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PNU-100480 In Newly Diagnosed, Drug Sensitive Patients With Pulmonary TB; Early Bactericidal Activity; Whole Blood Assay

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ClinicalTrials.gov Identifier: NCT01225640
Recruitment Status : Completed
First Posted : October 21, 2010
Last Update Posted : January 14, 2016
Sponsor:
Information provided by (Responsible Party):
Sequella, Inc.

Tracking Information
First Submitted Date  ICMJE October 19, 2010
First Posted Date  ICMJE October 21, 2010
Last Update Posted Date January 14, 2016
Study Start Date  ICMJE August 2011
Actual Primary Completion Date December 2011   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 21, 2011)
The primary endpoint is rate of change in sputum log CFU/mL count (EBA) from Days 0-2. [ Time Frame: Days 0-2 ]
Original Primary Outcome Measures  ICMJE
 (submitted: October 19, 2010)
The primary endpoint is rate of change in sputum log CFU/mL count (EBA) from Days 0-1. [ Time Frame: Days 0-2 ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 7, 2011)
  • Rate of change in sputum log CFU/mL count (extended EBA). [ Time Frame: Days 2-14 ]
  • Rate of change in sputum log CFU/mL count (extended EBA). [ Time Frame: Days 0-14 ]
  • Rate of change in culture time to positivity (TTP) measured by MGIT and in log transformed TTP [ Time Frame: Days 02-; 2-14; 0-14 ]
  • Cumulative whole blood bactericidal activity (measured as log reduction in CFU) against intracellular M. tuberculosis relative to administered dose and drug PK [ Time Frame: Day 1 ]
  • Cumulative whole blood bactericidal activity (measured as log reduction in CFU) against intracellular M. tuberculosis relative to administered dose and drug PK [ Time Frame: Day 13-14 ]
  • Plasma concentrations of PNU-100480 and PNU-101603 will be used to determine PK parameters (AUCtau, AUC tau,ss, Cmax, Tmax, terminal half-life t1/2, Cavg, Rac) as data permit [ Time Frame: Day 1 ]
  • Plasma concentrations of PNU-100480 and PNU-101603 will be used to determine PK parameters (AUCtau, AUC tau,ss, Cmax, Tmax, terminal half-life t1/2, Cavg, Rac) as data permit [ Time Frame: Day 13-14 ]
  • Safety assessments including physical exams, AEs, laboratory tests, ECGs, and vital signs. [ Time Frame: Phys exam, AEs, and vitals are done at every visit (Screening through Day 15, Day 42/Follow-up) ]
  • Safety assessments including physical exams, AEs, laboratory tests, ECGs, and vital signs. [ Time Frame: ECGs are done at Screening, Day 1, Day 14, 15 and 42/Follow-up ]
  • Safety assessments including physical exams, AEs, laboratory tests, ECGs, and vital signs. [ Time Frame: Lab tests at Screening, Day 1, Day 15 and 42/Follow-up ]
Original Secondary Outcome Measures  ICMJE
 (submitted: October 19, 2010)
  • Rate of change in sputum log CFU/mL count (extended EBA). [ Time Frame: Days 2-14 ]
  • Rate of change in sputum log CFU/mL count (extended EBA). [ Time Frame: Days 0-14 ]
  • Culture time to positivity (TTP) measured by MGIT [ Time Frame: Screening, Baseline, Days 1-15 ]
  • Culture time to positivity (TTP) measured by MGIT [ Time Frame: Day 42/Follow-up ]
  • Cumulative whole blood bactericidal activity (measured as log reduction in CFU) against intracellular M. tuberculosis relative to administered dose and drug PK [ Time Frame: Day 1 ]
  • Cumulative whole blood bactericidal activity (measured as log reduction in CFU) against intracellular M. tuberculosis relative to administered dose and drug PK [ Time Frame: Day 13-14 ]
  • Plasma concentrations of PNU-100480 and PNU-101603 will be used to determine PK parameters (AUCtau, AUC tau,ss, Cmax, Tmax, terminal half-life t1/2, Cavg, Rac) as data permit [ Time Frame: Day 1 ]
  • Plasma concentrations of PNU-100480 and PNU-101603 will be used to determine PK parameters (AUCtau, AUC tau,ss, Cmax, Tmax, terminal half-life t1/2, Cavg, Rac) as data permit [ Time Frame: Day 13-14 ]
  • Safety assessments including physical exams, AEs, laboratory tests, ECGs, and vital signs. [ Time Frame: Phys exam, AEs, and vitals are done at every visit (Screening through Day 15, Day 42/Follow-up) ]
  • Safety assessments including physical exams, AEs, laboratory tests, ECGs, and vital signs. [ Time Frame: ECGs are done at Screening, Day 1, Day 14, 15 and 42/Follow-up ]
  • Safety assessments including physical exams, AEs, laboratory tests, ECGs, and vital signs. [ Time Frame: lab tests at Screening, Day 1, Day 15 and 42/Follow-up ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE PNU-100480 In Newly Diagnosed, Drug Sensitive Patients With Pulmonary TB; Early Bactericidal Activity; Whole Blood Assay
Official Title  ICMJE A Phase 2a, Open-Label, Randomized Study In Treatment-Naive, Sputum Smear Positive Subjects With Drug-Sensitive Pulmonary Tuberculosis To Assess Early Bactericidal Activity (EBA) And Whole Blood Activity (WBA) Of PNU-100480 (PF-02341272)
Brief Summary PNU-100480 is being developed for the treatment of both drug resistant and sensitive tuberculosis. This is an efficacy and safety study to characterize the effect of PNU-100480 when given for 14 days to treatment-naive patients with drug-sensitive pulmonary tuberculosis.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Tuberculosis
Intervention  ICMJE
  • Drug: PNU-100480
    600 mg twice daily (BID) for 14 days
  • Drug: PNU-100480
    1200 mg once daily (QD) for 14 days
  • Drug: RHZE
    Combination tablet (RHZE) dosed by weight. Dosage strength per tablet is 150 mg Rifampicin (R)/75 mg Isoniazid (H)/400 mg Pyrazinamide (Z)/275 mg Ethambutol (E)
    Other Name: Rifafour, Rimstar
Study Arms  ICMJE
  • Experimental: PNU-100480 600 mg BID
    Intervention: Drug: PNU-100480
  • Experimental: PNU-100480 1200 mg QD
    Intervention: Drug: PNU-100480
  • Active Comparator: RHZE
    conjugated tablet with 4 drug combination of RHZE, Rifafour® e275 will be used in countries where can be sourced locally
    Intervention: Drug: RHZE
Publications * Wallis RS, Dawson R, Friedrich SO, Venter A, Paige D, Zhu T, Silvia A, Gobey J, Ellery C, Zhang Y, Eisenach K, Miller P, Diacon AH. Mycobactericidal activity of sutezolid (PNU-100480) in sputum (EBA) and blood (WBA) of patients with pulmonary tuberculosis. PLoS One. 2014 Apr 14;9(4):e94462. doi: 10.1371/journal.pone.0094462. eCollection 2014.

