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

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT01225640
First Posted: October 21, 2010
Last Update Posted: January 14, 2016
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
Sequella, Inc.
  Purpose
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.

Condition Intervention Phase
Tuberculosis Drug: PNU-100480 Drug: RHZE Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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)

Resource links provided by NLM:


Further study details as provided by Sequella, Inc.:

Primary Outcome Measures:
  • The primary endpoint is rate of change in sputum log CFU/mL count (EBA) from Days 0-2. [ Time Frame: Days 0-2 ]

Secondary Outcome Measures:
  • 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 ]

Enrollment: 59
Study Start Date: August 2011
Study Completion Date: December 2011
Primary Completion Date: December 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: PNU-100480 600 mg BID Drug: PNU-100480
600 mg twice daily (BID) for 14 days
Experimental: PNU-100480 1200 mg QD Drug: PNU-100480
1200 mg once daily (QD) for 14 days
Active Comparator: RHZE
conjugated tablet with 4 drug combination of RHZE, Rifafour® e275 will be used in countries where can be sourced locally
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

  Eligibility

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Ages Eligible for Study:   18 Years to 65 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01225640


Locations
South Africa
Pfizer Investigational Site
Bellville, Cape Town, South Africa, 7530
Pfizer Investigational Site
Cape Town, South Africa, 7700
Sponsors and Collaborators
Sequella, Inc.
Investigators
Study Director: Lisa Beth Ferstenberg, M.D. Sequella, Inc.
  More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Sequella, Inc.
ClinicalTrials.gov Identifier: NCT01225640     History of Changes
Other Study ID Numbers: B1171003
First Submitted: October 19, 2010
First Posted: October 21, 2010
Last Update Posted: January 14, 2016
Last Verified: December 2015

Keywords provided by Sequella, Inc.:
Tuberculosis
EBA
WBA

Additional relevant MeSH terms:
Tuberculosis
Mycobacterium Infections
Actinomycetales Infections
Gram-Positive Bacterial Infections
Bacterial Infections
Oxazolidinones
Anti-Infective Agents
Protein Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action