Evaluation of Early Bactericidal Activity in Pulmonary Tuberculosis
This study has been completed.
Sponsor:
Global Alliance for TB Drug Development
Information provided by (Responsible Party):
Global Alliance for TB Drug Development
ClinicalTrials.gov Identifier:
NCT00944021
First received: July 21, 2009
Last updated: September 21, 2012
Last verified: September 2012
- Full Text View
- Tabular View
- No Study Results Posted
- Disclaimer
- How to Read a Study Record
Purpose
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.
| Condition | Intervention | Phase |
|---|---|---|
|
Pulmonary Tuberculosis |
Drug: PA-824 Drug: Rifafour e-275 mg |
Phase 2 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment |
| 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 |
Resource links provided by NLM:
Further study details as provided by Global Alliance for TB Drug Development:
Primary Outcome Measures:
- Extended early bactericidal activity (EBA) measured as the rate of change in log CFUs (Colony forming units) in sputum [ Time Frame: 14 days of consecutive treatment ] [ Designated as safety issue: No ]
Secondary Outcome Measures:
- Standard EBA day 0-2 defined by change of CFU in sputum [ Time Frame: Day 0-2 ] [ Designated as safety issue: No ]
- Change in time to sputum culture positivity (TTP) [ Time Frame: 14 days ] [ Designated as safety issue: No ]
- Pharmacokinetics-Pharmacodynamics [ Time Frame: 14 days ] [ Designated as safety issue: No ]
- Proportion of patients with serious adverse events (SAEs) and proportion of patients who discontinue due to an adverse event (AE) [ Time Frame: 14 days plus 6 month follow-up for SAEs ] [ Designated as safety issue: Yes ]
| Enrollment: | 69 |
| Study Start Date: | July 2009 |
| Study Completion Date: | June 2010 |
| Primary Completion Date: | January 2010 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
| Experimental: PA-824 50 mg/qd |
Drug: PA-824
50mg
|
| Experimental: PA-824 100mg/qd |
Drug: PA-824
100mg
|
| Experimental: PA-824 150mg/qd |
Drug: PA-824
150 mg
|
| Experimental: PA-824 200mg/qd |
Drug: PA-824
200 mg
|
| Active Comparator: Rifafour e-275mg |
Drug: Rifafour e-275 mg
275 mg
|
Eligibility| Ages Eligible for Study: | 18 Years to 64 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
- 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.
Exclusion Criteria:
- 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
- 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).
Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00944021
Sponsors and Collaborators
Global Alliance for TB Drug Development
Investigators
| Principal Investigator: | Andreas Diacon, MD | Karl Bremer Hospital |
| Principal Investigator: | Rodney Dawson, MD | University of Cape Town Lung Institute |
More Information
Additional Information:
No publications provided
| Responsible Party: | Global Alliance for TB Drug Development |
| ClinicalTrials.gov Identifier: | NCT00944021 History of Changes |
| Other Study ID Numbers: | PA-824-CL-010 |
| Study First Received: | July 21, 2009 |
| Last Updated: | September 21, 2012 |
| Health Authority: | United States: Food and Drug Administration South Africa: Medicines Control Council |
Keywords provided by Global Alliance for TB Drug Development:
|
Early Bactericidal Activity EBA Pulmonary Tuberculosis PA-824 |
Additional relevant MeSH terms:
|
Tuberculosis Tuberculosis, Pulmonary Mycobacterium Infections Actinomycetales Infections Gram-Positive Bacterial Infections |
Bacterial Infections Lung Diseases Respiratory Tract Diseases Respiratory Tract Infections |
ClinicalTrials.gov processed this record on May 23, 2013