HOW TO USE THIS SNAPSHOT
The information provided in Snapshots highlights who participated in the key clinical trials that supported the original FDA approval of this drug, and whether there were differences among sex, race, age, and ethnic groups. The “MORE INFO” bar shows more detailed, technical content for each section. The Snapshot is intended as one tool for consumers to use when discussing the risks and benefits of the drugs.
LIMITATIONS OF THIS SNAPSHOT
Do not rely on Snapshots to make decisions regarding medical care. Always speak to your healthcare provider about the benefits and risks of a drug.
Some of the information in this Snapshot is for presentation purposes and does not represent the approved conditions of use of this drug. Refer to the VIZZ Prescribing Information for all the approved conditions of use of this drug (e.g., indication(s), population(s), dosing regimen(s), safety information).
Snapshots are limited to the information available at the time of the original approval of the drug and do not provide information on who participated in clinical trials that supported later approvals for additional uses of the drug (if applicable).
VIZZ (aceclidine ophthalmic solution)
viz
LENZ Therapeutics, Inc.
Approval date: July 31, 2025
DRUG TRIALS SNAPSHOT SUMMARY:
What is the drug for?
VIZZ is for the treatment of presbyopia in adults.
Presbyopia is a common age-related condition that affects the eyes’ ability to focus on near objects. As people age, the lens of the eye becomes less flexible, making it difficult to accommodate for close vision.
How is this drug used?
VIZZ is a topical ophthalmic solution. Patients are to instill one drop in each eye, wait two minutes and instill a second drop in each eye once daily.
Who participated in the clinical trials?
The FDA approved VIZZ based on evidence from three clinical trials. Two clinical trials (CLARITY 1 and CLARITY-2) were the main support for efficacy and were six weeks in duration and included 466 patients with presbyopia. The trials were conducted at 42 sites in the United States. One clinical trial (CLARITY-3) was the main support for safety and was 26 weeks in duration and included 361 patients with presbyopia. This trial was conducted at 40 sites in the United States.
How were the trials designed?
Two clinical trials (CLARITY-1 and CLARITY-2) demonstrated efficacy by showing superiority of VIZZ over brimonidine (CLARITY-1) or vehicle (CLARITY-2) for the primary efficacy endpoint (improvement of three lines [15 letters] or greater at 40 cm and no loss ≥5 letters at 4 m in monocular Best Corrected Distant Visual Acuity [BCDVA] at Visit 2 [Day 1] three hours postdose). The primary efficacy endpoint results were consistent across different analysis populations using different approaches for the intercurrent events. Additionally, secondary endpoint analyses were supportive of the primary efficacy results.
DEMOGRAPHICS SNAPSHOT
Figure 1 summarizes how many male and female patients were enrolled in the combined clinical trials used to evaluate the efficacy of VIZZ.
Figure 1. Baseline Demographics by Sex
Source: Adapted from FDA Review
Figure 2 summarizes how many patients by race were enrolled in the combined clinical trials used to evaluate the efficacy of VIZZ.
Figure 2. Baseline Demographics by Race
Source: Adapted from FDA Review
* Other includes: American Indian or Alaska Native (6 participants), other race (7 participants), and multiple races (2 participants).
Figure 3 summarizes how many patients by age were enrolled in the combined clinical trials used to evaluate the efficacy of VIZZ.
Figure 3. Baseline Demographics by Age
Source: Adapted from FDA Review
Figure 4 summarizes how many patients by ethnicity were enrolled in the combined clinical trials used to evaluate the efficacy of VIZZ.
Figure 4. Baseline Demographics by Ethnicity
Source: Adapted from FDA Review
Who participated in the trials?
Table 1. Baseline Demographics of Efficacy Trials by Age, Race, Sex, and Ethnicity
| Demographic |
LNZ1011 N=232 |
LNZ1002 N=234 |
Vehicle N=76 |
Brimonidine3 N=156 |
Total Population N=698 |
|---|---|---|---|---|---|
| Sex, n (%) | 232 (100) |
234 (100) |
76 (100) |
156 (100) |
698 (100) |
| Male | 82 (35.3) |
73 (31.2) |
30 (39.5) |
57 (36.5) |
242 (34.7) |
| Female | 150 (64.7) |
161 (68.8) |
46 (60.5) |
99 (63.5) |
456 (65.3) |
| Age, years |
|
|
|
|
|
| Mean (SD) | 55.7 (6.38) |
55.1 (5.85) |
53.6 (4.93) |
54.9 (6.45) |
55.1 (6.10) |
| Median (min, max) | 55.0 (45, 74) |
54.0 (45, 75) |
53.0 (45, 69) |
53.0 (45, 75) |
54.0 (45, 75) |
| Age group, years, n (%) |
|
|
|
|
|
| ≥44 to ≤55 | 119 (51.3) |
136 (58.1) |
52 (68.4) |
97 (62.2) |
404 (57.9) |
| >55 to ≤65 | 94 (40.5) |
85 (36.3) |
22 (28.9) |
44 (28.2) |
245 (35.1) |
| >65 | 19 (8.2) |
13 (5.6) |
2 (2.6) |
15 (9.6) |
49 (7.0) |
| Race, n (%) |
|
|
|
|
|
| White | 203 (87.5) |
210 (89.7) |
67 (88.2) |
135 (86.5) |
615 (88.1) |
| Black or African American | 14 (6.0) |
7 (3.0) |
1 (1.3) |
10 (6.4) |
32 (4.6) |
| Asian | 10 (4.3) |
12 (5.1) |
4 (5.3) |
8 (5.1) |
34 (4.9) |
| American Indian or Alaska Native | 2 (0.9) |
2 (0.9) |
1 (1.3) |
1 (0.6) |
6 (0.9) |
| Native Hawaiian or other Pacific Islander | 0 |
0 |
1 (1.3) |
1 (0.6) |
2 (0.3) |
| Other | 2 (0.9) |
3 (1.3) |
2 (2.6) |
0 |
7 (1.0) |
| Multiple | 1 (0.4) |
0 |
0 |
1 (0.6) |
2 (0.3) |
| Ethnicity, n (%) |
|
|
|
|
|
| Hispanic or Latino | 69 (29.7) |
42 (17.9) |
14 (18.4) |
47 (30.1) |
172 (24.6) |
| Not Hispanic or Latino | 163 (70.3) |
192 (82.1) |
62 (81.6) |
109 (69.9) |
526 (75.4) |
| Country of participation, n (%) |
|
|
|
|
|
| United States | 232 (100) |
234 (100) |
76 (100) |
156 (100) |
698 (100) |
| Clinical baseline characteristics, n (%) |
|
|
|
|
|
| Iris color (study eye) |
|
|
|
|
|
| Blue/Grey/Green | 63 (27.2) |
68 (29.1) |
28 (36.8) |
50 (32.1) |
209 (29.9) |
| Brown/Black/Hazel | 169 (72.8) |
166 (70.9) |
48 (63.2) |
106 (67.9) |
489 (70.1) |
| Refractive type, OD |
|
|
|
|
|
| Hyperopic | 157 (67.7) |
154 (65.8) |
44 (57.9) |
93 (59.6) |
448 (64.2) |
| Myopic | 75 (32.2) |
80 (34.2) |
32 (42.1) |
63 (40.4) |
250 (35.8) |
| Refractive type, OS |
|
|
|
|
|
| Hyperopic | 163 (70.3) |
150 (64.1) |
42 (55.3) |
101 (64.7) |
456 (65.3) |
| Myopic | 69 (29.7) |
84 (35.9) |
34 (44.7) |
55 (35.3) |
242 (34.7) |
Source: Adapted from FDA Review
1 LNZ101 = aceclidine hydrochloride 1.75%/brimonidine tartrate 0.8%
2 LNZ100 = aceclidine hydrochloride 1.75%
3 Brimonidine tartrate 0.8%
Abbreviations: OD, oculus dexter (right eye); OS, oculus sinister (left eye); SD, standard deviation
What are the benefits of this drug?
The clinical studies demonstrated that when patients with presbyopia used VIZZ as labeled, they had an improvement in seeing at a near distance when using their best corrected distance vision correction.
What are the benefits of this drug (results of trials used to assess efficacy)?
Table 2. Primary Efficacy Endpoint From CLARITY-1 and CLARITY-2 Studies Day 1, at 3 Hours Postdose, FAS Population
| Endpoint | CLARITY-1 |
CLARITY-2 |
||||
|---|---|---|---|---|---|---|
|
VIZZ N=157 |
Brimonidine N=156 |
p-value |
VIZZ N=77 |
Vehicle N=76 |
p-value |
|
| Proportion of participants gaining ≥3 lines in DCNVA at 40 cm, without losing ≥1 line (≥5 letters) of DCDVA at 4 m at Day 1, at 3 hours | 65% |
12% |
p<0.01 |
71% |
8% |
p<0.01 |
Source: VIZZ Prescribing Information
Abbreviations: DCNVA, distance corrected near visual acuity; FAS, full analysis set
Were there any differences in how well the drug worked in clinical trials among sex, race, and age?
- Sex: VIZZ worked similar in males and females.
- Race: The number of patients of races other than White was small; therefore, differences in how VIZZ worked among races could not be determined.
- Age: VIZZ worked similar in patients younger and older than 65 years of age.
Were there any differences in how well the drug worked in clinical trials among sex, race, and age groups?
