Acne Vulgaris
Conditions
Brief summary
The primary objective is to evaluate the clinical efficacy of azithromycin microspheres treatment in outpatients with moderate to severe inflammatory acne compared with first line treatment minocycline after 8 weeks of therapy
Detailed description
The study prematurely discontinued on the February 1, 2008 due to slow enrollment.It should be noted that safety concerns have not been seen in this study and have not factored into this decision.
Interventions
DRUGAzithromycin microspheres
Azithromycin microspheres, powder for oral suspension, 2 g a week, in unique administration PO, repeated weekly for 8 weeks and minocycline-placebo capsules daily for 8 weeks plus minocycline placebo
DRUGminocycline-placebo capsules
minocycline-placebo capsules daily for 8 weeks plus minocycline placebo
DRUGAzithromycin microspheres-placebo
Minocycline capsules, PO, 100 mg daily for 8 weeks and Azithromycin microspheres-placebo once a week for 8 weeks plus azithromycin placebo.
DRUGMinocycline capsules,
Capsules, PO, 100 mg daily for 8 weeks.
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE
Eligibility
Sex/Gender
ALL
Age
16 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* male and female, \> 16 years of age, with diagnosis of acne papulo-pustular, moderate (19-30 GAGS score) to severe (31-33 GAGS score)
Exclusion criteria
* pregnancy, gastrointestinal and endocrinological disease, specific systemic disease, hormonal contraceptives, isotretinoin, topic drugs for acne (except detergent allowed)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to End of Treatment in Global Acne Grading System (GAGS) Score | Baseline, Week 8 End of Treatment (EOT) | GAGS used to assess 6 locations on face/chest/upper back; factor for each location based on surface area, distribution, density of pilosebaceous units. Locations graded separately 0 - 4 (hi). Global score factored based on summing of local scores. Change: (Global) score at observation minus (global) score at baseline. |
| Change From Baseline to End of Treatment (EOT) in Global Acne Grading System (GAGS) Score - Per Protocol Population | Baseline, Week 8 EOT | GAGS used to assess 6 locations on face/chest/upper back; factor for each location based on surface area, distribution, density of pilosebaceous units. Locations graded separately 0 - 4 (hi). Global score factored based on summing of local scores. Change: (Global) score at observation minus (global) score at baseline. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Global Acne Grading System (GAGS) Score | Baseline, Week 4, Week 8 End of Treatment (EOT), 8 weeks after EOT | GAGS used to assess 6 locations on face/chest/upper back; factor for each location based on surface area, distribution, density of pilosebaceous units. Locations graded separately 0 - 4 (hi. Global score factored based on summing of local scores. Change: mean at observation minus baseline. |
| Improvement of Global Acne Grading System (GAGS) Score | Week 4, Week 8 End of Treatment (EOT), 8 weeks after EOT | Number of subjects by improvement category of GAGS score: Best improvement = reduction of GAGS score \>75% (pre-post evaluation); Good improvement = reduction score \> 50 - 75%; Moderate improvement : reduction score \> 25 - 50%; Light improvement : reduction score \> 0 - 25%; No change = reduction score = 0%; Worsening = increase score \> 0 %. |
| Change From Baseline in Acne Graded by Leeds Technique | Baseline, Week 4, Week 8 End of Treatment (EOT), 8 weeks after EOT | Leeds Grading technique: evaluates three sites (face, back, chest) on a 0 to 10 grading scale where 0 equals to no acne and 10 equals to most severe acne. |
Countries
Italy
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Azithromycin 2 grams per week administered orally (PO) for 8 weeks (azithromycin microspheres, powder for oral suspension) | 58 |
| Minocycline 100 milligrams (mg) administered PO (oral) QD (every day) for 8 weeks (minocycline capsules) | 60 |
| Total | 118 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 5 | 4 |
| Overall Study | Lost to Follow-up | 1 | 4 |
| Overall Study | Protocol Violation | 0 | 3 |
| Overall Study | Withdrawal by Subject | 3 | 2 |
Baseline characteristics
| Characteristic | Azithromycin | Minocycline | Total |
|---|---|---|---|
| Age, Customized <18 years | 10 participants | 17 participants | 27 participants |
| Age, Customized Between 18 and 44 years | 48 participants | 43 participants | 91 participants |
| Sex: Female, Male Female | 35 Participants | 36 Participants | 71 Participants |
| Sex: Female, Male Male | 23 Participants | 24 Participants | 47 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 29 / — | 21 / — |
| serious Total, serious adverse events | 0 / 58 | 0 / 60 |
Outcome results
Primary
Change From Baseline to End of Treatment (EOT) in Global Acne Grading System (GAGS) Score - Per Protocol Population
GAGS used to assess 6 locations on face/chest/upper back; factor for each location based on surface area, distribution, density of pilosebaceous units. Locations graded separately 0 - 4 (hi). Global score factored based on summing of local scores. Change: (Global) score at observation minus (global) score at baseline.
