Pulmonary TuberculosisPhase 2NCT00944021
Evaluation of Early Bactericidal Activity in Pulmonary Tuberculosis (CL-010)
A Phase 2 study testing PA-824 and Rifafour e-275 mg in people with Pulmonary Tuberculosis, run by Global Alliance for TB Drug Development.
Trial summary
The trial will evaluate the extended bactericidal activity of 14 consecutive days of oral administration of PA-824 at 50, 100, 150 and 200 mg per day in adult patients with newly diagnosed, uncomplicated, smear positive tuberculosis (TB). A control group will receive standard TB treatment. Read more about this study
- Who is it for?
- Ages 18 to 64 years
- Conditions the study is for
- Pulmonary Tuberculosis
- What is being tested?
- PA-824 and Rifafour e-275 mg
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 69 participants
- Where
- No sites listed yet
- Study dates
- Aug 2009to May 2010
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 64 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Informed Consent
- Body weight between 40 and 90 kg, inclusive.
- Newly diagnosed, previously untreated, uncomplicated, sputum smear-positive, pulmonary TB.
- A chest X-ray compatible with TB.
- Sputum positive
- Adequate volume of sputum
- Female participants of childbearing potential negative serum pregnancy and agree to use birth control
- Male participants must agree to use contraception throughout participation in the trial and for 12 weeks after last dose.
Who cannot join
- Poor general condition
- Rifampicin-resistant and/or Isoniazid-resistant
- MTB Treatment received within the 3 months prior
- Allergy to the IMP or related substances
- Evidence of extrathoracic TB
- A history of previous TB
Show all 26Show fewer
- Evidence of serious lung conditions other than TB or uncontrolled obstructive bronchial disease
- History of lens opacity or evidence of lens opacity on slit lamp ophthalmologic examination
- Any evidence of renal impairment
- For males, any evidence or history of abnormality in the reproductive system
- History and/or presence (or evidence) of neuropathy or epilepsy.
- Clinically relevant changes in the ECG
- A history of or current clinically relevant cardiovascular disorder
- Concomitant use of any drug known to prolong QTc interval
- Diabetics using insulin
- Evidence of clinically significant metabolic, gastrointestinal, neurological, psychiatric or endocrine diseases, malignancy, or other abnormalities (other than the indication being studied).
- Any diseases or conditions in which the use of the standard TB drugs or any of their components is contra-indicated, including but not limited to allergy to any TB drug, their component or to the IMP.
- Any disease or conditions in which any of the medicinal products listed in the section pertaining to prohibited medication is used.
- alcohol or drug abuse
- Administration of an IMP prior to Visit 1, within 5 half-lives for that IMP if known. If the half-life of the IMP is unknown within 1 month.
- Pregnant, breast-feeding, or planning to conceive or father a child within twelve weeks of cessation of treatment for males and within one week of cessation of treatment for females.
- Use of any drugs or substances within 30 days prior to dosing known to be strong inhibitors or inducers of cytochrome P450 enzymes
- Any therapeutic agents known to alter any major organ function (e.g., barbiturates, opiates, phenothiazines, cimetidine) within 30 days prior to dosing.
- glucocorticoids within one year prior to dosing.
- HIV infection with helper/inducer T lymphocyte (CD4 cell) count of less than or equal to 300x10-6/L.
- Receiving antiretroviral therapy (ART).
About this study
Official title: A Phase II Dose Ranging Trial to Evaluate the Extended Early Bactericidal Activity, Safety, Tolerability, and Pharmacokinetics of PA-824 in Adult Participants With Newly Diagnosed, Uncomplicated, Smear-Positive, Pulmonary Tuberculosis
The trial will evaluate the extended bactericidal activity of 14 consecutive days of oral administration of PA-824 at 50, 100, 150 and 200 mg per day in adult patients with newly diagnosed, uncomplicated, smear positive tuberculosis (TB). A control group will receive standard TB treatment.
Read the detailed description
The planned sample size of 15 participants per treatment group is in keeping with other Phase II trials of this type and accounts for the possibility of up to 3 drop-outs per arm, which based on previous studies of this type conducted at these sites, represents a conservative estimate of the expected drop-out rate.
- Conditions
- Pulmonary Tuberculosis
- Being tested
- PA-824, Rifafour e-275 mg
- Keywords
- Early Bactericidal Activity, EBA, Pulmonary Tuberculosis, PA-824, pretomanid
- Medical subject headings
- Tuberculosis, Pulmonary
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PA-824Drug
50mg
PA-824Drug
100mg
PA-824Drug
150 mg
Rifafour e-275 mgDrug
275 mg
PA-824Drug
200 mg
| Study group | Role | What they receive |
|---|---|---|
| PA-824 50 mg/qd | Experimental | Not described Receives: Drug: PA-824 |
| PA-824 100mg/qd | Experimental | Not described Receives: Drug: PA-824 |
| PA-824 150mg/qd | Experimental | Not described Receives: Drug: PA-824 |
| PA-824 200mg/qd | Experimental | Not described Receives: Drug: PA-824 |
| Rifafour e-275mg | Active comparator | Not described Receives: Drug: Rifafour e-275 mg |
What is being measured
The primary outcome is the main question the study is designed to answer.
