Efficacy and safety comparison of combination of 0.04% tretinoin microspheres plus 1% clindamycin versus their monotherapy in patients with acne vulgaris: a phase 3, randomized, double-blind study

Figures & data

Figure 1. Study design and patient disposition. ^aPatients had multiple reasons for withdrawal.

Table 1. Patient baseline demographics and clinical characteristics by treatment groups (ITT population).

	Tretinoin microsphere 0.04% + Clindamycin 1% (n = 300)	Tretinoin 0.025% (n = 300)	Clindamycin 1% (n = 150)
Sex, n (%)
Men	189 (63.00)	166 (55.33)	93 (62.00)
Women	111 (37.00)	134 (44.67)	57 (38.00)
Age (years), median (range)	20 (13, 43)	20 (14, 48)	20 (12, 42)
Duration of acne (months), n (%)	n = 299	n = 299	n = 150
<1	1 (0.33)	1 (0.33)	1 (0.67)
1–6	148 (49.50)	151 (50.50)	81 (54.00)
7–12	76 (25.42)	71 (23.75)	36 (24.00)
13–24	37 (12.37)	35 (11.71)	14 (9.33)
25–48	25 (8.36)	22 (7.36)	11 (7.33)
49–60	7 (2.34)	10 (3.34)	4 (2.67)
61–120	4 (1.34)	7 (2.34)	3 (2.00)
>120	1 (0.33)	2 (0.67)	0
Baseline acne lesion count, median (range)
Facial inflammatory lesion (Total)	28 (20, 50)	28 (20, 65)	28 (15, 50)
Facial non-inflammatory lesion (total)	35 (20, 96)	35 (10, 100)	35.5 (16, 97)
Total lesion count	65 (40, 126)	65 (40, 132)	65 (40, 140)
Baseline facial acne inflammatory lesion – nodules, n (%)
None	153 (51.00)	156 (52.00)	85 (56.67)
1 nodule	107 (35.67)	109 (36.33)	45 (30.00)
2 nodules	40 (13.33)	35 (11.67)	20 (13.33)
Baseline ISGA score, n (%)
Moderate (Grade 3)	262 (87.33)	265 (88.33)	130 (86.67)
Severe (Grade 4)	38 (12.67)	35 (11.67)	20 (13.33)
Prior anti-acne treatment, n (%)
Topical
Adapalene	2 (0.67)	2 (0.67)	0
Adapalene + Benzoyl peroxide	1 (0.33)	0	0
Adapalene + Clindamycin	1 (0.33)	0	0
Avobenzene	0	1 (0.33)	0
Benzoyl peroxide	5 (1.67)	3 (1)	2 (1.33)
Benzoyl peroxide + Clindamycin	1 (0.33)	0	0
Betamethasone valerate	2 (0.67)	1 (0.33)	1 (0.67)
Cetyl alcohol	0	2 (0.67)	0
Clindamycin	3 (1)	5 (1.67)	5 (3.33)
Tretinoin	2 (0.67)	4 (1.33)	1 (0.67)
Acne derma soap	0	1 (0.33)	0
Oral
Azithromycin	1 (0.33)	3 (1)	0
Doxycycline	2 (0.67)	3 (1)	0
Isotretinoin	1 (0.33)	0	0

ISGA: Investigators Static Global Assessment; ITT: intent-to-treat. Data are presented as median (range) or number (percentage). Note. Two patients received anti-acne treatment, but details are unavailable. Prior therapy details were unavailable for one patient.

Figure 2. Comparison of mean percentage change in inflammatory, non-inflammatory and total lesion counts between treatment groups (ITT analysis set). ^†††p < .001 combination vs. clindamycin monotherapy; *p < .05, **p < .01 combination vs. tretinoin monotherapy. ITT: intent-to-treat.

Table 2. Primary and secondary efficacy endpoints (ITT population).

