TELICAST : Telithromycin in Acute Exacerbations of Asthma

• Status: Completed
• Trial end date: 2004-05-01
• Target enrollment: 0
• Participant gender: All

Summary

Primary Objective:

• The primary objective is to evaluate the clinical efficacy of telithromycin versus placebo as a supplement to the usual standard of care during an acute exacerbation of asthma. Efficacy will be assessed by:

• Changes in the diary card summary symptom score assessed daily for 6 weeks, and

• Changes in the domiciliary morning Peak Expiratory Flow Rate (PEFR) following oral telithromycin treatment

Secondary Objectives:

The secondary objectives of the study are:

• To evaluate the microbial activity of telithromycin during an exacerbation of asthma by:

• Assessment of the patient's clinical improvement relative to initial C. pneumoniae or M. pneumoniae status, and

• Analysis of the quantitative changes from baseline in C. pneumonia or M. pneumoniae by culture and quantitative Polymerase Chain Reaction (PCR).

• To evaluate the safety of 10 days of oral telithromycin as a supplement to the standard of care for patients with acute exacerbations of asthma

• To assess additional efficacy endpoints and health outcome evaluations following 10 days of treatment with either oral telithromycin or placebo, with either treatment used as a supplement to the standard of care for patients with acute exacerbations of asthma:

• Changes and daily variability in the PEFR during the 6 weeks of study treatment,

• Health status at follow-up (6 weeks)

• Pulmonary function tests:

• Forced Expiratory Volume in 1 second (FEV1)

• Forced Vital Capacity (FVC)

• Forced Expiratory Flow Rate (FEF25-75%)

• Need for additional medications (e.g., inhaled corticosteroids, oral corticosteroids, bronchodilator use),

• Time to next acute exacerbation of asthma.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Sanofi
• Treatments: Telithromycin

Criteria

Inclusion criteria

Patients meeting all of the following criteria will be considered for enrollment in the study:

• A documented history of asthma for >6 months

• Presenting within 24 hours of initial medical care in an urgent care clinic, emergency room, or in-patient hospital setting. To qualify for enrollment they must present with the following signs and symptoms of an acute deterioration in asthma control: (reduced PEFR, increased wheeze, and dyspnea, with or without cough).

• A PEFR less than 80% of predicted normal

• Females who meet the following conditions:

• postmenopausal for at least 1 year, or

• surgically incapable of bearing children, or

• of childbearing potential, and all of the following conditions are met:

• had a normal menstrual flow within 1 month before study entry and

• has a negative pregnancy test (serum b-subunit human chorionic gonadotropin [hCG]) immediately before study entry and

• must agree to abstinence or use of an accepted method of contraception

Exclusion criteria

Patients presenting with any of the following will not be included in the study:

• Requiring immediate placement in an Intensive Care Unit

• Obvious known allergic precipitant for this episode of acute severe asthma (e.g., acute exposure to animal dander)

• Pneumonia

• Known long QT syndrome or familial history of long QT syndrome (if no previous electrocardiogram [ECG] has invalidated this risk factor), or personal history of coronary disease, ventricular arrhythmia, bradycardia <50 beats/min, or known uncorrected hypokalemia or magnesemia

• Known impaired hepatic or renal function

• Known diagnosis of myasthenia gravis

• Active or quiescent tuberculosis infections of the respiratory tract

• Acute exacerbation of chronic bronchitis, chronic obstructive pulmonary disease, cystic fibrosis, or emphysema

• A history of smoking of 10 pack-years or more

• Women who are breast feeding or are pregnant, as demonstrated by serum or urine pregnancy tests

• Suspected or known hypersensitivity to, or suspected serious adverse reaction to the macrolide class of antibiotics

• A concomitant condition (including clinically relevant cardiovascular, hepatic, neurologic, endocrine, or other major systemic disease) that would make implementation of the protocol or interpretation of the study results difficult

• A recent (within the previous 3 months) history of alcohol or recreational drug misuse.

• Immunocompromised patients, including but not limited to:

• patients with known human immunodeficiency virus (HIV) infection and have either had or have an AIDS defining condition (e.g., Kaposi's sarcoma, Pneumocystis carinii pneumonia) or a CD4 + T lymphocyte count of <200/mL

• patients with neutropenia (<1500 neutrophils/mm3)

• patients with metastatic or hematological malignancy

• splenectomized patients or patients with known hyposplenia or asplenia

• Planned surgical treatment at any time during the course of the study that would be incompatible with the objectives of this study

• Other disease conditions or infections that could interfere with the evaluation of study treatment efficacy or safety

• Oral steroid-dependent asthma

• Antibiotic use within 30 days prior to enrollment

• Treated within 2 weeks prior to inclusion with CYP3A4 inducers such as rifampicin, phenytoin, carbamazepine, and St. John's Wart

• Currently receiving medication known to prolong QT interval such as cisapride, pimozide, astemizole and terfenadine, or potent CYP3A4 inhibitors such as antiproteases or ketoconazole.

• Patients in whom an antibiotic is clearly indicated.

• Have received treatment with any other investigational drug within 1 month prior to study entry, or have such treatment planned for the study period during treatment and follow-up phase