Early Bactericidal Activity (EBA) Measured as the Mean Rate of Reduction of log10 Colony Forming Units (CFU) of M. Tuberculosis Per ml Sputum on Solid Medium Over Time (Days 0-14).
Measured: 14 consecutive days of treatment
Secondary outcomes (10)
Early Bactericidal Activity (EBA) Measured as the Mean Rate of Reduction of log10 Colony Forming Units (CFU) of M. Tuberculosis Per ml Sputum on Solid Medium Over Time (Days 0-2).
Measured: Two consecutive days of treatment
Early Bactericidal Activity (EBA) Measured as the Mean Rate of Reduction of log10 Colony Forming Units (CFU) of M. Tuberculosis Per ml Sputum on Solid Medium Over Time (Days 2-14).
Measured: Days 2-14 of 14 consecutive days of treatment
Rate of Change in Increased Time to Sputum Culture Positivity (TTP)(Hours) in Liquid Culture Media (Days 0-14).
Measured: Fourteen consecutive days of treatment
Rate of Change in Increased Time to Sputum Culture Positivity (TTP)(Hours) in Liquid Culture Media (Days 0-2).
Measured: Two consecutive days of treatment
Rate of Change in Increased Time to Sputum Culture Positivity (TTP)(Hours) in Liquid Culture Media (Days 2-14).
Measured: Days 2-14 of 14 consecutive days of treatment
Pharmacokinetics- Maximum Observed Plasma Concentration (Cmax) (Day 1).
Measured: 0 (pre-dose), 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 12, 16, and 24 hours post-dose on Day 1 of treatment
Pharmacokinetics- Area Under the Plasma Concentration Time Curve From Zero to Infinity (AUC 0 to Infinity) (Day 1).
Measured: 0 (pre-dose), 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 12, 16, and 24 hours post-dose on Day 1 of treatment
Pharmacokinetics- Terminal Elimination Phase Half-life (t1/2) (Day 1).
Measured: 0 (pre-dose), 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 12, 16, and 24 hours post-dose on Day 1 of treatment
Pharmacokinetics-Maximum Observed Plasma Concentration (Cmax) (Day 14).
Measured: 0 (pre-dose), 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 12,16, 24, and 30 hours post-dose on Day 14 of 14 consecutive days of treatment
Pharmacokinetics- Terminal Elimination Phase Half-life (t1/2) (Day 14).
Measured: 0 (pre-dose), 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 12, 16, 24 and 30 hours post-dose on Day 14 of 14 consecutive days of treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jul 2009 (estimated)
- Study startAug 2009
- Primary completionJan 2010
- Study completionMay 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Pulmonary 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
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 69 participants (actual)
Sponsor and investigators
- Lead sponsor
- Global Alliance for TB Drug Development
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Andreas Diacon, MD, Principal investigator, Karl Bremer HospitalRodney Dawson, MD, Principal investigator, University of Cape Town Lung Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00944021
- Sponsor's protocol ID
- PA-824-CL-010
- Status last verified
- Sep 2019
- First submitted
- 21 Jul 2009
- Last updated
- 20 Sep 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Diacon AH, Dawson R, du Bois J, Narunsky K, Venter A, Donald PR, van Niekerk C, Erondu N, Ginsberg AM, Becker P, Spigelman MK. Phase II dose-ranging trial of the early bactericidal activity of PA-824. Antimicrob Agents Chemother. 2012 Jun;56(6):3027-31. doi: 10.1128/AAC.06125-11. Epub 2012 Mar 19.
PubMed 22430968
Study at a glance
From the registry record, last updated by the sponsor on 20 Sep 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Dose Ranging Trial to Evaluate the Extended Early Bactericidal Activity, Safety, Tolerability, and Pharmacokinetics of PA-824 in Adult Participants With Newly Diagnosed, Uncomplicated, Smear-Positive, Pulmonary Tuberculosis
- ClinicalTrials.gov ID
- NCT00944021
- Acronym / sponsor ID
- PA-824-CL-010
- Conditions
- Pulmonary Tuberculosis
- Keywords
- Early Bactericidal Activity, EBA, Pulmonary Tuberculosis, PA-824, pretomanid
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 69 participants (actual)
- Lead sponsor
- Global Alliance for TB Drug DevelopmentUniversity, hospital or other
- Study start
- Aug 2009
- Primary completion
- Jan 2010 (actual)
- Study completion
- May 2010 (actual)
- First posted
- 22 Jul 2009 (estimated)
- Results
- Posted 9 Mar 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The trial will evaluate the extended bactericidal activity of 14 consecutive days of oral administration of PA-824 at 50, 100, 150 and 200 mg per day in adult patients with newly diagnosed, uncomplicated, smear positive tuberculosis (TB). A control group will receive standard TB treatment.
