Phase III trials examining the efficacy of cetirizine ophthalmic solution 0.24% compared to vehicle for the treatment of allergic conjunctivitis in the conjunctival allergen challenge model

Figures & data

Figure 1 Study design.

Notes: During the four study visits, evaluations and treatments proceeded as follows: Visit 1 (Day −21±3), screening procedures at Visit 1 determined subject eligibility; Visit 2 (Days −14±3), baseline procedures at Visit 2 confirmed subject eligibility; Visit 3 (Day 0), Visit 3 was divided into two office visits on the same day, such as Visit 3A and Visit 3B. During Visit 3A, eligible subjects who had satisfied the inclusion and exclusion criteria were enrolled into the study, randomized, and received their first dose of either cetirizine ophthalmic solution 0.24% or vehicle (1–2 drops) bilaterally. Visit 3B assessed ocular and nasal signs and symptoms before and after the CAC. Visit 4 (Days 14±3): subjects received their second dose of either cetirizine ophthalmic solution 0.24% or vehicle (1–2 drops). Fifteen minutes after instillation, subjects underwent the bilateral CAC and ocular and nasal signs and symptoms were assessed.
Abbreviations: AC, allergic conjunctivitis; CAC, conjunctival allergen challenge.

Table 1 Subject disposition

	Study 1: moderate allergic conjunctivitis		Study 2: severe allergic conjunctivitis
	Cetirizine	Vehicle	Cetirizine	Vehicle
Randomized	50	50	51	50
PP population	49 (98.0%)	47 (94.0%)	43 (84.3%)	44 (88.0%)
ITT population	50(100.0%)	50 (100.0%)	51 (100.0%)	50(100.0%)
ITT subjects who completed the study	49.0 (98.0%)	47 (94.0%)	43 (84.3%)	44 (88.0%)
Primary reason for withdrawal
Protocol violation	0 (0.0%)	0 (0.0%)	3 (5.9%)	2 (4.0%)
Administrative reasons	0 (0.0%)	1 (2.0%)	3 (5.9%)	2 (4.0%)
Manifest clinically active signs or symptoms of allergic conjunctivitis at Visit 4	0 (0.0%)	1 (2.0%)	2 (3.9%)	2 (4.0%)
Adverse event	1 (2.0%)	1 (2.0%)	0 (0.0%)	0 (0.0%)

Notes: The number of subjects enrolled in each study and those in each population are shown. Percentages are based on the total number of subjects randomized in each treatment group.

Abbreviations: ITT, intent to treat; PP, per protocol.

Table 2 Demographics

	Study 1: moderate allergic conjunctivitis		Study 2: severe allergic conjunctivitis
	Cetirizine n=50	Vehicle n=50	Cetirizine n=51	Vehicle n=50
Age (years), mean (SD)	39.5 (17.32)	38.1 (14.56)	40.6 (12.8)	39.2 (10.84)
Gender
Male	13 (26.0%)	20 (40.0%)	12 (23.5%)	20 (40.0%)
Female	37 (74.0%)	30 (60.0%)	39 (76.5%)	30 (60.0%)
Ethnicity
Hispanic or Latino	11 (22.0%)	4 (8.0%)	1 (2.0%)	0 (0.0%)
Non-Hispanic or Latino	39 (78.0%)	46 (92.0%)	50 (98.0%)	50 (100.0%)
Race
American Indian or Alaskan Native	2 (4.0%)	0 (0.0%)	0 (0.0%)	0 (0.0%)
Asian	1 (2.0%)	2 (4.0%)	0 (0.0%)	1 (2.0%)
Black or African American	3 (6.0%)	2 (4.0%)	10 (19.6.0%)	17 (34.0%)
White	44 (88.0%)	46 (92.0%)	41 (80.4%)	31 (62.0%)
Others	0 (0.0%)	0 (0.0%)	0 (0.0%)	1 (2.0%)
Iris color (per eye)
Black	2 (2.0%)	0 (0.0%)	2 (2.0%)	4 (4.0%)
Blue	34 (34.0%)	36 (36.0%)	36 (35.3%)	18 (18.0%)
Brown	38 (38.0%)	36 (36.0%)	38 (37.3%)	60 (60.0%)
Hazel	14 (14.0%)	14 (14.0%)	12 (11.8%)	6 (6.0%)
Green	12 (12.0%)	14 (14.0%)	14 (13.7%)	12 (12.0%)

Notes: The demographic information (age, gender, ethnicity, race, and iris color) of the ITT population is shown. Percentages are based on the total number of subjects in each treatment group except for iris color, which are based on the total number of eyes in each treatment group.