Table 3. Subgroup Analyses of the Primary Efficacy Endpoint: Improvement of ≥15 Letters at 40 cm and No Loss of ≥5 Letters at 4 m in Monocular BCDVA at Day 1, 3 Hours Postdose, CLARITY-1
| Subgroup |
VIZZ N=157 n/Ns (%) |
Brimonidine N=156 n/Ns (%) |
Difference (95% CI) |
|---|---|---|---|
| Sex |
|
|
|
| Female | 68/109 (62.4) |
11/99 (11.1) |
51.3 (40.3, 62.3) |
| Male | 33/48 (68.8) |
7/57 (12.3) |
56.5 (40.8, 72.1) |
| Age |
|
|
|
| ≤65 | 95/144 (66.0) |
16/138 (11.6) |
54.4 (45.0, 63.8) |
| >65 | 6/13 (46.2) |
2/18 (11.1) |
35.0 (4.3, 65.8) |
| Race |
|
|
|
| White | 90/138 (65.2) |
16/135 (11.9) |
53.4 (43.7, 63.0) |
| Asian | 5/10 (50.0) |
0/8 (0) |
50.0 (19.0, 81.0) |
| Black or African American | 3/6 (50.0) |
2/10 (20.0) |
30.0 (-17.1, 77.1) |
| Other | 3/3 (100.0) |
0/3 (0) |
N/A |
| Ethnicity |
|
|
|
| Hispanic or Latino | 25/36 (69.4) |
7/47 (14.9) |
54.6 (36.4, 72.7) |
| Not Hispanic or Latino | 76/121 (62.8) |
11/109 (10.1) |
52.7 (42.4, 63.0) |
Source: Adapted from FDA Review
Abbreviations: BCDVA, Best-Corrected Distance Visual Acuity; CI, confidence interval; N, number of patients in treatment arm; n, number of patients meeting criteria; N/A, not applicable; Ns, total number of patients for each specific subgroup and were assigned to that specific arm
Table 4. Subgroup Analyses of the Primary Efficacy Endpoint: Improvement of ≥15 Letters at 40 cm and No Loss of ≥5 Letters at 4 m in Monocular BCDVA at Day 1, 3 Hours Postdose, CLARITY-2
| Subgroup |
VIZZ N=77 n/Ns (%) |
Vehicle N=76 n/Ns (%) |
Difference (95% CI) |
|---|---|---|---|
| Sex |
|
|
|
| Female | 37/52 (71.2) |
3/46 (6.5) |
64.6 (50.4, 78.9) |
| Male | 18/25 (72.0) |
3/30 (10.0) |
62.0 (41.4, 82.6) |
| Age |
|
|
|
| ≤65 | 50/72 (69.4) |
6/74 (8.1) |
61.3 (49.0, 73.7) |
| >65 | 5/5 (100.0) |
0/2 (0) |
N/A |
| Race |
|
|
|
| White | 50/72 (69.4) |
6/67 (9.0) |
60.5 (47.8, 73.1) |
| Asian | 2/2 (100.0) |
0/4 (0) |
N/A |
| Black or African American | 1/1 (100.0) |
0/1 (0) |
N/A |
| Other | 2/2 (100.0) |
0/4 (0) |
N/A |
| Ethnicity |
|
|
|
| Hispanic or Latino | 3/6 (50.0) |
2/14 (14.3) |
35.7 (-8.3, 79.7) |
| Not Hispanic or Latino | 52/71 (73.2) |
4/62 (6.5) |
66.8 (54.8, 78.8) |
Source: Adapted from FDA Review
Abbreviations: BCDVA, Best-Corrected Distance Visual Acuity; CI, confidence interval; N, number of patients in treatment arm; n, number of patients meeting criteria; N/A, not applicable; Ns, total number of patients for each specific subgroup and were assigned to that specific arm
What are the possible side effects?
Most common side effects were instillation site irritation, dim vision, and headache.
What are the possible side effects (results of trials used to assess safety)?
The most frequent ocular adverse events occurring with aceclidine hydrochloride 1.75% (LNZ100) treatment group were instillation site irritation (20%) and visual impairment (16%). The most frequent non-ocular adverse event occurring with aceclidine hydrochloride 1.75% (LNZ100) treatment group was headache (13%). The most frequent treatment-emergent ocular adverse event reported were instillation site irritation (19.8%), visual impairment (15.6%), conjunctival hyperemia (7.7%), ocular hyperemia (7.1%), and vitreous floaters (5.0%).
Table 5. Patients With Adverse Events, Safety Population, CLARITY-1
| Preferred Term | LNZ100 |
LNZ101 |
Brimonidine |
LNZ100 vs. LNZ101 |
LNZ100 vs. Brimonidine |
LNZ101 vs. Brimonidine |
|---|---|---|---|---|---|---|
| Any AE | 61 (38.9) |
108 (69.2) |
46 (29.5) |
-30.4 (‑40.5, ‑19.5) * |
9.4 (‑1.2, 19.7) |
39.7 (29.1, 49.4) * |
| Instillation site erythema | 3 (1.9) |
0 |
1 (0.6) |
1.9 (‑0.5, 5.5) |
1.3 (‑1.8, 4.9) |
‑0.6 (‑3.5, 1.8) |
| Asthenopia | 4 (2.5) |
1 (0.6) |
0 |
1.9 (‑1.2, 5.8) |
2.5 (0.1, 6.4) * |
0.6 (‑1.8, 3.5) |
| Dizziness | 4 (2.5) |
2 (1.3) |
0 |
1.3 (‑2.3, 5.3) |
2.5 (0.1, 6.4) * |
1.3 (‑1.1, 4.6) |
| Abdominal discomfort | 1 (0.6) |
0 |
0 |
0.6 (‑1.8, 3.5) |
0.6 (‑1.8, 3.5) |
0.0 (‑2.4, 2.4) |
| Chalazion | 1 (0.6) |
0 |
1 (0.6) |
0.6 (‑1.8, 3.5) |
‑0.0 (‑3.0, 2.9) |
‑0.6 (‑3.5, 1.8) |
| Dermatitis contact | 1 (0.6) |
0 |
0 |
0.6 (‑1.8, 3.5) |
0.6 (‑1.8, 3.5) |
0.0 (‑2.4, 2.4) |
| Eye discharge | 1 (0.6) |
0 |
0 |
0.6 (‑1.8, 3.5) |
0.6 (‑1.8, 3.5) |
0.0 (‑2.4, 2.4) |
| Eyelid margin crusting | 1 (0.6) |
0 |
0 |
0.6 (‑1.8, 3.5) |
0.6 (‑1.8, 3.5) |
0.0 (‑2.4, 2.4) |
| Hypercholesterolaemia | 1 (0.6) |
0 |
0 |
0.6 (‑1.8, 3.5) |
0.6 (‑1.8, 3.5) |
0.0 (‑2.4, 2.4) |
| Instillation site pruritus | 1 (0.6) |
0 |
2 (1.3) |
0.6 (‑1.8, 3.5) |
‑0.6 (‑4.0, 2.4) |
‑1.3 (‑4.6, 1.1) |
| Pharyngitis | 1 (0.6) |
0 |
0 |
0.6 (‑1.8, 3.5) |
0.6 (‑1.8, 3.5) |
0.0 (‑2.4, 2.4) |
| Procedural headache | 1 (0.6) |
0 |
0 |
0.6 (‑1.8, 3.5) |
0.6 (‑1.8, 3.5) |
0.0 (‑2.4, 2.4) |
| Pruritus | 1 (0.6) |
0 |
0 |
0.6 (‑1.8, 3.5) |
0.6 (‑1.8, 3.5) |
0.0 (‑2.4, 2.4) |
| Upper respiratory tract infection | 1 (0.6) |
0 |
0 |
0.6 (‑1.8, 3.5) |
0.6 (‑1.8, 3.5) |
0.0 (‑2.4, 2.4) |
| Wrist fracture | 1 (0.6) |
0 |
0 |
0.6 (‑1.8, 3.5) |
0.6 (‑1.8, 3.5) |
0.0 (‑2.4, 2.4) |
| Conjunctival hyperaemia | 3 (1.9) |
2 (1.3) |
1 (0.6) |
0.6 (‑2.9, 4.3) |
1.3 (‑1.8, 4.9) |
0.6 (‑2.4, 4.0) |
| Blood pressure increased | 0 |
0 |
1 (0.6) |
0.0 (‑2.4, 2.4) |
‑0.6 (‑3.5, 1.8) |
‑0.6 (‑3.5, 1.8) |
| Cataract cortical | 0 |
0 |
1 (0.6) |
0.0 (‑2.4, 2.4) |
‑0.6 (‑3.5, 1.8) |
‑0.6 (‑3.5, 1.8) |
| Conjunctival disorder | 0 |
0 |
1 (0.6) |
0.0 (‑2.4, 2.4) |
‑0.6 (‑3.5, 1.8) |
‑0.6 (‑3.5, 1.8) |
| Cough | 0 |
0 |
1 (0.6) |
0.0 (‑2.4, 2.4) |
‑0.6 (‑3.5, 1.8) |
‑0.6 (‑3.5, 1.8) |
| Dellen | 0 |
0 |
1 (0.6) |
0.0 (‑2.4, 2.4) |
‑0.6 (‑3.5, 1.8) |
‑0.6 (‑3.5, 1.8) |
| Dermatochalasis | 0 |
0 |
1 (0.6) |
0.0 (‑2.4, 2.4) |
‑0.6 (‑3.5, 1.8) |
‑0.6 (‑3.5, 1.8) |
| Hypertension | 0 |
0 |
1 (0.6) |
0.0 (‑2.4, 2.4) |
‑0.6 (‑3.5, 1.8) |
‑0.6 (‑3.5, 1.8) |
| Hypothyroidism | 0 |
0 |
1 (0.6) |
0.0 (‑2.4, 2.4) |
‑0.6 (‑3.5, 1.8) |
‑0.6 (‑3.5, 1.8) |
| Instillation site dryness | 0 |
0 |
1 (0.6) |
0.0 (‑2.4, 2.4) |
