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Clinical Trial Results:
Clinical evaluation of efficacy at 2 weeks of Duac fixed dose combination gel in treatment of facial acne vulgaris in Japanese Subjects.

Summary
EudraCT number	2017-001575-23
Trial protocol	Outside EU/EEA
Global end of trial date	17 Feb 2016

Results information
Results version number	v1(current)
This version publication date	01 Nov 2017
First version publication date	01 Nov 2017
Other versions

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

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Trial information

Top of page

Sponsor protocol code

201884

ISRCTN number

US NCT number

WHO universal trial number (UTN)

Sponsor organisation name

GlaxoSmithKline

Sponsor organisation address

980 Great West Road, Brentford, Middlesex, United Kingdom,

Public contact

GSK Response Center, GlaxoSmithKline, 1 866-435-7343,

Scientific contact

GSK Response Center, GlaxoSmithKline, 1 866-435-7343,

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Yes

Analysis stage

Final

Date of interim/final analysis

14 Apr 2016

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

17 Feb 2016

Was the trial ended prematurely?

Main objective of the trial

To compare the early efficacy of Duac Combination Gel once daily (QD) to the combination therapy of ADA QD and CLDM twice daily (BID) at Week 2.

Protection of trial subjects

Not appicable

Background therapy

Evidence for comparator

Actual start date of recruitment

07 Oct 2015

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

Japan: 349

Worldwide total number of subjects

349

EEA total number of subjects

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

130

Adults (18-64 years)

219

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

Screening details

A total of 349 participants were randomized.

Period 1 title

Overall Study (overall period)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Single blind

Roles blinded

Investigator ^[1]

Are arms mutually exclusive

Yes

DUAC

Arm description

Participants were instructed to use DUAC, a fixed dose combination gel (clindamycin phosphate 1.2% and benzoyl peroxide 3%) with quantity of 2 finger tip unit (FTU) about 0.6 gram (g) which was sufficient to cover entire face (including the forehead, nose, cheeks and chin) once daily in the evening (at bedtime) for 12 weeks.

Arm type

Experimental

Investigational medicinal product name

DUAC

Investigational medicinal product code

Other name

Pharmaceutical forms

Gel

Routes of administration

Topical use

Dosage and administration details

Participants were instructed to use 2 FTU (about 0.6 g) of DUAC which was sufficient to cover entire face (including the forehead, nose, cheeks and chin) once daily in the evening (at bedtime) for 12 weeks.

ADA 0.1% +CLDM 1%

Arm description

Participants were instructed to use combination therapy of Adapalene (ADA) 0.1% gel with quantity of 1 FTU about 0.5 g sufficient to cover entire face (including the forehead, nose, cheeks and chin) once daily in the evening (at bedtime) and clindamycin (CLDM) 1% gel twice daily, once in the morning and once in the evening (at bedtime) for 12 weeks. The CLDM 1% gel was applied subsequent to the application of ADA 0.1% gel in the evening. The CLDM 1% gel was applied to inflammatory lesions (ILs) only.

Arm type

Active comparator

Investigational medicinal product name

ADA 0.1%

Investigational medicinal product code

Other name

Pharmaceutical forms

Gel

Routes of administration

Topical use

Dosage and administration details

Participants were instructed to use ADA 0.1% gel with quantity of 1 FTU (about 0.5 g) sufficient to cover entire face (including the forehead, nose, cheeks and chin) once daily in the evening (at bedtime) for 12 weeks.

Investigational medicinal product name

CLDM 1%

Investigational medicinal product code

Other name

Pharmaceutical forms

Gel

Routes of administration

Topical use

Dosage and administration details

Participants were instructed to use CLDM 1% gel twice daily, once in the morning and once in the evening (at bedtime) for 12 weeks. The CLDM 1% gel was applied subsequent to the application of ADA 0.1% gel in the evening. The CLDM 1% gel was applied to inflammatory lesions only.

Notes
[1] - The roles blinded appear inconsistent with a simple blinded trial.
Justification: Investigator was blinded for this study.

Number of subjects in period 1	DUAC	ADA 0.1% +CLDM 1%
Started	172	177
Completed	165	169
Not completed	7	8
Consent withdrawn by subject	1	1
Protocol-defined stopping criteria	-	1
Adverse event, non-fatal	6	5
Protocol deviation	-	1

Baseline characteristics

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Reporting group title

DUAC

Reporting group description

Reporting group title

ADA 0.1% +CLDM 1%

Reporting group description

Reporting group values	DUAC	ADA 0.1% +CLDM 1%	Total
Number of subjects	172	177
Age categorical
Units: Subjects
Age continuous
Age continuous description
Units: years
arithmetic mean (standard deviation)	20.3 ± 5.91	19.8 ± 4.90	-
Gender categorical
Gender categorical description
Units: Subjects
Female	97	110	207
Male	75	67	142
Race (NIH/OMB)
Units: Subjects
American Indian or Alaska Native	0	0	0
Asian	172	177	349
Native Hawaiian or Other Pacific Islander	0	0	0
Black or African American	0	0	0
White	0	0	0
More than one race	0	0	0
Unknown or Not Reported	0	0	0

End points

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Reporting group title

DUAC

Reporting group description

Reporting group title

ADA 0.1% +CLDM 1%

Reporting group description

Primary: Percent change in total lesion counts (TLs) from Baseline to Week 2

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End point title

Percent change in total lesion counts (TLs) from Baseline to Week 2

End point description

The assessor performed a count of IL (papules, pustules, nodular lesions), non-ILs (open and closed comedones) and total lesions (the sum of IL and non-IL) at each study visit. Lesion counts were confined to the face. Change from baseline was calculated as the value at endpoint minus the value at baseline. Data for adjusted mean has been reported. Percent change from Baseline is the change from Baseline divided by Baseline value multiplied by 100. The Baseline value was the latest pre-dose assessment value. The non-inflammatory lesions were counted by diagnosis based on palpation of the investigator (or sub-investigator). ITT population: comprise of all randomized participants who received at least one application of study product. Only those participants with data available at the specified time points were analyzed (represented by n=x ,x ,x) in the category titles.

End point type

Primary

End point timeframe

Baseline (Day 1) and Week 2

End point values	DUAC	ADA 0.1% +CLDM 1%
Number of subjects analysed	169 ^[1]	176 ^[2]
Units: Percent change in lesions
least squares mean (standard error)	-42.16 ± 1.890	-35.33 ± 1.850

Notes
[1] - ITT population
[2] - ITT population

Statistical analysis 1

Statistical analysis description

Comparison between DUAC and ADA 0.1% +CLDM 1% at Week 2

Comparison groups

DUAC v ADA 0.1% +CLDM 1%

Number of subjects included in analysis

345

Analysis specification

Pre-specified

Analysis type

P-value

= 0.008 ^[3]

Method

mixed model repeated measures analysis

Parameter type

difference in percent

Point estimate

-6.83

Confidence interval

level

95%

sides

2-sided

lower limit

-11.88

upper limit

-1.78

Notes
[3] - The analysis method was MMRM with treatment, center, visit, treatment-by-visit interaction, Baseline TLs counts, Baseline-by-visit interaction as fixed effects. A negative treatment difference indicates a benefit of Duac relative to ADA+CLDM.

Secondary: Percent change from Baseline in TLs to Weeks 1, 4, 8 and 12

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End point title

Percent change from Baseline in TLs to Weeks 1, 4, 8 and 12

End point description

The assessor performed a count of IL (papules, pustules, nodular lesions), non-ILs (open and closed comedones) and total lesions (the sum of IL and non-IL) at each study visit. Lesion counts were confined to the face. Change from Baseline was calculated as the value at endpoint minus the value at Baseline. Data for adjusted mean has been reported. Percent change from Baseline is the change from Baseline divided by Baseline value multiplied by 100. The Baseline value was the latest pre-dose assessment value. The non-ILs were counted by diagnosis based on palpation of the investigator (or sub-investigator). A negative treatment difference indicates a benefit of Duac relative to ADA+CLDM.

End point type

Secondary

End point timeframe

Baseline (Day 1) and Week 1, 4, 8, 12

End point values	DUAC	ADA 0.1% +CLDM 1%
Number of subjects analysed	172 ^[4]	177 ^[5]
Units: Percent change in lesions
least squares mean (standard error)
Week 1, n= 172, 176	-24.58 ± 1.729	-24.33 ± 1.697
Week 4, n=169, 174	-55.51 ± 1.670	-49.65 ± 1.637
Week 8, n= 167, 172	-65.23 ± 1.544	-62.88 ± 1.514
Week 12, n= 164, 169	-74.60 ± 1.314	-71.36 ± 1.288

Notes
[4] - ITT population
[5] - ITT population

Statistical analysis 1

Statistical analysis description

Comparison between DUAC and ADA 0.1% +CLDM 1% at Week 1

Comparison groups

DUAC v ADA 0.1% +CLDM 1%

Number of subjects included in analysis

349

Analysis specification

Pre-specified

Analysis type

P-value

= 0.916 ^[6]

Method

mixed model repeated measures analysis

Parameter type

difference in percent

Point estimate

-0.25

Confidence interval

level

95%

sides

2-sided

lower limit

-4.85

upper limit

4.35

Notes
[6] - The analysis method was mixed-model for repeated measures with treatment, center, visit, treatment-by-visit interaction, Baseline TLs counts, Baseline-by-visit interaction as fixed effects.

Statistical analysis 2

Statistical analysis description

Comparison between DUAC and ADA 0.1% +CLDM 1% at Week 4

Comparison groups

DUAC v ADA 0.1% +CLDM 1%

Number of subjects included in analysis

349

Analysis specification

Pre-specified

Analysis type

P-value

= 0.01 ^[7]

Method

mixed model repeated measures analysis

Parameter type

difference in percent

Point estimate

-5.85

Confidence interval

level

95%

sides

2-sided

lower limit

-10.29

upper limit

-1.42

Notes
[7] - The analysis method was mixed-model for repeated measures with treatment, center, visit, treatment-by-visit interaction, Baseline TLs counts, Baseline-by-visit interaction as fixed effects.