*   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: April 29, 2012)
59
Original Estimated Enrollment  ICMJE
 (submitted: October 19, 2010)
68
Actual Study Completion Date  ICMJE December 2011
Actual Primary Completion Date December 2011   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Adult males or females between 18 and 65 years; women of childbearing potential must be willing to adhere to lifestyle requirements regarding contraception/pregnancy prevention.
  • Newly diagnosed sputum smear-positive pulmonary TB confirmed with acid-fast bacillus (AFB) smear and chest x-ray. Patients with TB more than 5 years ago who completed treatment, are healthy, and meet other inclusion criteria may be included.
  • Body weight between 40 and 90 kg, inclusive (in light clothing, no shoes).
  • Reasonably normal hemoglobin (>=8 gm/dL), renal function (serum creatinine <2 mg/dL), hepatic function (serum AST <3xULN and total bilirubin <1.3 mg/dL), and random glucose <150 mg/dL.

Exclusion Criteria:

  • HIV infection with helper/inducer T-lymphocytes (CD4 cell) count of <=350x10-6/L.
  • Presence of significant hemoptysis. Subjects who cough up frank blood (more than blood streaked sputum) will not be eligible.
  • Pregnant or nursing females; females of childbearing potential unwilling or unable to adhere to contraception guidelines.
  • Significant respiratory impairment (respiratory rate >35/minute).
  • Clinical suspicion of disseminated TB or tuberculosis meningitis.
  • Subjects with diabetes mellitus on insulin and/or who have poorly controlled disease.
  • Subjects with confirmed or suspected multi-drug resistant TB.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE South Africa
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01225640
Other Study ID Numbers  ICMJE B1171003
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Sequella, Inc.
Study Sponsor  ICMJE Sequella, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Lisa Beth Ferstenberg, M.D. Sequella, Inc.
PRS Account Sequella, Inc.
Verification Date December 2015

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