Pharyngitis, Tonsillitis
Conditions
Keywords
Ocular safety, azithromycin, pharyngitis, tonsillitis
Brief summary
This Post-Authorization Safety Study (PASS) is intended to fulfill a regulatory post-marketing requirement to provide data regarding visual abilities in children taking azithromycin (immediate-release formulation) for acute pharyngitis/tonsillitis. The primary objective of the study is to examine the incidence of clinically significant worsening in any of the following ophthalmic exams: best corrected visual acuity (distance), color vision, Amsler grid testing, anterior segment biomicroscopy, and fundus examination, in a group of approximately 30 pediatric patients taking azithromycin oral solution for treatment of an authorized indication of use (pharyngitis/ tonsillitis).
Detailed description
Study was terminated prematurely on October 16, 2015 following FDA decision to release Sponsor from post-marketing commitment. No safety and/or efficacy concerns identified.
Interventions
DRUGAzithromycin
Azithromycin oral suspension (immediate release) 12 mg/kg/day x 5 days
Sponsors
Pfizer
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
12 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
* Male or female patient, aged 12 to 17 years. * Requires outpatient treatment for acute pharyngitis/tonsillitis infection. * Appropriate to treat with oral azithromycin as an alternative to intramuscular penicillin, in the opinion of the investigator. * Positive rapid antigen detection test.
Exclusion criteria
* History of clinically significant eye disorder that would interfere with protocol test procedures. * Hypersensitivity to azithromycin, erythromycin, any macrolide, or ketolide antibiotic. * Increased risk of QT prolongation. * Pregnant or breastfeeding.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Occurrence of a Clinically Significant Worsening Based on Five Ophthalmic Examinations | 14 days | Clinically significant worsening is an observed worsening in any of the five ophthalmic exams: 1) Clinically significant worsening in best corrected visual activity (BCVA) (distance) at the final visit, in either eye, is defined as a decrease in score of 5 or more letters from baseline in Early Treatment Diabetic Retinopathy Study (ETDRS) BCVA. 2) An assessment of abnormal clinically significant at final visit in color vision Farnsworth Munsell 100 Hue Test (FM-100) in either eye. 3) An assessment of abnormal clinically significant at final visit in Amsler Grid in either eye. 4) Assessments of abnormal clinically significant at final visit in anterior segment biomicroscopy, in any of the 10 eye structures in either eye. 5) Assessments of abnormal clinically significant at final visit in dilated indirect ophthalmoscopy in any of the 5 eye structures in either eye. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Occurrence of a Clinically Significant Improvement Based on Five Ophthalmic Examinations | 14 days | 1 or more of these conditions are clinically significant improvement based on five ophthalmic exams:1) clinically significant improvement in BCVA(distance) at the final visit, in either eye, defined as an increase in score of 5 or more letters from baseline in ETDRS BCVA.2) Assessment of abnormal clinically significant at baseline and normal or abnormal, non-clinically significant at final visit in color vision(FM-100) in either eye. 3) Assessment of abnormal clinically significant at baseline and normal/abnormal, non-clinically significant at final visit in Amsler Grid in either eye. 4) Assessments of abnormal clinically significant at baseline and normal/abnormal, non-clinically significant at final visit in anterior segment biomicroscopy, in any of the 10 eye structures in either eye. 5)Assessments of abnormal clinically significant at baseline and normal/abnormal, nonclinically significant at final visit in dilated ophthalmoscopy in any of the 5 eye structures in either eye. |
| Occurrence of a Clinically Significant Change (Improvement or Worsening) Based on Five Ophthalmic Examinations | 14 days | Clinically significant change (improvement or worsening) is based on five ophthalmic exams at baseline and the final visit. Any 1 or more of these conditions are a clinically significant change: 1) A worsening in BCVA (distance), as defined in outcome measure 1 OR an improvement in BCVA (distance) as defined in outcome measure 2. 2) A worsening in color vision (FM-100), as defined in outcome measure 1 OR an improvement in color vision (FM-100) as defined in outcome measure 2. 3) A worsening in Amsler Grid, as defined in outcome measure 1, OR an improvement in Amsler Grid, as defined in outcome measure 2. 4) A worsening in anterior segment biomicroscopy, as defined in outcome measure 1 OR an improvement in anterior segment biomicroscopy as defined in outcome measure 2. 5) A worsening in dilated indirect ophthalmoscopy, as defined in outcome measure 1 OR an improvement in dilated indirect ophthalmoscopy as defined in outcome measure 2. |
Countries
United States
Participant flow
Recruitment details
The sample size of 30 completed participants was specified by Food and Drug Administration (FDA) in the Post Marketing Commitment (PMC). Of the 30 pediatric participants planned for the study, 11 were screened and 8 participants received study treatment.
Pre-assignment details
This was a prospective, non-comparative, open-label, single-arm study of azithromycin oral solution in 30 pediatric participants (aged 12 to 17 years) with pharyngitis/ tonsillitis who could be treated with azithromycin for their infection. The study design was intended to align with request from FDA to conduct the study.
