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:
Pfizer
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT01225640
First received: October 19, 2010
Last updated: March 19, 2013
Last verified: March 2013
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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 Pfizer:
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
Pfizer
Investigators
| Study Director: | Pfizer CT.gov Call Center | Pfizer |
More Information
Additional Information:
No publications provided
| Responsible Party: | Pfizer |
| ClinicalTrials.gov Identifier: | NCT01225640 History of Changes |
| Other Study ID Numbers: | B1171003 |
| Study First Received: | October 19, 2010 |
| Last Updated: | March 19, 2013 |
| Health Authority: | United States: Food and Drug Administration |
Keywords provided by Pfizer:
|
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 May 22, 2013