Statistical analysis 3

Statistical analysis description

Comparison between DUAC and ADA 0.1% +CLDM 1% at Week 8

Comparison groups

DUAC v ADA 0.1% +CLDM 1%

Number of subjects included in analysis

349

Analysis specification

Pre-specified

Analysis type

P-value

= 0.257 ^[8]

Method

mixed model repeated measures analysis

Parameter type

difference in percent

Point estimate

-2.35

Confidence interval

level

95%

sides

2-sided

lower limit

-6.42

upper limit

1.72

Notes
[8] - The analysis method was mixed-model for repeated measures with treatment, center, visit, treatment-by-visit interaction, Baseline TLs counts, Baseline-by-visit interaction as fixed effects.

Statistical analysis 4

Statistical analysis description

Comparison between DUAC and ADA 0.1% +CLDM 1% at Week 12

Comparison groups

DUAC v ADA 0.1% +CLDM 1%

Number of subjects included in analysis

349

Analysis specification

Pre-specified

Analysis type

P-value

= 0.062 ^[9]

Method

mixed model repeated measures analysis

Parameter type

difference in percent

Point estimate

-3.24

Confidence interval

level

95%

sides

2-sided

lower limit

-6.64

upper limit

0.16

Notes
[9] - The analysis method was mixed-model for repeated measures with treatment, center, visit, treatment-by-visit interaction, Baseline TLs counts, Baseline-by-visit interaction as fixed effects.

Secondary: Percent change form Baseline in lesion counts (ILs and non-ILs) to Weeks 1, 2, 4, 8 and 12

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End point title

Percent change form Baseline in lesion counts (ILs and non-ILs) to Weeks 1, 2, 4, 8 and 12

End point description

The assessor performed a count of IL (papules, pustules, nodular lesions), non-ILs (open and closed comedones). Lesion counts were confined to the face. Change from Baseline was calculated as the value at endpoint minus the value at Baseline. Data for adjusted mean has been reported. Percent change from Baseline is the change from Baseline divided by Baseline value multiplied by 100. The Baseline value was the latest pre-dose assessment value. The non-ILs were counted by diagnosis based on palpation of the investigator (or sub-investigator).

End point type

Secondary

End point timeframe

Baseline (Day 1) and Week 1, 2, 4, 8, 12

End point values	DUAC	ADA 0.1% +CLDM 1%
Number of subjects analysed	172 ^[10]	177 ^[11]
Units: Percent change in lesions
least squares mean (standard error)
Week 1 ILs n= 172, 176	-42.97 ± 2.349	-37.89 ± 2.309
Week 2 ILs n= 169, 176	-60.92 ± 2.209	-52.49 ± 2.162
Week 4 ILs n= 169, 174	-70.68 ± 1.898	-61.30 ± 1.860
Week 8 ILs n= 167, 172	-76.33 ± 1.717	-69.64 ± 1.682
Week 12 ILs n= 164, 169	-82.07 ± 1.403	-77.58 ± 1.374
Week 1 non-ILs n= 172, 176	-15.13 ± 2.279	-17.85 ± 2.239
Week 2 non-ILs n= 169, 176	-32.71 ± 2.419	-27.01 ± 2.367
Week 4 non-ILs n= 169, 174	-47.64 ± 2.171	-43.74 ± 2.129
Week 8 non-ILs n= 167, 172	-59.50 ± 1.910	-58.91 ± 1.872
Week 12 non-ILs n= 164, 169	-71.07 ± 1.603	-67.29 ± 1.571

Notes
[10] - ITT population
[11] - ITT population

Statistical analysis 1

Statistical analysis description

Comparison between DUAC and ADA 0.1% +CLDM 1% at Week 1 for ILs. A negative treatment difference indicates a benefit of Duac relative to ADA+CLDM.

Comparison groups

ADA 0.1% +CLDM 1% v DUAC

Number of subjects included in analysis

349

Analysis specification

Pre-specified

Analysis type

P-value

= 0.115 ^[12]

Method

mixed model repeated measures analysis

Parameter type

difference in percent

Point estimate

-5.08

Confidence interval

level

95%

sides

2-sided

lower limit

-11.41

upper limit

1.25

Notes
[12] - The analysis method was mixed-model for repeated measures with treatment, center, visit, treatment-by-visit interaction, Baseline ILs counts, Baseline-by-visit interaction as fixed effects.

Statistical analysis 2

Statistical analysis description

Comparison between DUAC and ADA 0.1% +CLDM 1% at Week 2 for ILs. A negative treatment difference indicates a benefit of Duac relative to ADA+CLDM.

Comparison groups

ADA 0.1% +CLDM 1% v DUAC

Number of subjects included in analysis

349

Analysis specification

Pre-specified

Analysis type

P-value

= 0.005 ^[13]

Method

mixed model repeated measures analysis

Parameter type

difference in percent

Point estimate

-8.43

Confidence interval

level

95%

sides

2-sided

lower limit

-14.35

upper limit

-2.51

Notes
[13] - The analysis method was mixed-model for repeated measures with treatment, center, visit, treatment-by-visit interaction, Baseline ILs counts, Baseline-by-visit interaction as fixed effects.

Statistical analysis 3

Statistical analysis description

Comparison between DUAC and ADA 0.1% +CLDM 1% at Week 4 for ILs. A negative treatment difference indicates a benefit of Duac relative to ADA+CLDM.

Comparison groups

ADA 0.1% +CLDM 1% v DUAC

Number of subjects included in analysis

349

Analysis specification

Pre-specified

Analysis type

P-value

< 0.001 ^[14]

Method

mixed model repeated measures analysis

Parameter type

difference in percent

Point estimate

-9.37

Confidence interval

level

95%

sides

2-sided

lower limit

-14.42

upper limit

-4.33

Notes
[14] - The analysis method was mixed-model for repeated measures with treatment, center, visit, treatment-by-visit interaction, Baseline ILs counts, Baseline-by-visit interaction as fixed effects.

Statistical analysis 4

Statistical analysis description

Comparison between DUAC and ADA 0.1% +CLDM 1% at Week 8 for ILs. A negative treatment difference indicates a benefit of Duac relative to ADA+CLDM.

Comparison groups

ADA 0.1% +CLDM 1% v DUAC

Number of subjects included in analysis

349

Analysis specification

Pre-specified

Analysis type

P-value

= 0.004 ^[15]

Method

mixed model repeated measures analysis

Parameter type

difference in percent

Point estimate

-6.69

Confidence interval

level

95%

sides

2-sided

lower limit

-11.21

upper limit

-2.16

Notes
[15] - The analysis method was mixed-model for repeated measures with treatment, center, visit, treatment-by-visit interaction, Baseline ILs counts, Baseline-by-visit interaction as fixed effects.

Statistical analysis 5

Statistical analysis description

Comparison between DUAC and ADA 0.1% +CLDM 1% at Week 12 for ILs

Comparison groups

ADA 0.1% +CLDM 1% v DUAC

Number of subjects included in analysis

349

Analysis specification

Pre-specified

Analysis type

P-value

= 0.015 ^[16]

Method

mixed model repeated measures analysis

Parameter type

Mean difference (net)

Point estimate

-4.5

Confidence interval

level

95%

sides

2-sided

lower limit

-8.1

upper limit

-0.89

Notes
[16] - The analysis method was mixed-model for repeated measures with treatment, center, visit, treatment-by-visit interaction, Baseline ILs counts, Baseline-by-visit interaction as fixed effects.

Statistical analysis 6

Statistical analysis description

Comparison between DUAC and ADA 0.1% +CLDM 1% at Week 1 for non-ILs. A negative treatment difference indicates a benefit of Duac relative to ADA+CLDM.

Comparison groups

ADA 0.1% +CLDM 1% v DUAC

Number of subjects included in analysis

349

Analysis specification

Pre-specified

Analysis type

P-value

= 0.382 ^[17]

Method

mixed model repeated measures analysis

Parameter type

difference in percent

Point estimate

2.71

Confidence interval

level

95%

sides

2-sided

lower limit

-3.38

upper limit

8.8

Notes
[17] - The analysis method was mixed-model for repeated measures with treatment, center, visit, treatment-by-visit interaction, Baseline non-ILs counts, Baseline-by-visit interaction as fixed effects.

Statistical analysis 7

Statistical analysis description

Comparison between DUAC and ADA 0.1% +CLDM 1% at Week 2 for non-ILs. A negative treatment difference indicates a benefit of Duac relative to ADA+CLDM.

Comparison groups

ADA 0.1% +CLDM 1% v DUAC

Number of subjects included in analysis

349

Analysis specification

Pre-specified

Analysis type

P-value

= 0.085 ^[18]

Method

mixed model repeated measures analysis

Parameter type

difference in percent

Point estimate

-5.69

Confidence interval

level

95%

sides

2-sided

lower limit

-12.17

upper limit

0.78

Notes
[18] - The analysis method was mixed-model for repeated measures with treatment, center, visit, treatment-by-visit interaction, Baseline non-ILs counts, Baseline-by-visit interaction as fixed effects.

Statistical analysis 8

Statistical analysis description

Comparison between DUAC and ADA 0.1% +CLDM 1% at Week 4 for non-ILs. A negative treatment difference indicates a benefit of Duac relative to ADA+CLDM.

Comparison groups

ADA 0.1% +CLDM 1% v DUAC

Number of subjects included in analysis

349

Analysis specification

Pre-specified

Analysis type

P-value

= 0.186 ^[19]

Method

mixed model repeated measures analysis

Parameter type

difference in percent

Point estimate

-3.89

Confidence interval

level

95%

sides

2-sided

lower limit

-9.67

upper limit

1.88

Notes
[19] - The analysis method was mixed-model for repeated measures with treatment, center, visit, treatment-by-visit interaction, Baseline non-ILs counts, Baseline-by-visit interaction as fixed effects.

Statistical analysis 9

Statistical analysis description

Comparison between DUAC and ADA 0.1% +CLDM 1% at Week 8 for non-ILs. A negative treatment difference indicates a benefit of Duac relative to ADA+CLDM.