Participants by arm
| Arm | Count |
|---|---|
| Azithromycin All participants had received open-label azithromycin oral suspension immediate release (12 mg/kg/day, up to a maximum daily dose of 500 mg) on Days 1, 2, 3, 4, and 5. | 8 |
| Total | 8 |
Baseline characteristics
| Characteristic | Azithromycin |
|---|---|
| Age, Continuous | 14.4 Years STANDARD_DEVIATION 2.1 |
| Sex: Female, Male Female | 6 Participants |
| Sex: Female, Male Male | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 8 |
| serious Total, serious adverse events | 0 / 8 |
Outcome results
Primary
Occurrence of a Clinically Significant Worsening Based on Five Ophthalmic Examinations
Clinically significant worsening is an observed worsening in any of the five ophthalmic exams: 1) Clinically significant worsening in best corrected visual activity (BCVA) (distance) at the final visit, in either eye, is defined as a decrease in score of 5 or more letters from baseline in Early Treatment Diabetic Retinopathy Study (ETDRS) BCVA. 2) An assessment of abnormal clinically significant at final visit in color vision Farnsworth Munsell 100 Hue Test (FM-100) in either eye. 3) An assessment of abnormal clinically significant at final visit in Amsler Grid in either eye. 4) Assessments of abnormal clinically significant at final visit in anterior segment biomicroscopy, in any of the 10 eye structures in either eye. 5) Assessments of abnormal clinically significant at final visit in dilated indirect ophthalmoscopy in any of the 5 eye structures in either eye.
Time frame: 14 days
Population: The safety population included all enrolled participants that took at least one dose of study medication. One participant was not evaluable because visual acuity was not corrected at Baseline (Day 1) and was corrected at Final Visit (Day 14).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Azithromycin | Occurrence of a Clinically Significant Worsening Based on Five Ophthalmic Examinations | Clinically significant worsening - Yes | 0.0 percentage of participants |
| Azithromycin | Occurrence of a Clinically Significant Worsening Based on Five Ophthalmic Examinations | Clinically significant worsening - No | 87.5 percentage of participants |
| Azithromycin | Occurrence of a Clinically Significant Worsening Based on Five Ophthalmic Examinations | Not Evaluable | 12.5 percentage of participants |
Secondary
Occurrence of a Clinically Significant Change (Improvement or Worsening) Based on Five Ophthalmic Examinations
Clinically significant change (improvement or worsening) is based on five ophthalmic exams at baseline and the final visit. Any 1 or more of these conditions are a clinically significant change: 1) A worsening in BCVA (distance), as defined in outcome measure 1 OR an improvement in BCVA (distance) as defined in outcome measure 2. 2) A worsening in color vision (FM-100), as defined in outcome measure 1 OR an improvement in color vision (FM-100) as defined in outcome measure 2. 3) A worsening in Amsler Grid, as defined in outcome measure 1, OR an improvement in Amsler Grid, as defined in outcome measure 2. 4) A worsening in anterior segment biomicroscopy, as defined in outcome measure 1 OR an improvement in anterior segment biomicroscopy as defined in outcome measure 2. 5) A worsening in dilated indirect ophthalmoscopy, as defined in outcome measure 1 OR an improvement in dilated indirect ophthalmoscopy as defined in outcome measure 2.
Time frame: 14 days
Population: The safety population included all enrolled participants that took at least one dose of study medication. One participant was not evaluable because visual acuity was not corrected at Baseline (Day 1) and was corrected at Final Visit (Day 14).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Azithromycin | Occurrence of a Clinically Significant Change (Improvement or Worsening) Based on Five Ophthalmic Examinations | Significant Change (Improvement or Worsening) -Yes | 12.5 percentage of participants |
| Azithromycin | Occurrence of a Clinically Significant Change (Improvement or Worsening) Based on Five Ophthalmic Examinations | Significant Change (Improvement or Worsening) - No | 75.0 percentage of participants |
| Azithromycin | Occurrence of a Clinically Significant Change (Improvement or Worsening) Based on Five Ophthalmic Examinations | Not Evaluable | 12.5 percentage of participants |
Secondary
Occurrence of a Clinically Significant Improvement Based on Five Ophthalmic Examinations
1 or more of these conditions are clinically significant improvement based on five ophthalmic exams:1) clinically significant improvement in BCVA(distance) at the final visit, in either eye, defined as an increase in score of 5 or more letters from baseline in ETDRS BCVA.2) Assessment of abnormal clinically significant at baseline and normal or abnormal, non-clinically significant at final visit in color vision(FM-100) in either eye. 3) Assessment of abnormal clinically significant at baseline and normal/abnormal, non-clinically significant at final visit in Amsler Grid in either eye. 4) Assessments of abnormal clinically significant at baseline and normal/abnormal, non-clinically significant at final visit in anterior segment biomicroscopy, in any of the 10 eye structures in either eye. 5)Assessments of abnormal clinically significant at baseline and normal/abnormal, nonclinically significant at final visit in dilated ophthalmoscopy in any of the 5 eye structures in either eye.
Time frame: 14 days
Population: The safety population included all enrolled participants that took at least one dose of study medication. One participant was not evaluable because visual acuity was not corrected at Baseline (Day 1) and was corrected at Final Visit (Day 14).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Azithromycin | Occurrence of a Clinically Significant Improvement Based on Five Ophthalmic Examinations | Clinically Significant Improvement - No | 75.0 percentage of participants |
| Azithromycin | Occurrence of a Clinically Significant Improvement Based on Five Ophthalmic Examinations | Not Evaluable | 12.5 percentage of participants |
| Azithromycin | Occurrence of a Clinically Significant Improvement Based on Five Ophthalmic Examinations | Clinically Significant Improvement - Yes | 12.5 percentage of participants |