Pulmonary TuberculosisPhase 2NCT02349841
Phase 2 Trial to Evaluate the Early Bactericidal Activity, Safety and Tolerability of Meropenem Plus Amoxycillin/CA and Faropenem Plus Amoxycillin/CA in Adult Patients With Newly Diagnosed Pulmonary Tuberculosis
A Phase 2 study testing Meropenem, Faropenem and Amoxycillin/clavulanic acid in people with Pulmonary Tuberculosis, run by TASK Applied Science at 1 site in South Africa.
Trial summary
To evaluate the early bactericidal activity (EBA), safety, tolerability and pharmacokinetics of meropenem administered intravenously three times a day, plus amoxycillin/CA administered orally three times a day; and of faropenem administered orally three times a day, plus amoxycillin/CA administered orally three times… Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Pulmonary Tuberculosis
- What is being tested?
- Meropenem, Faropenem and Amoxycillin/clavulanic acid
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 46 participants
- Where
- 1 siteSouth Africa
- Study dates
- Sep 2014to Dec 2014
- 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
- Provide written, informed consent prior to all trial-related procedures including HIV testing.
- Male or female, aged between 18 and 65 years, inclusive.
- Body weight (in light clothing and with no shoes) between 40 and 90 kg, inclusive.
- Newly diagnosed, previously untreated, pulmonary TB.
- A chest X-ray picture which in the opinion of the Investigator is consistent with TB.
- Sputum positive GeneXpert or TB smear from TB clinic or site of initial diagnosis.
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- Sputum positive on direct microscopy for acid-fast bacilli on at least one sputum sample at the trial appointed laboratory(at least 1+ on the IUATLD/WHO scale).
- Ability to produce an adequate volume of sputum as estimated from a spot assessment (estimated 10 ml or more overnight production).
- Be of non-childbearing potential or using effective methods of birth control, as defined below:
- Non-childbearing potential:
- Participant - not heterosexually active or practice sexual abstinence; or
- Female participant/sexual partner - bilateral oophorectomy, bilateral tubal ligation and/or hysterectomy or has been postmenopausal with a history of no menses for at least 12 consecutive months; or
- Male participant/sexual partner - vasectomised or has had a bilateral orchidectomy minimally three month prior to screening;
- Effective birth control methods:
- Double barrier method which can include a male condom, diaphragm, cervical cap, or female condom; or
- Barrier method combined with hormone-based contraceptives or an intra-uterine device for the female partner; and are willing to continue practicing birth control methods throughout participation in the study until Visit 19 (day 28). (Note: hormone-based contraception alone may not be reliable when taking IMP; therefore, hormone-based contraceptives alone cannot be used by female participants to prevent pregnancy).
Who cannot join
- Evidence of clinically significant (as judged by the investigator), metabolic, gastrointestinal, cardiovascular, musculoskeletal, ophthalmological, pulmonary, neurological, psychiatric or endocrine diseases, malignancy, or other abnormalities (other than the indication being studied) including malaria.
- Poor general condition where any delay in treatment cannot be tolerated per discretion of the Investigator.
- A history of previous TB less than 5 years ago.
- Clinically significant evidence of extrathoracic TB (miliary TB, abdominal TB, urogenital TB, osteoarthritic TB, TB meningitis), as judged by the Investigator.
- History of allergy to any of the trial IMP/s or related substances i.e. β-lactams and penicillin, as confirmed by the clinical judgement of the Investigator.
- Isoniazid-resistant and/or rifampicin-resistant bacteria detected with a sputum specimen collected within the pre-treatment period and tested at the study laboratory.
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- Known or suspected, current or history of within the past 2 years, alcohol or drug abuse, that is, in the opinion of the Investigator, sufficient to compromise the safety or cooperation of the participant.
- For HIV infected participants:
- having a CD4+ count <350 cells/µL;
- or having received antiretroviral therapy medication within the last 90 days;
- or having received oral or intravenous antifungal medication within the last 90 days;
- or with an AIDS-defining opportunistic infection or malignancies (except pulmonary TB).
- Having participated in other clinical studies with investigational agents within 8 weeks prior to trial start.
- Female participant who is pregnant, breast-feeding, or planning to conceive a child within the anticipated period of participating in the trial. Male participant planning to conceive a child within the anticipated period of participating in the trial.
- Diabetes mellitus requiring insulin.
- Specific Treatments
- Treatment received with any drug active against MTB within the 3 months prior to Visit 1 (including but not limited to isoniazid, ethambutol, amikacin, cycloserine, fluoroquinolones, rifabutin, rifampicin, streptomycin, kanamycin, para-aminosalicylic acid, rifapentine, pyrazinamide, thioacetazone, capreomycin, thioamides, metronidazole).
- Participants receiving sodium valproate, furosemide, imipenem or probenecid.