Comparison groups

ADA 0.1% +CLDM 1% v DUAC

Number of subjects included in analysis

349

Analysis specification

Pre-specified

Analysis type

P-value

= 0.818 ^[20]

Method

mixed model repeated measures analysis

Parameter type

difference in percent

Point estimate

-0.59

Confidence interval

level

95%

sides

2-sided

lower limit

-5.61

upper limit

4.44

Notes
[20] - The analysis method was mixed-model for repeated measures with treatment, center, visit, treatment-by-visit interaction, Baseline non-ILs counts, Baseline-by-visit interaction as fixed effects.

Statistical analysis 10

Statistical analysis description

Comparison between DUAC and ADA 0.1% +CLDM 1% at Week 12 for non-ILs. A negative treatment difference indicates a benefit of Duac relative to ADA+CLDM.

Comparison groups

ADA 0.1% +CLDM 1% v DUAC

Number of subjects included in analysis

349

Analysis specification

Pre-specified

Analysis type

P-value

= 0.073 ^[21]

Method

mixed model repeated measures analysis

Parameter type

difference in percent

Point estimate

-3.78

Confidence interval

level

95%

sides

2-sided

lower limit

-7.92

upper limit

0.35

Notes
[21] - The analysis method was mixed-model for repeated measures with treatment, center, visit, treatment-by-visit interaction, Baseline non-ILs counts, Baseline-by-visit interaction as fixed effects.

Secondary: Absolute Change from Baseline in lesion counts (TLs, ILs and non-ILs) to Weeks 1, 2, 4, 8 and 12

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End point title

Absolute Change from Baseline in lesion counts (TLs, ILs and non-ILs) to Weeks 1, 2, 4, 8 and 12

End point description

End point type

Secondary

End point timeframe

Baseline (Day 1) and Week 1, 2, 4, 8, 12

End point values	DUAC	ADA 0.1% +CLDM 1%
Number of subjects analysed	172 ^[22]	177 ^[23]
Units: Change in lesion count
least squares mean (standard error)
Week 1 =TLs n= 172, 176	-24.4 ± 1.70	-24.3 ± 1.67
Week 2 TLs n= 169, 176	-41.8 ± 1.88	-35.6 ± 1.84
Week 4 TLs n= 169, 174	-56.3 ± 1.71	-51.6 ± 1.67
Week 8 TLs n= 167, 172	-66.4 ± 1.60	-65.7 ± 1.57
Week 12 TLs n= 164, 169	-76.2 ± 1.37	-74.5 ± 1.34
Week 1 ILs n= 172, 176	-13.3 ± 0.74	-11.5 ± 0.72
Week 2 ILs n= 169, 176	-19.3 ± 0.70	-16.3 ± 0.68
Week 4 ILs n= 169, 174	-22.4 ± 0.62	-19.8 ± 0.60
Week 8 ILs n= 167, 172	-24.3 ± 0.56	-22.4 ± 0.55
Week 12 ILs n= 164, 169	-26.0 ± 0.48	-24.9 ± 0.47
Week 1 non-ILs n= 172, 176	-11.1 ± 1.46	-12.9 ± 1.43
Week 2 non-ILs n= 169, 176	-22.5 ± 1.59	-19.3 ± 1.56
Week 4 non-ILs n= 169, 174	-34.0 ± 1.46	-32.0 ± 1.44
Week 8 non-ILs n= 167, 172	-42.2 ± 1.33	-43.4 ± 1.31
Week 12 non-ILs n= 164, 169	-50.2 ± 1.11	-49.6 ± 1.09

Notes
[22] - ITT population
[23] - ITT population

Statistical analysis 1

Statistical analysis description

Comparison between DUAC and ADA 0.1% +CLDM 1% at Week 1 for TLs. negative treatment difference indicates a benefit of Duac relative to ADA+CLDM.

Comparison groups

ADA 0.1% +CLDM 1% v DUAC

Number of subjects included in analysis

349

Analysis specification

Pre-specified

Analysis type

P-value

= 0.961 ^[24]

Method

mixed model repeated measures analysis

Parameter type

Mean difference (net)

Point estimate

-0.1

Confidence interval

level

95%

sides

2-sided

lower limit

-4.6

upper limit

4.4

Notes
[24] - The analysis method was mixed-model for repeated measures with treatment, center, visit, treatment-by-visit interaction, Baseline TLs counts, Baseline-by-visit interaction as fixed effects.

Statistical analysis 2

Statistical analysis description

Comparison between DUAC and ADA 0.1% +CLDM 1% at Week 2 for TLs. A negative treatment difference indicates a benefit of Duac relative to ADA+CLDM.

Comparison groups

ADA 0.1% +CLDM 1% v DUAC

Number of subjects included in analysis

349

Analysis specification

Pre-specified

Analysis type

P-value

= 0.015 ^[25]

Method

mixed model repeated measures analysis

Parameter type

Mean difference (net)

Point estimate

-6.2

Confidence interval

level

95%

sides

2-sided

lower limit

-11.2

upper limit

-1.2

Notes
[25] - The analysis method was mixed-model for repeated measures with treatment, center, visit, treatment-by-visit interaction, Baseline TLs counts, Baseline-by-visit interaction as fixed effects.

Statistical analysis 3

Statistical analysis description

Comparison between DUAC and ADA 0.1% +CLDM 1% at Week 4 for TLs. A negative treatment difference indicates a benefit of Duac relative to ADA+CLDM.

Comparison groups

ADA 0.1% +CLDM 1% v DUAC

Number of subjects included in analysis

349

Analysis specification

Pre-specified

Analysis type

P-value

= 0.044 ^[26]

Method

mixed model repeated measures analysis

Parameter type

Mean difference (net)

Point estimate

-4.7

Confidence interval

level

95%

sides

2-sided

lower limit

-9.2

upper limit

-0.1

Notes
[26] - The analysis method was mixed-model for repeated measures with treatment, center, visit, treatment-by-visit interaction, Baseline TLs counts, Baseline-by-visit interaction as fixed effects.

Statistical analysis 4

Statistical analysis description

Comparison between DUAC and ADA 0.1% +CLDM 1% at Week 8 for TLs. A negative treatment difference indicates a benefit of Duac relative to ADA+CLDM.

Comparison groups

ADA 0.1% +CLDM 1% v DUAC

Number of subjects included in analysis

349

Analysis specification

Pre-specified

Analysis type

P-value

= 0.747 ^[27]

Method

mixed model repeated measures analysis

Parameter type

Mean difference (net)

Point estimate

-0.7

Confidence interval

level

95%

sides

2-sided

lower limit

-4.9

upper limit

3.5

Notes
[27] - The analysis method was mixed-model for repeated measures with treatment, center, visit, treatment-by-visit interaction, Baseline TLs counts, Baseline-by-visit interaction as fixed effects.

Statistical analysis 5

Statistical analysis description

Comparison between DUAC and ADA 0.1% +CLDM 1% at Week 12 for TLs. A negative treatment difference indicates a benefit of Duac relative to ADA+CLDM.

Comparison groups

ADA 0.1% +CLDM 1% v DUAC

Number of subjects included in analysis

349

Analysis specification

Pre-specified

Analysis type

P-value

= 0.338 ^[28]

Method

mixed model repeated measures analysis

Parameter type

Mean difference (net)

Point estimate

-1.7

Confidence interval

level

95%

sides

2-sided

lower limit

-5.3

upper limit

1.8

Notes
[28] - The analysis method was mixed-model for repeated measures with treatment, center, visit, treatment-by-visit interaction, Baseline TLs counts, Baseline-by-visit interaction as fixed effects.

Statistical analysis 6

Statistical analysis description

Comparison between DUAC and ADA 0.1% +CLDM 1% at Week 1 for ILs. A negative treatment difference indicates a benefit of Duac relative to ADA+CLDM.

Comparison groups

ADA 0.1% +CLDM 1% v DUAC

Number of subjects included in analysis

349

Analysis specification

Pre-specified

Analysis type

P-value

= 0.068 ^[29]

Method

mixed model repeated measures analysis

Parameter type

Mean difference (net)

Point estimate

-1.8

Confidence interval

level

95%

sides

2-sided

lower limit

-3.8

upper limit

0.1

Notes
[29] - The analysis method was mixed-model for repeated measures with treatment, center, visit, treatment-by-visit interaction, Baseline ILs counts, Baseline-by-visit interaction as fixed effects.

Statistical analysis 7

Statistical analysis description

Comparison between DUAC and ADA 0.1% +CLDM 1% at Week 2 for ILs. A negative treatment difference indicates a benefit of Duac relative to ADA+CLDM.

Comparison groups

ADA 0.1% +CLDM 1% v DUAC

Number of subjects included in analysis

349

Analysis specification

Pre-specified

Analysis type

P-value

= 0.002 ^[30]

Method

mixed model repeated measures analysis

Parameter type

Mean difference (net)

Point estimate

-3

Confidence interval

level

95%

sides

2-sided

lower limit

-4.8

upper limit

-1.1

Notes
[30] - The analysis method was mixed-model for repeated measures with treatment, center, visit, treatment-by-visit interaction, Baseline ILs counts, Baseline-by-visit interaction as fixed effects.

Statistical analysis 8

Statistical analysis description

Comparison between DUAC and ADA 0.1% +CLDM 1% at Week 4 for ILs. A negative treatment difference indicates a benefit of Duac relative to ADA+CLDM.

Comparison groups

ADA 0.1% +CLDM 1% v DUAC

Number of subjects included in analysis

349

Analysis specification

Pre-specified

Analysis type

P-value

= 0.002 ^[31]

Method

mixed model repeated measures analysis

Parameter type

Mean difference (net)

Point estimate

-2.6

Confidence interval

level

95%

sides

2-sided

lower limit

-4.3

upper limit

-1

Notes
[31] - The analysis method was mixed-model for repeated measures with treatment, center, visit, treatment-by-visit interaction, Baseline ILs counts, Baseline-by-visit interaction as fixed effects.

Statistical analysis 9

Statistical analysis description

Comparison between DUAC and ADA 0.1% +CLDM 1% at Week 8 for ILs. A negative treatment difference indicates a benefit of Duac relative to ADA+CLDM.

