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
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

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 April 15, 2014