‑0.6 (‑3.5, 1.8) |
‑0.6 (‑3.5, 1.8) |
| Meibomian gland dysfunction | 0 |
0 |
1 (0.6) |
0.0 (‑2.4, 2.4) |
‑0.6 (‑3.5, 1.8) |
‑0.6 (‑3.5, 1.8) |
| Palpitations | 0 |
0 |
1 (0.6) |
0.0 (‑2.4, 2.4) |
‑0.6 (‑3.5, 1.8) |
‑0.6 (‑3.5, 1.8) |
| Pingueculitis | 0 |
0 |
1 (0.6) |
0.0 (‑2.4, 2.4) |
‑0.6 (‑3.5, 1.8) |
‑0.6 (‑3.5, 1.8) |
| Punctate keratitis | 0 |
0 |
1 (0.6) |
0.0 (‑2.4, 2.4) |
‑0.6 (‑3.5, 1.8) |
‑0.6 (‑3.5, 1.8) |
| Rash | 0 |
0 |
1 (0.6) |
0.0 (‑2.4, 2.4) |
‑0.6 (‑3.5, 1.8) |
‑0.6 (‑3.5, 1.8) |
| Rhinitis | 0 |
0 |
1 (0.6) |
0.0 (‑2.4, 2.4) |
‑0.6 (‑3.5, 1.8) |
‑0.6 (‑3.5, 1.8) |
| Conjunctival papillae | 1 (0.6) |
1 (0.6) |
0 |
‑0.0 (‑3.0, 2.9) |
0.6 (‑1.8, 3.5) |
0.6 (‑1.8, 3.5) |
| Lacrimation increased | 1 (0.6) |
1 (0.6) |
1 (0.6) |
‑0.0 (‑3.0, 2.9) |
‑0.0 (‑3.0, 2.9) |
‑0.0 (‑3.0, 3.0) |
| Muscle tightness | 1 (0.6) |
1 (0.6) |
0 |
‑0.0 (‑3.0, 2.9) |
0.6 (‑1.8, 3.5) |
0.6 (‑1.8, 3.5) |
| Nasopharyngitis | 1 (0.6) |
1 (0.6) |
2 (1.3) |
‑0.0 (‑3.0, 2.9) |
‑0.6 (‑4.0, 2.4) |
‑0.6 (‑4.0, 2.4) |
| Paranasal sinus discomfort | 1 (0.6) |
1 (0.6) |
0 |
‑0.0 (‑3.0, 2.9) |
0.6 (‑1.8, 3.5) |
0.6 (‑1.8, 3.5) |
| Photopsia | 1 (0.6) |
1 (0.6) |
0 |
‑0.0 (‑3.0, 2.9) |
0.6 (‑1.8, 3.5) |
0.6 (‑1.8, 3.5) |
| Eye pain | 6 (3.8) |
6 (3.8) |
5 (3.2) |
‑0.0 (‑4.8, 4.7) |
0.6 (‑4.0, 5.3) |
0.6 (‑3.9, 5.4) |
| Blepharal papilloma | 0 |
1 (0.6) |
0 |
‑0.6 (‑3.5, 1.8) |
0.0 (‑2.4, 2.4) |
0.6 (‑1.8, 3.5) |
| Dyschromatopsia | 0 |
1 (0.6) |
0 |
‑0.6 (‑3.5, 1.8) |
0.0 (‑2.4, 2.4) |
0.6 (‑1.8, 3.5) |
| Facial discomfort | 0 |
1 (0.6) |
0 |
‑0.6 (‑3.5, 1.8) |
0.0 (‑2.4, 2.4) |
0.6 (‑1.8, 3.5) |
| Foreign body sensation in eyes | 0 |
1 (0.6) |
0 |
‑0.6 (‑3.5, 1.8) |
0.0 (‑2.4, 2.4) |
0.6 (‑1.8, 3.5) |
| Gastroenteritis viral | 0 |
1 (0.6) |
0 |
‑0.6 (‑3.5, 1.8) |
0.0 (‑2.4, 2.4) |
0.6 (‑1.8, 3.5) |
| Glucose tolerance impaired | 0 |
1 (0.6) |
0 |
‑0.6 (‑3.5, 1.8) |
0.0 (‑2.4, 2.4) |
0.6 (‑1.8, 3.5) |
| Head discomfort | 0 |
1 (0.6) |
0 |
‑0.6 (‑3.5, 1.8) |
0.0 (‑2.4, 2.4) |
0.6 (‑1.8, 3.5) |
| Heart rate increased | 0 |
1 (0.6) |
0 |
‑0.6 (‑3.5, 1.8) |
0.0 (‑2.4, 2.4) |
0.6 (‑1.8, 3.5) |
| Hot flush | 0 |
1 (0.6) |
0 |
‑0.6 (‑3.5, 1.8) |
0.0 (‑2.4, 2.4) |
0.6 (‑1.8, 3.5) |
| Influenza | 0 |
1 (0.6) |
0 |
‑0.6 (‑3.5, 1.8) |
0.0 (‑2.4, 2.4) |
0.6 (‑1.8, 3.5) |
| Instillation site foreign body sensation | 0 |
1 (0.6) |
2 (1.3) |
‑0.6 (‑3.5, 1.8) |
‑1.3 (‑4.6, 1.1) |
‑0.6 (‑4.0, 2.4) |
| Instillation site pain | 0 |
1 (0.6) |
0 |
‑0.6 (‑3.5, 1.8) |
0.0 (‑2.4, 2.4) |
0.6 (‑1.8, 3.5) |
| Joint injury | 0 |
1 (0.6) |
0 |
‑0.6 (‑3.5, 1.8) |
0.0 (‑2.4, 2.4) |
0.6 (‑1.8, 3.5) |
| Migraine | 0 |
1 (0.6) |
0 |
‑0.6 (‑3.5, 1.8) |
0.0 (‑2.4, 2.4) |
0.6 (‑1.8, 3.5) |
| Nasal congestion | 0 |
1 (0.6) |
1 (0.6) |
‑0.6 (‑3.5, 1.8) |
‑0.6 (‑3.5, 1.8) |
‑0.0 (‑3.0, 3.0) |
| Nasal discomfort | 0 |
1 (0.6) |
0 |
‑0.6 (‑3.5, 1.8) |
0.0 (‑2.4, 2.4) |
0.6 (‑1.8, 3.5) |
| Osteoarthritis | 0 |
1 (0.6) |
0 |
‑0.6 (‑3.5, 1.8) |
0.0 (‑2.4, 2.4) |
0.6 (‑1.8, 3.5) |
| Pulmonary hypertension | 0 |
1 (0.6) |
0 |
‑0.6 (‑3.5, 1.8) |
0.0 (‑2.4, 2.4) |
0.6 (‑1.8, 3.5) |
| Retinal haemorrhage | 0 |
1 (0.6) |
0 |
‑0.6 (‑3.5, 1.8) |
0.0 (‑2.4, 2.4) |
0.6 (‑1.8, 3.5) |
| Retinal pigmentation | 0 |
1 (0.6) |
0 |
‑0.6 (‑3.5, 1.8) |
0.0 (‑2.4, 2.4) |
0.6 (‑1.8, 3.5) |
| Retinal tear | 0 |
1 (0.6) |
0 |
‑0.6 (‑3.5, 1.8) |
0.0 (‑2.4, 2.4) |
0.6 (‑1.8, 3.5) |
| Sinus pain | 0 |
1 (0.6) |
0 |
‑0.6 (‑3.5, 1.8) |
0.0 (‑2.4, 2.4) |
0.6 (‑1.8, 3.5) |
| Somnolence | 0 |
1 (0.6) |
0 |
‑0.6 (‑3.5, 1.8) |
0.0 (‑2.4, 2.4) |
0.6 (‑1.8, 3.5) |
| Tooth abscess | 0 |
1 (0.6) |
0 |
‑0.6 (‑3.5, 1.8) |
0.0 (‑2.4, 2.4) |
0.6 (‑1.8, 3.5) |
| Urinary tract infection | 0 |
1 (0.6) |
0 |
‑0.6 (‑3.5, 1.8) |
0.0 (‑2.4, 2.4) |
0.6 (‑1.8, 3.5) |
| Visual acuity reduced | 0 |
1 (0.6) |
0 |
‑0.6 (‑3.5, 1.8) |
0.0 (‑2.4, 2.4) |
0.6 (‑1.8, 3.5) |
| Vision blurred | 5 (3.2) |
6 (3.8) |
15 (9.6) |
‑0.7 (‑5.4, 3.9) |
‑6.4 (‑12.5, ‑1.1) * |
‑5.8 (‑11.9, ‑0.2) * |
| Vitreous floaters | 6 (3.8) |
7 (4.5) |
1 (0.6) |
‑0.7 (‑5.6, 4.2) |
3.2 (‑0.1, 7.5) |
3.8 (0.4, 8.4) * |
| Ocular hyperaemia | 7 (4.5) |
8 (5.1) |
0 |
‑0.7 (‑5.9, 4.5) |
4.5 (2.0, 8.9) * |
5.1 (2.6, 9.8) * |
| Instillation site irritation | 30 (19.1) |
31 (19.9) |
10 (6.4) |
‑0.8 (‑9.6, 8.1) |
12.7 (5.5, 20.3) * |
13.5 (6.2, 21.2) * |
| COVID-19 | 0 |
2 (1.3) |
1 (0.6) |
‑1.3 (‑4.6, 1.1) |
‑0.6 (‑3.5, 1.8) |
0.6 (‑2.4, 4.0) |
| Dry eye | 0 |
2 (1.3) |
2 (1.3) |
‑1.3 (‑4.6, 1.1) |
‑1.3 (‑4.6, 1.1) |
‑0.0 (‑3.4, 3.4) |
| Eye pruritus | 0 |
2 (1.3) |
1 (0.6) |
‑1.3 (‑4.6, 1.1) |
‑0.6 (‑3.5, 1.8) |
0.6 (‑2.4, 4.0) |
| Upper-airway cough syndrome | 0 |
2 (1.3) |
0 |
‑1.3 (‑4.6, 1.1) |
0.0 (‑2.4, 2.4) |
1.3 (‑1.1, 4.6) |
| Vertigo | 0 |
2 (1.3) |
2 (1.3) |
‑1.3 (‑4.6, 1.1) |
‑1.3 (‑4.6, 1.1) |
‑0.0 (‑3.4, 3.4) |
| Vomiting | 0 |
2 (1.3) |
0 |
‑1.3 (‑4.6, 1.1) |
0.0 (‑2.4, 2.4) |
1.3 (‑1.1, 4.6) |
| Vitreous detachment | 1 (0.6) |
3 (1.9) |
1 (0.6) |
‑1.3 (‑4.9, 1.8) |
‑0.0 (‑3.0, 2.9) |
1.3 (‑1.8, 4.9) |
| Rhinorrhoea | 3 (1.9) |
5 (3.2) |
1 (0.6) |
‑1.3 (‑5.6, 2.7) |
1.3 (‑1.8, 4.9) |
2.6 (‑0.7, 6.7) |
| Photophobia | 1 (0.6) |
4 (2.6) |
0 |
‑1.9 (‑5.9, 1.2) |
0.6 (‑1.8, 3.5) |
2.6 (0.1, 6.4) * |
| Eye irritation | 2 (1.3) |
6 (3.8) |
1 (0.6) |
‑2.6 (‑7.0, 1.2) |
0.6 (‑2.4, 4.0) |
3.2 (‑0.1, 7.6) |
| Ocular discomfort | 2 (1.3) |
6 (3.8) |
0 |
‑2.6 (‑7.0, 1.2) |
1.3 (‑1.2, 4.5) |
3.8 (1.4, 8.1) * |
| Facial pain | 3 (1.9) |
7 (4.5) |
0 |
‑2.6 (‑7.3, 1.6) |
1.9 (‑0.5, 5.5) |
4.5 (2.0, 9.0) * |
| Nausea | 1 (0.6) |
10 (6.4) |
1 (0.6) |
‑5.8 (‑10.9, ‑2.1) * |
‑0.0 (‑3.0, 2.9) |
5.8 (2.1, 10.8) * |
| Visual impairment | 16 (10.2) |
28 (17.9) |
0 |
‑7.8 (‑15.7, ‑0.0) * |
10.2 (6.4, 15.9) * |
17.9 (12.7, 24.7) * |
| Headache | 19 (12.1) |
59 (37.8) |
5 (3.2) |
-25.7 (‑34.8, ‑16.4) * |
8.9 (3.2, 15.3) * |
34.6 (26.6, 42.8) * |
Source: Adapted from FDA Review
Treatment-emergent adverse events defined as any AE that started or worsened in severity on or after the first dose date.