Time frame: Baseline, Week 8 EOT
Population: Per Protocol population
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Azithromycin | Change From Baseline to End of Treatment (EOT) in Global Acne Grading System (GAGS) Score - Per Protocol Population | -9.35 score on scale |
| Minocycline | Change From Baseline to End of Treatment (EOT) in Global Acne Grading System (GAGS) Score - Per Protocol Population | -10.22 score on scale |
95% CI: [-2.58, 0.84]
Primary
Change From Baseline to End of Treatment in Global Acne Grading System (GAGS) Score
GAGS used to assess 6 locations on face/chest/upper back; factor for each location based on surface area, distribution, density of pilosebaceous units. Locations graded separately 0 - 4 (hi). Global score factored based on summing of local scores. Change: (Global) score at observation minus (global) score at baseline.
Time frame: Baseline, Week 8 End of Treatment (EOT)
Population: Full Analysis Set, Last Observation Carried Forward (LOCF)
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Azithromycin | Change From Baseline to End of Treatment in Global Acne Grading System (GAGS) Score | -8.69 score on scale |
| Minocycline | Change From Baseline to End of Treatment in Global Acne Grading System (GAGS) Score | -9.16 score on scale |
95% CI: [-2.48, 1.54]
Secondary
Change From Baseline in Acne Graded by Leeds Technique
Leeds Grading technique: evaluates three sites (face, back, chest) on a 0 to 10 grading scale where 0 equals to no acne and 10 equals to most severe acne.
Time frame: Baseline, Week 4, Week 8 End of Treatment (EOT), 8 weeks after EOT
Population: Full Analysis Set. Where noted: LOCF = Last Observation Carried Forward technique was used. Number of subjects with analyzable data: n=azithromycin, minocycline (respectively).
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Azithromycin | Change From Baseline in Acne Graded by Leeds Technique | Face Week 8 EOT (LOCF) (n=53,59) | -2.5 score on scale |
| Azithromycin | Change From Baseline in Acne Graded by Leeds Technique | Chest Week 4 (n=50,56) | -0.8 score on scale |
| Azithromycin | Change From Baseline in Acne Graded by Leeds Technique | Face Week 8 EOT (n=52, 56) | -2.5 score on scale |
| Azithromycin | Change From Baseline in Acne Graded by Leeds Technique | Chest Week 8 EOT (n=52,56) | -1.5 score on scale |
| Azithromycin | Change From Baseline in Acne Graded by Leeds Technique | Back Week 8 EOT (LOCF) (n=53,59) | -1.5 score on scale |
| Azithromycin | Change From Baseline in Acne Graded by Leeds Technique | Chest Week 8 EOT (LOCF) (n=53,59) | -1.5 score on scale |
| Azithromycin | Change From Baseline in Acne Graded by Leeds Technique | Chest 8 weeks after EOT (n=49,49) | -1.5 score on scale |
| Azithromycin | Change From Baseline in Acne Graded by Leeds Technique | Face 8 weeks after EOT (n=49,49) | -3.0 score on scale |
| Azithromycin | Change From Baseline in Acne Graded by Leeds Technique | Back Week 4 (n=50,56) | -1.1 score on scale |
| Azithromycin | Change From Baseline in Acne Graded by Leeds Technique | Back 8 weeks after EOT (n=49,49) | -1.5 score on scale |
| Azithromycin | Change From Baseline in Acne Graded by Leeds Technique | Back Week 8 EOT (n=52,56) | -1.5 score on scale |
| Azithromycin | Change From Baseline in Acne Graded by Leeds Technique | Face Week 4 (n=50, 56) | -1.5 score on scale |
| Minocycline | Change From Baseline in Acne Graded by Leeds Technique | Chest Week 8 EOT (LOCF) (n=53,59) | -1.1 score on scale |
| Minocycline | Change From Baseline in Acne Graded by Leeds Technique | Face Week 4 (n=50, 56) | -1.3 score on scale |
