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Completed

NCT Number: NCT01225640

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

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.

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Key information

Conditions

Tuberculosis Actinomycetales Infections Bacterial Infections Bacterial Infections and Mycoses Gram-Positive Bacterial Infections Infections Mycobacterium Infections

Age range

18 year–65 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Pfizer Investigational Site, Bellville, Cape Town, South Africa

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

PNU-100480

Drug

600 mg twice daily (BID) for 14 days

RHZE

Drug

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 names: Rifafour, Rimstar

Primary outcomes

  1. The primary endpoint is rate of change in sputum log CFU/mL count (EBA) from Days 0-2.

    Time frame: Days 0-2

Secondary outcomes

  1. Rate of change in sputum log CFU/mL count (extended EBA).

    Time frame: Days 2-14

  2. Rate of change in sputum log CFU/mL count (extended EBA).

    Time frame: Days 0-14

  3. 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

  4. 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

  5. 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

  6. 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

  7. 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

  8. 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)

  9. 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

  10. 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

Sponsors and collaborators

Lead sponsor

Sequella, Inc.

Industry

Registry information

Official study 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)

Important dates

Study start
2011
Primary completion
2011
Study completion
2011
First posted
Oct 21, 2010
Registry last updated
Jan 14, 2016

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

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This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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