Duration is 6 weeks.
Coded as MedDRA preferred terms.
Risk difference (with 95% confidence interval) is shown between total treatment and comparator.
Asterisk (*) indicates rows where the 95% confidence interval excludes zero.
Abbreviations: AE, adverse event; CI, confidence interval; LNZ100, aceclidine hydrochloride 1.75% ophthalmic solution; LNZ101, aceclidine hydrochloride 1.75% and brimonidine tartrate 0.08% ophthalmic solution; MedDRA, Medical Dictionary for Regulatory Activities; N, number of patients in treatment arm; n, number of patients with adverse event
Table 6. Patients With Adverse Events, Safety Population, CLARITY-2
| Preferred Term | LNZ100 |
LNZ101 |
Vehicle |
LNZ100 vs. LNZ101 |
LNZ100 vs. Vehicle |
LNZ101 vs. Vehicle |
|---|---|---|---|---|---|---|
| Any AE | 41 (53.2) |
52 (68.4) |
20 (26.3) |
-15.2 (‑30.0, 0.4) |
26.9 (11.5, 41.1) * |
42.1 (26.8, 55.4) * |
| Conjunctival hyperaemia | 9 (11.7) |
1 (1.3) |
1 (1.3) |
10.4 (3.1, 19.7) * |
10.4 (3.1, 19.7) * |
‑0.0 (‑5.9, 5.9) |
| Eye irritation | 4 (5.2) |
0 |
0 |
5.2 (0.2, 12.6) * |
5.2 (0.2, 12.6) * |
0.0 (‑4.8, 4.8) |
| Eye pain | 2 (2.6) |
0 |
0 |
2.6 (‑2.3, 9.0) |
2.6 (‑2.3, 9.0) |
0.0 (‑4.8, 4.8) |
| Eye pruritus | 2 (2.6) |
0 |
1 (1.3) |
2.6 (‑2.3, 9.0) |
1.3 (‑4.8, 7.9) |
‑1.3 (‑7.1, 3.6) |
| Ocular hyperaemia | 2 (2.6) |
0 |
1 (1.3) |
2.6 (‑2.3, 9.0) |
1.3 (‑4.8, 7.9) |
‑1.3 (‑7.1, 3.6) |
| Pyrexia | 2 (2.6) |
0 |
0 |
2.6 (‑2.3, 9.0) |
2.6 (‑2.3, 9.0) |
0.0 (‑4.8, 4.8) |
| Visual impairment | 15 (19.5) |
13 (17.1) |
1 (1.3) |
2.4 (‑10.1, 14.9) |
18.2 (9.7, 28.6) * |
15.8 (7.7, 26.0) * |
| Bronchitis | 1 (1.3) |
0 |
1 (1.3) |
1.3 (‑3.6, 7.0) |
‑0.0 (‑5.9, 5.8) |
‑1.3 (‑7.1, 3.6) |
| Chills | 1 (1.3) |
0 |
0 |
1.3 (‑3.6, 7.0) |
1.3 (‑3.6, 7.0) |
0.0 (‑4.8, 4.8) |
| Dysgeusia | 1 (1.3) |
0 |
0 |
1.3 (‑3.6, 7.0) |
1.3 (‑3.6, 7.0) |
0.0 (‑4.8, 4.8) |
| Dysphotopsia | 1 (1.3) |
0 |
0 |
1.3 (‑3.6, 7.0) |
1.3 (‑3.6, 7.0) |
0.0 (‑4.8, 4.8) |
| Eczema | 1 (1.3) |
0 |
0 |
1.3 (‑3.6, 7.0) |
1.3 (‑3.6, 7.0) |
0.0 (‑4.8, 4.8) |
| Facial discomfort | 1 (1.3) |
0 |
0 |
1.3 (‑3.6, 7.0) |
1.3 (‑3.6, 7.0) |
0.0 (‑4.8, 4.8) |
| Lethargy | 1 (1.3) |
0 |
0 |
1.3 (‑3.6, 7.0) |
1.3 (‑3.6, 7.0) |
0.0 (‑4.8, 4.8) |
| Limb injury | 1 (1.3) |
0 |
0 |
1.3 (‑3.6, 7.0) |
1.3 (‑3.6, 7.0) |
0.0 (‑4.8, 4.8) |
| Product residue present | 1 (1.3) |
0 |
0 |
1.3 (‑3.6, 7.0) |
1.3 (‑3.6, 7.0) |
0.0 (‑4.8, 4.8) |
| Swelling of eyelid | 1 (1.3) |
0 |
0 |
1.3 (‑3.6, 7.0) |
1.3 (‑3.6, 7.0) |
0.0 (‑4.8, 4.8) |
| Upper respiratory tract infection | 1 (1.3) |
0 |
0 |
1.3 (‑3.6, 7.0) |
1.3 (‑3.6, 7.0) |
0.0 (‑4.8, 4.8) |
| Vitreous degeneration | 1 (1.3) |
0 |
0 |
1.3 (‑3.6, 7.0) |
1.3 (‑3.6, 7.0) |
0.0 (‑4.8, 4.8) |
| Instillation site erythema | 2 (2.6) |
1 (1.3) |
0 |
1.3 (‑4.8, 7.9) |
2.6 (‑2.3, 9.0) |
1.3 (‑3.6, 7.1) |
| Constipation | 0 |
0 |
1 (1.3) |
0.0 (‑4.8, 4.8) |
‑1.3 (‑7.1, 3.5) |
‑1.3 (‑7.1, 3.6) |
| Cyst | 0 |
0 |
1 (1.3) |
0.0 (‑4.8, 4.8) |
‑1.3 (‑7.1, 3.5) |
‑1.3 (‑7.1, 3.6) |
| Decreased appetite | 0 |
0 |
1 (1.3) |
0.0 (‑4.8, 4.8) |
‑1.3 (‑7.1, 3.5) |
‑1.3 (‑7.1, 3.6) |
| Dermatitis | 0 |
0 |
1 (1.3) |
0.0 (‑4.8, 4.8) |
‑1.3 (‑7.1, 3.5) |
‑1.3 (‑7.1, 3.6) |
| Eye discharge | 0 |
0 |
1 (1.3) |
0.0 (‑4.8, 4.8) |
‑1.3 (‑7.1, 3.5) |
‑1.3 (‑7.1, 3.6) |
| Telangiectasia | 0 |
0 |
1 (1.3) |
0.0 (‑4.8, 4.8) |
‑1.3 (‑7.1, 3.5) |
‑1.3 (‑7.1, 3.6) |
| Rhinorrhoea | 1 (1.3) |
1 (1.3) |
0 |
‑0.0 (‑5.9, 5.8) |
1.3 (‑3.6, 7.0) |
1.3 (‑3.6, 7.1) |
| Vitreous detachment | 1 (1.3) |
1 (1.3) |
0 |
‑0.0 (‑5.9, 5.8) |
1.3 (‑3.6, 7.0) |
1.3 (‑3.6, 7.1) |
| Vision blurred | 5 (6.5) |
5 (6.6) |
2 (2.6) |
‑0.1 (‑8.9, 8.7) |
3.9 (‑3.5, 12.1) |
3.9 (‑3.4, 12.3) |
| Asthenopia | 0 |
1 (1.3) |
1 (1.3) |
‑1.3 (‑7.1, 3.5) |
‑1.3 (‑7.1, 3.5) |
‑0.0 (‑5.9, 5.9) |
| Dizziness | 0 |
1 (1.3) |
0 |
‑1.3 (‑7.1, 3.5) |
0.0 (‑4.8, 4.8) |
1.3 (‑3.6, 7.1) |
| Dry eye | 0 |
1 (1.3) |
1 (1.3) |
‑1.3 (‑7.1, 3.5) |
‑1.3 (‑7.1, 3.5) |
‑0.0 (‑5.9, 5.9) |
| Hordeolum | 0 |
1 (1.3) |
0 |
‑1.3 (‑7.1, 3.5) |
0.0 (‑4.8, 4.8) |
1.3 (‑3.6, 7.1) |
| Instillation site papules | 0 |
1 (1.3) |
0 |
‑1.3 (‑7.1, 3.5) |
0.0 (‑4.8, 4.8) |
1.3 (‑3.6, 7.1) |
| Menstrual disorder | 0 |
1 (1.3) |
0 |
‑1.3 (‑7.1, 3.5) |
0.0 (‑4.8, 4.8) |
1.3 (‑3.6, 7.1) |
| Musculoskeletal pain | 0 |
1 (1.3) |
0 |
‑1.3 (‑7.1, 3.5) |
0.0 (‑4.8, 4.8) |
1.3 (‑3.6, 7.1) |
| Photophobia | 0 |
1 (1.3) |
0 |
‑1.3 (‑7.1, 3.5) |
0.0 (‑4.8, 4.8) |
1.3 (‑3.6, 7.1) |
| Presyncope | 0 |
1 (1.3) |
0 |
‑1.3 (‑7.1, 3.5) |
0.0 (‑4.8, 4.8) |
1.3 (‑3.6, 7.1) |
| Instillation site foreign body sensation | 1 (1.3) |
2 (2.6) |
1 (1.3) |
‑1.3 (‑8.0, 4.7) |
‑0.0 (‑5.9, 5.8) |
1.3 (‑4.7, 8.0) |
| Lacrimation increased | 2 (2.6) |
3 (3.9) |
0 |
‑1.3 (‑8.7, 5.6) |
2.6 (‑2.3, 9.0) |
3.9 (‑1.0, 11.0) |
| Vitreous floaters | 5 (6.5) |
6 (7.9) |
1 (1.3) |
‑1.4 (‑10.6, 7.6) |
5.2 (‑1.3, 13.2) |
6.6 (‑0.1, 15.1) |
| Nausea | 2 (2.6) |
4 (5.3) |
0 |
‑2.7 (‑10.6, 4.4) |
2.6 (‑2.3, 9.0) |
5.3 (0.3, 12.8) * |
| Punctate keratitis | 2 (2.6) |
4 (5.3) |
1 (1.3) |
‑2.7 (‑10.6, 4.4) |
1.3 (‑4.8, 7.9) |
3.9 (‑2.4, 11.7) |
| Instillation site irritation | 17 (22.1) |
20 (26.3) |
8 (10.5) |
‑4.2 (‑17.9, 9.4) |
11.6 (‑0.2, 23.5) |
15.8 (3.6, 28.1) * |
| Facial pain | 3 (3.9) |
8 (10.5) |
0 |
‑6.6 (‑16.1, 1.8) |
3.9 (‑1.0, 10.9) |
10.5 (5.4, 19.5) * |
| Headache | 8 (10.4) |
31 (40.8) |
3 (3.9) |
-30.4 (‑43.1, ‑17.1) * |
6.4 (‑2.0, 15.8) |
36.8 (25.0, 48.7) * |
Source: Adapted from FDA Review
Treatment-emergent adverse events defined as any AE that started or worsened in severity on or after the first dose date.