- 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.
- Laboratory Abnormalities
- Participants with the following toxicities at screening as defined by the enhanced CTCEA toxicity table
- creatinine grade 2 or greater (>1.5 times upper limit of normal [ULN]);
- hemoglobin grade 4 (<6.5 g/dL);
- platelets grade 2 or greater (under 50x109 cells/L);
- serum potassium grade 2 or greater (<3.0 mEq/L);
- aspartate aminotransferase (AST) grade 3 (≥3.0 x ULN) to be excluded;
- alanine aminotransferase (ALT) grade 3 (≥3.0 x ULN) to be excluded;
- APTT grade 3
- INR grade 3
- Total white cell count grade 3
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase 2 Trial to Evaluate the Early Bactericidal Activity, Safety and Tolerability of Meropenem, Administered Intravenously, Plus Amoxycillin/CA and Faropenem, Administered Orally, Plus Amoxycillin/CA in Adult Patients With Newly Diagnosed, Smear-positive Pulmonary Tuberculosis.
To evaluate the early bactericidal activity (EBA), safety, tolerability and pharmacokinetics of meropenem administered intravenously three times a day, plus amoxycillin/CA administered orally three times a day; and of faropenem administered orally three times a day, plus amoxycillin/CA administered orally three times a day; for 14 consecutive days, in adult participants with newly diagnosed, smear positive pulmonary tuberculosis, in order to help establish proof-of-concept for carbapenem antibiotics as antituberculosis agents and to select the appropriate agent and route of administration for later stage clinical development.
Read the detailed description
A single-centre, open-label clinical trial including a total of 45 male or female participants (2 groups of 15 participants receiving an IMP and 1 group of 15 participants receiving Rifafour e-275), aged between 18 and 65 years (inclusive), with newly diagnosed, smear-positive, pulmonary tuberculosis will be enrolled into this trial.
Treatment will be administered for 14 consecutive days in the following dosing schemes:
- Meropenem 2g intravenously 8-hourly; plus amoxycillin/CA 500mg/125mg orally 8- hourly on days 1-14.
- Faropenem 600mg orally 8-hourly; plus amoxycillin/CA 500mg/125mg orally 8-hourly on days 1-14.
- The third arm will receive standard first line TB treatment as per the South African TB guidelines (Rifafour e-275) and is included as a control for the EBA quantitative mycobacteriology and to evaluate whether HRZE gives similar EBA results to that demonstrated in prior studies with this combination. The mycobacteriology laboratory will remain blinded until closure of the EBA results.
Participants will be admitted to the in hospital facility for a period of up to 24 days. During this period they will await their screening results after which they will receive 14 day of IMP. on day 14 intensive PK sampling will be done. They will be discharged on day 15 to the clinic where they will continue on the national TB programme treatment regime. Participants will return to the clinical trial site 14 days after receipt of their last study drug. for a safety evaluation.
- Conditions
- Pulmonary Tuberculosis
- Being tested
- Meropenem, Faropenem, Amoxycillin/clavulanic acid, Rifafour e275
- Medical subject headings
- Tuberculosis, Pulmonary
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MeropenemDrug
To administer 2g daily 8 hourly for 14 days
FaropenemDrug
To adminster 600mg 8 hourly daily for 14 days
Amoxycillin/clavulanic acidDrug
To administer 625mg 8 hourly daily for 14 days together with the faropenem and meropenem
Rifafour e275Drug
To be taken as per the National TB treatment programme for 14 days
| Study group | Role | What they receive |
|---|---|---|
| Meropenem;amoxycillin/clavulanic acid | Experimental | Meropenem 2g will be administered intravenously 8-hourly; plus amoxycillin/CA 500mg/125mg will be administered orally 8-hourly for 14 days Receives: Drug: Meropenem; Drug: Amoxycillin/clavulanic acid |
| Faropenem; amoxycillin/CA | Experimental | Faropenem 600mg will be administered orally 8-hourly; plus amoxycillin/CA 500mg/125mg will be administered orally 8-hourly for 14 days Receives: Drug: Faropenem; Drug: Amoxycillin/clavulanic acid |
| Rifafour e-275 | Active comparator | Rifafour e-275 will be administered orally once daily for 14 days as per South African National TB Treatment Guidelines Receives: Drug: Rifafour e275 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Primary Endpoint (The EBA CFU(0-14) as determined by the rate of change in logCFU per ml sputum)
The EBA CFU(0-14) as determined by the rate of change in logCFU per ml sputum over the period Day 0 to Day 14 which will be described with at most 3 parameters from a linear, bi-linear or non-linear regression of logCFU on time
Measured: 14 days
Secondary outcomes (4)
Efficacy (The EBA CFU(0-2) and EBA CFU(2-14) as determined by the rate of change of logCFU in sputum)
The EBA CFU(0-2) and EBA CFU(2-14) as determined by the rate of change of logCFU in sputum over the period Day 0 to Day 2 and Day 2 to Day 14, which will be described with at most 3 parameters from an appropriate function of logCFU on time.