Comparison groups

ADA 0.1% +CLDM 1% v DUAC

Number of subjects included in analysis

349

Analysis specification

Pre-specified

Analysis type

P-value

= 0.012 ^[32]

Method

mixed model repeated measures analysis

Parameter type

Mean difference (net)

Point estimate

-1.9

Confidence interval

level

95%

sides

2-sided

lower limit

-3.4

upper limit

-0.4

Notes
[32] - The analysis method was mixed-model for repeated measures with treatment, center, visit, treatment-by-visit interaction, Baseline ILs counts, Baseline-by-visit interaction as fixed effects.

Statistical analysis 10

Statistical analysis description

Comparison between DUAC and ADA 0.1% +CLDM 1% at Week 12 for ILs. A negative treatment difference indicates a benefit of Duac relative to ADA+CLDM.

Comparison groups

ADA 0.1% +CLDM 1% v DUAC

Number of subjects included in analysis

349

Analysis specification

Pre-specified

Analysis type

P-value

= 0.078 ^[33]

Method

mixed model repeated measures analysis

Parameter type

Mean difference (net)

Point estimate

-1.1

Confidence interval

level

95%

sides

2-sided

lower limit

-2.4

upper limit

0.1

Notes
[33] - The analysis method was mixed-model for repeated measures with treatment, center, visit, treatment-by-visit interaction, Baseline ILs counts, Baseline-by-visit interaction as fixed effects.

Statistical analysis 11

Statistical analysis description

Comparison between DUAC and ADA 0.1% +CLDM 1% at Week 1 for non-ILs. A negative treatment difference indicates a benefit of Duac relative to ADA+CLDM.

Comparison groups

ADA 0.1% +CLDM 1% v DUAC

Number of subjects included in analysis

349

Analysis specification

Pre-specified

Analysis type

P-value

= 0.367 ^[34]

Method

mixed model repeated measures analysis

Parameter type

Mean difference (net)

Point estimate

1.8

Confidence interval

level

95%

sides

2-sided

lower limit

-2.1

upper limit

5.7

Notes
[34] - The analysis method was mixed-model for repeated measures with treatment, center, visit, treatment-by-visit interaction, Baseline non-ILs counts, Baseline-by-visit interaction as fixed effects.

Statistical analysis 12

Statistical analysis description

Comparison between DUAC and ADA 0.1% +CLDM 1% at Week 2 for non-ILs. A negative treatment difference indicates a benefit of Duac relative to ADA+CLDM.

Comparison groups

ADA 0.1% +CLDM 1% v DUAC

Number of subjects included in analysis

349

Analysis specification

Pre-specified

Analysis type

P-value

= 0.148 ^[35]

Method

mixed model repeated measures analysis

Parameter type

Mean difference (net)

Point estimate

-3.1

Confidence interval

level

95%

sides

2-sided

lower limit

-7.4

upper limit

1.1

Notes
[35] - The analysis method was mixed-model for repeated measures with treatment, center, visit, treatment-by-visit interaction, Baseline non-ILs counts, Baseline-by-visit interaction as fixed effects.

Statistical analysis 13

Statistical analysis description

Comparison between DUAC and ADA 0.1% +CLDM 1% at Week 4 for non-ILs. A negative treatment difference indicates a benefit of Duac relative to ADA+CLDM.

Comparison groups

ADA 0.1% +CLDM 1% v DUAC

Number of subjects included in analysis

349

Analysis specification

Pre-specified

Analysis type

P-value

= 0.314 ^[36]

Method

mixed model repeated measures analysis

Parameter type

Mean difference (net)

Point estimate

-2

Confidence interval

level

95%

sides

2-sided

lower limit

-5.9

upper limit

1.9

Notes
[36] - The analysis method was mixed-model for repeated measures with treatment, center, visit, treatment-by-visit interaction, Baseline non-ILs counts, Baseline-by-visit interaction as fixed effects.

Statistical analysis 14

Statistical analysis description

Comparison between DUAC and ADA 0.1% +CLDM 1% at Week 8 for non-ILs. A negative treatment difference indicates a benefit of Duac relative to ADA+CLDM.

Comparison groups

ADA 0.1% +CLDM 1% v DUAC

Number of subjects included in analysis

349

Analysis specification

Pre-specified

Analysis type

P-value

= 0.494 ^[37]

Method

mixed model repeated measures analysis

Parameter type

Mean difference (net)

Point estimate

1.2

Confidence interval

level

95%

sides

2-sided

lower limit

-2.3

upper limit

4.7

Notes
[37] - The analysis method was mixed-model for repeated measures with treatment, center, visit, treatment-by-visit interaction, Baseline non-ILs counts, Baseline-by-visit interaction as fixed effects.

Statistical analysis 15

Statistical analysis description

Comparison between DUAC and ADA 0.1% +CLDM 1% at Week 12 for non-ILs. A negative treatment difference indicates a benefit of Duac relative to ADA+CLDM.

Comparison groups

ADA 0.1% +CLDM 1% v DUAC

Number of subjects included in analysis

349

Analysis specification

Pre-specified

Analysis type

P-value

= 0.684 ^[38]

Method

mixed model repeated measures analysis

Parameter type

Mean difference (net)

Point estimate

-0.6

Confidence interval

level

95%

sides

2-sided

lower limit

-3.5

upper limit

2.3

Notes
[38] - The analysis method was mixed-model for repeated measures with treatment, center, visit, treatment-by-visit interaction, Baseline non-ILs counts, Baseline-by-visit interaction as fixed effects.

Secondary: Percentage of participants with a minimum of 2-grade improvement in investigator's static global assessment (ISGA) score from Baseline to Weeks 1, 2, 4, 8 and 12

Top of page

End point title

Percentage of participants with a minimum of 2-grade improvement in investigator's static global assessment (ISGA) score from Baseline to Weeks 1, 2, 4, 8 and 12

End point description

Responder was defined as participants with a minimum 2-grade improvement in ISGA score from Baseline. ISGA scale was scored from 0-5 (0= Clear skin with no inflammatory or non-ILs, 1= Almost clear: rare non-ILs present, with no more than rare papules, 2= Mild severity: greater than Grade 1, some non-ILs with no more than few inflammatory lesions, 3= Moderate severity: greater than Grade 2, many non-ILS, may have some ILs, but no more than 1 small nodular lesion, 4= Severe: greater than Grade 3, up to many non-ILs and ILs, but no more than a few nodular lesions, 5= Very severe: many non -ILs and ILs and more than a few nodular lesions. May have cystic lesions). Percentage of participants was calculated by dividing number of participants with 2-grade improvement in ISGA score from Baseline by total number of participants value multiplied by 100.

End point type

Secondary

End point timeframe

Week 1, 2, 4, 8, 12

End point values	DUAC	ADA 0.1% +CLDM 1%
Number of subjects analysed	172 ^[39]	177 ^[40]
Units: Percentage of participants
Week 1	2	0
Week 2	6	3
Week 4	12	8
Week 8	22	12
Week 12	37	27

Notes
[39] - ITT population
[40] - ITT population

Statistical analysis 1

Statistical analysis description

Comparison between DUAC and ADA 0.1% +CLDM 1% at Week 1.The participants with missing data at a visit were included in the denominator (n) at the visit. That is, those participants were treated as non-responder at the visit.

Comparison groups

ADA 0.1% +CLDM 1% v DUAC

Number of subjects included in analysis

349

Analysis specification

Pre-specified

Analysis type

P-value

= 0.047 ^[41]

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in percentage

Point estimate

2.3

Confidence interval

level

95%

sides

2-sided

lower limit

0.1

upper limit

4.6

Notes
[41] - The P-value was based on the Cochran-Mantel-Haenszel test stratified by center.

Statistical analysis 2

Statistical analysis description

Comparison between DUAC and ADA 0.1% +CLDM 1% at Week 2. The participants with missing data at a visit were included in the denominator (n) at the visit. That is, those participants were treated as non-responder at the visit.

Comparison groups

ADA 0.1% +CLDM 1% v DUAC

Number of subjects included in analysis

349

Analysis specification

Pre-specified

Analysis type

P-value

= 0.185 ^[42]

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in percentage

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-1.3

upper limit

7.3

Notes
[42] - The P-value was based on the Cochran-Mantel-Haenszel test stratified by center.

Statistical analysis 3

Statistical analysis description

Comparison between DUAC and ADA 0.1% +CLDM 1% at Week 4. The participants with missing data at a visit were included in the denominator (n) at the visit. That is, those participants were treated as non-responder at the visit.

Comparison groups

ADA 0.1% +CLDM 1% v DUAC

Number of subjects included in analysis

349

Analysis specification

Pre-specified

Analysis type

P-value

= 0.251 ^[43]

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in percentage

Point estimate

3.7

Confidence interval

level

95%

sides

2-sided

lower limit

-2.5

upper limit

9.9

Notes
[43] - The P-value was based on the Cochran-Mantel-Haenszel test stratified by center.

Statistical analysis 4

Statistical analysis description

Comparison between DUAC and ADA 0.1% +CLDM 1% at Week 8. The participants with missing data at a visit were included in the denominator (n) at the visit. That is, those participants were treated as non-responder at the visit.

Comparison groups

ADA 0.1% +CLDM 1% v DUAC

Number of subjects included in analysis

349

Analysis specification

Pre-specified

Analysis type

P-value

= 0.006 ^[44]

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in percentage

Point estimate

10.2

Confidence interval

level

95%

sides

2-sided

lower limit

2.4

upper limit

Notes
[44] - The P-value was based on the Cochran-Mantel-Haenszel test stratified by center.

Statistical analysis 5

Statistical analysis description

Comparison between DUAC and ADA 0.1% +CLDM 1% at Week 12. The participants with missing data at a visit were included in the denominator (n) at the visit. That is, those participants were treated as non-responder at the visit.

Comparison groups

ADA 0.1% +CLDM 1% v DUAC

Number of subjects included in analysis

349

Analysis specification

Pre-specified

Analysis type

P-value

= 0.022 ^[45]

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in percentage

Point estimate

10.7

Confidence interval

level

95%

sides

2-sided

lower limit

0.9

upper limit

20.4

Notes
[45] - The P-value was based on the Cochran-Mantel-Haenszel test stratified by center.

Secondary: Percentage of participants with ISGA score of 0 or 1 at Weeks 1, 2, 4, 8 and 12

Top of page

End point title

Percentage of participants with ISGA score of 0 or 1 at Weeks 1, 2, 4, 8 and 12

End point description

Responder was defined as participant with ISGA score of 0 or 1. ISGA scale was scored from 0-5 (0= Clear skin with no inflammatory or non-ILs, 1= Almost clear: rare non-ILs present, with no more than rare papules, 2= Mild severity: greater than Grade 1, some non-ILs with no more than few inflammatory lesions, 3= Moderate severity: greater than Grade 2, many non-ILS, may have some ILs, but no more than 1 small nodular lesion, 4= Severe: greater than Grade 3, up to many non-ILs and ILs, but no more than a few nodular lesions, 5= Very severe: many non -ILs and ILs and more than a few nodular lesions. May have cystic lesions). Percentage of participants was calculated by dividing number of participants with 0-1 ISGA score post Baseline by total number of participants value multiplied by 100.

End point type

Secondary

End point timeframe

Week 1, 2, 4, 8 and 12

End point values	DUAC	ADA 0.1% +CLDM 1%
Number of subjects analysed	172 ^[46]	177 ^[47]
Units: Percentage of participants
Week 1	2	1
Week 2	6	5
Week 4	13	6
Week 8	20	12
Week 12	41	29

Notes
[46] - ITT population
[47] - ITT population

Statistical analysis 1

Statistical analysis description

Comparison between DUAC and ADA 0.1% +CLDM 1% at Week 1. The participants with missing data at a visit were included in the denominator (n) at the visit. That is, those participants were treated as non-responder at the visit.

Comparison groups

ADA 0.1% +CLDM 1% v DUAC

Number of subjects included in analysis

349

Analysis specification

Pre-specified

Analysis type

P-value

= 0.129 ^[48]

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in percentage

Point estimate

1.8

Confidence interval

level

95%

sides

2-sided

lower limit

-0.7

upper limit

4.3

Notes
[48] - The P-value was based on the Cochran-Mantel-Haenszel test stratified by center.

Statistical analysis 2

Statistical analysis description

Comparison groups

ADA 0.1% +CLDM 1% v DUAC

Number of subjects included in analysis

349

Analysis specification

Pre-specified

Analysis type

P-value

= 0.612 ^[49]

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in percentage

Point estimate

1.3

Confidence interval

level

95%

sides

2-sided

lower limit

-3.4

upper limit

5.9

Notes
[49] - The P-value was based on the Cochran-Mantel-Haenszel test stratified by center.

Statistical analysis 3

Statistical analysis description

Comparison groups

ADA 0.1% +CLDM 1% v DUAC

Number of subjects included in analysis

349

Analysis specification

Pre-specified

Analysis type

P-value

= 0.016 ^[50]

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in percentage

Point estimate

7.1

Confidence interval

level

95%

sides

2-sided

lower limit

1.1

upper limit

13.2

Notes
[50] - The P-value was based on the Cochran-Mantel-Haenszel test stratified by center.

Statistical analysis 4

Statistical analysis description

Comparison groups

ADA 0.1% +CLDM 1% v DUAC

Number of subjects included in analysis

349

Analysis specification

Pre-specified

Analysis type

P-value

= 0.034 ^[51]

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in percentage

Point estimate

7.9

Confidence interval

level

95%

sides

2-sided

lower limit

0.3

upper limit

15.5

Notes
[51] - The P-value was based on the Cochran-Mantel-Haenszel test stratified by center.

Statistical analysis 5

Statistical analysis description

Comparison groups

ADA 0.1% +CLDM 1% v DUAC

Number of subjects included in analysis

349

Analysis specification

Pre-specified

Analysis type

P-value

= 0.018 ^[52]

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in percentage

Point estimate

11.3

Confidence interval

level

95%

sides

2-sided

lower limit

1.4

upper limit

21.3

Notes
[52] - The P-value was based on the Cochran-Mantel-Haenszel test stratified by center.

Secondary: Percentage of participants with at least 50% reduction in lesion counts (TLs, ILs and non-ILs) from Baseline at Weeks 1, 2, 4, 8 and 12

Top of page

End point title

Percentage of participants with at least 50% reduction in lesion counts (TLs, ILs and non-ILs) from Baseline at Weeks 1, 2, 4, 8 and 12

End point description

Responder was defined as participants with at least a 50% reduction in TLs, ILs and non-ILs. Data for number of participants is reported. Percentage of participants was calculated by dividing number of responders by total number of participants value multiplied by 100.

End point type

Secondary

End point timeframe

Week 1, 2, 4, 8 and 12

End point values	DUAC	ADA 0.1% +CLDM 1%
Number of subjects analysed	172 ^[53]	177 ^[54]
Units: Percentage of participants
Week 1 TLs, n= 172, 176	22	18
Week 2 TLs, n= 172, 177	47	42
Week 4 TLs, n= 172, 177	67	60
Week 8 TLs, n= 172, 177	81	81
Week 12 TLs, n= 172, 177	88	86
Week 1 ILs, n= 172, 176	51	42
Week 2 ILs, n= 172, 177	77	66
Week 4 ILs, n= 172, 177	85	76
Week 8 ILs, n= 172, 177	87	84
Week 12 ILs, n= 172, 177	92	89
Week 1 non-ILs, n= 172, 176	14	16
Week 2 non-ILs, n= 172, 177	37	34
Week 4 non-ILs, n= 172, 177	58	54
Week 8 non-ILs, n= 172, 177	73	73
Week 12 non-ILs, n= 172, 177	83	80

Notes
[53] - ITT population
[54] - ITT population

Statistical analysis 1

Statistical analysis description

Comparison between DUAC and ADA 0.1% +CLDM 1% at Week 1 for TLs. The participants with missing data at a visit were included in the denominator (n) at the visit. That is, those participants were treated as non-responder at the visit.

Comparison groups

ADA 0.1% +CLDM 1% v DUAC

Number of subjects included in analysis

349

Analysis specification

Pre-specified

Analysis type

P-value

= 0.379 ^[55]

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in percentage

Point estimate

3.9

Confidence interval

level

95%

sides

2-sided

lower limit

-4.5

upper limit

12.3

Notes
[55] - The P-value was based on the Cochran-Mantel-Haenszel test stratified by center.

Statistical analysis 2

Statistical analysis description

Comparison between DUAC and ADA 0.1% +CLDM 1% at Week 2 for TLs. The participants with missing data at a visit were included in the denominator (n) at the visit. That is, those participants were treated as non-responder at the visit.

Comparison groups

ADA 0.1% +CLDM 1% v DUAC

Number of subjects included in analysis

349

Analysis specification

Pre-specified

Analysis type

P-value

= 0.409 ^[56]

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in percentage

Point estimate

4.7

Confidence interval

level

95%

sides

2-sided

lower limit

-5.7

upper limit

15.1

Notes
[56] - The P-value was based on the Cochran-Mantel-Haenszel test stratified by center.

Statistical analysis 3

Statistical analysis description

Comparison between DUAC and ADA 0.1% +CLDM 1% at Week 4 for TLs. The participants with missing data at a visit were included in the denominator (n) at the visit. That is, those participants were treated as non-responder at the visit.

Comparison groups

ADA 0.1% +CLDM 1% v DUAC

Number of subjects included in analysis

349

Analysis specification

Pre-specified

Analysis type

P-value

= 0.18 ^[57]

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in percentage

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-3.1

upper limit

Notes
[57] - The P-value was based on the Cochran-Mantel-Haenszel test stratified by center.

Statistical analysis 4

Statistical analysis description

Comparison between DUAC and ADA 0.1% +CLDM 1% at Week 8 for TLs. The participants with missing data at a visit were included in the denominator (n) at the visit. That is, those participants were treated as non-responder at the visit.

Comparison groups

ADA 0.1% +CLDM 1% v DUAC

Number of subjects included in analysis

349

Analysis specification

Pre-specified

Analysis type

P-value

= 0.81 ^[58]

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in percentage

Point estimate

-0.5

Confidence interval

level

95%

sides

2-sided

lower limit

-8.8

upper limit

7.7

Notes
[58] - The P-value was based on the Cochran-Mantel-Haenszel test stratified by center.

Statistical analysis 5

Statistical analysis description

Comparison between DUAC and ADA 0.1% +CLDM 1% at Week 12 for TLs. The participants with missing data at a visit were included in the denominator (n) at the visit. That is, those participants were treated as non-responder at the visit.

Comparison groups

ADA 0.1% +CLDM 1% v DUAC

Number of subjects included in analysis

349

Analysis specification

Pre-specified

Analysis type

P-value

= 0.648 ^[59]

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in percentage

Point estimate

1.9

Confidence interval

level

95%

sides

2-sided

lower limit

-5.2

upper limit

Notes
[59] - The P-value was based on the Cochran-Mantel-Haenszel test stratified by center.

Statistical analysis 6

Statistical analysis description

Comparison between DUAC and ADA 0.1% +CLDM 1% at Week 1 for ILs. The participants with missing data at a visit were included in the denominator (n) at the visit. That is, those participants were treated as non-responder at the visit.

Comparison groups

ADA 0.1% +CLDM 1% v DUAC

Number of subjects included in analysis

349

Analysis specification

Pre-specified

Analysis type

P-value

= 0.048 ^[60]

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in percentage

Point estimate

9.1

Confidence interval

level

95%

sides

2-sided

lower limit

-1.3

upper limit

19.6

Notes
[60] - The P-value was based on the Cochran-Mantel-Haenszel test stratified by center.

Statistical analysis 7

Statistical analysis description

Comparison between DUAC and ADA 0.1% +CLDM 1% at Week 2 for ILs. The participants with missing data at a visit were included in the denominator (n) at the visit. That is, those participants were treated as non-responder at the visit.

Comparison groups

ADA 0.1% +CLDM 1% v DUAC

Number of subjects included in analysis

349

Analysis specification

Pre-specified

Analysis type

P-value

= 0.016 ^[61]

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in percentage

Point estimate

11.2

Confidence interval

level

95%

sides

2-sided

lower limit

1.8

upper limit

20.6

Notes
[61] - The P-value was based on the Cochran-Mantel-Haenszel test stratified by center.

