A Study of Safety and Efficacy of UNR844 Chloride (UNR844-Cl) Eye Drops in Subjects With Presbyopia.

• Sponsor: Novartis Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03809611
• Collaborator: (none)
• Enrollment: 125
• Locations: 14
• Arms: 2
• Actual Duration (Months): 7.7
• Patients Per Site: 8.9
• Patients Per Site Per Month: 1.2

Study Details

Study Description

Brief Summary

The purpose of this study was to assess the effect of topical UNR844-Cl (lipoic acid choline ester chloride) ophthalmic solution on near visual function in presbyopic subjects.

Condition or Disease	Intervention/Treatment	Phase
Presbyopia	Drug: UNR844-Cl; Drug: Placebo	Phase 2

Detailed Description

This was a multi-center, double-masked, placebo-controlled, randomized, parallel-group study. The total duration of the study was approximately 3 months. Approximately 120 presbyopic subjects were to be enrolled into the study.

Presbyopic subjects aged 45 to 55 years were the primary age group in this study.

Screening and Baseline: Subjects were screened for eligibility followed by a baseline visit after which they were randomized to receive either UNR844-Cl (1.5%, equivalent to 1.3% freebase) or Placebo, dosed one drop in each eye twice daily, for 3 months.

Randomized subjects attended the following study visits after baseline: at Week 2, Month 1, Month 2 and Month 3.

The primary objective of this study was to assess the efficacy of UNR844-Cl on binocular distance corrected near visual acuity (DCNVA) in presbyopic subjects aged 45 to 55 years with the primary endpoint being the change from baseline in binocular DCNVA in subjects aged 45 to 55 years at Month 3 after UNR844-Cl or Placebo treatment.

There were two secondary endpoints:

1. To assess the efficacy of UNR844-Cl on achieving 75 or more Early Treatment Diabetic Retinopathy Study (ETDRS) letters in binocular DCNVA in presbyopic subjects aged 45 to 55 years with endpoint being the proportion of subjects aged 45 to 55 years achieving 75 or more ETDRS letters in binocular DCNVA at Month 3 after UNR844-Cl or Placebo treatment.

2. To assess the safety of UNR844-Cl in presbyopic subjects by the frequency of treatment emergent adverse events (AEs) and treatment emergent serious adverse events (SAEs) in all subjects after UNR844-Cl or Placebo treatment.

Study Design

• Study Type: Interventional
• Actual Enrollment: 125 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Masking Description: double-mask(Investigator, patient)
• Primary Purpose: Treatment
• Official Title: A 3-month, Randomized, Placebo-controlled, Double-masked, Multi-center Study to Evaluate the Safety and Efficacy of Topical Ocular UNR844-Cl in Subjects With Presbyopia
• Actual Study Start Date: Apr 26, 2019
• Actual Primary Completion Date: Dec 16, 2019
• Actual Study Completion Date: Dec 16, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: UNR844-Cl Ophthalmic Solution 1.5% UNR844-Cl ophthalmic solution for twice-daily dosing	Drug: UNR844-Cl; 1.5% Ophthalmic solution for topical ocular administration; Other Names: Lipoic acid choline ester chloride, EV06
Placebo Comparator: Placebo Ophthalmic Solution placebo ophthalmic solution for twice-daily dosing	Drug: Placebo; placebo; Other Names: Vehicle

Outcome Measures

Primary Outcome Measures

1. Change in Binocular Distance-corrected Near Visual Acuity (DCNVA) From Baseline [Baseline and at Month 3]

   Change from baseline in binocular DCNVA in subjects aged 45 to 55 years at Month 3 after UNR844-Cl or placebo treatment. Low contrast (10% contrast) DCNVA at 40 cm is measured binocularly using an electronic visual acuity testing system. This assessment was performed with subjects corrected for any distance refractive errors. The system provided distance-corrected low contrast near visual acuity in an Early Treatment Diabetic Retinopathy Study (ETDRS) letter numerical score. High monocular DCNVA ETDRS letter scores represent good vision; Low monocular DCNVA ETDRS letter scores represent poor vision.