| Minocycline | Change From Baseline in Acne Graded by Leeds Technique | Face Week 8 EOT (n=52, 56) | -2.4 score on scale |
| Minocycline | Change From Baseline in Acne Graded by Leeds Technique | Face Week 8 EOT (LOCF) (n=53,59) | -2.3 score on scale |
| Minocycline | Change From Baseline in Acne Graded by Leeds Technique | Face 8 weeks after EOT (n=49,49) | -2.9 score on scale |
| Minocycline | Change From Baseline in Acne Graded by Leeds Technique | Back Week 8 EOT (n=52,56) | -1.4 score on scale |
| Minocycline | Change From Baseline in Acne Graded by Leeds Technique | Back Week 8 EOT (LOCF) (n=53,59) | -1.4 score on scale |
| Minocycline | Change From Baseline in Acne Graded by Leeds Technique | Back 8 weeks after EOT (n=49,49) | -2.0 score on scale |
| Minocycline | Change From Baseline in Acne Graded by Leeds Technique | Chest Week 4 (n=50,56) | -0.7 score on scale |
| Minocycline | Change From Baseline in Acne Graded by Leeds Technique | Chest Week 8 EOT (n=52,56) | -1.2 score on scale |
| Minocycline | Change From Baseline in Acne Graded by Leeds Technique | Chest 8 weeks after EOT (n=49,49) | -1.8 score on scale |
| Minocycline | Change From Baseline in Acne Graded by Leeds Technique | Back Week 4 (n=50,56) | -0.9 score on scale |
Secondary
Change From Baseline in Global Acne Grading System (GAGS) Score
GAGS used to assess 6 locations on face/chest/upper back; factor for each location based on surface area, distribution, density of pilosebaceous units. Locations graded separately 0 - 4 (hi. Global score factored based on summing of local scores. Change: mean at observation minus baseline.
Time frame: Baseline, Week 4, Week 8 End of Treatment (EOT), 8 weeks after EOT
Population: Full Analysis Set. Where noted: LOCF = Last Observation Carried Forward technique was used. Number of subjects with analyzable data: n=azithromycin, minocycline (respectively).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Azithromycin | Change From Baseline in Global Acne Grading System (GAGS) Score | Week 4 (n=50,56) | -7.0 score on scale | 95% Confidence Interval 7.05 |
| Azithromycin | Change From Baseline in Global Acne Grading System (GAGS) Score | Week 8 EOT (End of Treatment) (n=52,56) | -9.7 score on scale | — |
| Azithromycin | Change From Baseline in Global Acne Grading System (GAGS) Score | Week 8 EOT (LOCF) (n=53,59) | -9.5 score on scale | — |
| Azithromycin | Change From Baseline in Global Acne Grading System (GAGS) Score | 8 weeks after EOT (n=49,49) | -11.1 score on scale | — |
| Minocycline | Change From Baseline in Global Acne Grading System (GAGS) Score | 8 weeks after EOT (n=49,49) | -12.9 score on scale | — |
| Minocycline | Change From Baseline in Global Acne Grading System (GAGS) Score | Week 4 (n=50,56) | -6.5 score on scale | 95% Confidence Interval 6.45 |
| Minocycline | Change From Baseline in Global Acne Grading System (GAGS) Score | Week 8 EOT (LOCF) (n=53,59) | -9.8 score on scale | — |
| Minocycline | Change From Baseline in Global Acne Grading System (GAGS) Score | Week 8 EOT (End of Treatment) (n=52,56) | -10.2 score on scale | — |
Secondary
Improvement of Global Acne Grading System (GAGS) Score
Number of subjects by improvement category of GAGS score: Best improvement = reduction of GAGS score \>75% (pre-post evaluation); Good improvement = reduction score \> 50 - 75%; Moderate improvement : reduction score \> 25 - 50%; Light improvement : reduction score \> 0 - 25%; No change = reduction score = 0%; Worsening = increase score \> 0 %.