Duration is 6 weeks.
Coded as MedDRA preferred terms.
Risk difference (with 95% confidence interval) is shown between total treatment and comparator.
Asterisk (*) indicates rows where the 95% confidence interval excludes zero.
Abbreviations: AE, adverse event; CI, confidence interval; LNZ100, aceclidine hydrochloride 1.75% ophthalmic solution; LNZ101, aceclidine hydrochloride 1.75% and brimonidine tartrate 0.08% ophthalmic solution; MedDRA, Medical Dictionary for Regulatory Activities; N, number of patients in treatment arm; n, number of patients with adverse event
Table 7. Patients With Adverse Events, Safety Population, CLARITY-3
| Preferred Term | LNZ100 |
LNZ101 |
Vehicle |
LNZ100 vs. LNZ101 |
LNZ100 vs. Vehicle |
LNZ101 vs. Vehicle |
|---|---|---|---|---|---|---|
| Any AE | 89 (61.8) |
113 (78.5) |
25 (34.2) |
-16.7 (‑26.9, ‑6.1) * |
27.6 (13.6, 40.3) * |
44.2 (30.8, 56.1) * |
| Ocular hyperaemia | 18 (12.5) |
5 (3.5) |
0 |
9.0 (3.0, 15.9) * |
12.5 (7.3, 18.9) * |
3.5 (‑1.6, 7.9) |
| Conjunctival hyperaemia | 17 (11.8) |
8 (5.6) |
1 (1.4) |
6.2 (‑0.3, 13.2) |
10.4 (3.6, 17.0) * |
4.2 (‑2.2, 9.5) |
| Instillation site erythema | 6 (4.2) |
3 (2.1) |
0 |
2.1 (‑2.3, 7.0) |
4.2 (‑0.9, 8.8) |
2.1 (‑3.0, 6.0) |
| Acute sinusitis | 1 (0.7) |
0 |
0 |
0.7 (‑1.9, 3.8) |
0.7 (‑4.3, 3.8) |
0.0 (‑5.0, 2.6) |
| Anisocoria | 1 (0.7) |
0 |
0 |
0.7 (‑1.9, 3.8) |
0.7 (‑4.3, 3.8) |
0.0 (‑5.0, 2.6) |
| Asthenopia | 2 (1.4) |
1 (0.7) |
0 |
0.7 (‑2.6, 4.3) |
1.4 (‑3.7, 4.9) |
0.7 (‑4.3, 3.8) |
| Calculus bladder | 1 (0.7) |
0 |
0 |
0.7 (‑1.9, 3.8) |
0.7 (‑4.3, 3.8) |
0.0 (‑5.0, 2.6) |
| Cataract cortical | 1 (0.7) |
0 |
1 (1.4) |
0.7 (‑1.9, 3.8) |
‑0.7 (‑6.7, 2.6) |
‑1.4 (‑7.4, 1.3) |
| Chalazion | 1 (0.7) |
0 |
0 |
0.7 (‑1.9, 3.8) |
0.7 (‑4.3, 3.8) |
0.0 (‑5.0, 2.6) |
| Chest pain | 1 (0.7) |
0 |
0 |
0.7 (‑1.9, 3.8) |
0.7 (‑4.3, 3.8) |
0.0 (‑5.0, 2.6) |
| Conjunctivitis | 1 (0.7) |
0 |
0 |
0.7 (‑1.9, 3.8) |
0.7 (‑4.3, 3.8) |
0.0 (‑5.0, 2.6) |
| Conjunctivitis allergic | 1 (0.7) |
0 |
0 |
0.7 (‑1.9, 3.8) |
0.7 (‑4.3, 3.8) |
0.0 (‑5.0, 2.6) |
| Conjunctivochalasis | 1 (0.7) |
0 |
1 (1.4) |
0.7 (‑1.9, 3.8) |
‑0.7 (‑6.7, 2.6) |
‑1.4 (‑7.4, 1.3) |
| Contusion | 1 (0.7) |
0 |
0 |
0.7 (‑1.9, 3.8) |
0.7 (‑4.3, 3.8) |
0.0 (‑5.0, 2.6) |
| Corneal abrasion | 1 (0.7) |
0 |
0 |
0.7 (‑1.9, 3.8) |
0.7 (‑4.3, 3.8) |
0.0 (‑5.0, 2.6) |
| Corneal dystrophy | 1 (0.7) |
0 |
0 |
0.7 (‑1.9, 3.8) |
0.7 (‑4.3, 3.8) |
0.0 (‑5.0, 2.6) |
| Corneal pigmentation | 1 (0.7) |
0 |
0 |
0.7 (‑1.9, 3.8) |
0.7 (‑4.3, 3.8) |
0.0 (‑5.0, 2.6) |
| Deep vein thrombosis | 1 (0.7) |
0 |
0 |
0.7 (‑1.9, 3.8) |
0.7 (‑4.3, 3.8) |
0.0 (‑5.0, 2.6) |
| Electric shock | 1 (0.7) |
0 |
0 |
0.7 (‑1.9, 3.8) |
0.7 (‑4.3, 3.8) |
0.0 (‑5.0, 2.6) |
| Endometrial adenocarcinoma | 1 (0.7) |
0 |
0 |
0.7 (‑1.9, 3.8) |
0.7 (‑4.3, 3.8) |
0.0 (‑5.0, 2.6) |
| Eye infection viral | 1 (0.7) |
0 |
0 |
0.7 (‑1.9, 3.8) |
0.7 (‑4.3, 3.8) |
0.0 (‑5.0, 2.6) |
| Eye irritation | 2 (1.4) |
1 (0.7) |
0 |
0.7 (‑2.6, 4.3) |
1.4 (‑3.7, 4.9) |
0.7 (‑4.3, 3.8) |
| Eye pain | 6 (4.2) |
5 (3.5) |
0 |
0.7 (‑4.3, 5.8) |
4.2 (‑0.9, 8.8) |
3.5 (‑1.6, 7.9) |
| Hand fracture | 1 (0.7) |
0 |
0 |
0.7 (‑1.9, 3.8) |
0.7 (‑4.3, 3.8) |
0.0 (‑5.0, 2.6) |
| Hypothyroidism | 1 (0.7) |
0 |
0 |
0.7 (‑1.9, 3.8) |
0.7 (‑4.3, 3.8) |
0.0 (‑5.0, 2.6) |
| Instillation site pruritus | 1 (0.7) |
0 |
1 (1.4) |
0.7 (‑1.9, 3.8) |
‑0.7 (‑6.7, 2.6) |
‑1.4 (‑7.4, 1.3) |
| Intraocular pressure increased | 1 (0.7) |
0 |
0 |
0.7 (‑1.9, 3.8) |
0.7 (‑4.3, 3.8) |
0.0 (‑5.0, 2.6) |
| Iris transillumination defect | 1 (0.7) |
0 |
0 |
0.7 (‑1.9, 3.8) |
0.7 (‑4.3, 3.8) |
0.0 (‑5.0, 2.6) |
| Ligament sprain | 1 (0.7) |
0 |
0 |
0.7 (‑1.9, 3.8) |
0.7 (‑4.3, 3.8) |
0.0 (‑5.0, 2.6) |
| Meibomian gland dysfunction | 1 (0.7) |
0 |
0 |
0.7 (‑1.9, 3.8) |
0.7 (‑4.3, 3.8) |
0.0 (‑5.0, 2.6) |
| Nasopharyngitis | 1 (0.7) |
0 |
1 (1.4) |
0.7 (‑1.9, 3.8) |
‑0.7 (‑6.7, 2.6) |
‑1.4 (‑7.4, 1.3) |
| Otorrhoea | 1 (0.7) |
0 |
0 |
0.7 (‑1.9, 3.8) |
0.7 (‑4.3, 3.8) |
0.0 (‑5.0, 2.6) |
| Pharyngitis | 1 (0.7) |
0 |
0 |
0.7 (‑1.9, 3.8) |
0.7 (‑4.3, 3.8) |
0.0 (‑5.0, 2.6) |
| Restless legs syndrome | 1 (0.7) |
0 |
0 |
0.7 (‑1.9, 3.8) |
0.7 (‑4.3, 3.8) |
0.0 (‑5.0, 2.6) |
| Retinal haemorrhage | 1 (0.7) |
0 |
0 |
0.7 (‑1.9, 3.8) |
0.7 (‑4.3, 3.8) |
0.0 (‑5.0, 2.6) |
| Rhinalgia | 1 (0.7) |
0 |
0 |
0.7 (‑1.9, 3.8) |
0.7 (‑4.3, 3.8) |
0.0 (‑5.0, 2.6) |
| Rosacea | 1 (0.7) |
0 |
0 |
0.7 (‑1.9, 3.8) |
0.7 (‑4.3, 3.8) |
0.0 (‑5.0, 2.6) |
| Skin laceration | 1 (0.7) |
0 |
0 |
0.7 (‑1.9, 3.8) |
0.7 (‑4.3, 3.8) |
0.0 (‑5.0, 2.6) |
| Urobilinogen urine increased | 1 (0.7) |
0 |
0 |
0.7 (‑1.9, 3.8) |
0.7 (‑4.3, 3.8) |
0.0 (‑5.0, 2.6) |
| Vitreous floaters | 8 (5.6) |
7 (4.9) |
0 |
0.7 (‑4.9, 6.4) |
5.6 (0.4, 10.6) * |
4.9 (‑0.2, 9.7) |
| Allergic keratitis | 0 |
0 |
1 (1.4) |
0.0 (‑2.6, 2.6) |
‑1.4 (‑7.4, 1.3) |
‑1.4 (‑7.4, 1.3) |
| Back pain | 0 |
0 |
1 (1.4) |
0.0 (‑2.6, 2.6) |
‑1.4 (‑7.4, 1.3) |
‑1.4 (‑7.4, 1.3) |
| Blood glucose increased | 0 |
0 |
1 (1.4) |
0.0 (‑2.6, 2.6) |
‑1.4 (‑7.4, 1.3) |
‑1.4 (‑7.4, 1.3) |
| Cellulitis | 0 |
0 |
1 (1.4) |
0.0 (‑2.6, 2.6) |
‑1.4 (‑7.4, 1.3) |
‑1.4 (‑7.4, 1.3) |
| Dental caries | 0 |
0 |
1 (1.4) |
0.0 (‑2.6, 2.6) |
‑1.4 (‑7.4, 1.3) |
‑1.4 (‑7.4, 1.3) |
| Dysphagia | 0 |
0 |
1 (1.4) |
0.0 (‑2.6, 2.6) |
‑1.4 (‑7.4, 1.3) |
‑1.4 (‑7.4, 1.3) |
| Eye swelling | 0 |
0 |
1 (1.4) |
0.0 (‑2.6, 2.6) |