Statistical analysis 8

Statistical analysis description

Comparison between DUAC and ADA 0.1% +CLDM 1% at Week 4 for ILs. The participants with missing data at a visit were included in the denominator (n) at the visit. That is, those participants were treated as non-responder at the visit.

Comparison groups

ADA 0.1% +CLDM 1% v DUAC

Number of subjects included in analysis

349

Analysis specification

Pre-specified

Analysis type

P-value

= 0.044 ^[62]

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in percentage

Point estimate

8.6

Confidence interval

level

95%

sides

2-sided

lower limit

0.4

upper limit

16.9

Notes
[62] - The P-value was based on the Cochran-Mantel-Haenszel test stratified by center.

Statistical analysis 9

Statistical analysis description

Comparison between DUAC and ADA 0.1% +CLDM 1% at Week 8 for ILs. The participants with missing data at a visit were included in the denominator (n) at the visit. That is, those participants were treated as non-responder at the visit.

Comparison groups

ADA 0.1% +CLDM 1% v DUAC

Number of subjects included in analysis

349

Analysis specification

Pre-specified

Analysis type

P-value

= 0.345 ^[63]

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in percentage

Point estimate

3.6

Confidence interval

level

95%

sides

2-sided

lower limit

-3.8

upper limit

Notes
[63] - The P-value was based on the Cochran-Mantel-Haenszel test stratified by center.

Statistical analysis 10

Statistical analysis description

Comparison between DUAC and ADA 0.1% +CLDM 1% at Week 12 for ILs. The participants with missing data at a visit were included in the denominator (n) at the visit. That is, those participants were treated as non-responder at the visit.

Comparison groups

ADA 0.1% +CLDM 1% v DUAC

Number of subjects included in analysis

349

Analysis specification

Pre-specified

Analysis type

P-value

= 0.424 ^[64]

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in percentage

Point estimate

2.6

Confidence interval

level

95%

sides

2-sided

lower limit

-3.5

upper limit

8.7

Notes
[64] - The P-value was based on the Cochran-Mantel-Haenszel test stratified by center.

Statistical analysis 11

Statistical analysis description

Comparison between DUAC and ADA 0.1% +CLDM 1% at Week 1 for non-ILs. The participants with missing data at a visit were included in the denominator (n) at the visit. That is, those participants were treated as non-responder at the visit.

Comparison groups

ADA 0.1% +CLDM 1% v DUAC

Number of subjects included in analysis

349

Analysis specification

Pre-specified

Analysis type

P-value

= 0.527 ^[65]

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in percentage

Point estimate

-2

Confidence interval

level

95%

sides

2-sided

lower limit

-9.4

upper limit

5.5

Notes
[65] - The P-value was based on the Cochran-Mantel-Haenszel test stratified by center.

Statistical analysis 12

Statistical analysis description

Comparison between DUAC and ADA 0.1% +CLDM 1% at Week 2 for non-ILs. The participants with missing data at a visit were included in the denominator (n) at the visit. That is, those participants were treated as non-responder at the visit.

Comparison groups

ADA 0.1% +CLDM 1% v DUAC

Number of subjects included in analysis

349

Analysis specification

Pre-specified

Analysis type

P-value

= 0.584 ^[66]

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in percentage

Point estimate

3.3

Confidence interval

level

95%

sides

2-sided

lower limit

-6.7

upper limit

13.4

Notes
[66] - The P-value was based on the Cochran-Mantel-Haenszel test stratified by center.

Statistical analysis 13

Statistical analysis description

Comparison between DUAC and ADA 0.1% +CLDM 1% at Week 4 for non-ILs. The participants with missing data at a visit were included in the denominator (n) at the visit. That is, those participants were treated as non-responder at the visit.

Comparison groups

ADA 0.1% +CLDM 1% v DUAC

Number of subjects included in analysis

349

Analysis specification

Pre-specified

Analysis type

P-value

= 0.519 ^[67]

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in percentage

Point estimate

3.9

Confidence interval

level

95%

sides

2-sided

lower limit

-6.5

upper limit

14.3

Notes
[67] - The P-value was based on the Cochran-Mantel-Haenszel test stratified by center.

Statistical analysis 14

Statistical analysis description

Comparison between DUAC and ADA 0.1% +CLDM 1% at Week 8 for non-ILs. The participants with missing data at a visit were included in the denominator (n) at the visit. That is, those participants were treated as non-responder at the visit.

Comparison groups

ADA 0.1% +CLDM 1% v DUAC

Number of subjects included in analysis

349

Analysis specification

Pre-specified

Analysis type

P-value

= 0.766 ^[68]

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in percentage

Point estimate

-0.8

Confidence interval

level

95%

sides

2-sided

lower limit

-10.1

upper limit

8.5

Notes
[68] - The P-values are based on the Cochran-Mantel-Haenszel test stratified by center.

Statistical analysis 15

Statistical analysis description

Comparison between DUAC and ADA 0.1% +CLDM 1% at Week 12 for non-ILs. The participants with missing data at a visit were included in the denominator (n) at the visit. That is, those participants were treated as non-responder at the visit.

Comparison groups

ADA 0.1% +CLDM 1% v DUAC

Number of subjects included in analysis

349

Analysis specification

Pre-specified

Analysis type

P-value

= 0.666 ^[69]

Method

Cochran-Mantel-Haenszel

Parameter type

Odds ratio (OR)

Point estimate

2.3

Confidence interval

level

95%

sides

2-sided

lower limit

-5.8

upper limit

10.5

Notes
[69] - The P-value was based on the Cochran-Mantel-Haenszel test stratified by center.

Secondary: Number of participants with treatment adherence rate at Weeks 1, 2, 4, 8 and 12

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End point title

Number of participants with treatment adherence rate at Weeks 1, 2, 4, 8 and 12

End point description

The investigator (or sub-investigator), the product storage manager, or the blinded coordinator dispensed a study compliance log to record participant’s compliance with investigational product application from Baseline to the end of study treatment. The product storage manager or the blinded coordinator evaluated the participant’s compliance with study treatment, using the study compliance log at each visit, and recorded the compliance data in the eCRF. Data for this outcome measure was not analyzed.

End point type

Secondary

End point timeframe

Week 1, 2, 4, 8 and 12

End point values	DUAC	ADA 0.1% +CLDM 1%
Number of subjects analysed	0 ^[70]	0 ^[71]
Units: Participants

Notes
[70] - Subjects were not analysed.
[71] - Subjects were not analysed.

No statistical analyses for this end point

Secondary: Number of participants who continue treatment at Weeks 1, 2, 4, 8 and 12

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End point title

Number of participants who continue treatment at Weeks 1, 2, 4, 8 and 12

End point description

Number of participants who continue treatment till Weeks 12 was measured. Data for this outcome measure was not analyzed.

End point type

Secondary

End point timeframe

Week 1, 2, 4, 8 and 12

End point values	DUAC	ADA 0.1% +CLDM 1%
Number of subjects analysed	0 ^[72]	0 ^[73]
Units: Participants

Notes
[72] - Subjects were not analysed.
[73] - Subjects were not analysed.

No statistical analyses for this end point

Secondary: Participant's treatment preference at Weeks 1, 2, 4, 8 and 12

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End point title

Participant's treatment preference at Weeks 1, 2, 4, 8 and 12

End point description

Participants had to rate each question on a 5-point scale of 0 to 4 (4: yes, very easy to use, 3: yes, easy, 2: slightly easy, 1: slightly difficult, 0: No) where larger score indicates more preferable participant's feeling. There were 5 questions in the questionnaire: ease of application, comfort, satisfaction with treatment (ST), comparison with prior therapies (CPT) and willingness to continue using the product (WCP).

End point type

Secondary

End point timeframe

Week 1, 2, 4, 8 and 12

End point values	DUAC	ADA 0.1% +CLDM 1%
Number of subjects analysed	172 ^[74]	177 ^[75]
Units: Participants
Week 1: Ease of application, Score 4, n= 172, 176	131	95
Week 1: Ease of application, Score 3, n= 172, 176	38	66
Week 1: Ease of application, Score 2, n= 172, 176	2	13
Week 1: Ease of application, Score 1, n= 172, 176	1	2
Week 2: Ease of application, Score 4, n= 169, 176	128	83
Week 2: Ease of application, Score 3, n= 169, 176	38	75
Week 2: Ease of application, Score 2, n= 169, 176	2	17
Week 2: Ease of application, Score 1, n= 169, 176	1	1
Week 4: Ease of application, Score 4, n= 169, 174	118	85
Week 4: Ease of application, Score 3, n= 169, 174	49	70
Week 4: Ease of application, Score 2, n= 169, 174	2	18
Week 4: Ease of application, Score 1, n= 169, 174	0	1
Week 8: Ease of application, Score 4, n= 167, 172	114	90
Week 8: Ease of application, Score 3, n= 167, 172	50	60
Week 8: Ease of application, Score 2, n= 167, 172	3	19
Week 8: Ease of application, Score 1, n= 167, 172	0	3
Week 12: Ease of application, Score 4, n= 164, 169	116	81
Week 12: Ease of application, Score 3, n= 164, 169	44	68
Week 12: Ease of application, Score 2, n= 164, 169	4	18
Week 12: Ease of application, Score 1, n= 164, 169	0	2
Week 1: Comfort, Score 4, n= 172, 176	37	24
Week 1: Comfort, Score 3, n= 172, 176	86	69
Week 1: Comfort, Score 2, n= 172, 176	37	45
Week 1: Comfort, Score 1, n= 172, 176	7	32
Week 1: Comfort, Score 0, n= 172, 176	5	6
Week 2: Comfort, Score 4, n= 169, 176	56	35
Week 2: Comfort, Score 3, n= 169, 176	70	81
Week 2: Comfort, Score 2, n= 169, 176	36	42
Week 2: Comfort, Score 1, n= 169, 176	6	17
Week 2: Comfort, Score 0, n= 169, 176	1	1
Week 4: Comfort, Score 4, n= 169, 174	72	47
Week 4: Comfort, Score 3, n= 169, 174	75	80
Week 4: Comfort, Score 2, n= 169, 174	17	31
Week 4: Comfort, Score 1, n= 169, 174	5	15
Week 4: Comfort, Score 0, n= 169, 174	0	1
Week 8: Comfort, Score 4, n= 167, 172	79	53
Week 8: Comfort, Score 3, n= 167, 172	69	68
Week 8: Comfort, Score 2, n= 167, 172	18	36
Week 8: Comfort, Score 1, n= 167, 172	1	13
Week 8: Comfort, Score 0, n= 167, 172	0	2
Week 12: Comfort, Score 4, n= 164, 169	84	56
Week 12: Comfort, Score 3, n= 164, 169	66	73
Week 12: Comfort, Score 2, n= 164, 169	13	26
Week 12: Comfort, Score 1, n= 164, 169	1	13
Week 12: Comfort, Score 0, n= 164, 169	0	1
Week 1: ST, Score 4, n= 172, 176	36	21
Week 1: ST, Score 3, n= 172, 176	79	75
Week 1: ST, Score 2, n= 172, 176	46	49
Week 1: ST, Score 1, n= 172, 176	11	23
Week 1: ST, Score 0, n= 172, 176	0	8
Week 2: ST, Score 4, n= 169, 176	58	38
Week 2: ST, Score 3, n= 169, 176	70	81
Week 2: ST, Score 2, n= 169, 176	37	47
Week 2: ST, Score 1, n= 169, 176	4	7
Week 2: ST, Score 0, n= 169, 176	0	3
Week 4: ST, Score 4, n= 169, 174	66	44
Week 4: ST, Score 3, n= 169, 174	72	81
Week 4: ST, Score 2, n= 169, 174	27	40
Week 4: ST, Score 1, n= 169, 174	4	8
Week 4: ST, Score 0, n= 169, 174	0	1
Week 8: ST, Score 4, n= 167, 172	78	58
Week 8: ST, Score 3, n= 167, 172	67	72
Week 8: ST, Score 2, n= 167, 172	17	33
Week 8: ST, Score 1, n= 167, 172	5	6
Week 8: ST, Score 0, n= 167, 172	0	3
Week 12: ST, Score 4, n= 164, 169	82	63
Week 12: ST, Score 3, n= 164, 169	61	70
Week 12: ST, Score 2, n= 164, 169	20	29
Week 12: ST, Score 1, n= 164, 169	1	6
Week 12: ST, Score 0, n= 164, 169	0	1
Week 1: CPT, Score 4, n= 172, 176	77	53
Week 1: CPT, Score 3, n= 172, 176	50	45
Week 1: CPT, Score 2, n= 172, 176	38	61
Week 1: CPT, Score 1, n= 172, 176	7	11
Week 1: CPT, Score 0, n= 172, 176	0	6
Week 2: CPT, Score 4, n= 169, 176	90	57
Week 2: CPT, Score 3, n= 169, 176	51	55
Week 2: CPT, Score 2, n= 169, 176	25	54
Week 2: CPT, Score 1, n= 169, 176	2	10
Week 2: CPT, Score 0, n= 169, 176	1	0
Week 4: CPT, Score 4, n= 169, 174	100	67
Week 4: CPT, Score 3, n= 169, 174	47	52
Week 4: CPT, Score 2, n= 169, 174	18	46
Week 4: CPT, Score 1, n= 169, 174	4	8
Week 4: CPT, Score 0, n= 169, 174	0	1
Week 8: CPT, Score 4, n= 167, 172	109	73
Week 8: CPT, Score 3, n= 167, 172	38	50
Week 8: CPT, Score 2, n= 167, 172	19	40
Week 8: CPT, Score 1, n= 167, 172	1	8
Week 8: CPT, Score 0, n= 167, 172	0	1
Week 12: CPT, Score 4, n= 164, 169	112	78
Week 12: CPT, Score 3, n= 164, 169	42	47
Week 12: CPT, Score 2, n= 164, 169	8	35
Week 12: CPT, Score 1, n= 164, 169	2	7
Week 12: CPT, Score 0, n= 164, 169	0	2
Week 1: WCP, Score 4, n= 172, 176	64	36
Week 1: WCP, Score 3, n= 172, 176	79	78
Week 1: WCP, Score 2, n= 172, 176	25	39
Week 1: WCP, Score 1, n= 172, 176	4	19
Week 1: WCP, Score 0, n= 172, 176	0	4
Week 2: WCP, Score 4, n= 169, 176	75	55
Week 2: WCP, Score 3, n= 169, 176	72	70
Week 2: WCP, Score 2, n= 169, 176	19	38
Week 2: WCP, Score 1, n= 169, 176	3	13
Week 4: WCP, Score 4, n= 169, 174	88	63
Week 4: WCP, Score 3, n= 169, 174	63	75
Week 4: WCP, Score 2, n= 169, 174	15	26
Week 4: WCP, Score 1, n= 169, 174	3	10
Week 8: WCP, Score 4, n= 167, 172	90	62
Week 8: WCP, Score 3, n= 167, 172	59	74
Week 8: WCP, Score 2, n= 167, 172	15	27
Week 8: WCP, Score 1, n= 167, 172	3	9
Week 12: WCP, Score 4, n= 164, 169	94	70
Week 12: WCP, Score 3, n= 164, 169	56	65
Week 12: WCP, Score 2, n= 164, 169	12	23
Week 12: WCP, Score 1, n= 164, 169	1	11
Week 12: WCP, Score 0, n= 164, 169	1	0

Notes
[74] - ITT population
[75] - ITT population

No statistical analyses for this end point

Secondary: Change from Baseline in Quality of life (QoL) score at Week 2, 4, 8 and 12

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End point title

Change from Baseline in Quality of life (QoL) score at Week 2, 4, 8 and 12

End point description

QOL questionnaire was assessed using Skindex-16 with 16 questions in 3 multi-item scales: symptoms, emotions and functioning for the past week: skin condition-itching, burning or stinging, hurting, being irritated, persistence/reoccurrence of skin condition, worry about condition, appearance of skin, frustration about skin, embarrassment about skin, being annoyed about your skin, feeling depressed about skin, effects of your skin on your interactions with others, effects of your skin condition on your desire to be with people, skin condition making it hard to show affection, effects of your skin condition on your daily activities and skin condition making it hard to work or do what you enjoy. Data for adjusted mean has been reported. The baseline value was the latest pre-dose assessment value. Change from baseline was calculated as the value at endpoint minus the value at Baseline. Scores range from 0-never bothered to 100-always bothered.

End point type

Secondary

End point timeframe

Baseline(Day 1) and Week 2, 4, 8 and 12

End point values	DUAC	ADA 0.1% +CLDM 1%
Number of subjects analysed	172 ^[76]	177
Units: Score on scale
least squares mean (standard error)
Week 2, n= 169, 176	-0.71 ± 0.070	-0.49 ± 0.068
Week 4, n= 169, 174	-1.02 ± 0.069	-0.80 ± 0.068
Week 8, n= 167, 172	-1.14 ± 0.073	-0.92 ± 0.071
Week 12, n= 164, 169	-1.27 ± 0.073	-1.10 ± 0.072

Notes
[76] - ITT population

Statistical analysis 1

Statistical analysis description

Comparison between DUAC and ADA 0.1% +CLDM 1% at Week 2. A negative treatment difference indicates a benefit of Duac relative to ADA+CLDM.

Comparison groups

DUAC v ADA 0.1% +CLDM 1%

Number of subjects included in analysis

349

Analysis specification

Pre-specified

Analysis type

P-value

= 0.017

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-0.22

Confidence interval

level

95%

sides

2-sided

lower limit

-0.4

upper limit

-0.04

Statistical analysis 2

Statistical analysis description

Comparison between DUAC and ADA 0.1% +CLDM 1% at Week 4. A negative treatment difference indicates a benefit of Duac relative to ADA+CLDM.

Comparison groups

DUAC v ADA 0.1% +CLDM 1%

Number of subjects included in analysis

349

Analysis specification

Pre-specified

Analysis type

P-value

= 0.017

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-0.22

Confidence interval

level

95%

sides

2-sided

lower limit

-0.4

upper limit

-0.04

Statistical analysis 3

Statistical analysis description

Comparison between DUAC and ADA 0.1% +CLDM 1% at Week 8. A negative treatment difference indicates a benefit of Duac relative to ADA+CLDM.

Comparison groups

DUAC v ADA 0.1% +CLDM 1%

Number of subjects included in analysis

349

Analysis specification

Pre-specified

Analysis type

P-value

= 0.024

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-0.22

Confidence interval

level

95%

sides

2-sided

lower limit

-0.41

upper limit

-0.03

Statistical analysis 4

Statistical analysis description

Comparison between DUAC and ADA 0.1% +CLDM 1% at Week 12. A negative treatment difference indicates a benefit of Duac relative to ADA+CLDM.

Comparison groups

DUAC v ADA 0.1% +CLDM 1%

Number of subjects included in analysis

349

Analysis specification

Pre-specified

Analysis type

P-value

= 0.08

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-0.17

Confidence interval

level

95%

sides

2-sided

lower limit

-0.36

upper limit

0.02

Secondary: Number of participants with any adverse events (AEs) and serious adverse events (SAEs)

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End point title

Number of participants with any adverse events (AEs) and serious adverse events (SAEs)

End point description

An AE was defined as any untoward medical occurrence that occurred during the course of the trial after study treatment had started. An adverse event was therefore any unfavorable and unintended sign, symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug. A SAE is any untoward medical occurrence that at any dose results in death, are life threatening, requires hospitalization or prolongation of hospitalization or results in disability/incapacity, and congenital anomaly/birth defect. Medical or scientific judgment was exercised in deciding whether reporting was appropriate. For liver injury and impaired liver function, alanine aminotransferase greater than or equal to (>=)3 times upper limit of normal (ULN) and total bilirubin >=2xULN (less than [>] 35% direct) was defined.

