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Study Comparing the Safety and Efficacy of Cethromycin to Clarithromycin for the Treatment of Community-Acquired Pneumonia

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ClinicalTrials.gov Identifier: NCT00336544
Recruitment Status : Completed
First Posted : June 13, 2006
Results First Posted : February 26, 2010
Last Update Posted : February 26, 2010
Sponsor:
Information provided by:
Advanced Life Sciences, Inc.

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Pneumonia
Interventions Drug: Cethromycin
Drug: Clarithromycin
Enrollment 522
Recruitment Details Subjects were recruited globally from July 2006 through May 2007.
Pre-assignment Details In the clarithromycin treatment arm, one subject was enrolled and randomized to a blinded treatment but discontinued from study prior to administration of the first dose of drug. Thus, while official enrollment totaled 522 subjects, only 521 were randomized and dosed with blinded study drug.
Arm/Group Title Cethromycin Clarithromycin
Hide Arm/Group Description 300 mg once per day (QD) for 7 days, administered orally 250 mg twice per day (BID) for 7 days, administered orally
Period Title: Overall Study
Started 261 [1] 260 [1]
Completed 242 [2] 238 [2]
Not Completed 19 22
Reason Not Completed
Lack of Efficacy             8             5
Adverse Event             4             9
Withdrawal by Subject             4             3
Other             3             5
[1]
All subjects who were randomized and dosed.
[2]
Number of subjects completing the test of cure (TOC) visit.
Arm/Group Title Cethromycin Clarithromycin Total
Hide Arm/Group Description 300 mg once per day (QD) for 7 days, administered orally 250 mg twice per day (BID) for 7 days, administered orally Total of all reporting groups
Overall Number of Baseline Participants 261 260 521
Hide Baseline Analysis Population Description
[Not Specified]
Age Continuous   [1] 
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 261 participants 260 participants 521 participants
47.7  (16.8) 46.8  (17.6) 47.3  (17.2)
[1]
Measure Description: All subjects who were randomized and dosed.
Sex: Female, Male   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 261 participants 260 participants 521 participants
Female
123
  47.1%
134
  51.5%
257
  49.3%
Male
138
  52.9%
126
  48.5%
264
  50.7%
[1]
Measure Description: All subjects who were randomized and dosed.
1.Primary Outcome
Title Clinical Cures in the Intent to Treat Population
Hide Description Investigators evaluated subjects for a clinical response of cure, failure, or indeterminate. Cure: Improvement or return to preinfection state or lack of progression of all pulmonary infiltrates, and resolution of all signs/symptoms present at enrollment. Failure: Persistence or worsening of signs/symptoms, the need for additional antibiotic, new pulmonary infection, progression of the chest radiograph, or death due to pneumonia. Indeterminate: Evaluation was not possible (lost to follow up, adverse event, major protocol violation). Indeterminates default to failure for analysis.
Time Frame Test of Cure Visit, defined as 14-22 days after the first dose of study
Hide Outcome Measure Data
Hide Analysis Population Description
The Intent to Treat Population is defined as all subjects with a confirmed diagnosis of community acquired pneumonia who took at least one dose of study medication. Subjects without a radiologist-confirmed chest X-ray for pneumonia were not included in the efficacy populations.
Arm/Group Title Cethromycin Clarithromycin
Hide Arm/Group Description:
300 mg once per day (QD) for 7 days, administered orally
250 mg twice per day (BID) for 7 days, administered orally
Overall Number of Participants Analyzed 257 253
Measure Type: Number
Unit of Measure: Participants
Clinical Cures 213 224
Clinical Failures 21 9
Indeterminates 23 20
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cethromycin, Clarithromycin
Comments The rate of clinical cure in each treatment group was calculated (number of cures/number of patient eligible for analysis). Non-inferiority will be demonstrated when the lower limit of the two-sided 95% confidence interval for the difference in the clinical cure rate at the Test-of-Cure visit between treatment groups (Cethromycin –Clarithromycin) is greater than delta, and includes zero, for both Per-Protocol (PP) and Intent-to-Treat (ITT) analyses.
