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Trial record 9 of 172 for:    "Pulmonary Tuberculosis"

Evaluation of Early Bactericidal Activity in Pulmonary Tuberculosis (CL-010)

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ClinicalTrials.gov Identifier: NCT00944021
Recruitment Status : Completed
First Posted : July 22, 2009
Results First Posted : March 9, 2016
Last Update Posted : April 12, 2017
Sponsor:
Information provided by (Responsible Party):
Global Alliance for TB Drug Development

Tracking Information
First Submitted Date  ICMJE July 21, 2009
First Posted Date  ICMJE July 22, 2009
Results First Submitted Date  ICMJE February 19, 2014
Results First Posted Date  ICMJE March 9, 2016
Last Update Posted Date April 12, 2017
Study Start Date  ICMJE August 2009
Actual Primary Completion Date January 2010   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 11, 2016)
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 ]
Original Primary Outcome Measures  ICMJE
 (submitted: July 21, 2009)
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 ]
Change History Complete list of historical versions of study NCT00944021 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: February 11, 2016)
  • 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 ]
Original Secondary Outcome Measures  ICMJE
 (submitted: July 21, 2009)
  • Standard EBA day 0-2 defined by change of CFU in sputum [ Time Frame: Day 0-2 ]
  • Change in time to sputum culture positivity (TTP) [ Time Frame: 14 days ]
  • Pharmacokinetics-Pharmacodynamics [ Time Frame: 14 days ]
  • 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 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Evaluation of Early Bactericidal Activity in Pulmonary Tuberculosis (CL-010)
Official Title  ICMJE 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
Brief 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.
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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Pulmonary Tuberculosis
Intervention  ICMJE
  • Drug: PA-824
    50mg
  • Drug: PA-824
    100mg
  • Drug: PA-824
    150 mg
  • Drug: Rifafour e-275 mg
    275 mg
  • Drug: PA-824
    200 mg
Study Arms  ICMJE
  • Experimental: PA-824 50 mg/qd
    Intervention: Drug: PA-824
  • Experimental: PA-824 100mg/qd
    Intervention: Drug: PA-824
  • Experimental: PA-824 150mg/qd
    Intervention: Drug: PA-824
  • Experimental: PA-824 200mg/qd
    Intervention: Drug: PA-824
  • Active Comparator: Rifafour e-275mg
    Intervention: Drug: Rifafour e-275 mg
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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: September 17, 2010)
69
Original Estimated Enrollment  ICMJE
 (submitted: July 21, 2009)
68
Actual Study Completion Date  ICMJE May 2010
Actual Primary Completion Date January 2010   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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).
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 64 Years   (Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Not Provided
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00944021
Other Study ID Numbers  ICMJE PA-824-CL-010
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Global Alliance for TB Drug Development
Study Sponsor  ICMJE Global Alliance for TB Drug Development
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Andreas Diacon, MD Karl Bremer Hospital
Principal Investigator: Rodney Dawson, MD University of Cape Town Lung Institute
PRS Account Global Alliance for TB Drug Development
Verification Date January 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP