Efficacy And Safety Of Azithromycin SR Compared With Minocycline In Acne - Study Results

Study Type:	Interventional
Study Design:	Randomized, Double-Blind, Parallel Assignment
Condition:	Acne Vulgaris
Interventions:	Drug: Azithromycin microspheres Drug: minocycline-placebo capsules Drug: Azithromycin microspheres-placebo Drug: Minocycline capsules,

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
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Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
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	Azithromycin	Minocycline
STARTED	58	60
COMPLETED	49	47
NOT COMPLETED	9	13
Adverse Event	5	4
Lost to Follow-up	1	4
Protocol Violation	0	3
Withdrawal by Subject	3	2

	Azithromycin	Minocycline	Total
Number of Participants [units: participants]	58	60	118
Age, Customized [units: participants]
<18 years	10	17	27
Between 18 and 44 years	48	43	91
Gender [units: participants]
Female	35	36	71
Male	23	24	47

Outcome Measures

1. Primary:

Change From Baseline to End of Treatment in Global Acne Grading System (GAGS) Score [ Baseline, Week 8 EOT (End of Treatment) ]

Measure Type	Primary
Measure Title	Change From Baseline to End of Treatment in Global Acne Grading System (GAGS) Score
Measure Description	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 (End of Treatment)
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Full Analysis Set, Last Observation Carried Forward (LOCF)

Reporting Groups

	Description
Azithromycin	2 grams per week administered administered orally (PO) for 8 weeks (azithromycin microspheres, powder for oral suspension)
Minocycline	100 milligrams (mg) administered PO (oral) QD (every day) for 8 weeks (minocycline capsules)

Measured Values

	Azithromycin	Minocycline
Number of Participants Analyzed [units: participants]	53	59
Change From Baseline to End of Treatment in Global Acne Grading System (GAGS) Score [units: score on scale] Least Squares Mean ( 95% Confidence Interval )	-8.69 ( -10.33 to -7.05 )	-9.16 ( -10.62 to -7.71 )

Statistical Analysis 1 for Change From Baseline to End of Treatment in Global Acne Grading System (GAGS) Score

Groups ^[1]	All groups
Non-Inferiority/Equivalence Test ^[2]	Yes
Mean Difference (Final Values) ^[3]	-0.47
95% Confidence Interval	( -2.48 to 1.54 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	If applicable, provided by Rhiannon.
[2]	Details of power calculation, definition of non-inferiority margin, and other key parameters:
	Analysis performed to assess non-inferiority by calculation & examination of 95% CI. Analysis conducted via analysis of covariance (ANCOVA) including corresponding baseline value and centre as covariates. Non-inferiority margin was chosen as largest clinically acceptable difference. This was set as difference of 3 in GAGS global score. Azithromycin declared non-inferior to minocycline when two-sided 95% confidence interval for difference lied entirely to right of non-inferiority margin.
[3]	Other relevant estimation information:
	Comparison between treatment groups was performed using an analysis of covariance (ANCOVA) method, with treatment, center, and baseline value GAGS global score included as covariates.

2. Primary:

Change From Baseline to End of Treatment in Global Acne Grading System (GAGS) Score - Per Protocol Population [ Baseline, Week 8 EOT (End of Treatment) ]

Measure Type	Primary
Measure Title	Change From Baseline to End of Treatment in Global Acne Grading System (GAGS) Score - Per Protocol Population
Measure Description	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 (End of Treatment)
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Per Protocol population

Reporting Groups

	Description
Azithromycin	2 grams per week administered administered orally (PO) for 8 weeks (azithromycin microspheres, powder for oral suspension)
Minocycline	100 milligrams (mg) administered PO (oral) QD (every day) for 8 weeks (minocycline capsules)

Measured Values

	Azithromycin	Minocycline
Number of Participants Analyzed [units: participants]	48	48
Change From Baseline to End of Treatment in Global Acne Grading System (GAGS) Score - Per Protocol Population [units: score on scale] Least Squares Mean ( 95% Confidence Interval )	-9.35 ( -10.75 to -7.94 )	-10.22 ( -11.54 to -8.90 )

Statistical Analysis 1 for Change From Baseline to End of Treatment in Global Acne Grading System (GAGS) Score - Per Protocol Population

Groups ^[1]	All groups
Non-Inferiority/Equivalence Test ^[2]	Yes
Mean Difference (Final Values) ^[3]	-0.87
95% Confidence Interval	( -2.58 to 0.84 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Details of power calculation, definition of non-inferiority margin, and other key parameters:
	Analysis performed to assess non-inferiority by calculation & examination of 95% CI. Analysis conducted via analysis of covariance (ANCOVA) including corresponding baseline value and centre as covariates. Non-inferiority margin was chosen as largest clinically acceptable difference. This was set as difference of 3 in GAGS global score. Azithromycin declared non-inferior to minocycline when two-sided 95% confidence interval for difference lied entirely to right of non-inferiority margin.
[3]	Other relevant estimation information:
	ANCOVA adjusted for baseline, center and treatment.