Detailed description
The planned sample size of 15 participants per treatment group is in keeping with other Phase II trials of this type and accounts for the possibility of up to 3 drop-outs per arm, which based on previous studies of this type conducted at these sites, represents a conservative estimate of the expected drop-out rate.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| PA-824 50 mg/qd | Experimental | Drug: PA-824 |
| PA-824 100mg/qd | Experimental | Drug: PA-824 |
| PA-824 150mg/qd | Experimental | Drug: PA-824 |
| PA-824 200mg/qd | Experimental | Drug: PA-824 |
| Rifafour e-275mg | Active comparator | Drug: Rifafour e-275 mg |
Who may qualify
- Ages
- 18 to 64 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (8 listed)
- Informed Consent
- Body weight between 40 and 90 kg, inclusive.
- Newly diagnosed, previously untreated, uncomplicated, sputum smear-positive, pulmonary TB.
- A chest X-ray compatible with TB.
- Sputum positive
Key exclusion criteria (26 listed)
- Poor general condition
- Rifampicin-resistant and/or Isoniazid-resistant
- MTB Treatment received within the 3 months prior
- Allergy to the IMP or related substances
- Evidence of extrathoracic TB
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 |
|---|---|---|
| PA-82450mg | Drug | PA-824 50 mg/qd |
| PA-824100mg | Drug | PA-824 100mg/qd |
| PA-824150 mg | Drug | PA-824 150mg/qd |
| Rifafour e-275 mg275 mg | Drug | Rifafour e-275mg |
| PA-824200 mg | Drug | PA-824 200mg/qd |
Primary outcome
Early Bactericidal Activity (EBA) Measured as the Mean Rate of Reduction of log10 Colony Forming Units (CFU) of M. Tuberculosis Per ml Sputum on Solid Medium Over Time (Days 0-14).
Time frame: 14 consecutive days of treatment
10 secondary outcomes
Early Bactericidal Activity (EBA) Measured as the Mean Rate of Reduction of log10 Colony Forming Units (CFU) of M. Tuberculosis Per ml Sputum on Solid Medium Over Time (Days 0-2).
Time frame: Two consecutive days of treatment
Early Bactericidal Activity (EBA) Measured as the Mean Rate of Reduction of log10 Colony Forming Units (CFU) of M. Tuberculosis Per ml Sputum on Solid Medium Over Time (Days 2-14).
Time frame: Days 2-14 of 14 consecutive days of treatment
Rate of Change in Increased Time to Sputum Culture Positivity (TTP)(Hours) in Liquid Culture Media (Days 0-14).
Time frame: Fourteen consecutive days of treatment
Rate of Change in Increased Time to Sputum Culture Positivity (TTP)(Hours) in Liquid Culture Media (Days 0-2).
Time frame: Two consecutive days of treatment
Rate of Change in Increased Time to Sputum Culture Positivity (TTP)(Hours) in Liquid Culture Media (Days 2-14).
Time frame: Days 2-14 of 14 consecutive days of treatment
Pharmacokinetics- Maximum Observed Plasma Concentration (Cmax) (Day 1).
Time frame: 0 (pre-dose), 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 12, 16, and 24 hours post-dose on Day 1 of treatment
Pharmacokinetics- Area Under the Plasma Concentration Time Curve From Zero to Infinity (AUC 0 to Infinity) (Day 1).
Time frame: 0 (pre-dose), 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 12, 16, and 24 hours post-dose on Day 1 of treatment
Pharmacokinetics- Terminal Elimination Phase Half-life (t1/2) (Day 1).
Time frame: 0 (pre-dose), 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 12, 16, and 24 hours post-dose on Day 1 of treatment
Pharmacokinetics-Maximum Observed Plasma Concentration (Cmax) (Day 14).
Time frame: 0 (pre-dose), 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 12,16, 24, and 30 hours post-dose on Day 14 of 14 consecutive days of treatment
Pharmacokinetics- Terminal Elimination Phase Half-life (t1/2) (Day 14).
Time frame: 0 (pre-dose), 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 12, 16, 24 and 30 hours post-dose on Day 14 of 14 consecutive days of treatment
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Sep 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 22430968Diacon AH, Dawson R, du Bois J, Narunsky K, Venter A, Donald PR, van Niekerk C, Erondu N, Ginsberg AM, Becker P, Spigelman MK. Phase II dose-ranging trial of the early bactericidal activity of PA-824. Antimicrob Agents Chemother. 2012 Jun;56(6):3027-31. doi: 10.1128/AAC.06125-11. Epub 2012 Mar 19.
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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.
Andreas Diacon, MD principal investigator
Karl Bremer Hospital
Rodney Dawson, MD principal investigator
University of Cape Town Lung Institute
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing PA-824 and Rifafour e-275 mg in people with Pulmonary Tuberculosis, run by Global Alliance for TB Drug Development.
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 8 inclusion and 26 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 20 Sep 2019. Status can change between updates, so confirm with the study contact before making plans.
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?
Yes. Results are posted in the registry (first posted 9 Mar 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Early Bactericidal Activity (EBA) Measured as the Mean Rate of Reduction of log10 Colony Forming Units (CFU) of M. Tuberculosis Per ml Sputum on Solid Medium Over Time (Days 0-14). (time frame: 14 consecutive days of treatment). 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 NCT00944021, 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 20 Sep 2019.