Type of Statistical Test Non-Inferiority or Equivalence
Comments Delta will be determined by the highest clinical cure-rate between the Cethromycin treatment group and the Clarithromycin treatment group, as follows: Greater than or equal to 90%, delta = -10%; Greater than or equal to 80% and less than 90%, delta = -15%, Greater than or equal to 70% and less than 80%, -20%)
Statistical Test of Hypothesis P-Value 0.0769
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -5.7
Confidence Interval 95%
-11.9 to 0.6
Estimation Comments [Not Specified]
2.Primary Outcome
Title Clinical Cures in the Per Protocol Clinically Evaluable Population
Hide Description Investigators evaluated subjects for a clinical response of cure, failure, or indeterminate. Cure: Improvement or return to preinfection state or lack of progression of all pulmonary infiltrates, and resolution of all signs/symptoms present at enrollment. Failure: Persistence or worsening of signs/symptoms, the need for additional antibiotic, new pulmonary infection, progression of the chest radiograph, or death due to pneumonia. Indeterminate: Evaluation was not possible (lost to follow up, adverse event, major protocol violation). Indeterminates default to failure for analysis.
Time Frame Test of Cure Visit, defined as 14-22 days after the first dose of study
Hide Outcome Measure Data
Hide Analysis Population Description
The Per Protocol Clinically Evaluable Population included all ITT subjects who took the protocol-defined minimum therapy duration, were dosed with no other antimicrobials (unless allowed by protocol), and had no other major protocol violations
Arm/Group Title Cethromycin Clarithromycin
Hide Arm/Group Description:
300 mg once per day (QD) for 7 days, administered orally
250 mg twice per day (BID) for 7 days, administered orally
Overall Number of Participants Analyzed 224 221
Measure Type: Number
Unit of Measure: Participants
Clinical Cures 205 212
Clinical Failures 19 9
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cethromycin, Clarithromycin
Comments The rate of clinical cure in each treatment group was calculated (number of cures/number of patient eligible for analysis). Non-inferiority will be demonstrated when the lower limit of the two-sided 95% confidence interval for the difference in the clinical cure rate at the Test-of-Cure visit between treatment groups (Cethromycin –Clarithromycin) is greater than delta, and includes zero, for both Per-Protocol (PP) and Intent-to-Treat (ITT) analyses.
Type of Statistical Test Non-Inferiority or Equivalence
Comments Delta will be determined by the highest clinical cure-rate between the Cethromycin treatment group and the Clarithromycin treatment group, as follows: Greater than or equal to 90%, delta = -10%; Greater than or equal to 80% and less than 90%, delta = -15%, Greater than or equal to 70% and less than 80%, -20%)
Statistical Test of Hypothesis P-Value 0.0775
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -4.4
Confidence Interval 95%
-9.1 to 0.3
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Bacteriologic Cures in the Intent to Treat Population
Hide Description All bacteriologically evaluable subjects (ie., the subject had at least one, protocol-defined evaluable pathogen) who demonstrated eradication of all evaluable pathogens (S. pneumoniae, S. aureus, H. influenzae, M. catarrhalis, M. pneumoniae, C. pneumoniae, L. pneumophila).
Time Frame Test of Cure Visit, defined as 14-22 days after the first dose of study
Hide Outcome Measure Data
Hide Analysis Population Description
Includes all Intent to Treat subjects that were bacteriologically evaluable (ie., subjects with at least 1 evaluable pathogen) who showed eradication of all evaluable pathogens.
Arm/Group Title Cethromycin Clarithromycin
Hide Arm/Group Description:
300 mg once per day (QD) for 7 days, administered orally
250 mg twice per day (BID) for 7 days, administered orally
Overall Number of Participants Analyzed 76 72
Measure Type: Number
Unit of Measure: Participants
Bacteriologic Cures 62 62
4.Secondary Outcome
Title Bacteriologic Cures in the Per Protocol Clinically Evaluable Population
Hide Description All bacteriologically evaluable subjects (ie., the subject had at least one, protocol-defined evaluable pathogen) who demonstrated eradication of all evaluable pathogens (S. pneumoniae, S. aureus, H. influenzae, M. catarrhalis, M. pneumoniae, C. pneumoniae, L. pneumophila).
Time Frame Test of Cure Visit, defined as 14-22 days after the first dose of study
Hide Outcome Measure Data
Hide Analysis Population Description
Includes all Per Protocol Clinically Evaluable subjects that were bacteriologically evaluable (ie., subjects with at least 1 evaluable pathogen) who showed eradication of all evaluable pathogens.
Arm/Group Title Cethromycin Clarithromycin
Hide Arm/Group Description:
300 mg once per day (QD) for 7 days, administered orally
250 mg twice per day (BID) for 7 days, administered orally
Overall Number of Participants Analyzed 64 63
Measure Type: Number
Unit of Measure: Participants
Bacteriologic Cures 56 60
Time Frame Reported adverse events were recorded for 30 days after the last dose of study drug for individual subjects.