‑1.4 (‑7.4, 1.3) |
‑1.4 (‑7.4, 1.3) |
| Eyelid margin crusting | 0 |
0 |
1 (1.4) |
0.0 (‑2.6, 2.6) |
‑1.4 (‑7.4, 1.3) |
‑1.4 (‑7.4, 1.3) |
| Gingival abscess | 0 |
0 |
1 (1.4) |
0.0 (‑2.6, 2.6) |
‑1.4 (‑7.4, 1.3) |
‑1.4 (‑7.4, 1.3) |
| Hypercholesterolaemia | 0 |
0 |
1 (1.4) |
0.0 (‑2.6, 2.6) |
‑1.4 (‑7.4, 1.3) |
‑1.4 (‑7.4, 1.3) |
| Infective keratitis | 0 |
0 |
1 (1.4) |
0.0 (‑2.6, 2.6) |
‑1.4 (‑7.4, 1.3) |
‑1.4 (‑7.4, 1.3) |
| Instillation site lacrimation | 0 |
0 |
1 (1.4) |
0.0 (‑2.6, 2.6) |
‑1.4 (‑7.4, 1.3) |
‑1.4 (‑7.4, 1.3) |
| Anxiety | 2 (1.4) |
2 (1.4) |
0 |
‑0.0 (‑3.7, 3.7) |
1.4 (‑3.7, 4.9) |
1.4 (‑3.7, 4.9) |
| Conjunctival haemorrhage | 1 (0.7) |
1 (0.7) |
0 |
‑0.0 (‑3.2, 3.2) |
0.7 (‑4.3, 3.8) |
0.7 (‑4.3, 3.8) |
| Conjunctival oedema | 1 (0.7) |
1 (0.7) |
0 |
‑0.0 (‑3.2, 3.2) |
0.7 (‑4.3, 3.8) |
0.7 (‑4.3, 3.8) |
| Eye pruritus | 2 (1.4) |
2 (1.4) |
2 (2.7) |
‑0.0 (‑3.7, 3.7) |
‑1.4 (‑8.2, 2.7) |
‑1.4 (‑8.2, 2.7) |
| Ocular discomfort | 1 (0.7) |
1 (0.7) |
0 |
‑0.0 (‑3.2, 3.2) |
0.7 (‑4.3, 3.8) |
0.7 (‑4.3, 3.8) |
| Pneumonia | 3 (2.1) |
3 (2.1) |
0 |
‑0.0 (‑4.1, 4.1) |
2.1 (‑3.0, 6.0) |
2.1 (‑3.0, 6.0) |
| Sinus headache | 1 (0.7) |
1 (0.7) |
0 |
‑0.0 (‑3.2, 3.2) |
0.7 (‑4.3, 3.8) |
0.7 (‑4.3, 3.8) |
| Sinusitis | 1 (0.7) |
1 (0.7) |
0 |
‑0.0 (‑3.2, 3.2) |
0.7 (‑4.3, 3.8) |
0.7 (‑4.3, 3.8) |
| Upper respiratory tract infection | 2 (1.4) |
2 (1.4) |
0 |
‑0.0 (‑3.7, 3.7) |
1.4 (‑3.7, 4.9) |
1.4 (‑3.7, 4.9) |
| Abdominal pain upper | 0 |
1 (0.7) |
0 |
‑0.7 (‑3.8, 1.9) |
0.0 (‑5.0, 2.6) |
0.7 (‑4.3, 3.8) |
| Abnormal sensation in eye | 0 |
1 (0.7) |
0 |
‑0.7 (‑3.8, 1.9) |
0.0 (‑5.0, 2.6) |
0.7 (‑4.3, 3.8) |
| Adenoviral conjunctivitis | 0 |
1 (0.7) |
0 |
‑0.7 (‑3.8, 1.9) |
0.0 (‑5.0, 2.6) |
0.7 (‑4.3, 3.8) |
| Alanine aminotransferase abnormal | 0 |
1 (0.7) |
0 |
‑0.7 (‑3.8, 1.9) |
0.0 (‑5.0, 2.6) |
0.7 (‑4.3, 3.8) |
| Amaurosis fugax | 0 |
1 (0.7) |
0 |
‑0.7 (‑3.8, 1.9) |
0.0 (‑5.0, 2.6) |
0.7 (‑4.3, 3.8) |
| Aspartate aminotransferase | 0 |
1 (0.7) |
0 |
‑0.7 (‑3.8, 1.9) |
0.0 (‑5.0, 2.6) |
0.7 (‑4.3, 3.8) |
| Asthma | 1 (0.7) |
2 (1.4) |
0 |
‑0.7 (‑4.3, 2.6) |
0.7 (‑4.3, 3.8) |
1.4 (‑3.7, 4.9) |
| Blepharitis | 0 |
1 (0.7) |
1 (1.4) |
‑0.7 (‑3.8, 1.9) |
‑1.4 (‑7.4, 1.3) |
‑0.7 (‑6.7, 2.6) |
| Cerebrovascular accident | 0 |
1 (0.7) |
0 |
‑0.7 (‑3.8, 1.9) |
0.0 (‑5.0, 2.6) |
0.7 (‑4.3, 3.8) |
| Conjunctivitis bacterial | 0 |
1 (0.7) |
0 |
‑0.7 (‑3.8, 1.9) |
0.0 (‑5.0, 2.6) |
0.7 (‑4.3, 3.8) |
| Constipation | 0 |
1 (0.7) |
0 |
‑0.7 (‑3.8, 1.9) |
0.0 (‑5.0, 2.6) |
0.7 (‑4.3, 3.8) |
| COVID-19 | 3 (2.1) |
4 (2.8) |
1 (1.4) |
‑0.7 (‑5.1, 3.5) |
0.7 (‑5.4, 4.8) |
1.4 (‑4.8, 5.8) |
| COVID-19 pneumonia | 0 |
1 (0.7) |
0 |
‑0.7 (‑3.8, 1.9) |
0.0 (‑5.0, 2.6) |
0.7 (‑4.3, 3.8) |
| Diarrhoea | 0 |
1 (0.7) |
0 |
‑0.7 (‑3.8, 1.9) |
0.0 (‑5.0, 2.6) |
0.7 (‑4.3, 3.8) |
| Dysgeusia | 0 |
1 (0.7) |
0 |
‑0.7 (‑3.8, 1.9) |
0.0 (‑5.0, 2.6) |
0.7 (‑4.3, 3.8) |
| Ear pain | 0 |
1 (0.7) |
0 |
‑0.7 (‑3.8, 1.9) |
0.0 (‑5.0, 2.6) |
0.7 (‑4.3, 3.8) |
| Eye injury | 0 |
1 (0.7) |
0 |
‑0.7 (‑3.8, 1.9) |
0.0 (‑5.0, 2.6) |
0.7 (‑4.3, 3.8) |
| Foreign body sensation in eyes | 1 (0.7) |
2 (1.4) |
0 |
‑0.7 (‑4.3, 2.6) |
0.7 (‑4.3, 3.8) |
1.4 (‑3.7, 4.9) |
| Fungal infection | 0 |
1 (0.7) |
0 |
‑0.7 (‑3.8, 1.9) |
0.0 (‑5.0, 2.6) |
0.7 (‑4.3, 3.8) |
| Hepatic enzyme increased | 0 |
1 (0.7) |
0 |
‑0.7 (‑3.8, 1.9) |
0.0 (‑5.0, 2.6) |
0.7 (‑4.3, 3.8) |
| Hypersensitivity | 0 |
1 (0.7) |
0 |
‑0.7 (‑3.8, 1.9) |
0.0 (‑5.0, 2.6) |
0.7 (‑4.3, 3.8) |
| Hypoxia | 0 |
1 (0.7) |
0 |
‑0.7 (‑3.8, 1.9) |
0.0 (‑5.0, 2.6) |
0.7 (‑4.3, 3.8) |
| Influenza | 0 |
1 (0.7) |
0 |
‑0.7 (‑3.8, 1.9) |
0.0 (‑5.0, 2.6) |
0.7 (‑4.3, 3.8) |
| Injection site pain | 0 |
1 (0.7) |
0 |
‑0.7 (‑3.8, 1.9) |
0.0 (‑5.0, 2.6) |
0.7 (‑4.3, 3.8) |
| Instillation site foreign body sensation | 0 |
1 (0.7) |
0 |
‑0.7 (‑3.8, 1.9) |
0.0 (‑5.0, 2.6) |
0.7 (‑4.3, 3.8) |
| Joint injury | 0 |
1 (0.7) |
0 |
‑0.7 (‑3.8, 1.9) |
0.0 (‑5.0, 2.6) |
0.7 (‑4.3, 3.8) |
| Loss of visual contrast sensitivity | 5 (3.5) |
6 (4.2) |
0 |
‑0.7 (‑5.8, 4.3) |
3.5 (‑1.6, 7.9) |
4.2 (‑0.9, 8.8) |
| Macrocytosis | 0 |
1 (0.7) |
0 |
‑0.7 (‑3.8, 1.9) |
0.0 (‑5.0, 2.6) |
0.7 (‑4.3, 3.8) |
| Metapneumovirus infection | 0 |
1 (0.7) |
0 |
‑0.7 (‑3.8, 1.9) |
0.0 (‑5.0, 2.6) |
0.7 (‑4.3, 3.8) |
| Ovarian cyst | 0 |
1 (0.7) |
0 |
‑0.7 (‑3.8, 1.9) |
0.0 (‑5.0, 2.6) |
0.7 (‑4.3, 3.8) |
| Pain | 0 |
1 (0.7) |
0 |
‑0.7 (‑3.8, 1.9) |
0.0 (‑5.0, 2.6) |
0.7 (‑4.3, 3.8) |
| Paranasal sinus discomfort | 0 |
1 (0.7) |
0 |
‑0.7 (‑3.8, 1.9) |
0.0 (‑5.0, 2.6) |
0.7 (‑4.3, 3.8) |
| Prostate cancer | 0 |
1 (0.7) |
0 |
‑0.7 (‑3.8, 1.9) |
0.0 (‑5.0, 2.6) |
0.7 (‑4.3, 3.8) |
| Prostatitis | 0 |
1 (0.7) |
0 |
‑0.7 (‑3.8, 1.9) |
0.0 (‑5.0, 2.6) |
0.7 (‑4.3, 3.8) |
| Punctate keratitis | 1 (0.7) |
2 (1.4) |
0 |
‑0.7 (‑4.3, 2.6) |
0.7 (‑4.3, 3.8) |
1.4 (‑3.7, 4.9) |
| Rib fracture | 0 |
1 (0.7) |
0 |
‑0.7 (‑3.8, 1.9) |
0.0 (‑5.0, 2.6) |
0.7 (‑4.3, 3.8) |
| Rotator cuff syndrome | 0 |
1 (0.7) |
0 |
‑0.7 (‑3.8, 1.9) |
0.0 (‑5.0, 2.6) |
0.7 (‑4.3, 3.8) |
| Salivary gland mass | 0 |
1 (0.7) |
0 |
‑0.7 (‑3.8, 1.9) |
0.0 (‑5.0, 2.6) |
0.7 (‑4.3, 3.8) |
| Skin abrasion | 0 |
1 (0.7) |
0 |
‑0.7 (‑3.8, 1.9) |
0.0 (‑5.0, 2.6) |
0.7 (‑4.3, 3.8) |
| Skin tightness | 0 |
1 (0.7) |
0 |
‑0.7 (‑3.8, 1.9) |
0.0 (‑5.0, 2.6) |
0.7 (‑4.3, 3.8) |
| Superficial injury of eye | 0 |
1 (0.7) |
0 |
