Safety, Efficacy and Pharmacokinetics of OPC-67683 in Patients With Pulmonary Tuberculosis

NCT00401271 | Completed Phase 2

• 1 other identifier: 242-06-101
• Study Type: interventional
• Target: 54
• Locations: 1 country
• Sites: 3

Brief Summary

The purpose of this trial is to evaluate the safety, efficacy and pharmacokinetics of 100mg, 200mg , 300mg and 400mg once daily of OPC-67683, administered orally for 14 consecutive days, in patients with uncomplicated, smear-positive pulmonary TB. The four OPC-67683 treatment groups will comprise 12 patients each and the one standard therapy (Rifafour e-275) group six patients. Trial 242-06-101 is an exploratory and not a confirmatory trial and as such no hypothesis will be tested statistically. The control group, six patients treated with Rifafour, will serve as an control to confirm the microbiological assessments during the trial.

Conditions

Pulmonary Tuberculosis

Outcome Measures

Primary Outcomes (1)

• TB bacterial load in sputum measured as colony forming units

Secondary Outcomes (3)

• Early Bactericidal Activity (EBA)

• Slope 0-14

• Tme to culture positivity

Interventions

OPC-67683 DRUG

Rifafour e-275 DRUG

Eligibility Criteria

• Age: 18 Years - 64 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Provide written, informed consent prior to all trial-related procedures.
• Male and female patients aged between 18 and 64 years, inclusive.
• Newly diagnosed, previously untreated, uncomplicated, smear positive, pulmonary TB.
• A chest X-ray finding compatible with TB.
• Sputum positive on direct microscopy for acid-fast bacilli (AFB) (at least 1+).
• Able to produce an adequate volume of sputum (10mL or more estimated overnight production).
• Female patients of childbearing potential must demonstrate a negative pregnancy test result. Furthermore they must agree to use a highly effective method of contraception.
• Male patients must agree to use an adequate method of contraception.

You may not qualify if:

• Poor general condition where no delay in treatment can be tolerated or where immediate hospital admission is warranted.
• Rifampicin-resistant bacteria detected in the sputum susceptibility testing at Screening.
• Treatment received with any drug active against M. tuberculosis within the 3 months prior to Screening.
• History of allergy to any nitro-imidazole derivates, rifamycin derivatives, isoniazid derivatives, pyrazinamide or ethambutol.
• Clinical evidence of severe extrathoracic TB (miliary TB, abdominal TB, urogenital TB, osteoarthritic TB, TB meningitis).
• Evidence of pulmonary silicosis, lung fibrosis, or other lung condition considered as severe by the investigator (other than TB).
• Presence of chronic obstructive pulmonary disease or asthma.
• Any clinically relevant concomitant conditions or renal impairment characterized by serum creatinine levels \>= 1.5xULN or hepatic impairment or alcohol abuse characterized by ALT and/or aspartate transferase (AST) levels 3xULN and/or gamma-glutamyl transpeptidase (GGT) levels 3xULN of the laboratory reference range.
• Known or suspected alcohol or drug abuse, that is, abuse sufficient enough to compromise the safety or cooperation of the patient, in the opinion of the investigator, and as evident by a positive urine drug screen.
• Neuropathy, psychosis or epilepsy.
• Clinically relevant changes in the ECG such as atrioventricular (AV) block, prolongation of the QRS complex \>120 milliseconds (in both male and female patients), or QTcB interval \>430 milliseconds in male patients and \>450 milliseconds in female patients. Family history of long QT syndromes and/or Torsade de Pointes.
• History of or current clinically relevant cardiovascular disorder such as hypokalaemia, heart failure, coronary heart disease, hypertension, arrhythmia or symptom strongly suggestive of such a problem (for example, syncope or palpitations), tachyarrhythmia or status after myocardial infarction.
• Known bleeding disorders or family history of bleeding disorders.
• Diabetes treated with insulin.
• Evidence of clinically significant metabolic, gastrointestinal, neurological, psychiatric or endocrine diseases, malignancy, or other abnormalities (other than the indication being studied).

Sponsors & Collaborators

• Otsuka Frankfurt Research Institute GmbH: lead

Study Sites (3)

Tiervlei Trial Center, Karl Bremer Hospital

Bellville, W Cape, 7531, South Africa

Location

University of Cape Town Lung Institute

Mowbray, W Cape, 7700, South Africa

Location

Medical Research Council

Durban, 4000, South Africa

Location

MeSH Terms

Conditions

Tuberculosis, Pulmonary

Interventions

OPC-67683

Condition Hierarchy (Ancestors)

Tuberculosis; Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Respiratory Tract Infections; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Andreas H Diacon, Dr.

  Tiervlei Trial Center

  PRINCIPAL INVESTIGATOR

• Roxana Rustomjee, Dr.

  Medical Research Council

  PRINCIPAL INVESTIGATOR

• Rodney Dawson, Dr.

  University of Cape Town Lung Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: November 17, 2006
• First Posted: November 20, 2006
• Study Start: November 1, 2006
• Study Completion: March 1, 2007
• Last Updated: March 7, 2007

Record last verified: 2007-03

Locations

ZA (3)