Table 1.

Efficacy of varenicline solution nasal spray 0.03 mg twice daily in the treatment of dry eye disease: results of randomized, double-masked, vehicle-controlled, multicentre phase II (ONSET-1; MYSTIC) and III (ONSET-2) trials

Study	Regimen (no. of pts)	STSa			EDSb
		LSM ΔBLc (mm) [BLd]	LSM-TD (mm) [95% CI]	≥ 10 mm ΔBLc (% of pts)	LSM ΔBLe (mm) [BLd]	LSM-TD (mm) [95% CI]
Short-term studies
ONSET-1 [25]	VAR (48)	11.4f [4.8]	8.5 [5.0–12.1]**	52**	− 16.0 [63.7]	− 11.6 [− 20.1 to − 3.0]*
	VEH (43)	3.2f [4.5]		14	− 4.4 [65.2]
ONSET-2 [26]	VAR (260)	11.3 [5.1]	5.0 [3.4–6.6]**	47.3**f	− 10.3g [58.5]	− 2.9 [− 7.4 to 1.6]
	VEH (252)	6.3 [4.9]		27.8f	− 7.4g [58.1]
Longer-term study
MYSTIC [27]	VAR (41)	10.8* [5.5]	NR	36.6	NR
	VEH (41)	6.0 [5.3]	NR	24.4	NR

Results are for the ITT population using the LOCF approach, except where indicated. Results for ONSET-1 are from post hoc analyses

BL baseline, ΔBL change from BL, CAE controlled adverse environment, EDS eye dryness score, ITT intent-to-treat, LOCF last observation carried forward, LSM least squares mean, NR not reported, pts patients, STS Schirmer test score (with anaesthesia), TD treatment difference, VAR varenicline solution, VAS visual analogue scale, VEH vehicle

*p = 0.006, **p ≤ 0.0003 vs VEH

^aOn a 0–35 mm scale; a higher score indicates a better outcome

^bOn a 100 mm VAS, where 0 = ‘no discomfort’ and 100 = ‘maximal discomfort’. Assessed in a CAE

^cTo day 28/week 4 (ONSET-1 and -2) or day 84/week 12 (MYSTIC)

^dMean value

^eTo day 21/week 3 in ONSET-1; to day 28/week 4 in ONSET-2

^fPrimary endpoint

^gModified ITT (VAR, n = 187; PL, n = 169)