Study Assessing the Safety and Efficacy of DE-117 Ophthalmic Solution Once Daily and Twice Daily in Subjects With Primary Open-Angle Glaucoma SPECTRUM 6

• Sponsor: Santen Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03858894
• Collaborator: (none)
• Enrollment: 98
• Locations: 13
• Arms: 2
• Actual Duration (Months): 4.7
• Patients Per Site: 7.5
• Patients Per Site Per Month: 1.6

Study Details

Study Description

Brief Summary

This is a randomized, double-masked, parallel-group, multi-center study. Subjects diagnosed with POAG or OHT who meet eligibility criteria at Visit 1 (Screening) will wash out their current topical IOP lowering medication(s), if any. After completing the required washout period, subjects will return for Visit 2 (Baseline, Day 1). Subjects who meet all eligibility criteria at Visit 2 (Baseline, Day 1) will be randomized to receive study medication for up to 6 weeks.

Approximately 100 subjects with POAG or OHT will be randomized in a 1:1 ratio to either:

• DE-117 ophthalmic solution 0.002% QD (Once Daily)

• DE-117 ophthalmic solution 0.002% BID (Twice Daily)

This study will consist of a screening period of up to 35 days including a washout period of up to 28 days (+ 7 days window), and a 6-week double-masked treatment period.

Condition or Disease	Intervention/Treatment	Phase
Primary Open-angle Glaucoma and Ocular Hypertension	Drug: DE-117 Ophthalmic Solution QD; Drug: DE-117 Ophthalmic Solution BID	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 98 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Randomized, Double-Masked, Parallel-Group, Multicenter Study Assessing the Safety and Efficacy of DE-117 Ophthalmic Solution 0.002% Once Daily and Twice Daily in Subjects With Primary Open-Angle Glaucoma or Ocular Hypertension SPECTRUM 6 Study.
• Actual Study Start Date: Jan 28, 2019
• Actual Primary Completion Date: Jun 20, 2019
• Actual Study Completion Date: Jun 20, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Drug Arm: DE-117 QD DE-117 Ophthalmic Solution QD (20:00) and Vehicle (8:00; no active DE-117 ingredient) QD	Drug: DE-117 Ophthalmic Solution QD; DE-117 ophthalmic solution QD and Vehicle (no active DE-117 ingredient) QD add one drop in each eye
Experimental: Test Arm: DE-117 BID DE-117 Ophthalmic Solution BID Twice daily (20:00 and 8:00)	Drug: DE-117 Ophthalmic Solution BID; DE-117 ophthalmic solution BID twice Daily (20:00 and 8:00) add one drop in each eye

Outcome Measures

Primary Outcome Measures

1. Intraocular Pressure (IOP) at Week 2 [08:00 at week 2]

   Intraocular pressure (IOP), the fluid pressure inside the eye, was measured by applanation tonometry in millimeters mercury (mmHg).

2. Intraocular Pressure (IOP) at Week 2 [12:00 at week 2]

   Intraocular pressure (IOP), the fluid pressure inside the eye, was measured by applanation tonometry in millimeters mercury (mmHg).

3. Intraocular Pressure (IOP) at Week 2 [16:00 at week 2]

   Intraocular pressure (IOP), the fluid pressure inside the eye, was mea...

4. Intraocular Pressure (IOP) at Week 6 [08:00 at week 6]

   Intraocular pressure (IOP), the fluid pressure inside the eye, was measured by applanation tonometry in millimeters mercury (mmHg).

5. Intraocular Pressure (IOP) at Week 6 [12:00 at week 6]

   Intraocular pressure (IOP), the fluid pressure inside the eye, was measured by applanation tonometry in millimeters mercury (mmHg).

6. Intraocular Pressure (IOP) at Week 6 [16:00 at week 6]

   Intraocular pressure (IOP), the fluid pressure inside the eye, was mea...

Secondary Outcome Measures

1. Mean Diurnal Intraocular Pressure (IOP) [6 weeks]

   Intraocular pressure (IOP), the fluid pressure inside the eye, was measured by applanation tonometry in millimeters mercury (mmHg).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

Provide signed written informed consent

• Have a diagnosis of POAG or OHT in both eyes, or one eye with POAG and the other with OHT.