3. Secondary:

Change From Baseline in GAGS Score [ Baseline, Week 4, Week 8 (EOT), 8 weeks after EOT ]

Measure Type	Secondary
Measure Title	Change From Baseline in GAGS Score
Measure Description	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 (EOT), 8 weeks after EOT
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Full Analysis Set. Where noted: LOCF = Last Observation Carried Forward technique was used. Number of subjects with analyzable data: n=azithromycin, minocycline (respectively).

Reporting Groups

	Description
Azithromycin	2 grams per week administered administered orally (PO) for 8 weeks (azithromycin microspheres, powder for oral suspension)
Minocycline	100 milligrams (mg) administered PO (oral) QD (every day) for 8 weeks (minocycline capsules)

Measured Values

	Azithromycin	Minocycline
Number of Participants Analyzed [units: participants]	53	59
Change From Baseline in GAGS Score [units: score on scale] Mean ( 95% Confidence Interval )
Week 4 (n=50,56)	-7.0 ( -8.33 to -5.59 )	-6.5 ( -7.77 to -5.16 )
Week 8 EOT (End of Treatment) (n=52,56)	-9.7 ( -11.66 to -7.77 )	-10.2 ( -11.86 to -8.57 )
Week 8 EOT (LOCF) (n=53,59)	-9.5 ( -11.47 to -7.59 )	-9.8 ( -11.48 to -8.12 )
8 weeks after EOT (n=49,49)	-11.1 ( -13.42 to -8.82 )	-12.9 ( -14.79 to -11.01 )

No statistical analysis provided for Change From Baseline in GAGS Score

4. Secondary:

Improvement of Global Acne Grading System (GAGS) Score [ Week 4, Week 8 (EOT), 8 weeks after EOT ]

Measure Type	Secondary
Measure Title	Improvement of Global Acne Grading System (GAGS) Score
Measure Description	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 (EOT), 8 weeks after EOT
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Full Analysis Set. Where noted: LOCF = Last Observation Carried Forward technique was used.

Reporting Groups

	Description
Azithromycin	2 grams per week administered administered orally (PO) for 8 weeks (azithromycin microspheres, powder for oral suspension)
Minocycline	100 milligrams (mg) administered PO (oral) QD (every day) for 8 weeks (minocycline capsules)

Measured Values

	Azithromycin	Minocycline
Number of Participants Analyzed [units: participants]	53	59
Improvement of Global Acne Grading System (GAGS) Score [units: participants]
Week 4 Best Improvement	1	1
Week 4 Good Improvement	4	2
Week 4 Moderate Improvement	19	25
Week 4 Light Improvement	23	24
Week 4 No Change	2	2
Week 4 Worsening	1	2
Week 4 Missing	3	3
Week 8 EOT Best Improvement	4	3
Week 8 EOT Good Improvement	11	16
Week 8 EOT Moderate Improvement	21	20
Week 8 EOT Light Improvement	11	15
Week 8 EOT No Change	2	2
Week 8 EOT Worsening	3	0
Week 8 EOT Missing	1	3
Week 8 EOT LOCF Best Improvement	4	3
Week 8 EOT LOCF Good Improvement	11	16
Week 8 EOT LOCF Moderate Improvement	21	20
Week 8 EOT LOCF Light Improvement	11	17
Week 8 EOT LOCF No Change	3	2
Week 8 EOT LOCF Worsening	3	1
Week 8 EOT LOCF Missing	0	0
8 weeks after EOT Best Improvement	7	6
8 weeks after EOT Good Improvement	15	17
8 weeks after EOT Moderate Improvement	13	18
8 weeks after EOT Light Improvement	6	8
8 weeks after EOT No Change	3	0
8 weeks after EOT Worsening	5	0
8 weeks after EOT Missing	4	10

No statistical analysis provided for Improvement of Global Acne Grading System (GAGS) Score

5. Secondary:

Change From Baseline in Acne Graded by Leeds Technique [ Baseline, Week 4, Week 8 EOT, 8 weeks after EOT ]

Measure Type	Secondary
Measure Title	Change From Baseline in Acne Graded by Leeds Technique
Measure Description	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 EOT, 8 weeks after EOT
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Full Analysis Set. Where noted: LOCF = Last Observation Carried Forward technique was used. Number of subjects with analyzable data: n=azithromycin, minocycline (respectively).