Adverse Event Reporting Description The safety population was defined as all randomized and dosed subjects with at least one follow up safety assessment.
 
Arm/Group Title Cethromycin Clarithromycin
Hide Arm/Group Description 300 mg once per day (QD) for 7 days, administered orally 250 mg twice per day (BID) for 7 days, administered orally
All-Cause Mortality
Cethromycin Clarithromycin
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Cethromycin Clarithromycin
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   12/260 (4.62%)      9/257 (3.50%)    
Cardiac disorders     
Supraventricular tachycardia * 1  0/260 (0.00%)  0 1/257 (0.39%)  1
Gastrointestinal disorders     
Gastric mucosal hypertrophy * 2  1/260 (0.38%)  1 0/257 (0.00%)  0
Gastritis * 2  1/260 (0.38%)  1 0/257 (0.00%)  0
Immune system disorders     
Sarcoidosis * 2  1/260 (0.38%)  1 0/257 (0.00%)  0
Infections and infestations     
Pneumonia  2  2/260 (0.77%)  2 2/257 (0.78%)  2
Appendicitis * 2  1/260 (0.38%)  1 0/257 (0.00%)  0
Lung abscess * 2  1/260 (0.38%)  1 0/257 (0.00%)  0
Empyema  2  0/260 (0.00%)  0 1/257 (0.39%)  1
Lobar pneumonia  2  0/260 (0.00%)  0 2/257 (0.78%)  2
Otitis media * 2  0/260 (0.00%)  0 1/257 (0.39%)  1
Pulmonary tuberculosis * 2  0/260 (0.00%)  0 1/257 (0.39%)  1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Lung neoplasm malignant * 2  1/260 (0.38%)  1 1/257 (0.39%)  1
Small cell lung cancer stage unspecified * 2  1/260 (0.38%)  1 0/257 (0.00%)  0
Respiratory, thoracic and mediastinal disorders     
Asthmatic crisis * 2  1/260 (0.38%)  1 0/257 (0.00%)  0
Bronchospasm * 2  1/260 (0.38%)  1 0/257 (0.00%)  0
Dyspnea paroxysmal nocturnal * 2  1/260 (0.38%)  1 0/257 (0.00%)  0
Hemoptysis * 2  1/260 (0.38%)  1 0/257 (0.00%)  0
Pulmonary edema * 2  1/260 (0.38%)  1 0/257 (0.00%)  0
Chronic obstructive pulmonary disease * 2  0/260 (0.00%)  0 1/257 (0.39%)  1
Vascular disorders     
Hypotension * 2  1/260 (0.38%)  1 0/257 (0.00%)  0
Indicates events were collected by systematic assessment
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA 8.0
2
Term from vocabulary, MedDRA (8.0)
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 2%
Cethromycin Clarithromycin
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   77/260 (29.62%)      65/257 (25.29%)    
Gastrointestinal disorders     
Diarrhea * 1  13/260 (5.00%)  13 12/257 (4.67%)  12
Nausea * 1  7/260 (2.69%)  7 9/257 (3.50%)  9
Vomiting * 1  7/260 (2.69%)  7 3/257 (1.17%)  3
Investigations     
Alanine aminotransferase increased  1  7/260 (2.69%)  7 7/257 (2.72%)  7
Aspartate aminotransferase increased  1  6/260 (2.31%)  6 3/257 (1.17%)  3
Nervous system disorders     
Dysgeusia * 1  29/260 (11.15%)  29 16/257 (6.23%)  16
Headache * 1  8/260 (3.08%)  8 15/257 (5.84%)  16
Indicates events were collected by systematic assessment
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA (8.0)
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
 
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: David Eiznhamer, PhD, Executive Vice President, Clinical Development
Organization: Advanced Life Sciences
Phone: 630-739-6744
EMail: deiznhamer@advancedlifesciences.com
Layout table for additonal information
Responsible Party: David Eiznhamer, PhD, Executive Vice President, Clinical Development, Advanced Life Sciences
ClinicalTrials.gov Identifier: NCT00336544     History of Changes
Other Study ID Numbers: CL06-001
First Submitted: June 9, 2006
First Posted: June 13, 2006
Results First Submitted: September 3, 2009
Results First Posted: February 26, 2010
Last Update Posted: February 26, 2010