Symptom Relief Following a Single Dose of Propylene Glycol-Hydroxypropyl Guar Nanoemulsion in Patients with Dry Eye Disease: A Phase IV, Multicenter Trial

Figures & data

Table 1 Key Eligibility Criteria

Key Inclusion Criteria

Key Exclusion Criteria

1. Had a TFBUT of ≤5 seconds in at least one eye at Screening Visit. 2. Exhibited symptoms of dry eye at the Screening Visit (IDEEL symptom bother score of >16 to 65). 3. Met at least one of the 3 criteria below in at least one eye at the Screening Visit (randomization stratified based on the criteria below): (a) Unanesthetized Schirmer I test score of ≤9 mm (aqueous-deficient dry eye stratum). (b) Had a meibum quality score of ≥1 (on a 0 to 3 scale) or meibum expressibility score of >1 (on a 0 to 3 scale) in either eye lid (evaporative dry eye stratum). (c) Patients who met both entry criteria (a) and (b) (mixed dry eye stratum). 4. Had best corrected visual acuity (BCVA) of ≥20/80 (or ≥55 letters score or ≥0.6 Early Treatment Diabetic Retinopathy Study log of the minimum angle of resolution value in both eyes at the Screening Visit).

History of hypersensitivity to the study drug or any of its excipients or to drugs of similar chemical classes History of malignancy of any organ system (other than localized basal cell carcinoma of the skin or in situ cervical cancer), treated or untreated, within the past 5 years, regardless of whether there was evidence of local recurrence or metastases Use of any topical ocular medication preserved with benzalkonium chloride or other products known to be toxic to the tear film lipid layer within 1 month prior to the Screening Visit Lid hygiene therapy initiated ≤4 weeks prior to the Screening Visit Ocular abnormalities that could adversely affect the safety or efficacy outcome Uncontrolled active systemic diseases, active ocular infection Punctal plug insertion or diathermy procedure initiated within 30 days prior to the Screening Visit

Abbreviations: IDEEL, impact of dry eye on everyday life; TFBUT, tear film break-up time.

Table 2 Demographic and Baseline Characteristics (Full Analysis Set)

Characteristics	PG-HPG N=134
Mean (SD) age, n (%) years	56.6 (14.78)
Age, n (%)
≤65 years	88 (65.7)
≥65 years	46 (34.3)
Female, n (%)	101 (75.4)
Race, n (%)
White	100 (74.6)
Black or African American	23 (17.2)
Asian	6 (4.5)
Other	4 (3.0)
Multiracial	1 (0.7)
Dry eye subtype, n (%)
Aqueous-deficient	41 (30.6)
Evaporative	44 (32.8)
Mixed	49 (36.6)
Dry eye symptom score, n (%)
0–5	72 (53.7)
6−10	61 (45.5)
Missing	1 (0.7)

Notes: All baseline characteristics were assessed before instillation. Percentages are based on the number of patients in the full analysis set. Full analysis set consisted of all patients who received at least one drop of PG-HPG lubricant eye drops.

Abbreviations: PG-HPG, propylene glycol-hydroxypropyl guar lubricant eye drops; SD, standard deviation.

Figure 1 (A) Change from baseline in dry eye symptom scores on Day 1 (Overall population, N=134). Baseline data for one patient was missing. The change from baseline in median (95% CI) dry eye symptom scores at 0 h, 4 h, and 8 h post-dose were –1 (–3, –1), –2 (–3, –2), and –2 (–2, –1), respectively. Patient-reported outcome assessment of dry eye symptoms was performed using 0 −10 visual analog scale at 4 time points on Day 1 (baseline, 0 (immediate), 4 (±1), and 8 (±1) hours post-drop instillation; 0–5 = none to minimal symptoms; 6–10 = moderate to severe symptoms). Baseline was defined as the last available, non-missing, scheduled or unscheduled value collected prior to exposure to study treatment. (B) Change from baseline in dry eye symptom scores on Day 1 (by subtype). Baseline and 0 h data for one patient each in aqueous deficient group was missing. Median reduction in symptom score was >1 point at all post-dose time points for all the subtypes. Patient-reported outcome assessment of dry eye symptoms was performed using 0 (no symptoms/eyes feeling good) –10 (worst symptoms/no feeling at all) visual analog scale at 4 time points on Day 1 (baseline, 0 (immediate), 4 (±1), and 8 (±1) h post-drop instillation; 0–5 = none to minimal symptoms; 6–10 = moderate to severe symptoms). Baseline was defined as the last available, non-missing, scheduled or unscheduled value collected prior to exposure to study treatment.

