Trial Outcomes & Findings for Study Comparing the Safety and Efficacy of Cethromycin to Clarithromycin for the Treatment of Community-Acquired Pneumonia (CAP) (NCT NCT00336505)

Last Updated: 2010-02-26

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

584 participants

Primary outcome timeframe

Test of Cure Visit, defined as 14-22 days after the first dose of study drug.

Results posted on

2010-02-26

Participant Flow

Subjects were recruited globally from January 2006 through October 2007.

In each 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 totalled 584 subjects, only 582 were randomized and dosed with blinded study drug.

Participant milestones

Participant milestones
Measure	Cethromycin 300 mg once per day (QD) for 7 days, administered orally	Clarithromycin 250 mg twice per day (BID) for 7 days, administered orally
Overall Study STARTED	291	291
Overall Study COMPLETED	254	264
Overall Study NOT COMPLETED	37	27

Reasons for withdrawal

Reasons for withdrawal
Measure	Cethromycin 300 mg once per day (QD) for 7 days, administered orally	Clarithromycin 250 mg twice per day (BID) for 7 days, administered orally
Overall Study Adverse Event	10	9
Overall Study Lack of Efficacy	8	4
Overall Study Lost to Follow-up	7	4
Overall Study Withdrawal by Subject	5	3
Overall Study Other	7	7

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Cethromycin n=291 Participants 300 mg once per day (QD) for 7 days, administered orally	Clarithromycin n=291 Participants 250 mg twice per day (BID) for 7 days, administered orally	Total n=582 Participants Total of all reporting groups
Age Continuous	48.6 years STANDARD_DEVIATION 14.5 • n=5 Participants	50.3 years STANDARD_DEVIATION 16.3 • n=7 Participants	49.5 years STANDARD_DEVIATION 15.4 • n=5 Participants
Sex: Female, Male Female	140 Participants n=5 Participants	143 Participants n=7 Participants	283 Participants n=5 Participants
Sex: Female, Male Male	151 Participants n=5 Participants	148 Participants n=7 Participants	299 Participants n=5 Participants

PRIMARY outcome

Timeframe: Test of Cure Visit, defined as 14-22 days after the first dose of study drug.

Population: 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.

Outcome measures

Outcome measures
Measure	Cethromycin n=261 Participants 300 mg once per day (QD) for 7 days, administered orally	Clarithromycin n=254 Participants 250 mg twice per day (BID) for 7 days, administered orally
Clinical Cures in the Intent to Treat Population Indeterminates	30 Participants	35 Participants
Clinical Cures in the Intent to Treat Population Clinical Cures	217 Participants	206 Participants
Clinical Cures in the Intent to Treat Population Clinical Failures	14 Participants	13 Participants

PRIMARY outcome

Timeframe: Test of Cure Visit, defined as 14-22 days after the first dose of study drug

Population: 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

Outcome measures

Outcome measures
Measure	Cethromycin n=218 Participants 300 mg once per day (QD) for 7 days, administered orally	Clarithromycin n=208 Participants 250 mg twice per day (BID) for 7 days, administered orally
Clinical Cures in the Per Protocol Clinically Evaluable Population Clinical Failures	13 Participants	13 Participants
Clinical Cures in the Per Protocol Clinically Evaluable Population Clinical Cures	205 Participants	195 Participants

SECONDARY outcome

Timeframe: Test of Cure Visit, defined as 14-22 days after the first dose of study drug.

Population: 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.

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).

Outcome measures

Outcome measures
Measure	Cethromycin n=81 Participants 300 mg once per day (QD) for 7 days, administered orally	Clarithromycin n=85 Participants 250 mg twice per day (BID) for 7 days, administered orally
Bacteriologic Cures in the Intent to Treat Population Bacteriologic Cures	73 Participants	73 Participants

SECONDARY outcome

Timeframe: Test of Cure Visit, defined as 14-22 days after the first dose of study drug.

Population: 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.

Outcome measures

Outcome measures
Measure	Cethromycin n=73 Participants 300 mg once per day (QD) for 7 days, administered orally	Clarithromycin n=69 Participants 250 mg twice per day (BID) for 7 days, administered orally
Bacteriologic Cures in the Per Protocol Clinically Evaluable Population Bacteriologic Cures	71 Participants	67 Participants