Secondary Outcome Measures

1. Number and Percentage of Subjects Aged 45 to 55 Years Achieving 75 or More Early Treatment Diabetic Retinopathy Study (ETDRS) Letters in Binocular DCNVA at Month 3 [month 3]

   Change from baseline in binocular DCNVA in subjects aged 45 to 55 years at Month 3 after UNR844-Cl or placebo treatment. Low contrast (10% contrast) DCNVA at 40 cm is measured binocularly using an electronic visual acuity testing system. This assessment was performed with subjects corrected for any distance refractive errors. The system provided distance-corrected low contrast near visual acuity in an Early Treatment Diabetic Retinopathy Study (ETDRS) letter numerical score. High monocular DCNVA ETDRS letter scores represent good vision; Low monocular DCNVA ETDRS letter scores represent poor vision.

2. Number of Subjects With Adverse Events, Ocular Adverse Events, Deaths, Other Serious Adverse Events, or Adverse Events Leading to Study Drug Discontinuation [4 months]

   Frequency of treatment emergent adverse events and treatment emergent serious adverse events in all subjects. Adverse events were collected from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 120 days.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 45 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Written informed consent must be obtained before any assessment is performed

• Impaired near vision in each eye and when using both eyes, without any near correction

• Need a certain level of near correction

Exclusion Criteria:

• Impaired distance vision in either eye, with distance correction (if any)

• Severe short- or long-sightedness

• Any significant medical or clinical conditions affecting vision, the eyes or general health

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novartis Investigative Site	Mission Hills	California	United States	91345
2	Novartis Investigative Site	Newport Beach	California	United States	92663
3	Novartis Investigative Site	Largo	Florida	United States	33773
4	Novartis Investigative Site	Mount Dora	Florida	United States	32757
5	Novartis Investigative Site	Washington	Missouri	United States	63090
6	Novartis Investigative Site	Allenwood	Pennsylvania	United States	17810
7	Novartis Investigative Site	Cranberry Township	Pennsylvania	United States	16066
8	Novartis Investigative Site	Kingston	Pennsylvania	United States	18704
9	Novartis Investigative Site	Memphis	Tennessee	United States	38119
10	Novartis Investigative Site	Nashville	Tennessee	United States	37205-2013
11	Novartis Investigative Site	Nashville	Tennessee	United States	37205
12	Novartis Investigative Site	Cedar Park	Texas	United States	78613
13	Novartis Investigative Site	Houston	Texas	United States	77204
14	Novartis Investigative Site	Norfolk	Virginia	United States	23502

Sponsors and Collaborators

• Novartis Pharmaceuticals

Investigators

• Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study Documents (Full-Text)

• Study Protocol - Jul 2, 2019
• Statistical Analysis Plan - Jan 15, 2020

More Information

Publications

None provided.

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT03809611
• Other Study ID Numbers: CUNR844A2203
• First Posted: Jan 18, 2019
• Last Update Posted: May 11, 2022
• Last Verified: Apr 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Novartis Pharmaceuticals: Presbyopia, adults, randomized study, placebo
• Additional relevant MeSH terms: Presbyopia; Choline

Study Results

Participant Flow

Arm/Group Title	UNR844-Cl	Placebo Ophthalmic Solution
Arm/Group Description	1.5% UNR844-Cl	placebo
Period Title: Overall Study
STARTED	62	62
COMPLETED	61	61
NOT COMPLETED	1	1