Time frame: Week 4, Week 8 End of Treatment (EOT), 8 weeks after EOT
Population: Full Analysis Set. Where noted: LOCF = Last Observation Carried Forward technique was used.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Azithromycin | Improvement of Global Acne Grading System (GAGS) Score | Week 4 Best Improvement | 1 participants |
| Azithromycin | Improvement of Global Acne Grading System (GAGS) Score | Week 4 Good Improvement | 4 participants |
| Azithromycin | Improvement of Global Acne Grading System (GAGS) Score | Week 4 Moderate Improvement | 19 participants |
| Azithromycin | Improvement of Global Acne Grading System (GAGS) Score | Week 4 Light Improvement | 23 participants |
| Azithromycin | Improvement of Global Acne Grading System (GAGS) Score | Week 4 No Change | 2 participants |
| Azithromycin | Improvement of Global Acne Grading System (GAGS) Score | Week 4 Worsening | 1 participants |
| Azithromycin | Improvement of Global Acne Grading System (GAGS) Score | Week 4 Missing | 3 participants |
| Azithromycin | Improvement of Global Acne Grading System (GAGS) Score | Week 8 EOT Best Improvement | 4 participants |
| Azithromycin | Improvement of Global Acne Grading System (GAGS) Score | Week 8 EOT Moderate Improvement | 21 participants |
| Azithromycin | Improvement of Global Acne Grading System (GAGS) Score | Week 8 EOT Light Improvement | 11 participants |
| Azithromycin | Improvement of Global Acne Grading System (GAGS) Score | Week 8 EOT No Change | 2 participants |
| Azithromycin | Improvement of Global Acne Grading System (GAGS) Score | Week 8 EOT Worsening | 3 participants |
| Azithromycin | Improvement of Global Acne Grading System (GAGS) Score | Week 8 EOT Missing | 1 participants |
| Azithromycin | Improvement of Global Acne Grading System (GAGS) Score | Week 8 EOT LOCF Best Improvement | 4 participants |
| Azithromycin | Improvement of Global Acne Grading System (GAGS) Score | Week 8 EOT LOCF Good Improvement | 11 participants |
| Azithromycin | Improvement of Global Acne Grading System (GAGS) Score | Week 8 EOT LOCF Moderate Improvement | 21 participants |
| Azithromycin | Improvement of Global Acne Grading System (GAGS) Score | Week 8 EOT LOCF Light Improvement | 11 participants |
| Azithromycin | Improvement of Global Acne Grading System (GAGS) Score | Week 8 EOT LOCF No Change | 3 participants |
| Azithromycin | Improvement of Global Acne Grading System (GAGS) Score | Week 8 EOT LOCF Worsening | 3 participants |
| Azithromycin | Improvement of Global Acne Grading System (GAGS) Score | Week 8 EOT LOCF Missing | 0 participants |
| Azithromycin | Improvement of Global Acne Grading System (GAGS) Score | 8 weeks after EOT Best Improvement | 7 participants |
| Azithromycin | Improvement of Global Acne Grading System (GAGS) Score | 8 weeks after EOT Good Improvement | 15 participants |
| Azithromycin | Improvement of Global Acne Grading System (GAGS) Score | 8 weeks after EOT Moderate Improvement | 13 participants |
| Azithromycin | Improvement of Global Acne Grading System (GAGS) Score | 8 weeks after EOT Light Improvement | 6 participants |
| Azithromycin | Improvement of Global Acne Grading System (GAGS) Score | 8 weeks after EOT Worsening | 5 participants |
| Azithromycin | Improvement of Global Acne Grading System (GAGS) Score | 8 weeks after EOT Missing | 4 participants |
| Azithromycin | Improvement of Global Acne Grading System (GAGS) Score | Week 8 EOT Good Improvement | 11 participants |
| Azithromycin | Improvement of Global Acne Grading System (GAGS) Score | 8 weeks after EOT No Change | 3 participants |
| Minocycline | Improvement of Global Acne Grading System (GAGS) Score | Week 8 EOT LOCF Good Improvement | 16 participants |
| Minocycline | Improvement of Global Acne Grading System (GAGS) Score | Week 4 Best Improvement | 1 participants |
| Minocycline | Improvement of Global Acne Grading System (GAGS) Score | 8 weeks after EOT Missing | 10 participants |
| Minocycline | Improvement of Global Acne Grading System (GAGS) Score | Week 4 Good Improvement | 2 participants |
| Minocycline | Improvement of Global Acne Grading System (GAGS) Score | Week 8 EOT LOCF Moderate Improvement | 20 participants |
| Minocycline | Improvement of Global Acne Grading System (GAGS) Score | Week 4 Moderate Improvement | 25 participants |
| Minocycline | Improvement of Global Acne Grading System (GAGS) Score | 8 weeks after EOT Moderate Improvement | 18 participants |
| Minocycline | Improvement of Global Acne Grading System (GAGS) Score | Week 4 Light Improvement | 24 participants |
| Minocycline | Improvement of Global Acne Grading System (GAGS) Score | Week 8 EOT LOCF Light Improvement | 17 participants |
| Minocycline | Improvement of Global Acne Grading System (GAGS) Score | Week 4 No Change | 2 participants |
| Minocycline | Improvement of Global Acne Grading System (GAGS) Score | Week 8 EOT Best Improvement | 3 participants |
| Minocycline | Improvement of Global Acne Grading System (GAGS) Score | Week 4 Worsening | 2 participants |
| Minocycline | Improvement of Global Acne Grading System (GAGS) Score | Week 8 EOT LOCF No Change | 2 participants |
| Minocycline | Improvement of Global Acne Grading System (GAGS) Score | Week 4 Missing | 3 participants |
| Minocycline | Improvement of Global Acne Grading System (GAGS) Score | 8 weeks after EOT Light Improvement | 8 participants |
| Minocycline | Improvement of Global Acne Grading System (GAGS) Score | Week 8 EOT LOCF Worsening | 1 participants |
| Minocycline | Improvement of Global Acne Grading System (GAGS) Score | Week 8 EOT Moderate Improvement | 20 participants |
| Minocycline | Improvement of Global Acne Grading System (GAGS) Score | 8 weeks after EOT No Change | 0 participants |
| Minocycline | Improvement of Global Acne Grading System (GAGS) Score | Week 8 EOT Light Improvement | 15 participants |
| Minocycline | Improvement of Global Acne Grading System (GAGS) Score | Week 8 EOT LOCF Missing | 0 participants |
| Minocycline | Improvement of Global Acne Grading System (GAGS) Score | Week 8 EOT No Change | 2 participants |
| Minocycline | Improvement of Global Acne Grading System (GAGS) Score | 8 weeks after EOT Worsening | 0 participants |
| Minocycline | Improvement of Global Acne Grading System (GAGS) Score | Week 8 EOT Worsening | 0 participants |
| Minocycline | Improvement of Global Acne Grading System (GAGS) Score | 8 weeks after EOT Best Improvement | 6 participants |
| Minocycline | Improvement of Global Acne Grading System (GAGS) Score | Week 8 EOT Missing | 3 participants |
| Minocycline | Improvement of Global Acne Grading System (GAGS) Score | Week 8 EOT Good Improvement | 16 participants |
| Minocycline | Improvement of Global Acne Grading System (GAGS) Score | Week 8 EOT LOCF Best Improvement | 3 participants |
| Minocycline | Improvement of Global Acne Grading System (GAGS) Score | 8 weeks after EOT Good Improvement | 17 participants |
Post Hoc
Number of Subjects With Mild, Moderate, and Severe Acne
Global Acne Grading System score used to assess 6 locations on face/chest/upper back; factor for each based on area, distribution, density of pilosebaceous units. Locations graded separately 0 - 4 (hi). Global score factored based on sum of local scores and se verity: 0=no acne, 1-18=mild, 19-30=moderate, 31-38=severe, \>39=very severe.
Time frame: Baseline, Week 8 End of Treatment (EOT)
Population: Full Analysis Set. Where noted: LOCF = Last Observation Carried Forward technique was used.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Azithromycin | Number of Subjects With Mild, Moderate, and Severe Acne | Baseline Mild acne | 0 participants |
| Azithromycin | Number of Subjects With Mild, Moderate, and Severe Acne | Baseline Severe acne | 3 participants |
| Azithromycin | Number of Subjects With Mild, Moderate, and Severe Acne | Baseline Very severe acne | 1 participants |
| Azithromycin | Number of Subjects With Mild, Moderate, and Severe Acne | Baseline Missing | 0 participants |
| Azithromycin | Number of Subjects With Mild, Moderate, and Severe Acne | Week 8 EOT (LOCF) Mild acne | 31 participants |
| Azithromycin | Number of Subjects With Mild, Moderate, and Severe Acne | Week 8 EOT (LOCF) Severe acne | 1 participants |
| Azithromycin | Number of Subjects With Mild, Moderate, and Severe Acne | Week 8 EOT (LOCF) Very severe acne | 0 participants |
| Azithromycin | Number of Subjects With Mild, Moderate, and Severe Acne | Week 8 EOT (LOCF) Missing | 2 participants |
| Azithromycin | Number of Subjects With Mild, Moderate, and Severe Acne | Baseline Moderate acne | 49 participants |
| Azithromycin | Number of Subjects With Mild, Moderate, and Severe Acne | Week 8 EOT (LOCF) Moderate acne | 19 participants |
| Minocycline | Number of Subjects With Mild, Moderate, and Severe Acne | Week 8 EOT (LOCF) Missing | 1 participants |
| Minocycline | Number of Subjects With Mild, Moderate, and Severe Acne | Baseline Mild acne | 1 participants |
| Minocycline | Number of Subjects With Mild, Moderate, and Severe Acne | Week 8 EOT (LOCF) Severe acne | 0 participants |
| Minocycline | Number of Subjects With Mild, Moderate, and Severe Acne | Baseline Severe acne | 5 participants |
| Minocycline | Number of Subjects With Mild, Moderate, and Severe Acne | Week 8 EOT (LOCF) Moderate acne | 16 participants |
| Minocycline | Number of Subjects With Mild, Moderate, and Severe Acne | Baseline Very severe acne | 1 participants |
| Minocycline | Number of Subjects With Mild, Moderate, and Severe Acne | Week 8 EOT (LOCF) Very severe acne | 1 participants |
| Minocycline | Number of Subjects With Mild, Moderate, and Severe Acne | Baseline Missing | 0 participants |
| Minocycline | Number of Subjects With Mild, Moderate, and Severe Acne | Baseline Moderate acne | 52 participants |
| Minocycline | Number of Subjects With Mild, Moderate, and Severe Acne | Week 8 EOT (LOCF) Mild acne | 41 participants |