Dermal sensitization, safety, and tolerability of triple-combination clindamycin phosphate 1.2%/benzoyl peroxide 3.1%/adapalene 0.15% gel from three clinical trials

Figures & data

Figure 1. Study designs for the phase 1 RIPT (A) and CIPT (B) studies. RIPT study: determines the potential of a topical treatment to induce sensitization (allergic potential) via repeated applications over 6–12 weeks. CIPT study: evaluates a topical treatment’s irritancy potential as a result of direct damage to the epidermal cells (without involvement of allergic or immunologic mechanism) via repeated applications over 21 days. ^aParticipants were only re-challenged to a study material if there were signs suggestive of contact sensitization observed at any challenge evaluations or at the investigator’s discretion; this occurred approximately 4 weeks after the completion of the Challenge phase. BPO/ADAP: benzoyl peroxide 2.5%/adapalene 0.3% gel; CIPT: cumulative irritancy patch test; IDP-126: clindamycin phosphate 1.2%/benzoyl peroxide 3.1%/adapalene 0.15% gel; RIPT: repeat insult patch test; SLS: sodium lauryl sulfate; tiw: three times weekly.

Table 1. Clinical Grading and Corresponding Numeric Scores (Phase 1 Studies).

Clinical Grade^a	Score^b	Definition of Dermal Response
Numerical Grades
0	0	No evidence of irritation
1	1	Minimal erythema; barely perceptible
2	2	Definite erythema, readily visible; or minimal edema; or minimal papular response
3	3	Erythema and papules
4	3	Definite edema
5	3	Erythema, edema, and papules
6	3	Vesicular eruption
7	3	Strong reaction spreading beyond test site
Letter Grades
A	0	Slight glazed appearance
C	1	Marked glazing
E	2	Glazing with peeling and cracking
F	3	Glazing with fissures
G	3	Film of dried serous exudate covering all or portion of the patch site
H	3	Small petechial erosions and/or scabs
Patch test sum score = score from numerical grade + score from letter grade.

^aClinical grades were conducted throughout the study by the trained evaluator.

^bScores were utilized during the statistical analysis process of the study.

Table 2. Participant Demographics and Baseline Characteristics (Safety Populations).

	Phase 1		Phase 2^a
	RIPT	CIPT
	All Participants^b(n = 234)	All Participants^b(n = 45)	IDP-126 Gel (n = 146)	BPO / ADAP Gel (n = 150)	CLIN / BPO Gel (n = 146)	CLIN / ADAP Gel (n = 150)	Vehicle Gel (n = 148)
Age, mean (SD), y	55.0 (12.5)	54.8 (15.4)	19.9 (7.0)	19.2 (8.0)	19.6 (6.9)	19.4 (6.5)	19.6 (7.1)
Female, n (%)	167 (71.4)	35 (77.8)	94 (64.4)	86 (57.3)	91 (62.3)	93 (62.0)	89 (60.1)
Race, n (%)
White	71 (30.3)	14 (31.1)	98 (67.1)	109 (72.7)	101 (69.2)	109 (72.7)	95 (64.2)
Black	160 (68.4)	31 (68.9)	24 (16.4)	26 (17.3)	30 (20.5)	20 (13.3)	26 (17.6)
Asian	1 (0.4)	0	10 (6.8)	6 (4.0)	8 (5.5)	9 (6.0)	17 (11.5)
Other^c	2 (0.9)	0	14 (9.6)	9 (6.0)	7 (4.8)	12 (8.0)	10 (6.8)
Ethnicity, n (%)
Hispanic/Latino	25 (10.7)	4 (8.9)	33 (22.6)	30 (20.0)	29 (19.9)	27 (18.0)	34 (23.0)
Fitzpatrick skin type
I-III	81 (34.6)^d	9 (20.0)^d	--	--	--	--	--
IV-VI	153 (65.4)	36 (80.0)	--	--	--	--	--
Lesion count, mean (SD)
Inflammatory	--	--	39.0 (11.8)	39.0 (10.2)	40.0 (12.8)	38.2 (7.9)	38.2 (9.2)
Noninflammatory	--	--	51.8 (20.3)	48.0 (14.7)	49.2 (17.6)	51.1 (18.4)	50.7 (18.7)
Evaluator’s Global Severity Score, n (%)
3 – Moderate	--	--	124 (84.9)	119 (79.3)	124 (84.9)	129 (86.0)	127 (85.8)
4 – Severe	--	--	22 (15.1)	31 (20.7)	22 (15.1)	21 (14.0)	21 (14.2)

^aDemographic and baseline characteristics data were not available for the safety population (IDP-126, n = 141; BPO/ADAP, n = 146; CLIN/BPO, n = 144; CLIN/ADAP, n = 148; vehicle gel, n = 146); data shown are from the intent-to-treat population.

^bAll participants received patches with active, vehicle, control(s) (RIPT and CIPT) and comparator (CIPT only).

^cAmerican Indian/Alaska Native, Native Hawaiian/Other Pacific Islander, and Other/Multiple.

^dNo participants had Fitzpatrick skin type I.

–: not reported/not applicable; ADAP: adapalene 0.15%; BPO: benzoyl peroxide 3.1%; CIPT: cumulative irritancy patch test; CLIN: clindamycin phosphate 1.2%; IDP-126: clindamycin phosphate 1.2%/benzoyl peroxide 3.1%/adapalene 0.15%; RIPT: repeat insult patch test; SD: standard deviation.