Baseline Characteristics

Arm/Group Title	UNR844-Cl	Placebo Ophthalmic Solution	Total
Arm/Group Description	1.5% UNR844-Cl	placebo	Total of all reporting groups
Overall Participants	62	62	124
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	53.9 (4.97)	54.2 (5.01)	54.1 (4.97)
Sex: Female, Male (Count of Participants)
Female	40 64.5%	41 66.1%	81 65.3%
Male	22 35.5%	21 33.9%	43 34.7%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	1 1.6%	0 0%	1 0.8%
Asian	3 4.8%	3 4.8%	6 4.8%
Native Hawaiian or Other Pacific Islander	1 1.6%	0 0%	1 0.8%
Black or African American	7 11.3%	8 12.9%	15 12.1%
White	50 80.6%	51 82.3%	101 81.5%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Change in Binocular Distance-corrected Near Visual Acuity (DCNVA) From Baseline
Description	Change from baseline in binocular DCNVA in subjects aged 45 to 55 years at Month 3 after UNR844-Cl or placebo treatment. Low contrast (10% contrast) DCNVA at 40 cm is measured binocularly using an electronic visual acuity testing system. This assessment was performed with subjects corrected for any distance refractive errors. The system provided distance-corrected low contrast near visual acuity in an Early Treatment Diabetic Retinopathy Study (ETDRS) letter numerical score. High monocular DCNVA ETDRS letter scores represent good vision; Low monocular DCNVA ETDRS letter scores represent poor vision.
Time Frame	Baseline and at Month 3

Outcome Measure Data

Analysis Population Description

All randomized subjects aged 45 to 55 years at baseline

Arm/Group Title	UNR844-Cl	Placebo Ophthalmic Solution
Arm/Group Description	1.5% UNR844-Cl	placebo
Measure Participants	40	38
Least Squares Mean (Standard Error) [number of letters read correctly]	6.1 (1.24)	4.5 (1.27)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	UNR844-Cl, Placebo Ophthalmic Solution
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1832
	Comments	One-sided p-value for treatment difference
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	1.6
	Confidence Interval	(2-Sided) 90%; -1.34 to 4.56
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.77
	Estimation Comments

2. Secondary Outcome

Title	Number and Percentage of Subjects Aged 45 to 55 Years Achieving 75 or More Early Treatment Diabetic Retinopathy Study (ETDRS) Letters in Binocular DCNVA at Month 3
Description	Change from baseline in binocular DCNVA in subjects aged 45 to 55 years at Month 3 after UNR844-Cl or placebo treatment. Low contrast (10% contrast) DCNVA at 40 cm is measured binocularly using an electronic visual acuity testing system. This assessment was performed with subjects corrected for any distance refractive errors. The system provided distance-corrected low contrast near visual acuity in an Early Treatment Diabetic Retinopathy Study (ETDRS) letter numerical score. High monocular DCNVA ETDRS letter scores represent good vision; Low monocular DCNVA ETDRS letter scores represent poor vision.
Time Frame	month 3

Outcome Measure Data

Analysis Population Description

l randomized subjects aged 45 to 55 years at baseline

Arm/Group Title	UNR844-Cl	Placebo Ophthalmic Solution
Arm/Group Description	1.5% UNR844-Cl	placebo
Measure Participants	40	38
Count of Participants [Participants]	10 16.1%	6 9.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	UNR844-Cl, Placebo Ophthalmic Solution
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.2830
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.9
	Confidence Interval	(2-Sided) 90%; 0.72 to 4.78
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Number of Subjects With Adverse Events, Ocular Adverse Events, Deaths, Other Serious Adverse Events, or Adverse Events Leading to Study Drug Discontinuation
Description	Frequency of treatment emergent adverse events and treatment emergent serious adverse events in all subjects. Adverse events were collected from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 120 days.
Time Frame	4 months