• Qualifying corrected visual acuity in each eye

• Qualifying central corneal thickness in each eye

• Qualifying Day 1 IOP measurement at 3 time-points in both eyes

• Qualifying Anterior chamber angle

Exclusion Criteria:

• History of ocular surgery specifically intended to lower IOP

• Subjects who cannot safely discontinue use of ocular hypotensive medications during the wait/washout period

• Advanced glaucoma in either eye

• Any corneal abnormality or other condition interfering with or preventing reliable Goldmann applanation tonometry

• Any ocular surgery or ocular laser treatment within 180 days prior to Screening and throughout the study in either eye

• Females who are pregnant, nursing, or planning a pregnancy

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	East West Eye Institute	Los Angeles	California	United States	90013
2	Danbury Eye Specialist	Danbury	Connecticut	United States	06810
3	Hernando Eye Institute	Brooksville	Florida	United States	34613
4	Levenson Eye Associates	Jacksonville	Florida	United States	32204
5	Seidenberg Protzko Eye Associates	Havre De Grace	Maryland	United States	21078
6	Tekwani Vision Center	Saint Louis	Missouri	United States	63128
7	Eye Associates/SurgiCenter of Vineland	Vineland	New Jersey	United States	08361
8	Ophthalmic Consultants of Long Island	Lynbrook	New York	United States	11563
9	Apex Eye Clinical Research, LLC	Cincinnati	Ohio	United States	45242
10	Abrams Eye Center	Cleveland	Ohio	United States	44115
11	Scott & Christie and Associates PC	Cranberry Township	Pennsylvania	United States	16066
12	University Eye Specialist	Maryville	Tennessee	United States	37803
13	Advanced Vision Research	Nashville	Tennessee	United States	37205

Sponsors and Collaborators

• Santen Inc.

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol - Nov 13, 2018
• Statistical Analysis Plan - Jul 11, 2019

More Information

Publications

None provided.

• Responsible Party: Santen Inc.
• ClinicalTrials.gov Identifier: NCT03858894
• Other Study ID Numbers: 011712IN
• First Posted: Mar 1, 2019
• Last Update Posted: Aug 4, 2020
• Last Verified: Jul 1, 2020

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Glaucoma; Glaucoma, Open-Angle; Ocular Hypertension; Hypertension; Pharmaceutical Solutions; Ophthalmic Solutions

Study Results

Participant Flow

Arm/Group Title	Test Arm: DE-117 BID	Drug Arm: DE-117 QD
Arm/Group Description	DE-117 Ophthalmic Solution BID Twice daily (20:00 and 8:00) DE-117 Ophthalmic Solution BID: DE-117 ophthalmic solution BID twice Daily (20:00 and 8:00) add one drop in each eye	DE-117 Ophthalmic Solution QD (20:00) and Vehicle (8:00; no active DE-117 ingredient) QD DE-117 Ophthalmic Solution QD: DE-117 ophthalmic solution QD and Vehicle (no active DE-117 ingredient) QD add one drop in each eye
Period Title: Overall Study
STARTED	48	50
COMPLETED	44	50
NOT COMPLETED	4	0

Baseline Characteristics

Arm/Group Title	Test Arm: DE-117 BID	Drug Arm: DE-117 QD	Total
Arm/Group Description	DE-117 Ophthalmic Solution BID Twice daily (20:00 and 8:00) DE-117 Ophthalmic Solution BID: DE-117 ophthalmic solution BID twice Daily (20:00 and 8:00) add one drop in each eye	DE-117 Ophthalmic Solution QD (20:00) and Vehicle (8:00; no active DE-117 ingredient) QD DE-117 Ophthalmic Solution QD: DE-117 ophthalmic solution QD and Vehicle (no active DE-117 ingredient) QD add one drop in each eye	Total of all reporting groups
Overall Participants	48	50	98
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	67.3 (9.45)	66.3 (8.73)	66.8 (9.05)
Sex: Female, Male (Count of Participants)
Female	27 56.3%	25 50%	52 53.1%
Male	21 43.8%	25 50%	46 46.9%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	2 4.2%	2 4%	4 4.1%
Not Hispanic or Latino	46 95.8%	48 96%	94 95.9%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	1 2%	1 1%
Black or African American	13 27.1%	14 28%	27 27.6%
White	35 72.9%	35 70%	70 71.4%
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	Intraocular Pressure (IOP) at Week 2
Description	Intraocular pressure (IOP), the fluid pressure inside the eye, was measured by applanation tonometry in millimeters mercury (mmHg).
Time Frame	08:00 at week 2