Adverse Events

Cethromycin

Serious events: 13 serious events

Other events: 55 other events

Deaths: 0 deaths

Clarithromycin

Serious events: 9 serious events

Other events: 37 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Cethromycin n=288 participants at risk 300 mg once per day (QD) for 7 days, administered orally	Clarithromycin n=291 participants at risk 250 mg twice per day (BID) for 7 days, administered orally
Gastrointestinal disorders Diarrhea	4.5% 13/288 • Number of events 13 • Reported adverse events were recorded for 30 days after the last dose of study drug for individual subjects. The safety population was defined as all randomized and dosed subjects with at least one follow up safety assessment.	4.1% 12/291 • Number of events 13 • Reported adverse events were recorded for 30 days after the last dose of study drug for individual subjects. The safety population was defined as all randomized and dosed subjects with at least one follow up safety assessment.
Gastrointestinal disorders Nausea	4.5% 13/288 • Number of events 14 • Reported adverse events were recorded for 30 days after the last dose of study drug for individual subjects. The safety population was defined as all randomized and dosed subjects with at least one follow up safety assessment.	1.4% 4/291 • Number of events 4 • Reported adverse events were recorded for 30 days after the last dose of study drug for individual subjects. The safety population was defined as all randomized and dosed subjects with at least one follow up safety assessment.
Infections and infestations Urinary tract infection	0.00% 0/288 • Reported adverse events were recorded for 30 days after the last dose of study drug for individual subjects. The safety population was defined as all randomized and dosed subjects with at least one follow up safety assessment.	2.4% 7/291 • Number of events 8 • Reported adverse events were recorded for 30 days after the last dose of study drug for individual subjects. The safety population was defined as all randomized and dosed subjects with at least one follow up safety assessment.
Nervous system disorders Dysgeusia	7.6% 22/288 • Number of events 23 • Reported adverse events were recorded for 30 days after the last dose of study drug for individual subjects. The safety population was defined as all randomized and dosed subjects with at least one follow up safety assessment.	2.1% 6/291 • Number of events 6 • Reported adverse events were recorded for 30 days after the last dose of study drug for individual subjects. The safety population was defined as all randomized and dosed subjects with at least one follow up safety assessment.
Nervous system disorders Headache	2.4% 7/288 • Number of events 7 • Reported adverse events were recorded for 30 days after the last dose of study drug for individual subjects. The safety population was defined as all randomized and dosed subjects with at least one follow up safety assessment.	2.7% 8/291 • Number of events 9 • Reported adverse events were recorded for 30 days after the last dose of study drug for individual subjects. The safety population was defined as all randomized and dosed subjects with at least one follow up safety assessment.