Outcome Measure Data

Analysis Population Description

All randomized and treated participants

Arm/Group Title	UNR844-Cl	Placebo Ophthalmic Solution
Arm/Group Description	1.5% UNR844-Cl	placebo
Measure Participants	62	62
Any adverse events (AEs)	14 22.6%	5 8.1%
Any ocular adverse events	4 6.5%	4 6.5%
Any non-ocular adverse events	11 17.7%	2 3.2%
Any severe adverse events	0 0%	0 0%
Any ocular severe adverse events	0 0%	0 0%
Any non-ocular severe adverse events	0 0%	0 0%
Any study drug related adverse events	4 6.5%	1 1.6%
Any study drug related ocular adverse events	0 0%	1 1.6%
Any study drug related non-ocular adverse events	4 6.5%	0 0%
Any adverse events leading to study drug disc.	0 0%	0 0%
Any ocular AEs leading to study drug disc.	0 0%	0 0%
Any non-ocular AEs leading to study drug disc.	0 0%	0 0%
Any serious adverse events	0 0%	0 0%
Any ocular serious adverse events	0 0%	0 0%
Any non-ocular serious adverse events	0 0%	0 0%
Any study drug related serious adverse events	0 0%	0 0%
Any study drug related ocular serious AEs	0 0%	0 0%
Any study drug related non-ocular serious AEs	0 0%	0 0%
Death	0 0%	0 0%

Adverse Events

Time Frame	Adverse events were collected from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 120 days.
Arm/Group Title	UNR844-Cl		Placebo		Total
Arm/Group Description	UNR844-Cl		Placebo		Total
All Cause Mortality
	UNR844-Cl		Placebo		Total
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/62 (0%)		0/62 (0%)		0/124 (0%)
Serious Adverse Events
	UNR844-Cl		Placebo		Total
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/62 (0%)		0/62 (0%)		0/124 (0%)
Other (Not Including Serious) Adverse Events
	UNR844-Cl		Placebo		Total
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	14/62 (22.6%)		5/62 (8.1%)		19/124 (15.3%)
Ear and labyrinth disorders
Ear pain	1/62 (1.6%)		0/62 (0%)		1/124 (0.8%)
Eye disorders
Blepharitis	1/62 (1.6%)		0/62 (0%)		1/124 (0.8%)
Conjunctival hyperaemia	1/62 (1.6%)		0/62 (0%)		1/124 (0.8%)
Lenticular opacities	0/62 (0%)		1/62 (1.6%)		1/124 (0.8%)
Visual impairment	1/62 (1.6%)		0/62 (0%)		1/124 (0.8%)
Gastrointestinal disorders
Gastrooesophageal reflux disease	1/62 (1.6%)		0/62 (0%)		1/124 (0.8%)
General disorders
Instillation site pain	0/62 (0%)		1/62 (1.6%)		1/124 (0.8%)
Sensation of foreign body	1/62 (1.6%)		0/62 (0%)		1/124 (0.8%)
Immune system disorders
Drug hypersensitivity	0/62 (0%)		1/62 (1.6%)		1/124 (0.8%)
Infections and infestations
Atypical pneumonia	1/62 (1.6%)		0/62 (0%)		1/124 (0.8%)
Sinusitis	1/62 (1.6%)		0/62 (0%)		1/124 (0.8%)
Urinary tract infection	0/62 (0%)		1/62 (1.6%)		1/124 (0.8%)
Injury, poisoning and procedural complications
Chemical burns of eye	0/62 (0%)		1/62 (1.6%)		1/124 (0.8%)
Meniscus injury	1/62 (1.6%)		0/62 (0%)		1/124 (0.8%)
Tooth fracture	1/62 (1.6%)		0/62 (0%)		1/124 (0.8%)
Investigations
Vital dye staining cornea present	0/62 (0%)		1/62 (1.6%)		1/124 (0.8%)
Metabolism and nutrition disorders
Hyperlipidaemia	0/62 (0%)		1/62 (1.6%)		1/124 (0.8%)
Musculoskeletal and connective tissue disorders
Arthralgia	1/62 (1.6%)		0/62 (0%)		1/124 (0.8%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma	1/62 (1.6%)		0/62 (0%)		1/124 (0.8%)
Nervous system disorders
Dysgeusia	3/62 (4.8%)		0/62 (0%)		3/124 (2.4%)
Headache	2/62 (3.2%)		0/62 (0%)		2/124 (1.6%)
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain	1/62 (1.6%)		0/62 (0%)		1/124 (0.8%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial.