NCT00944021

Brief Summary

The trial will evaluate the extended bactericidal activity of 14 consecutive days of oral administration of PA-824 at 50, 100, 150 and 200 mg per day in adult patients with newly diagnosed, uncomplicated, smear positive tuberculosis (TB). A control group will receive standard TB treatment.

Trial Health

100
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
69

participants targeted

Target at P50-P75 for phase_2

Timeline
Completed

Started Aug 2009

Shorter than P25 for phase_2

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

July 21, 2009

Completed
1 day until next milestone

First Posted

Study publicly available on registry

July 22, 2009

Completed
10 days until next milestone

Study Start

First participant enrolled

August 1, 2009

Completed
5 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 1, 2010

Completed
4 months until next milestone

Study Completion

Last participant's last visit for all outcomes

May 1, 2010

Completed
5.9 years until next milestone

Results Posted

Study results publicly available

March 9, 2016

Completed
Last Updated

September 20, 2019

Status Verified

September 1, 2019

Enrollment Period

5 months

First QC Date

July 21, 2009

Results QC Date

February 19, 2014

Last Update Submit

September 4, 2019

Conditions

Keywords

Early Bactericidal ActivityEBAPulmonary TuberculosisPA-824pretomanid

Outcome Measures

Primary Outcomes (1)

  • Early Bactericidal Activity (EBA) Measured as the Mean Rate of Reduction of log10 Colony Forming Units (CFU) of M. Tuberculosis Per ml Sputum on Solid Medium Over Time (Days 0-14).

    14 consecutive days of treatment

Secondary Outcomes (10)

  • Early Bactericidal Activity (EBA) Measured as the Mean Rate of Reduction of log10 Colony Forming Units (CFU) of M. Tuberculosis Per ml Sputum on Solid Medium Over Time (Days 0-2).

    Two consecutive days of treatment

  • Early Bactericidal Activity (EBA) Measured as the Mean Rate of Reduction of log10 Colony Forming Units (CFU) of M. Tuberculosis Per ml Sputum on Solid Medium Over Time (Days 2-14).

    Days 2-14 of 14 consecutive days of treatment

  • Rate of Change in Increased Time to Sputum Culture Positivity (TTP)(Hours) in Liquid Culture Media (Days 0-14).

    Fourteen consecutive days of treatment

  • Rate of Change in Increased Time to Sputum Culture Positivity (TTP)(Hours) in Liquid Culture Media (Days 0-2).

    Two consecutive days of treatment

  • Rate of Change in Increased Time to Sputum Culture Positivity (TTP)(Hours) in Liquid Culture Media (Days 2-14).

    Days 2-14 of 14 consecutive days of treatment

  • +5 more secondary outcomes

Study Arms (5)

PA-824 50 mg/qd

EXPERIMENTAL
Drug: PA-824

PA-824 100mg/qd

EXPERIMENTAL
Drug: PA-824

PA-824 150mg/qd

EXPERIMENTAL
Drug: PA-824

PA-824 200mg/qd

EXPERIMENTAL
Drug: PA-824

Rifafour e-275mg

ACTIVE COMPARATOR
Drug: Rifafour e-275 mg

Interventions

PA-824DRUG

50mg

PA-824 50 mg/qd

275 mg

Rifafour e-275mg

Eligibility Criteria

Age18 Years - 64 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64)

You may qualify if:

  • Informed Consent
  • Body weight between 40 and 90 kg, inclusive.
  • Newly diagnosed, previously untreated, uncomplicated, sputum smear-positive, pulmonary TB.
  • A chest X-ray compatible with TB.
  • Sputum positive
  • Adequate volume of sputum
  • Female participants of childbearing potential negative serum pregnancy and agree to use birth control
  • Male participants must agree to use contraception throughout participation in the trial and for 12 weeks after last dose.

You may not qualify if:

  • Poor general condition
  • Rifampicin-resistant and/or Isoniazid-resistant
  • MTB Treatment received within the 3 months prior
  • Allergy to the IMP or related substances
  • Evidence of extrathoracic TB
  • A history of previous TB
  • Evidence of serious lung conditions other than TB or uncontrolled obstructive bronchial disease
  • History of lens opacity or evidence of lens opacity on slit lamp ophthalmologic examination
  • Any evidence of renal impairment
  • For males, any evidence or history of abnormality in the reproductive system
  • History and/or presence (or evidence) of neuropathy or epilepsy.
  • Clinically relevant changes in the ECG
  • A history of or current clinically relevant cardiovascular disorder
  • Concomitant use of any drug known to prolong QTc interval
  • Diabetics using insulin
  • +11 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Related Publications (1)

  • Diacon AH, Dawson R, du Bois J, Narunsky K, Venter A, Donald PR, van Niekerk C, Erondu N, Ginsberg AM, Becker P, Spigelman MK. Phase II dose-ranging trial of the early bactericidal activity of PA-824. Antimicrob Agents Chemother. 2012 Jun;56(6):3027-31. doi: 10.1128/AAC.06125-11. Epub 2012 Mar 19.

MeSH Terms

Conditions

Tuberculosis, Pulmonary

Interventions

pretomanid

Condition Hierarchy (Ancestors)

TuberculosisMycobacterium InfectionsActinomycetales InfectionsGram-Positive Bacterial InfectionsBacterial InfectionsBacterial Infections and MycosesInfectionsRespiratory Tract InfectionsLung DiseasesRespiratory Tract Diseases

Results Point of Contact

Title
Daniel E. Everitt, MD, Vice President and Senior Medical Officer
Organization
Global Alliance for TB Drug Development

Study Officials

  • Andreas Diacon, MD

    Karl Bremer Hospital

    PRINCIPAL INVESTIGATOR
  • Rodney Dawson, MD

    University of Cape Town Lung Institute

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
OTHER
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

July 21, 2009

First Posted

July 22, 2009

Study Start

August 1, 2009

Primary Completion

January 1, 2010

Study Completion

May 1, 2010

Last Updated

September 20, 2019

Results First Posted

March 9, 2016

Record last verified: 2019-09