Abbreviations: CI, confidence interval; h, hour; n, number of patients.

Figure 2 (A) Soothing sensation scores on Day 1 (Overall population, N=134). The median (range) soothing sensation scores at 0, 4, and 8 h post-dose were 3 (0–10), 3.0 (0–10), and 3.5 (0–10), respectively. Patient-reported outcome assessment of soothing sensation was performed using 0 (no symptoms/eyes feeling good) −10 (worst symptoms/no feeling at all) visual analog scale at 4 time points on Day 1 (baseline, 0 (immediate), 4 (±1), and 8 (±1) h post-drop instillation; 0–5 = none to minimal symptoms; 6–10 = moderate to severe symptoms). (B) Soothing sensation scores on Day 1 (by subtype). Patient-reported outcome assessment of soothing sensation was performed using 0 (no symptoms/eyes feeling good) −10 (worst symptoms/no feeling at all) visual analog scale at 4 time points on Day 1 (baseline, 0 (immediate), 4 (±1), and 8 (±1) h post-drop instillation; 0–5 = none to minimal symptoms; 6–10 = moderate to severe symptoms).

Abbreviations: h, hours; N, total number of patients.

Table 3 Dry Eye Symptom Score (0–5, 6–10): Shift Table Between Subsequent Time Points on Day 1

N=134
Baseline Score	n	0 Hours	n/M (%)		Post-Baseline Scores
					4 Hours		n/M (%)	8 Hours	n/M (%)
(A) Overall population
0‒5	72	0‒5	69/72 (95.8)		0‒5		66/69 (95.7)	0‒5	65/66 (98.5)
								6‒10	1/66 (1.5)
					6‒10		3/69 (4.3)	0‒5	1/3 (33.3)
								6‒10	2/66 (66.7)
		6‒10	3/72 (4.2)		0‒5		3/3 (100.0)	0‒5	3/3 (100.0)
6‒10	61	0‒5	41/41 (67.2)		0‒5		32/41 (78.0)	0‒5	27/32 (84.4)
								6‒10	5/32 (15.6)
					6‒10		9/41 (22.0)	0‒5	2/9 (22.2)
								6‒10	7/9 (77.8)
		6‒10	19/61 (31.1)		0‒5		14/19 (73.7)	0‒5	12/14 (85.7)
								6‒10	2/14 (14.3)
					6‒10		5/19 (26.3)	0‒5	1/5 (20.0)
								6‒10	4/5 (80.0)
		Missing	1/61 (1.6)		0‒5		1/1 (100.0)	0‒5	1/1 (100.0)
Missing	1	0‒5	1/1 (100.0)		0‒5		1/1 (100.0)	6‒10	1/1 (100.0)
(B) Subgroup analysis
Aqueous-deficient dry eye subtype (n=41)
0‒5	18	0‒5	16/18 (88.9)		0‒5		15/16 (93.8)	0‒5	15/15 (100.0)
					6‒10		1/16 (6.3)	6‒10	1/1 (100.0)
		6‒10	2/18 (11.1)		0‒5		2/2 (100.0)	0‒5	2/2 (100.0)
6‒10	22	0‒5	15/22 (68.2)		0‒5		12/15 (80.0)	0‒5	9/12 (75.0)
								6‒10	3/12 (25.0)
					6‒10		3/15 (20.0)	6‒10	3/3 (100.0)
		6‒10	6/22 (27.3)		0‒5		5/6 (83.3)	0‒5	4/5 (80.0)
								6‒10	1/5 (20.0)
					6‒10		1/6 (16.7)	6‒10	1/1 (100.0)
		Missing	1/22 (4.5)		0‒5		1/1 (100.0)	0‒5	1/1 (100.0)
Missing	1	0‒5	1/1 (100.0)		0‒5		1/1 (100.0)	6‒10	1/1 (100.0)
Evaporative dry eye subtype (n=44)
0‒5	26	0‒5	25/26 (96.2)		0‒5		23/25 (92.0)	0‒5	23/23 (100.0)
					6‒10		2/25 (8.0)	0‒5	1/2 (50.0)
								6‒10	1/2 (50.0)
		6‒10	1/26 (3.8)		0‒5		1/1 (100.0)	0‒5	1/1 (100.0)
6‒10	18	0‒5	14/18 (77.8)		0‒5		9/14 (64.3)	0‒5	7/9 (77.8)
								6‒10	2/9 (22.2)
					6‒10		5/14 (35.7)	0‒5	2/5 (40.0)
								6‒10	3/5 (60.0)
		6‒10	4/18 (22.2)		0‒5		3/4 (75.0)	0‒5	3/3 (100.0)
					6‒10		1/4 (25.0)	0‒5	1/1 (100.0)
Mixed dry eye subtype (n=49)
0‒5	28	0‒5	28/28 (100.0)		0‒5		28/28 (100.0)	0‒5	27/28 (96.4)
								6‒10	1/28 (3.6)
6‒10	21	0‒5	12/21 (57.1)		0‒5		11/12 (91.7)	0‒5	11/11 (100.0)
					6‒10		1/12 (8.3)	6‒10	1/1 (100.0)
		6‒10	9/21 (42.9)		0‒5		6/9 (66.7)	0‒5	5/6 (83.3)
								6‒10	1/6 (16.7)
					6‒10		3/9 (33.3)	6‒10	3/3 (100.0