Figure 2. Mean cumulative irritation scores (RIPT cumulative irritancy population; CIPT safety population). ***p < 0.001 vs IDP-126 gel. BPO/ADAP: benzoyl peroxide 2.5%/adapalene 0.3% gel; CIPT: cumulative irritancy patch test; IDP-126: clindamycin phosphate 1.2%/benzoyl peroxide 3.1%/adapalene 0.15% gel; RIPT: repeat insult patch test; SD: standard deviation; SLS: sodium lauryl sulfate.

Figure 3. Normalized total irritation scores (CIPT safety population). ***p < 0.001 vs IDP-126 gel. Normalized irritation scoring: 0–49 = no significant irritation; 50–199 = slightly irritating; 200–449 = moderately irritating; 450–630 = highly irritating. BPO/ADAP: benzoyl peroxide 2.5%/adapalene 0.3% gel; CIPT: cumulative irritancy patch test; IDP-126: clindamycin phosphate 1.2%/benzoyl peroxide 3.1%/adapalene 0.15% gel; SLS: sodium lauryl sulfate.

Table 3. Treatment-Emergent Adverse Events (Safety Populations).

n (%)	Phase 1		Phase 2
	RIPT	CIPT
	All Participants^a (n = 234)	All Participants^a (n = 45)	IDP-126 Gel (n = 141)	BPO / ADAP Gel (n = 146)	CLIN / BPO Gel (n = 144)	CLIN / ADAP Gel (n = 148)	Vehicle Gel (n = 146)
Participants reporting any TEAE	4 (1.7)	1 (2.2)	51 (36.2)	52 (35.6)	26 (18.1)	40 (27.0)	22 (15.1)
Participants reporting any SAE^b	1 (0.4)	1 (2.2)	1 (0.7)	0	0	3 (2.0)	0
Participants discontinuing due to AE/TEAE^c	3 (1.3)	1 (2.2)	4 (2.8)	8 (5.5)	0	3 (2.0)	2 (1.4)
Deaths	1 (0.4)^d	0	0	0	0	0	0
Severity of TEAEs reported
Mild	2 (0.9)	0	26 (18.4)	25 (17.1)	16 (11.1)	20 (13.5)	11 (7.5)
Moderate	1 (0.4)	1 (2.2)	18 (12.8)	22 (15.1)	10 (6.9)	17 (11.5)	10 (6.8)
Severe	1 (0.4)	0	7 (5.0)	5 (3.4)	0	3 (2.0)	1 (0.7)
Relationship to study drug
Related	0	0	28 (19.9)	32 (21.9)	3 (2.1)	18 (12.2)	2 (1.4)
Unrelated	4 (1.7)	1 (2.2)	23 (16.3)	20 (13.7)	23 (16.0)	22 (14.9)	20 (13.7)
TEAEs reported in ≥3% of participants in any treatment group
AS pain	--	--	11 (7.8)	16 (11.0)	1 (0.7)	5 (3.4)	1 (0.7)
AS dryness	--	--	9 (6.4)	8 (5.5)	2 (1.4)	9 (6.1)	0
AS exfoliation	--	--	5 (3.5)	3 (2.1)	0	2 (1.4)	1 (0.7)

^aAll participants received patches with active, vehicle, control(s) (RIPT and CIPT) and comparator (CIPT only).

^bNone of the participants had SAEs that were considered treatment related.

^cDiscontinuing from the study or study drug; none of the AEs were deemed related to treatment in the phase 1 studies and all but 3 of the AEs were deemed related to treatment in the phase 2 study (n = 1 each: BPO/ADAP, CLIN/BPO, and vehicle).

^dPatient died during hospitalization for suspected COVID-19; no proof of death could be obtained.

–: not reported/not applicable; ADAP: adapalene 0.15%; AE: adverse event; AS: application site; BPO: benzoyl peroxide 3.1%; CIPT: cumulative irritancy patch test; CLIN: clindamycin phosphate 1.2%; IDP-126: clindamycin phosphate 1.2%/benzoyl peroxide 3.1%/adapalene 0.15%; RIPT: repeat insult patch test; SAE: serious adverse event; TEAE: treatment-emergent adverse event.

Figure 4. Cutaneous safety and tolerability by visit (Phase 2 safety population). Data for “none” are not shown. No imputation of missing data. Investigator-assessed cutaneous safety (scaling, erythema, hypopigmentation, hyperpigmentation) and participant-assessed tolerability (itching, burning, stinging) were evaluated using a 4-point scale where 0 = none and 3 = severe. ADAP: adapalene 0.15%; BPO: benzoyl peroxide 3.1%; CLIN: clindamycin phosphate 1.2%; IDP-126: clindamycin phosphate 1.2%/benzoyl peroxide 3.1%/adapalene 0.15% gel; VEH: vehicle gel. Baseline N values: IDP-126 gel, n = 141; BPO/ADAP gel, n = 146; CLIN/BPO gel, n = 144; CLIN/ADAP gel, n = 148; VEH gel, n = 146.

Figure 5. Participants treated with IDP-126 (Phase 2 study). Individual results may vary. EGSS: Evaluator’s Global Severity Score; IDP-126: clindamycin phosphate 1.2%/benzoyl peroxide 3.1%/adapalene 0.15% gel.

Data availability statement

Data available upon request.