Abbreviation: ITT, intent to treat.

Table 3 Change in ocular itching and conjunctival redness

Assessment	Study 1: moderate allergic conjunctivitis		Study 2: severe allergic conjunctivitis
	Δ mean score	P-value	Δ mean score	P-value
Ocular itching 15 minutes post-treatment
Post-CAC: 3 minutes	−1.38	<0.0001	−1.53	<0.0001
Post-CAC: 5 minutes	−1.25	<0.0001	−1.34	<0.0001
Post-CAC: 7 minutes	−1.00	<0.0001	−1.07	<0.0001
Ocular itching 8 hours post-treatment
Post-CAC: 3 minutes	−0.93	<0.0001	−0.92	<0.0001
Post-CAC: 5 minutes	−0.89	<0.0001	−0.90	<0.0001
Post-CAC: 7 minutes	−0.99	<0.0001	−0.84	<0.0001
Conjunctival redness 15 minutes post-treatment
Post-CAC: 3 minutes	−0.33	0.0006	−0.46	0.0069
Post-CAC: 5 minutes	−0.15	0.1708	−0.18	0.5763
Post-CAC: 7 minutes	−0.14	0.3281	−0.25	0.2600
Conjunctival redness 8 hours post-treatment
Post-CAC: 3 minutes	−0.30	0.0259	−0.42	0.0129
Post-CAC: 5 minutes	−0.03	0.9551	−0.24	0.2924
Post-CAC: 7 minutes	−0.01	0.8790	−0.31	0.1327

Notes: Ocular itching and conjunctival redness were the primary endpoints for the symptoms and signs of allergic conjunctivitis, respectively. Ocular itching and conjunctival redness measurements were assessed on a 5-point scale described in the “Methods” section. Data shown are from the ITT population with last observation carried forward to account for missing data. P-value was calculated using an ANCOVA model with treatment and baseline (Visit 2) score in the model and comparing cetirizine ophthalmic solution 0.24% group with vehicle group.

Abbreviations: ANCOVA, analysis of covariance; CAC, conjunctival allergen challenge; ITT, intent to treat.

Figure 2 Ocular itching.

Notes: Mean scores of the cetirizine ophthalmic solution 0.24% (blue) and the vehicle (green) group are shown from each study. Data shown are mean and standard error of the mean for each time point (3, 5, or 7 minutes post-CAC) after treatment (15 minutes or 8 hours postdosing). (A) Study 1, n=50 in each treatment group. (B) Study 2, n=51 and 50 in the cetirizine and vehicle treatments, respectively. *P<0.05.
Abbreviations: AC, allergic conjunctivitis; CAC, conjunctival allergen challenge; PT, post-treatment.

Table 4 Change in secondary ocular efficacy endpoints post-treatment, post-CAC, all time points

Assessment	Study 1: moderate allergic conjunctivitis		Study 2: severe allergic conjunctivitis
	Δ mean score	P-value	Δ mean score	P-value
Chemosis (conjunctival swelling)
15 minutes post-treatment	−0.38	<0.0001	−0.17	0.0478
8 hours post-treatment	−0.32	0.0070	−0.26	0.0087
Eyelid swelling
15 minutes post-treatment	−0.30	0.0207	−0.60	<0.0001
8 hours post-treatment	−0.40	0.0022	−0.50	<0.0001
Tearing
15 minutes post-treatment	−0.30	0.0191	−0.50	0.0004
8 hours post-treatment	−0.10	0.3876	−0.30	0.0278
Ciliary redness
15 minutes post-treatment	−0.26	0.0007	−0.30	0.0337
8 hours post-treatment	−0.20	0.0719	−0.20	0.0873
Episcleral redness
15 minutes post-treatment	−0.16	0.0338	−0.14	0.2105
8 hours post-treatment	−0.15	0.1077	−0.16	0.0911

Notes: Data shown are pooled mean change from vehicle of all time points post-CAC (7, 15, and 20 minutes) from the ITT population with observation data only for secondary ocular efficacy endpoints: chemosis, tearing, eyelid swelling, ciliary redness, and episcleral redness. P-value calculated using a repeated measures ANCOVA model with treatment, time point, and baseline (visit two post-CAC average) score in the model and comparing cetirizine ophthalmic solution 0.24% group to vehicle group.

Abbreviations: ANCOVA, analysis of covariance; CAC, conjunctival allergen challenge; ITT, intent to treat.

Figure 3 Eyelid swelling.