‑0.7 (‑3.8, 1.9) |
0.0 (‑5.0, 2.6) |
0.7 (‑4.3, 3.8) |
| Taste disorder | 0 |
1 (0.7) |
0 |
‑0.7 (‑3.8, 1.9) |
0.0 (‑5.0, 2.6) |
0.7 (‑4.3, 3.8) |
| Urinary tract infection | 3 (2.1) |
4 (2.8) |
1 (1.4) |
‑0.7 (‑5.1, 3.5) |
0.7 (‑5.4, 4.8) |
1.4 (‑4.8, 5.8) |
| Vertigo | 0 |
1 (0.7) |
0 |
‑0.7 (‑3.8, 1.9) |
0.0 (‑5.0, 2.6) |
0.7 (‑4.3, 3.8) |
| Eye naevus | 0 |
2 (1.4) |
0 |
‑1.4 (‑4.9, 1.2) |
0.0 (‑5.0, 2.6) |
1.4 (‑3.7, 4.9) |
| Fatigue | 0 |
2 (1.4) |
0 |
‑1.4 (‑4.9, 1.2) |
0.0 (‑5.0, 2.6) |
1.4 (‑3.7, 4.9) |
| Hypertension | 0 |
2 (1.4) |
1 (1.4) |
‑1.4 (‑4.9, 1.2) |
‑1.4 (‑7.4, 1.3) |
0.0 (‑6.1, 3.8) |
| Migraine | 0 |
2 (1.4) |
0 |
‑1.4 (‑4.9, 1.2) |
0.0 (‑5.0, 2.6) |
1.4 (‑3.7, 4.9) |
| Rhinorrhoea | 0 |
2 (1.4) |
0 |
‑1.4 (‑4.9, 1.2) |
0.0 (‑5.0, 2.6) |
1.4 (‑3.7, 4.9) |
| Dizziness | 0 |
3 (2.1) |
1 (1.4) |
‑2.1 (‑6.0, 0.6) |
‑1.4 (‑7.4, 1.3) |
0.7 (‑5.4, 4.8) |
| Lacrimation increased | 2 (1.4) |
5 (3.5) |
0 |
‑2.1 (‑6.7, 1.9) |
1.4 (‑3.7, 4.9) |
3.5 (‑1.6, 7.9) |
| Visual acuity reduced | 0 |
3 (2.1) |
0 |
‑2.1 (‑6.0, 0.6) |
0.0 (‑5.0, 2.6) |
2.1 (‑3.0, 6.0) |
| Vitreous detachment | 1 (0.7) |
4 (2.8) |
0 |
‑2.1 (‑6.3, 1.3) |
0.7 (‑4.3, 3.8) |
2.8 (‑2.3, 6.9) |
| Vomiting | 0 |
3 (2.1) |
0 |
‑2.1 (‑6.0, 0.6) |
0.0 (‑5.0, 2.6) |
2.1 (‑3.0, 6.0) |
| Dry eye | 1 (0.7) |
5 (3.5) |
0 |
‑2.8 (‑7.3, 0.7) |
0.7 (‑4.3, 3.8) |
3.5 (‑1.6, 7.9) |
| Vision blurred | 4 (2.8) |
9 (6.2) |
7 (9.6) |
‑3.5 (‑9.0, 1.5) |
‑6.8 (‑16.0, ‑0.6) * |
‑3.3 (‑12.8, 3.8) |
| Photophobia | 0 |
6 (4.2) |
0 |
‑4.2 (‑8.8, ‑1.5) * |
0.0 (‑5.0, 2.6) |
4.2 (‑0.9, 8.8) |
| Instillation site irritation | 28 (19.4) |
35 (24.3) |
9 (12.3) |
‑4.9 (‑14.4, 4.7) |
7.1 (‑3.9, 16.6) |
12.0 (0.7, 21.8) * |
| Nausea | 1 (0.7) |
11 (7.6) |
1 (1.4) |
‑6.9 (‑12.6, ‑2.8) * |
‑0.7 (‑6.7, 2.6) |
6.3 (‑0.3, 12.1) |
| Facial pain | 9 (6.2) |
20 (13.9) |
2 (2.7) |
‑7.6 (‑15.0, ‑0.7) * |
3.5 (‑3.7, 9.3) |
11.1 (3.3, 18.3) * |
| Visual impairment | 28 (19.4) |
42 (29.2) |
0 |
‑9.7 (‑19.6, 0.2) |
19.4 (13.8, 26.7) * |
29.2 (22.3, 37.1) * |
| Headache | 21 (14.6) |
51 (35.4) |
5 (6.8) |
-20.8 (‑30.5, ‑11.0) * |
7.7 (‑1.7, 15.7) |
28.6 (17.9, 37.9) * |
Source: Adapted from FDA Review
Treatment-emergent adverse events defined as any AE that started or worsened in severity on or after the first dose date.
Duration is 26 weeks.
Coded as MedDRA preferred terms.
Risk difference (with 95% confidence interval) is shown between total treatment and comparator.
Asterisk (*) indicates rows where the 95% confidence interval excludes zero.
Abbreviations: AE, adverse event; CI, confidence interval; LNZ100, aceclidine hydrochloride 1.75% ophthalmic solution; LNZ101, aceclidine hydrochloride 1.75% and brimonidine tartrate 0.08% ophthalmic solution; MedDRA, Medical Dictionary for Regulatory Activities; N, number of patients in treatment arm; n, number of patients with adverse event
Were there any differences in side effects among sex, race, and age?
- Sex: The occurrence of side effects was similar in males and females.
- Race: The number of patients of races other than White was small; therefore, differences in the side effects of VIZZ among races could not be determined.
- Age: The occurrence of side effects was similar in patients below and above 65 years of age.
Were there any differences in side effects of the clinical trials among sex, race, and age groups?
Table 8. Overview of Adverse Events by Demographic Subgroup, Safety Population, CLARITY-1
| Characteristic | LNZ100 |
LNZ101 |
Brimonidine |
LNZ100 vs. LNZ101 |
LNZ100 vs. Brimonidine |
LNZ101 vs. Brimonidine |
|---|---|---|---|---|---|---|
| Sex |
|
|
|
|
|
|
| Female | 41/109 (37.6) |
75/99 (75.8) |
31/99 (31.3) |
-38.1 (‑49.8, ‑25.1) * |
44.4 (31.2, 56.0) * |
41/109 (37.6) |
| Male | 20/48 (41.7) |
33/57 (57.9) |
15/57 (26.3) |
-16.2 (‑34.3, 3.1) |
31.6 (13.6, 47.6) * |
20/48 (41.7) |
| Age group, years |
|
|
|
|
|
|
| <65 | 58/144 (40.3) |
95/139 (68.3) |
42/138 (30.4) |
-28.1 (‑38.8, ‑16.6) * |
37.9 (26.5, 48.2) * |
58/144 (40.3) |
| ≥65 | 3/13 (23.1) |
13/17 (76.5) |
4/18 (22.2) |
-53.4 (‑76.8, ‑17.2) * |
54.2 (21.4, 76.1) * |
3/13 (23.1) |
| Age group ≥75, years |
|
|
|
|
|
|
| ≥75 | 0/1 (0) |
0/0 (NA) |
0/1 (0) |
NA |
NA |
0/1 (0) |
| Race |
|
|
|
|
|
|
| American Indian or Alaska Native | 0/2 (0) |
0/0 (NA) |
0/1 (0) |
NA |
NA |
0/2 (0) |
| Asian | 5/10 (50.0) |
4/7 (57.1) |
2/8 (25.0) |
‑7.1 (‑49.6, 38.7) |
32.1 (‑18.5, 69.8) |
5/10 (50.0) |
| Black or African American | 2/6 (33.3) |
9/12 (75.0) |
3/10 (30.0) |
-41.7 (‑74.8, 7.0) |
45.0 (2.2, 74.0) * |
2/6 (33.3) |
| Multiple | 0/0 (NA) |
1/1 (100) |
0/1 (0) |
NA |
100.0 (‑58.7, 100.0) |
0/0 (NA) |
| Native Hawaiian or other Pacific Islander | 0/0 (NA) |
0/0 (NA) |
0/1 (0) |
NA |
NA |
0/0 (NA) |
| Other | 1/1 (100) |
0/2 (0) |
0/0 (NA) |
100.0 (‑31.5, 100.0) |
NA |
1/1 (100) |
| White | 53/138 (38.4) |
94/134 (70.1) |
41/135 (30.4) |
-31.7 (‑42.5, ‑20.1) * |
39.8 (28.3, 50.1) * |
53/138 (38.4) |
| Ethnicity |
|
|
|
|
|
|
| Hispanic or Latino | 11/36 (30.6) |
37/55 (67.3) |
14/47 (29.8) |
-36.7 (‑54.3, ‑15.8) * |
37.5 (18.3, 53.9) * |
11/36 (30.6) |
| Not Hispanic or Latino | 50/121 (41.3) |
71/101 (70.3) |
32/109 (29.4) |
-29.0 (‑40.9, ‑16.0) * |
40.9 (27.9, 52.5) * |
50/121 (41.3) |
Source: Adapted from FDA Review
Risk difference (with 95% confidence interval) is shown between total treatment and comparator.
