Trial Outcomes & Findings for Study Comparing the Safety and Efficacy of Cethromycin to Clarithromycin for the Treatment of Community-Acquired Pneumonia (NCT NCT00336544)

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

522 participants

Primary outcome timeframe

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

Results posted on

2010-02-26

Participant Flow

Subjects were recruited globally from July 2006 through May 2007.

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.

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	261	260
Overall Study COMPLETED	242	238
Overall Study NOT COMPLETED	19	22

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 Lack of Efficacy	8	5
Overall Study Adverse Event	4	9
Overall Study Withdrawal by Subject	4	3
Overall Study Other	3	5

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Cethromycin n=261 Participants 300 mg once per day (QD) for 7 days, administered orally	Clarithromycin n=260 Participants 250 mg twice per day (BID) for 7 days, administered orally	Total n=521 Participants Total of all reporting groups
Age Continuous	47.7 years STANDARD_DEVIATION 16.8 • n=5 Participants	46.8 years STANDARD_DEVIATION 17.6 • n=7 Participants	47.3 years STANDARD_DEVIATION 17.2 • n=5 Participants
Sex: Female, Male Female	123 Participants n=5 Participants	134 Participants n=7 Participants	257 Participants n=5 Participants
Sex: Female, Male Male	138 Participants n=5 Participants	126 Participants n=7 Participants	264 Participants n=5 Participants

PRIMARY outcome

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

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=257 Participants 300 mg once per day (QD) for 7 days, administered orally	Clarithromycin n=253 Participants 250 mg twice per day (BID) for 7 days, administered orally
Clinical Cures in the Intent to Treat Population Indeterminates	23 Participants	20 Participants
Clinical Cures in the Intent to Treat Population Clinical Cures	213 Participants	224 Participants
Clinical Cures in the Intent to Treat Population Clinical Failures	21 Participants	9 Participants

PRIMARY outcome

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

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=224 Participants 300 mg once per day (QD) for 7 days, administered orally	Clarithromycin n=221 Participants 250 mg twice per day (BID) for 7 days, administered orally
Clinical Cures in the Per Protocol Clinically Evaluable Population Clinical Cures	205 Participants	212 Participants
Clinical Cures in the Per Protocol Clinically Evaluable Population Clinical Failures	19 Participants	9 Participants

SECONDARY outcome

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

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=76 Participants 300 mg once per day (QD) for 7 days, administered orally	Clarithromycin n=72 Participants 250 mg twice per day (BID) for 7 days, administered orally
Bacteriologic Cures in the Intent to Treat Population Bacteriologic Cures	62 Participants	62 Participants

SECONDARY outcome

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

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=64 Participants 300 mg once per day (QD) for 7 days, administered orally	Clarithromycin n=63 Participants 250 mg twice per day (BID) for 7 days, administered orally
Bacteriologic Cures in the Per Protocol Clinically Evaluable Population Bacteriologic Cures	56 Participants	60 Participants

Adverse Events

Cethromycin

Serious events: 12 serious events

Other events: 77 other events

Deaths: 0 deaths

Clarithromycin

Serious events: 9 serious events

Other events: 65 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Cethromycin n=260 participants at risk 300 mg once per day (QD) for 7 days, administered orally	Clarithromycin n=257 participants at risk 250 mg twice per day (BID) for 7 days, administered orally
Gastrointestinal disorders Diarrhea	5.0% 13/260 • 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.	4.7% 12/257 • Number of events 12 • 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	2.7% 7/260 • 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.	3.5% 9/257 • 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.
Gastrointestinal disorders Vomiting	2.7% 7/260 • 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.	1.2% 3/257 • Number of events 3 • 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.
Investigations Alanine aminotransferase increased	2.7% 7/260 • 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% 7/257 • 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.
Investigations Aspartate aminotransferase increased	2.3% 6/260 • 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.	1.2% 3/257 • Number of events 3 • 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	11.2% 29/260 • Number of events 29 • 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.	6.2% 16/257 • Number of events 16 • 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	3.1% 8/260 • 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.	5.8% 15/257 • Number of events 16 • 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=260 participants at risk 300 mg once per day (QD) for 7 days, administered orally	Clarithromycin n=257 participants at risk 250 mg twice per day (BID) for 7 days, administered orally
Cardiac disorders Supraventricular tachycardia	0.00% 0/260 • 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.	0.39% 1/257 • 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.
Gastrointestinal disorders Gastric mucosal hypertrophy	0.38% 1/260 • 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% 0/257 • 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 Gastritis	0.38% 1/260 • 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% 0/257 • 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.
Immune system disorders Sarcoidosis	0.38% 1/260 • 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% 0/257 • 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	0.77% 2/260 • 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.	0.78% 2/257 • 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 Appendicitis	0.38% 1/260 • 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% 0/257 • 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 Lung abscess	0.38% 1/260 • 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% 0/257 • 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	0.00% 0/260 • 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.	0.39% 1/257 • 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% 0/260 • 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.	0.78% 2/257 • 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 Otitis media	0.00% 0/260 • 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.	0.39% 1/257 • 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 Pulmonary tuberculosis	0.00% 0/260 • 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.	0.39% 1/257 • 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) Lung neoplasm malignant	0.38% 1/260 • 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.	0.39% 1/257 • 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 stage unspecified	0.38% 1/260 • 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% 0/257 • 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 Asthmatic crisis	0.38% 1/260 • 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% 0/257 • 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 Bronchospasm	0.38% 1/260 • 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% 0/257 • 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 Dyspnea paroxysmal nocturnal	0.38% 1/260 • 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% 0/257 • 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 Hemoptysis	0.38% 1/260 • 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% 0/257 • 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 Pulmonary edema	0.38% 1/260 • 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% 0/257 • 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	0.00% 0/260 • 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.	0.39% 1/257 • 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.
Vascular disorders Hypotension	0.38% 1/260 • 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% 0/257 • 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.