Notes: Mean scores of the cetirizine ophthalmic solution 0.24% (blue) and the vehicle (green) group are shown from each study. Data shown are mean and standard error of the mean for each time point (7, 15, or 20 minutes post-CAC) after treatment (15 minutes or 8 hours postdosing). (A) Study 1, n=50 in each treatment group. (B) Study 2, n=51 and 50 in the cetirizine and vehicle treatments, respectively. *P<0.05.
Abbreviations: AC, allergic conjunctivitis; PT, post-treatment; CAC, conjunctival allergen challenge.

Table 5 Change in nasal symptoms post-treatment, post-CAC, all time points

Assessment	Study 1: moderate allergic conjunctivitis		Study 2: severe allergic conjunctivitis
	Δ mean score	P-value	Δ mean score	P-value
Rhinorrhea
15 minutes post-treatment	−0.4	0.0080	−0.7	0.0001
8 hours post-treatment	−0.7	<0.0001	−0.5	0.0030
Nasal pruritus
15 minutes post-treatment	−0.1	0.5429	−0.5	0.0043
8 hours post-treatment	−0.3	0.0184	−0.3	0.0536
Ear or palatal pruritus
15 minutes post-treatment	−0.3	0.0548	−0.5	0.0025
8 hours post-treatment	−0.2	0.1412	−0.6	<0.0001
Nasal congestion
15 minutes post-treatment	−0.2	0.2614	−0.7	0.0003
8 hours post-treatment	−0.4	0.0209	−0.4	0.0020

Notes: Data shown are mean change from vehicle of all time points post-CAC (7, 15, and 20 minutes) from the ITT population with observation data only for nasal symptoms of allergic conjunctivitis: rhinorrhea, nasal pruritus, ear or palatal pruritus, and nasal congestion. P-value calculated using a repeated measures ANCOVA model with treatment, time point, and baseline (Visit 2 post-CAC average) score in the model and comparing cetirizine ophthalmic solution 0.24% group with vehicle group.

Abbreviation: ANCOVA, analysis of covariance; CAC, conjunctival allergen challenge; ITT, intent to treat.

Table 6 Proportion of subjects with nasal symptoms

Assessment	Study 1: moderate allergic conjunctivitis		Study 2: severe allergic conjunctivitis
	Cetirizine n=50	Vehicle n=50	Cetirizine n=51	Vehicle n=50
15 minutes post-treatment
Pre-CAC	9 (18.4%)	10 (20.4%)	6 (13.3%)	5 (11.1%)
Post-CAC: 7 minutes	32 (65.3%)*	39 (83.0%)	22 (51.2%)*	36 (81.8%)
Post-CAC: 15 minutes	40 (81.6%)	43 (91.5%)	25 (58.1%)*	38 (86.4%)
Post-CAC: 20 minutes	38 (77.6%)*	44 (93.6%)	31 (72.1%)	39 (88.6%)
8 hours post-treatment
Pre-CAC	7 (14.3%)	6 (12.0%)	3 (6.0%)	1 (2.1%)
Post-CAC: 7 minutes	30 (61.2%)*	41 (82.0%)	29 (58.0%)*	42 (87.5%)
Post-CAC: 15 minutes	40 (81.6%)	47 (94.0%)	39 (78.0%)	43 (89.6%)
Post-CAC: 20 minutes	41 (83.7%)	47 (94.0%)	42 (84.0%)	43 (89.6%)

Notes: The composite score is calculated based on the presence or absence of at least one nasal symptom.

* In the cetirizine column, the P-value is <0.05 (exact P-values are in the corresponding text). P-values were calculated using a Fisher’s exact test, comparing cetirizine ophthalmic solution 0.24% group with the vehicle group.

Abbreviation: CAC, conjunctival allergen challenge.

Table 7 Drop comfort assessments

Assessment	Study 1: moderate allergic conjunctivitis		Study 2: severe allergic conjunctivitis
	Cetirizine n=50	Vehicle n=50	Cetirizine n=51	Vehicle n=50
Drop comfort, mean (SD)
Upon installation	1.2 (1.42)	1.0 (1.49)	1.6 (2.02)	0.8 (1.22)
1 minute postinstallation	1.4 (1.44)	1.2 (1.60)	3.0 (2.33)	1.1 (1.14)
2 minutes postinstallation	1.3 (1.44)	1.0 (1.50)	2.6 (2.14)	1.1 (1.13)

Notes: Drop comfort was measured on a scale of 0–10, where 0 was the most comfortable and 10 was the least comfortable. Analysis was performed using the safety populations in both studies.