The EBA TTP(0-2), EBA TTP(0-14), and EBA TTP(2-14) in the Mycobacterial Growth Indicator Tube (BactecTM MGITTM 960) system as determined by the rate of change in TTP in sputum over the periods Day 0 to Day 2, Day 0 to Day 14, and will be described with at most 3 parameters from an appropriate function of TTP on time.
Measured: 14 days
Safety and Tolerability (Incidence of treatment emergent adverse events (TEAEs)
will be presented by severity, IMP relatedness, seriousness, leading to early withdrawal and leading to death
Measured: 28 days
Pharmacokinetics (The maximum observed plasma concentration (Cmax), time to reach Cmax (Tmax), the minimum observed plasma concentration (Cmin)
The maximum observed plasma concentration (Cmax), time to reach Cmax (Tmax), the minimum observed plasma concentration (Cmin) 24 hours following the intake if the first daily dosing on day 14, area under the plasma concentration time (t) curve from zero to 24 hours (AUC(0-24)) will be estimated for the following, on Day 14
Measured: 14 days
Pharmacokinetics - Pharmacodynamics (descriptive analyses, and no inferential tests will be carried out, of EBA CFU(0-14), EBA CFU(0-2), and EBA CFU(2-14) vs. AUC(0-24) • Time over Minimum inhibitory concentrations (TMIC) (for meropenem; faropenem)
The EBA CFU(0-14), EBA CFU(0-2), and EBA CFU(2-14) vs. the following PK variables will be presented for meropenem and faropenem:
- Cmax
- AUC(0-24)
- Time over Minimum inhibitory concentrations (TMIC) (for meropenem; faropenem)
- These data will be presented as descriptive analyses, and no inferential tests will be carried out.
Measured: 14 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Jan 2015 (estimated)
- Study startSep 2014
- Primary completionDec 2014
- Study completionDec 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- 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
- Single group
- Masking
- None (open label)
- Enrolment
- 46 participants (actual)
Sponsor and investigators
- Lead sponsor
- TASK Applied Science
- Sponsor type
- University, hospital or other
- Collaborators
- Eduardo Mondlane University, GlaxoSmithKline, Barcelona Centre for International Health Research, Research Center Borstel
- Responsible party
- Principal investigator, Andreas Henri Diacon, TASK Applied Science
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02349841
- Sponsor's protocol ID
- TASK-001
- Status last verified
- Sep 2018
- First submitted
- 23 Jan 2015
- Last updated
- 13 Sep 2018
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 Sep 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2 Trial to Evaluate the Early Bactericidal Activity, Safety and Tolerability of Meropenem, Administered Intravenously, Plus Amoxycillin/CA and Faropenem, Administered Orally, Plus Amoxycillin/CA in Adult Patients With Newly Diagnosed, Smear-positive Pulmonary Tuberculosis.
- ClinicalTrials.gov ID
- NCT02349841
- Acronym / sponsor ID
- TASK-001
- Conditions
- Pulmonary Tuberculosis
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 46 participants (actual)
- Lead sponsor
- TASK Applied ScienceUniversity, hospital or other
- Collaborators
- Eduardo Mondlane University, GlaxoSmithKline, Barcelona Centre for International Health Research, Research Center Borstel
- Study start
- Sep 2014
- Primary completion
- Dec 2014 (actual)
- Study completion
- Dec 2014 (actual)
- First posted
- 29 Jan 2015 (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.
To evaluate the early bactericidal activity (EBA), safety, tolerability and pharmacokinetics of meropenem administered intravenously three times a day, plus amoxycillin/CA administered orally three times a day; and of faropenem administered orally three times a day, plus amoxycillin/CA administered orally three times a day; for 14 consecutive days, in adult participants with newly diagnosed, smear positive pulmonary tuberculosis, in order to help establish proof-of-concept for carbapenem antibiotics as antituberculosis agents and to select the appropriate agent and route of administration for later stage clinical development.
Detailed description
A single-centre, open-label clinical trial including a total of 45 male or female participants (2 groups of 15 participants receiving an IMP and 1 group of 15 participants receiving Rifafour e-275), aged between 18 and 65 years (inclusive), with newly diagnosed, smear-positive, pulmonary tuberculosis will be enrolled into this trial.
Treatment will be administered for 14 consecutive days in the following dosing schemes:
- Meropenem 2g intravenously 8-hourly; plus amoxycillin/CA 500mg/125mg orally 8- hourly on days 1-14.
- Faropenem 600mg orally 8-hourly; plus amoxycillin/CA 500mg/125mg orally 8-hourly on days 1-14.