Notes: Full analysis set n is the number of patients on the respective category at the particular time point. M is the number of patients included in the respective category of the previous time point. Percentages are based on M. Baseline dry eye symptom assessment is obtained prior to dosing.

Table 4 Soothing Sensation Score (0–5, 6–10): Shift Table Between Subsequent Time Points on Day 1

N=134
0 Hours	n	4 Hours	n/M (%)	8 Hours	n/M (%)
(A) Overall population
0‒5	110	0‒5	98/110 (89.1)	0‒5	91/98 (92.9)
				6‒10	7/98 (7.1)
		6‒10	12/110 (10.9)	0‒5	6/12 (50.0)
				6‒10	6/12 (50.0)
6‒10	24	0‒5	11/24 (45.8)	0‒5	9/11 (81.8)
				6‒10	2/11 (18.2)
		6‒10	13/24 (54.2)	0‒5	4/13 (30.8)
				6‒10	9/13 (69.2)
(B) Subgroup analysis
Aqueous-deficient dry eye subtype (n=41)
0‒5	34	0‒5	30/34 (88.2)	0‒5	29/30 (96.7)
				6‒10	1/30 (3.3)
		6‒10	4/34 (11.8)	6‒10	4/4 (100.0)
6‒10	7	0‒5	4/7 (57.1)	0‒5	4/4 (100.0)
		6‒10	3/7 (42.9)	0‒5	1/3 (33.3)
				6‒10	2/3 (66.7)
Evaporative dry eye subtype (n=44)
0‒5	33	0‒5	28/33 (84.8)	0‒5	26/28 (92.9)
				6‒10	2/28 (7.1)
		6‒10	5/33 (15.2)	0‒5	3/5 (60.0)
				6‒10	2/5 (40.0)
6‒10	11	0‒5	6/11 (54.5)	0‒5	5/6 (83.3)
				6‒10	1/6 (16.7)
		6‒10	5/11 (45.5)	0‒5	2/5 (40.0)
				6‒10	3/5 (60.0)
Mixed dry eye subtype (n=49)
0‒5	43	0‒5	40/43 (93.0)	0‒5	36/40 (90.0)
				6‒10	4/40 (10.0)
		6‒10	3/43 (7.0)	0‒5	3/3 (100.0)
6‒10	6	0‒5	1/6 (16.7)	0‒5	1/1 (100.0)
		6‒10	5/6 (83.3)	0‒5	1/5 (20.0)
				6‒10	4/5 (80.0)

Notes: Full analysis set n is the number of patients on the respective category at the particular time point. M is the number of patients included in the respective category of the previous time point. Percentages are based on M.

Figure 3 (A) Tolerability assessment score on Day 1 (Overall population). Tolerability profile was assessed on a 0–10 scale (0=no symptoms; 10=worst imaginable symptom experienced; 0–5=none to mild symptoms; 6–10=moderate to severe symptoms). (B) Tolerability assessment score on Day 1 (by subtype). Tolerability profile was assessed on a 0–10 scale (0=no symptoms; 10=worst imaginable symptom experienced; 0–5=none to mild symptoms; 6–10=moderate to severe symptoms).