parameters (AUCtau, AUC tau,ss, Cmax, Tmax, terminal half-life t1/2, Cavg, Rac) as data permit
Time frame: Day 1
Plasma concentrations of PNU-100480 and PNU-101603 will be used to determine PK parameters (AUCtau, AUC tau,ss, Cmax, Tmax, terminal half-life t1/2, Cavg, Rac) as data permit
Time frame: Day 13-14
Safety assessments including physical exams, AEs, laboratory tests, ECGs, and vital signs.
Time frame: Phys exam, AEs, and vitals are done at every visit (Screening through Day 15, Day 42/Follow-up)
Safety assessments including physical exams, AEs, laboratory tests, ECGs, and vital signs.
Time frame: ECGs are done at Screening, Day 1, Day 14, 15 and 42/Follow-up
Safety assessments including physical exams, AEs, laboratory tests, ECGs, and vital signs.
Time frame: Lab tests at Screening, Day 1, Day 15 and 42/Follow-up
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 14 Jan 2016.
- Derived from this study: PubMed 24732289Wallis RS, Dawson R, Friedrich SO, Venter A, Paige D, Zhu T, Silvia A, Gobey J, Ellery C, Zhang Y, Eisenach K, Miller P, Diacon AH. Mycobactericidal activity of sutezolid (PNU-100480) in sputum (EBA) and blood (WBA) of patients with pulmonary tuberculosis. PLoS One. 2014 Apr 14;9(4):e94462. doi: 10.1371/journal.pone.0094462. eCollection 2014.
Related trials for Tuberculosis
RecruitingPhase 4
Short-term Antibiotic Therapy in Mycobacterium Avium Complex Pulmonary Disease
Mycobacterium Avium Complex Pulmonary Disease
RecruitingObservational study
Paradoxical Tuberculosis Reactions in Patients Without HIV Infection
Tuberculosis
Not yet recruitingPhase 2
Re-evaluating the Duration in Children of TB Treatment
Tuberculosis
RecruitingPhase 1/2
A Study of Daily Rifapentine Combined With Isoniazid (1HP) for Tuberculosis Prevention in Children Less Than 13 Years of Age With and Without HIV
Tuberculosis
Active, not recruitingPhase 3
Protecting Households On Exposure to Newly Diagnosed Index Multidrug-Resistant Tuberculosis Patients
Tuberculosis, MDR
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.
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing PNU-100480 and RHZE in people with Tuberculosis, run by Sequella, Inc. at 2 sites in South Africa.
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 4 inclusion and 7 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 14 Jan 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in South Africa. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 is rate of change in sputum log CFU/mL count (EBA) from Days 0-2. (time frame: Days 0-2). 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 NCT01225640, 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 14 Jan 2016.