End point type

Secondary

End point timeframe

Up to Week 12

End point values	DUAC	ADA 0.1% +CLDM 1%
Number of subjects analysed	172 ^[77]	177
Units: Participants
Any AE	53	100
Any SAE	1	0

Notes
[77] - ITT population

No statistical analyses for this end point

Secondary: Local tolerability score for erythema, dryness, peeling, itching, and burning or stinging

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End point title

Local tolerability score for erythema, dryness, peeling, itching, and burning or stinging

End point description

Local tolerability score for erythema (no redness, faint red or pink coloration, barely perceptible, light red or pink coloration, medium red coloration, beet red coloration), dryness (none, barely perceptible dryness with no flakes or fissure formation, easily perceptible dryness with no flakes or fissure formation, easily noted dryness and flakes but no fissure formation, easily noted dryness with flakes and fissure formation), peeling (no peeling, mild localized peeling, mild and diffuse peeling, moderate and diffuse peeling, moderate to prominent, dense peeling) and itching and burning/stinging (normal-no discomfort, noticeable discomfort that causes intermittent awareness, continuous awareness, intermittent awareness and interferes occasionally with normal daily activities, a definite continuous discomfort that interferes with normal daily activities) was assessed on a scale of 0 to 4 (0= absent, 1= slight, 2= mild, 3= moderate and 4= severe).

End point type

Secondary

End point timeframe

Week 1, 2, 4, 8 and 12

End point values	DUAC	ADA 0.1% +CLDM 1%
Number of subjects analysed	172 ^[78]	177
Units: Score on scale
arithmetic mean (standard deviation)
Erythema Week 1, n= 170, 175	0.0 ± 0.61	0.3 ± 0.72
Erythema Week 2, n= 169, 175	0.0 ± 0.68	0.0 ± 0.70
Erythema Week 4, n= 169, 174	-0.1 ± 0.57	-0.1 ± 0.64
Erythema Week 8, n= 165, 171	-0.2 ± 0.68	-0.2 ± 0.69
Erythema Week 12, n= 165, 168	-0.2 ± 0.78	-0.3 ± 0.67
Dryness Week 1, n= 170, 175	0.1 ± 0.54	0.6 ± 0.95
Dryness Week 2, n= 169, 175	0.0 ± 0.50	0.1 ± 0.58
Dryness Week 4, n= 169, 174	0.0 ± 0.52	0.1 ± 0.49
Dryness Week 8, n= 165, 171	0.0 ± 0.58	0.1 ± 0.46
Dryness Week 12, n= 165, 168	0.0 ± 0.45	0.0 ± 0.35
Peeling Week 1, n= 170, 175	0.1 ± 0.43	0.5 ± 0.88
Peeling Week 2, n= 169, 175	0.1 ± 0.33	0.2 ± 0.55
Peeling Week 4, n= 169, 174	0.0 ± 0.34	0.1 ± 0.42
Peeling Week 8, n= 165, 171	0.1 ± 0.39	0.1 ± 0.46
Peeling Week 12, n= 165, 168	0.0 ± 0.31	0.0 ± 0.32
Itching Week 1, n= 170, 175	0.0 ± 0.64	0.1 ± 0.81
Itching Week 2, n= 169, 175	0.0 ± 0.60	0.1 ± 0.77
Itching Week 4, n= 169, 174	-0.1 ± 0.68	-0.1 ± 0.62
Itching Week 8, n= 165, 171	-0.2 ± 0.63	-0.1 ± 0.58
Itching Week 12, n= 165, 168	-0.2 ± 0.66	-0.2 ± 0.56
Burning/Stinging Week 1, n= 170, 175	0.0 ± 0.48	0.5 ± 0.85
Burning/Stinging Week 2, n= 169, 175	0.0 ± 0.44	0.2 ± 0.66
Burning/Stinging Week 4, n= 169, 174	0.0 ± 0.44	0.0 ± 0.47
Burning/Stinging Week 8, n= 165, 171	0.0 ± 0.34	0.1 ± 0.53
Burning/Stinging Week 12, n= 165, 168	0.0 ± 0.39	0.0 ± 0.40

Notes
[78] - ITT population

No statistical analyses for this end point

Secondary: Number of participants with Severity of AEs

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End point title

Number of participants with Severity of AEs

End point description

The severity of AEs was assessed by the investigator; events were assigned to one of the following categories: mild, an event that was easily tolerated by the participant, causing minimal discomfort and not interfering with everyday activities; moderate, an event that was sufficiently discomforting to interfere with normal everyday activities; and severe, an event that prevented normal everyday activities.

End point type

Secondary

End point timeframe

Up to Week 12

End point values	DUAC	ADA 0.1% +CLDM 1%
Number of subjects analysed	172 ^[79]	177
Units: Participants
Mild	46	91
Modertae	6	7
Severe	1	2

Notes
[79] - ITT population

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

AE and SAE were collected up to Week 12.

Adverse event reporting additional description

For AE and SAE, ITT population was analyzed.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

18.1

Reporting group title

ADA 0.1% +CLDM 1%

Reporting group description

Reporting group title

Duac

Reporting group description

Participants were instructed to use DUAC, a fixed dose combination gel (clindamycin phosphate 1.2% and benzoyl peroxide 3%) with quantity of 2 FTU about 0.6 gram (g) which was sufficient to cover entire face (including the forehead, nose, cheeks and chin) once daily in the evening (at bedtime) for 12 weeks.

Serious adverse events	ADA 0.1% +CLDM 1%	Duac
Total subjects affected by serious adverse events
subjects affected / exposed	0 / 177 (0.00%)	1 / 172 (0.58%)
number of deaths (all causes)	0	0
number of deaths resulting from adverse events	0	0
Gastrointestinal disorders
Duodenal ulcer
subjects affected / exposed	0 / 177 (0.00%)	1 / 172 (0.58%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 5%

Non-serious adverse events	ADA 0.1% +CLDM 1%	Duac
Total subjects affected by non serious adverse events
subjects affected / exposed	78 / 177 (44.07%)	34 / 172 (19.77%)
General disorders and administration site conditions
Application site dryness
subjects affected / exposed	44 / 177 (24.86%)	16 / 172 (9.30%)
occurrences all number	46	16
Application site pain
subjects affected / exposed	20 / 177 (11.30%)	3 / 172 (1.74%)
occurrences all number	21	3
Application site erythema
subjects affected / exposed	11 / 177 (6.21%)	4 / 172 (2.33%)
occurrences all number	12	4
Skin and subcutaneous tissue disorders
Eczema
subjects affected / exposed	10 / 177 (5.65%)	2 / 172 (1.16%)
occurrences all number	11	2
Infections and infestations
Nasopharyngitis
subjects affected / exposed	15 / 177 (8.47%)	12 / 172 (6.98%)
occurrences all number	16	13

More information

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Were there any global substantial amendments to the protocol? No

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

None reported

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Clinical trials

Clinical Trial Results: Clinical evaluation of efficacy at 2 weeks of Duac fixed dose combination gel in treatment of facial acne vulgaris in Japanese Subjects.

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Percent change in total lesion counts (TLs) from Baseline to Week 2

Primary: Percent change in total lesion counts (TLs) from Baseline to Week 2

Secondary: Percent change from Baseline in TLs to Weeks 1, 4, 8 and 12

Secondary: Percent change from Baseline in TLs to Weeks 1, 4, 8 and 12

Secondary: Percent change form Baseline in lesion counts (ILs and non-ILs) to Weeks 1, 2, 4, 8 and 12

Secondary: Percent change form Baseline in lesion counts (ILs and non-ILs) to Weeks 1, 2, 4, 8 and 12

Secondary: Absolute Change from Baseline in lesion counts (TLs, ILs and non-ILs) to Weeks 1, 2, 4, 8 and 12

Secondary: Absolute Change from Baseline in lesion counts (TLs, ILs and non-ILs) to Weeks 1, 2, 4, 8 and 12

Secondary: Percentage of participants with a minimum of 2-grade improvement in investigator's static global assessment (ISGA) score from Baseline to Weeks 1, 2, 4, 8 and 12

Secondary: Percentage of participants with a minimum of 2-grade improvement in investigator's static global assessment (ISGA) score from Baseline to Weeks 1, 2, 4, 8 and 12

Secondary: Percentage of participants with ISGA score of 0 or 1 at Weeks 1, 2, 4, 8 and 12

Secondary: Percentage of participants with ISGA score of 0 or 1 at Weeks 1, 2, 4, 8 and 12

Secondary: Percentage of participants with at least 50% reduction in lesion counts (TLs, ILs and non-ILs) from Baseline at Weeks 1, 2, 4, 8 and 12

Secondary: Percentage of participants with at least 50% reduction in lesion counts (TLs, ILs and non-ILs) from Baseline at Weeks 1, 2, 4, 8 and 12

Secondary: Number of participants with treatment adherence rate at Weeks 1, 2, 4, 8 and 12

Secondary: Number of participants with treatment adherence rate at Weeks 1, 2, 4, 8 and 12

Secondary: Number of participants who continue treatment at Weeks 1, 2, 4, 8 and 12

Secondary: Number of participants who continue treatment at Weeks 1, 2, 4, 8 and 12

Secondary: Participant's treatment preference at Weeks 1, 2, 4, 8 and 12

Secondary: Participant's treatment preference at Weeks 1, 2, 4, 8 and 12

Secondary: Change from Baseline in Quality of life (QoL) score at Week 2, 4, 8 and 12

Secondary: Change from Baseline in Quality of life (QoL) score at Week 2, 4, 8 and 12

Secondary: Number of participants with any adverse events (AEs) and serious adverse events (SAEs)

Secondary: Number of participants with any adverse events (AEs) and serious adverse events (SAEs)

Secondary: Local tolerability score for erythema, dryness, peeling, itching, and burning or stinging

Secondary: Local tolerability score for erythema, dryness, peeling, itching, and burning or stinging

Secondary: Number of participants with Severity of AEs

Secondary: Number of participants with Severity of AEs

Adverse events

Adverse events

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Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

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Clinical Trial Results:
Clinical evaluation of efficacy at 2 weeks of Duac fixed dose combination gel in treatment of facial acne vulgaris in Japanese Subjects.