	Tretinoin microsphere 0.04% + Clindamycin 1% (n = 300)	Tretinoin 0.025% (n = 300)	p Value (T + C vs T)	Clindamycin 1% (n = 150)	p Value (T + C vs C)
Primary endpoint
Mean percent change in acne lesion count from baseline to week 12
Inflammatory lesion	77.11	70.87	.007	66.14	.000
Non-inflammatory lesion	71.27	67.14	.022	59.24	.000
Total acne count	73.29	68.73	.009	61.46	.000
Overall mean reduction in acne count at week 12, mean (SD)
Inflammatory lesion	22.61 (9.11)	21.27 (9.68)		19.81 (10.05)
Non-inflammatory lesion	27.37 (14.61)	26.45 (15.86)		22.93 (13.64)
Total acne count	49.53 (20.82)	47.63 (22.32)		42.20 (21.73)
Secondary endpoints
ISGA score at week 12, n (%)
Clear (Grade 0)	18 (6.00)	17 (5.67)		1 (0.67)
Almost clear (Grade 1)	105 (35.00)	78 (26.00)		40 (26.67)
Mild (Grade 2)	140 (46.67)	155 (51.67)		72 (48.00)
Moderate (Grade 3)	32 (10.67)	47 (15.67)		33 (22.00)
Severe (Grade 4)	5 (1.67)	3 (1.00)		4 (2.67)
Patients with clear or almost clear lesion, n (%)	123 (41.00)	95 (31.67)	.017	41 (27.33)	.005
Patients with clear or almost clear lesion AND 2 grade improvement in ISGA score, n (%)	137 (45.67)	108 (36.00)	.016	43 (28.67)	.001
Physician’s global evaluation of efficacy, n (%)	n = 277	n = 271		n = 133
Excellent	108 (38.99)	68 (25.09)	.009	23 (17.29)	.000
Good	159 (57.40)	194 (71.59)		96 (72.18)
No change	7 (2.53)	7 (2.58)		10 (7.52)
Poor	2 (0.72)	2 (0.74)		4 (3.01)
Worse	1 (0.36)	0		0

T + C: Tretinoin microsphere 0.04% + Clindamycin 1%; T: Tretinoin 0.025%; C: Clindamycin 1%; ISGA: Investigators Static Global Assessment; ITT: intent-to-treat.

Figure 3. Comparison of physician’s global evaluation of efficacy (ITT analysis set). ITT: intent-to-treat.

Table 3. Summary of adverse events.

	Tretinoin microsphere 0.04% + Clindamycin 1% (n = 300)	Tretinoin 0.025% (n = 300)	Clindamycin 1% (n = 150)
Any AE, n (%)	6 (2)	11 (3.7)	3 (2)
AEs by severity, n (%)
Mild	4 (1.3)	7 (2.3)	3 (2)
Moderate	2 (0.7)	3 (1)	0
Severe	0	1 (0.3)	0
AEs based on action taken, n (%)
None	0	2 (0.7)	1 (0.7)
Exclusion/termination of patient’s participation	0	2 (0.7)	0
Concomitant medication administered	5 (1.7)	6 (2)	0
Inpatient hospitalization	0	0	0
Other	1 (0.3)	1 (0.3)	2 (1.3)
AEs based on outcome, n (%)
Recovered	5 (1.7)	7 (2.3)	0
Improvement	0	1 (0.3)	0
AE ongoing, patient under treatment/observation	1 (0.3)	0	2 (1.3)
Residual effects-still persisting	0	0	0
Lost to follow up	0	1 (0.3)	0
Discontinued	0	2 (0.7)	0
Other	0	0	1 (0.7)
Distribution of AEs, n (%)
Constipation	1 (0.3)	0	0
Gastroesophageal reflux disorder	0	1 (0.3)	0
Blood glucose increased	0	1 (0.3)	1 (0.7)
Blood Bilirubin increased	0	0	1 (0.7)
Pyrexia	3 (1)	2 (0.7)	0
Upper respiratory tract infection	0	1 (0.3)	0
Dermatitis	0	2 (0.7)	0
Eczema asteatotic	1 (0.3)	0	0
Swelling face	0	1 (0.3)	0
Erythema	0	2 (0.7)	0
Acne	1 (0.3)	1 (0.3)	0
Urinary tract infection	0	0	1 (0.7)

AE: adverse event.