- The third arm will receive standard first line TB treatment as per the South African TB guidelines (Rifafour e-275) and is included as a control for the EBA quantitative mycobacteriology and to evaluate whether HRZE gives similar EBA results to that demonstrated in prior studies with this combination. The mycobacteriology laboratory will remain blinded until closure of the EBA results.
Participants will be admitted to the in hospital facility for a period of up to 24 days. During this period they will await their screening results after which they will receive 14 day of IMP. on day 14 intensive PK sampling will be done. They will be discharged on day 15 to the clinic where they will continue on the national TB programme treatment regime. Participants will return to the clinical trial site 14 days after receipt of their last study drug. for a safety evaluation.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Meropenem;amoxycillin/clavulanic acid | Experimental | Drug: Meropenem, Drug: Amoxycillin/clavulanic acidMeropenem 2g will be administered intravenously 8-hourly; plus amoxycillin/CA 500mg/125mg will be administered orally 8-hourly for 14 days |
| Faropenem; amoxycillin/CA | Experimental | Drug: Faropenem, Drug: Amoxycillin/clavulanic acidFaropenem 600mg will be administered orally 8-hourly; plus amoxycillin/CA 500mg/125mg will be administered orally 8-hourly for 14 days |
| Rifafour e-275 | Active comparator | Drug: Rifafour e275Rifafour e-275 will be administered orally once daily for 14 days as per South African National TB Treatment Guidelines |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- Provide written, informed consent prior to all trial-related procedures including HIV testing.
- Male or female, aged between 18 and 65 years, inclusive.
- Body weight (in light clothing and with no shoes) between 40 and 90 kg, inclusive.
- Newly diagnosed, previously untreated, pulmonary TB.
- A chest X-ray picture which in the opinion of the Investigator is consistent with TB.
Key exclusion criteria (30 listed)
- Evidence of clinically significant (as judged by the investigator), metabolic, gastrointestinal, cardiovascular, musculoskeletal, ophthalmological, pulmonary, neurological, psychiatric or endocrine diseases, malignancy, or other abnormalities (other than the indication being studied) including malaria.
- Poor general condition where any delay in treatment cannot be tolerated per discretion of the Investigator.
- A history of previous TB less than 5 years ago.
- Clinically significant evidence of extrathoracic TB (miliary TB, abdominal TB, urogenital TB, osteoarthritic TB, TB meningitis), as judged by the Investigator.
- History of allergy to any of the trial IMP/s or related substances i.e. β-lactams and penicillin, as confirmed by the clinical judgement of the Investigator.
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 |
|---|---|---|
| MeropenemTo administer 2g daily 8 hourly for 14 days | Drug | Meropenem;amoxycillin/clavulanic acid |
| FaropenemTo adminster 600mg 8 hourly daily for 14 days | Drug | Faropenem; amoxycillin/CA |
| Amoxycillin/clavulanic acidTo administer 625mg 8 hourly daily for 14 days together with the faropenem and meropenem | Drug | Faropenem; amoxycillin/CA, Meropenem;amoxycillin/clavulanic acid |
| Rifafour e275To be taken as per the National TB treatment programme for 14 days | Drug | Rifafour e-275 |
Primary outcome
Primary Endpoint (The EBA CFU(0-14) as determined by the rate of change in logCFU per ml sputum)
Time frame: 14 days
The EBA CFU(0-14) as determined by the rate of change in logCFU per ml sputum over the period Day 0 to Day 14 which will be described with at most 3 parameters from a linear, bi-linear or non-linear regression of logCFU on time
4 secondary outcomes
Efficacy (The EBA CFU(0-2) and EBA CFU(2-14) as determined by the rate of change of logCFU in sputum)
Time frame: 14 days
Safety and Tolerability (Incidence of treatment emergent adverse events (TEAEs)
Time frame: 28 days
Pharmacokinetics (The maximum observed plasma concentration (Cmax), time to reach Cmax (Tmax), the minimum observed plasma concentration (Cmin)
Time frame: 14 days
Pharmacokinetics - Pharmacodynamics (descriptive analyses, and no inferential tests will be carried out, of EBA CFU(0-14), EBA CFU(0-2), and EBA CFU(2-14) vs. AUC(0-24) • Time over Minimum inhibitory concentrations (TMIC) (for meropenem; faropenem)
Time frame: 14 days
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 13 Sep 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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Meropenem, Faropenem and Amoxycillin/clavulanic acid in people with Pulmonary Tuberculosis, run by TASK Applied Science at 1 site 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 16 inclusion and 30 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 13 Sep 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 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?
Primary Endpoint (The EBA CFU(0-14) as determined by the rate of change in logCFU per ml sputum) (time frame: 14 days). 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 13 Sep 2018.