Additional Information

David Eiznhamer, PhD, Executive Vice President, Clinical Development

Advanced Life Sciences

Phone: 630-739-6744

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: OTHER

Measure	Cethromycin n=288 participants at risk 300 mg once per day (QD) for 7 days, administered orally	Clarithromycin n=291 participants at risk 250 mg twice per day (BID) for 7 days, administered orally
Cardiac disorders Acute myocardial infarction	1.4% 4/288 • Number of events 4 • Reported adverse events were recorded for 30 days after the last dose of study drug for individual subjects. The safety population was defined as all randomized and dosed subjects with at least one follow up safety assessment.	0.34% 1/291 • Number of events 2 • Reported adverse events were recorded for 30 days after the last dose of study drug for individual subjects. The safety population was defined as all randomized and dosed subjects with at least one follow up safety assessment.
Cardiac disorders Atrial Fibrillation	0.35% 1/288 • Number of events 1 • Reported adverse events were recorded for 30 days after the last dose of study drug for individual subjects. The safety population was defined as all randomized and dosed subjects with at least one follow up safety assessment.	0.00% 0/291 • Reported adverse events were recorded for 30 days after the last dose of study drug for individual subjects. The safety population was defined as all randomized and dosed subjects with at least one follow up safety assessment.
Cardiac disorders Cardiac failure congestive	0.35% 1/288 • Number of events 1 • Reported adverse events were recorded for 30 days after the last dose of study drug for individual subjects. The safety population was defined as all randomized and dosed subjects with at least one follow up safety assessment.	0.00% 0/291 • Reported adverse events were recorded for 30 days after the last dose of study drug for individual subjects. The safety population was defined as all randomized and dosed subjects with at least one follow up safety assessment.
Cardiac disorders Pericardial effusion	0.35% 1/288 • Number of events 1 • Reported adverse events were recorded for 30 days after the last dose of study drug for individual subjects. The safety population was defined as all randomized and dosed subjects with at least one follow up safety assessment.	0.00% 0/291 • Reported adverse events were recorded for 30 days after the last dose of study drug for individual subjects. The safety population was defined as all randomized and dosed subjects with at least one follow up safety assessment.
Cardiac disorders Angina pectoris	0.00% 0/288 • Reported adverse events were recorded for 30 days after the last dose of study drug for individual subjects. The safety population was defined as all randomized and dosed subjects with at least one follow up safety assessment.	0.34% 1/291 • Number of events 1 • Reported adverse events were recorded for 30 days after the last dose of study drug for individual subjects. The safety population was defined as all randomized and dosed subjects with at least one follow up safety assessment.
Infections and infestations Pneumonia	1.4% 4/288 • Number of events 4 • Reported adverse events were recorded for 30 days after the last dose of study drug for individual subjects. The safety population was defined as all randomized and dosed subjects with at least one follow up safety assessment.	0.69% 2/291 • Number of events 2 • Reported adverse events were recorded for 30 days after the last dose of study drug for individual subjects. The safety population was defined as all randomized and dosed subjects with at least one follow up safety assessment.
Infections and infestations Empyema	0.35% 1/288 • Number of events 1 • Reported adverse events were recorded for 30 days after the last dose of study drug for individual subjects. The safety population was defined as all randomized and dosed subjects with at least one follow up safety assessment.	0.00% 0/291 • Reported adverse events were recorded for 30 days after the last dose of study drug for individual subjects. The safety population was defined as all randomized and dosed subjects with at least one follow up safety assessment.
Infections and infestations Appendicitis	0.00% 0/288 • Reported adverse events were recorded for 30 days after the last dose of study drug for individual subjects. The safety population was defined as all randomized and dosed subjects with at least one follow up safety assessment.	0.34% 1/291 • Number of events 1 • Reported adverse events were recorded for 30 days after the last dose of study drug for individual subjects. The safety population was defined as all randomized and dosed subjects with at least one follow up safety assessment.
Infections and infestations Lobar pneumonia	0.00% 0/288 • Reported adverse events were recorded for 30 days after the last dose of study drug for individual subjects. The safety population was defined as all randomized and dosed subjects with at least one follow up safety assessment.	0.34% 1/291 • Number of events 1 • Reported adverse events were recorded for 30 days after the last dose of study drug for individual subjects. The safety population was defined as all randomized and dosed subjects with at least one follow up safety assessment.
Injury, poisoning and procedural complications Ankle fracture	0.35% 1/288 • Number of events 1 • Reported adverse events were recorded for 30 days after the last dose of study drug for individual subjects. The safety population was defined as all randomized and dosed subjects with at least one follow up safety assessment.	0.00% 0/291 • Reported adverse events were recorded for 30 days after the last dose of study drug for individual subjects. The safety population was defined as all randomized and dosed subjects with at least one follow up safety assessment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung adenocarcinoma	0.35% 1/288 • Number of events 1 • Reported adverse events were recorded for 30 days after the last dose of study drug for individual subjects. The safety population was defined as all randomized and dosed subjects with at least one follow up safety assessment.	0.34% 1/291 • Number of events 1 • Reported adverse events were recorded for 30 days after the last dose of study drug for individual subjects. The safety population was defined as all randomized and dosed subjects with at least one follow up safety assessment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastatic neoplasm	0.35% 1/288 • Number of events 1 • Reported adverse events were recorded for 30 days after the last dose of study drug for individual subjects. The safety population was defined as all randomized and dosed subjects with at least one follow up safety assessment.	0.00% 0/291 • Reported adverse events were recorded for 30 days after the last dose of study drug for individual subjects. The safety population was defined as all randomized and dosed subjects with at least one follow up safety assessment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung squamous cell carcinoma stage unspecified	0.00% 0/288 • Reported adverse events were recorded for 30 days after the last dose of study drug for individual subjects. The safety population was defined as all randomized and dosed subjects with at least one follow up safety assessment.	0.34% 1/291 • Number of events 1 • Reported adverse events were recorded for 30 days after the last dose of study drug for individual subjects. The safety population was defined as all randomized and dosed subjects with at least one follow up safety assessment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Small cell lung cancer extensive stage	0.00% 0/288 • Reported adverse events were recorded for 30 days after the last dose of study drug for individual subjects. The safety population was defined as all randomized and dosed subjects with at least one follow up safety assessment.	0.34% 1/291 • Number of events 1 • Reported adverse events were recorded for 30 days after the last dose of study drug for individual subjects. The safety population was defined as all randomized and dosed subjects with at least one follow up safety assessment.
Renal and urinary disorders Renal failure acute	0.35% 1/288 • Number of events 1 • Reported adverse events were recorded for 30 days after the last dose of study drug for individual subjects. The safety population was defined as all randomized and dosed subjects with at least one follow up safety assessment.	0.00% 0/291 • Reported adverse events were recorded for 30 days after the last dose of study drug for individual subjects. The safety population was defined as all randomized and dosed subjects with at least one follow up safety assessment.
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	0.35% 1/288 • Number of events 1 • Reported adverse events were recorded for 30 days after the last dose of study drug for individual subjects. The safety population was defined as all randomized and dosed subjects with at least one follow up safety assessment.	0.34% 1/291 • Number of events 1 • Reported adverse events were recorded for 30 days after the last dose of study drug for individual subjects. The safety population was defined as all randomized and dosed subjects with at least one follow up safety assessment.
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.35% 1/288 • Number of events 1 • Reported adverse events were recorded for 30 days after the last dose of study drug for individual subjects. The safety population was defined as all randomized and dosed subjects with at least one follow up safety assessment.	0.00% 0/291 • Reported adverse events were recorded for 30 days after the last dose of study drug for individual subjects. The safety population was defined as all randomized and dosed subjects with at least one follow up safety assessment.
Respiratory, thoracic and mediastinal disorders Pneumothorax	0.00% 0/288 • Reported adverse events were recorded for 30 days after the last dose of study drug for individual subjects. The safety population was defined as all randomized and dosed subjects with at least one follow up safety assessment.	0.34% 1/291 • Number of events 1 • Reported adverse events were recorded for 30 days after the last dose of study drug for individual subjects. The safety population was defined as all randomized and dosed subjects with at least one follow up safety assessment.