A Study Of PNU-100480 In Newly Diagnosed, Treatment Sensitive Patients With Pulmonary Tuberculosis To Assess Early Bactericidal Activity (EBA) And Whole Blood Activity (WBA)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Sequella, Inc.
ClinicalTrials.gov Identifier:
NCT01225640
First received: October 19, 2010
Last updated: September 4, 2013
Last verified: September 2013
  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
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: 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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Rate of change in sputum log CFU/mL count (extended EBA). [ Time Frame: Days 2-14 ] [ Designated as safety issue: No ]
  • Rate of change in sputum log CFU/mL count (extended EBA). [ Time Frame: Days 0-14 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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) ] [ Designated as safety issue: Yes ]
  • 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 ] [ Designated as safety issue: Yes ]
  • 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 ] [ Designated as safety issue: Yes ]

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

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: 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

Additional Information:
No publications provided by Sequella, Inc.

Additional 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
Study First Received: October 19, 2010
Last Updated: September 4, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Sequella, Inc.:
Tuberculosis
EBA
WBA

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
Oxazolidinones
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Protein Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on August 26, 2014