Asterisk (*) indicates rows where the 95% confidence interval excludes zero.
Abbreviations: CI, confidence interval; LNZ100, aceclidine hydrochloride 1.75% ophthalmic solution; LNZ101, aceclidine hydrochloride 1.75% and brimonidine tartrate 0.08% ophthalmic solution; N, number of patients in treatment arm; n, number of patients with adverse event; NA, not applicable; Ns, total number of patients for each specific subgroup and were assigned to that specific arm
Table 9. Overview of Adverse Events by Demographic Subgroup, Safety Population, CLARITY-2
| Characteristic | LNZ100 |
LNZ101 |
Vehicle |
LNZ100 vs. LNZ101 |
LNZ100 vs. Vehicle |
LNZ101 vs. Vehicle |
|---|---|---|---|---|---|---|
| Sex | ||||||
| Female | 33/52 (63.5) |
37/51 (72.5) |
12/46 (26.1) |
‑9.1 (‑26.7, 9.0) |
37.4 (17.9, 54.0) * |
46.5 (27.2, 62.1) * |
| Male | 8/25 (32.0) |
15/25 (60.0) |
8/30 (26.7) |
-28.0 (‑51.9, ‑0.1) * |
5.3 (‑18.6, 29.6) |
33.3 (6.9, 55.6) * |
| Age group, years |
|
|
|
|
|
|
| <65 | 40/72 (55.6) |
50/73 (68.5) |
20/74 (27.0) |
-12.9 (‑28.2, 2.9) |
28.5 (12.7, 43.0) * |
41.5 (25.8, 55.0) * |
| ≥65 | 1/5 (20.0) |
2/3 (66.7) |
0/2 (0) |
-46.7 (‑86.0, 24.4) |
20.0 (‑56.3, 65.1) |
66.7 (‑29.1, 94.8) |
| Age group ≥75, years |
|
|
|
|
|
|
| ≥75 | 0/77 (0) |
0/76 (0) |
0/76 (0) |
0.0 (‑4.8, 4.8) |
0.0 (‑4.8, 4.8) |
0.0 (‑4.8, 4.8) |
| Race |
|
|
|
|
|
|
| American Indian or Alaska Native | 0/0 (NA) |
2/2 (100) |
0/1 (0) |
NA |
NA |
100.0 (‑31.5, 100.0) |
| Asian | 1/2 (50.0) |
3/3 (100) |
1/4 (25.0) |
-50.0 (‑92.0, 33.4) |
25.0 (‑48.5, 80.7) |
75.0 (‑5.2, 95.9) |
| Black or African American | 1/1 (100) |
1/2 (50.0) |
0/1 (0) |
50.0 (‑64.2, 93.1) |
100.0 (‑58.7, 100.0) |
50.0 (‑64.2, 93.1) |
| Native Hawaiian or other Pacific Islander | 0/0 (NA) |
0/0 (NA) |
1/1 (100) |
NA |
NA |
NA |
| Other | 0/2 (0) |
0/0 (NA) |
1/2 (50.0) |
NA |
-50.0 (‑92.4, 46.8) |
NA |
| White | 39/72 (54.2) |
46/69 (66.7) |
17/67 (25.4) |
-12.5 (‑28.1, 3.7) |
28.8 (12.6, 43.5) * |
41.3 (25.0, 55.3) * |
| Ethnicity |
|
|
|
|
|
|
| Hispanic or Latino | 4/6 (66.7) |
9/14 (64.3) |
4/14 (28.6) |
2.4 (‑42.6, 41.0) |
38.1 (‑9.2, 71.4) |
35.7 (‑1.9, 64.5) |
| Not Hispanic or Latino | 37/71 (52.1) |
43/62 (69.4) |
16/62 (25.8) |
-17.2 (‑32.9, ‑0.5) * |
26.3 (9.7, 41.4) * |
43.5 (26.5, 57.9) * |
Source: Adapted from FDA Review
Risk difference (with 95% confidence interval) is shown between total treatment and comparator.
Asterisk (*) indicates rows where the 95% confidence interval excludes zero.
Abbreviations: CI, confidence interval; LNZ100, aceclidine hydrochloride 1.75% ophthalmic solution; LNZ101, aceclidine hydrochloride 1.75% and brimonidine tartrate 0.08% ophthalmic solution; N, number of patients in treatment arm; n, number of patients with adverse event; NA, not applicable; Ns, total number of patients for each specific subgroup and were assigned to that specific arm
Table 10. Overview of Adverse Events by Demographic Subgroup, Safety Population, CLARITY-3
| Characteristic | LNZ100 |
LNZ101 |
Vehicle |
LNZ100 vs. LNZ101 |
LNZ100 vs. Vehicle |
LNZ101 vs. Vehicle |
|---|---|---|---|---|---|---|
| Sex | ||||||
| Female | 55/93 (59.1) |
78/98 (79.6) |
19/54 (35.2) |
-20.5 (‑33.0, ‑7.4) * |
24.0 (7.2, 39.2) * |
44.4 (28.5, 58.2) * |
| Male | 34/51 (66.7) |
35/46 (76.1) |
6/19 (31.6) |
‑9.4 (‑26.9, 8.9) |
35.1 (8.7, 56.2) * |
44.5 (18.2, 64.9) * |
| Age group, years |
|
|
|
|
|
|
| <65 | 77/128 (60.2) |
99/127 (78.0) |
23/66 (34.8) |
-17.8 (‑28.7, ‑6.5) * |
25.3 (10.5, 38.8) * |
43.1 (28.8, 55.7) * |
| ≥65 | 12/16 (75.0) |
14/17 (82.4) |
2/7 (28.6) |
‑7.4 (‑36.2, 21.7) |
46.4 (2.0, 75.4) * |
53.8 (10.7, 80.5) * |
| Age group ≥75, years |
|
|
|
|
|
|
| ≥75 | 0/144 (0) |
0/144 (0) |
0/73 (0) |
0.0 (‑2.6, 2.6) |
0.0 (‑5.0, 2.6) |
0.0 (‑5.0, 2.6) |
| Race |
|
|
|
|
|
|
| American Indian or Alaska Native | 1/1 (100) |
3/3 (100) |
0/0 (NA) |
0.0 (‑83.7, 63.1) |
NA |
NA |
| Asian | 1/6 (16.7) |
2/4 (50.0) |
1/3 (33.3) |
-33.3 (‑77.0, 25.9) |
-16.7 (‑70.9, 39.0) |
16.7 (‑52.4, 71.5) |
| Black or African American | 4/8 (50.0) |
5/8 (62.5) |
0/3 (0) |
-12.5 (‑54.7, 34.7) |
50.0 (‑18.5, 79.4) |
62.5 (‑6.9, 87.0) |
| Multiple | 1/2 (50.0) |
0/0 (NA) |
0/1 (0) |
NA |
50.0 (‑64.2, 93.1) |
NA |
| Other | 0/0 (NA) |
0/1 (0) |
1/2 (50.0) |
NA |
NA |
-50.0 (‑93.1, 64.2) |
| White | 82/127 (64.6) |
103/128 (80.5) |
23/64 (35.9) |
-15.9 (‑26.6, ‑5.0) * |
28.6 (13.7, 42.2) * |
44.5 (30.2, 57.1) * |
| Ethnicity |
|
|
|
|
|
|
| Hispanic or Latino | 7/16 (43.8) |
17/19 (89.5) |
5/8 (62.5) |
-45.7 (‑69.6, ‑15.1) * |
-18.8 (‑53.8, 23.1) |
27.0 (‑5.2, 61.7) |
| Not Hispanic or Latino | 82/128 (64.1) |
96/125 (76.8) |
20/65 (30.8) |
-12.7 (‑23.7, ‑1.5) * |
33.3 (18.6, 46.3) * |
46.0 (31.7, 58.3) * |
Source: Adapted from FDA Review
Risk difference (with 95% confidence interval) is shown between total treatment and comparator.
Asterisk (*) indicates rows where the 95% confidence interval excludes zero.
Abbreviations: AE, adverse event; CI, confidence interval; LNZ100, aceclidine hydrochloride 1.75% ophthalmic solution; LNZ101, aceclidine hydrochloride 1.75% and brimonidine tartrate 0.08% ophthalmic solution; N, number of patients in treatment arm; n, number of patients with adverse event; NA, not applicable; Ns, total number of patients for each specific subgroup and were assigned to that specific arm
GLOSSARY
CLINICAL TRIAL: Voluntary research studies conducted in people and designed to answer specific questions about the safety or effectiveness of drugs, vaccines, other therapies, or new ways of using existing treatments.
COMPARATOR: A previously available treatment or placebo used in clinical trials that is compared to the actual drug being tested.
EFFICACY: How well the drug achieves the desired response when it is taken as described in a controlled clinical setting, such as during a clinical trial.
PLACEBO: An inactive substance or “sugar pill” that looks the same as, and is given the same way as, an active drug or treatment being tested. The effects of the active drug or treatment are compared to the effects of the placebo.
SUBGROUP: A subset of the population studied in a clinical trial. Demographic subsets include sex, race, and age groups.