Reporting Groups

	Description
Azithromycin	2 grams per week administered administered orally (PO) for 8 weeks (azithromycin microspheres, powder for oral suspension)
Minocycline	100 milligrams (mg) administered PO (oral) QD (every day) for 8 weeks (minocycline capsules)

Measured Values

	Azithromycin	Minocycline
Number of Participants Analyzed [units: participants]	53	59
Change From Baseline in Acne Graded by Leeds Technique [units: score on scale] Mean ( 95% Confidence Interval )
Face Week 4 (n=50, 56)	-1.5 ( -1.82 to -1.14 )	-1.3 ( -1.60 to -1.05 )
Face Week 8 EOT (n=52, 56)	-2.5 ( -3.06 to -2.01 )	-2.4 ( -2.84 to -2.02 )
Face Week 8 EOT (LOCF) (n=53,59)	-2.5 ( -3.01 to -1.97 )	-2.3 ( -2.74 to -1.91 )
Face 8 weeks after EOT (n=49,49)	-3.0 ( -3.65 to -2.35 )	-2.9 ( -3.44 to -2.39 )
Back Week 4 (n=50,56)	-1.1 ( -1.58 to -0.70 )	-0.9 ( -1.21 to -0.61 )
Back Week 8 EOT (n=52,56)	-1.5 ( -1.98 to -1.02 )	-1.4 ( -1.83 to -1.06 )
Back Week 8 EOT (LOCF) (n=53,59)	-1.5 ( -1.96 to -1.02 )	-1.4 ( -1.76 to -0.99 )
Back 8 weeks after EOT (n=49,49)	-1.5 ( -2.03 to -0.95 )	-2.0 ( -2.52 to -1.40 )
Chest Week 4 (n=50,56)	-0.8 ( -1.12 to -0.48 )	-0.7 ( -0.99 to -0.40 )
Chest Week 8 EOT (n=52,56)	-1.5 ( -2.04 to -0.92 )	-1.2 ( -1.57 to -0.75 )
Chest Week 8 EOT (LOCF) (n=53,59)	-1.5 ( -2.00 to -0.90 )	-1.1 ( -1.51 to -0.73 )
Chest 8 weeks after EOT (n=49,49)	-1.5 ( -2.10 to -0.92 )	-1.8 ( -2.32 to -1.23 )

No statistical analysis provided for Change From Baseline in Acne Graded by Leeds Technique

6. Post-Hoc:

Number of Subjects With Mild, Moderate, and Severe Acne [ Baseline, Week 8 EOT ]

Measure Type	Post-Hoc
Measure Title	Number of Subjects With Mild, Moderate, and Severe Acne
Measure Description	GAGS 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 EOT
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Full Analysis Set. Where noted: LOCF = Last Observation Carried Forward technique was used.

Reporting Groups

	Description
Azithromycin	2 grams per week administered administered orally (PO) for 8 weeks (azithromycin microspheres, powder for oral suspension)
Minocycline	100 milligrams (mg) administered PO (oral) QD (every day) for 8 weeks (minocycline capsules)

Measured Values

	Azithromycin	Minocycline
Number of Participants Analyzed [units: participants]	53	59
Number of Subjects With Mild, Moderate, and Severe Acne [units: participants]
Baseline Mild acne	0	1
Baseline Moderate acne	49	52
Baseline Severe acne	3	5
Baseline Very severe acne	1	1
Baseline Missing	0	0
Week 8 EOT (LOCF) Mild acne	31	41
Week 8 EOT (LOCF) Moderate acne	19	16
Week 8 EOT (LOCF) Severe acne	1	0
Week 8 EOT (LOCF) Very severe acne	0	1
Week 8 EOT (LOCF) Missing	2	1

No statistical analysis provided for Number of Subjects With Mild, Moderate, and Severe Acne

Responsible Party:	Pfizer, Inc. ( Director, Clinical Trial Disclosure Group )
Study ID Numbers:	A0661150
Study First Received:	October 23, 2006
Results First Received:	June 11, 2009
Last Updated:	June 11, 2009
ClinicalTrials.gov Identifier:	NCT00392223 History of Changes
Health Authority:	Italy: The Italian Medicines Agency