Evaluation of Early Bactericidal Activity in Pulmonary Tuberculosis

This study has been completed.
Sponsor:
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
  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 April 17, 2014