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Test Arm: DE-117 BID	Drug Arm: DE-117 QD
Arm/Group Description	DE-117 Ophthalmic Solution BID Twice daily (20:00 and 8:00) DE-117 Ophthalmic Solution BID: DE-117 ophthalmic solution BID twice Daily (20:00 and 8:00) add one drop in each eye	DE-117 Ophthalmic Solution QD (20:00) and Vehicle (8:00; no active DE-117 ingredient) QD DE-117 Ophthalmic Solution QD: DE-117 ophthalmic solution QD and Vehicle (no active DE-117 ingredient) QD add one drop in each eye
Measure Participants	48	50
Least Squares Mean (Standard Error) [mmHg]	18.19 (0.46)	19.15 (0.45)

2. Primary Outcome

Title	Intraocular Pressure (IOP) at Week 2
Description	Intraocular pressure (IOP), the fluid pressure inside the eye, was measured by applanation tonometry in millimeters mercury (mmHg).
Time Frame	12:00 at week 2

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Test Arm: DE-117 BID	Drug Arm: DE-117 QD
Arm/Group Description	DE-117 Ophthalmic Solution BID Twice daily (20:00 and 8:00) DE-117 Ophthalmic Solution BID: DE-117 ophthalmic solution BID twice Daily (20:00 and 8:00) add one drop in each eye	DE-117 Ophthalmic Solution QD (20:00) and Vehicle (8:00; no active DE-117 ingredient) QD DE-117 Ophthalmic Solution QD: DE-117 ophthalmic solution QD and Vehicle (no active DE-117 ingredient) QD add one drop in each eye
Measure Participants	48	50
Least Squares Mean (Standard Error) [mmHg]	17.73 (0.49)	18.17 (0.46)

3. Primary Outcome

Title	Intraocular Pressure (IOP) at Week 2
Description	Intraocular pressure (IOP), the fluid pressure inside the eye, was mea...
Time Frame	16:00 at week 2

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Test Arm: DE-117 BID	Drug Arm: DE-117 QD
Arm/Group Description	DE-117 Ophthalmic Solution BID Twice daily (20:00 and 8:00) DE-117 Ophthalmic Solution BID: DE-117 ophthalmic solution BID twice Daily (20:00 and 8:00) add one drop in each eye	DE-117 Ophthalmic Solution QD (20:00) and Vehicle (8:00; no active DE-117 ingredient) QD DE-117 Ophthalmic Solution QD: DE-117 ophthalmic solution QD and Vehicle (no active DE-117 ingredient) QD add one drop in each eye
Measure Participants	48	50
Least Squares Mean (Standard Error) [mmHg]	16.73 (0.47)	17.81 (0.44)

4. Primary Outcome

Title	Intraocular Pressure (IOP) at Week 6
Description	Intraocular pressure (IOP), the fluid pressure inside the eye, was measured by applanation tonometry in millimeters mercury (mmHg).
Time Frame	08:00 at week 6

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Test Arm: DE-117 BID	Drug Arm: DE-117 QD
Arm/Group Description	DE-117 Ophthalmic Solution BID Twice daily (20:00 and 8:00) DE-117 Ophthalmic Solution BID: DE-117 ophthalmic solution BID twice Daily (20:00 and 8:00) add one drop in each eye	DE-117 Ophthalmic Solution QD (20:00) and Vehicle (8:00; no active DE-117 ingredient) QD DE-117 Ophthalmic Solution QD: DE-117 ophthalmic solution QD and Vehicle (no active DE-117 ingredient) QD add one drop in each eye
Measure Participants	48	50
Least Squares Mean (Standard Error) [mmHg]	18.33 (0.49)	19.01 (0.47)

5. Primary Outcome

Title	Intraocular Pressure (IOP) at Week 6
Description	Intraocular pressure (IOP), the fluid pressure inside the eye, was measured by applanation tonometry in millimeters mercury (mmHg).
Time Frame	12:00 at week 6

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Test Arm: DE-117 BID	Drug Arm: DE-117 QD
Arm/Group Description	DE-117 Ophthalmic Solution BID Twice daily (20:00 and 8:00) DE-117 Ophthalmic Solution BID: DE-117 ophthalmic solution BID twice Daily (20:00 and 8:00) add one drop in each eye	DE-117 Ophthalmic Solution QD (20:00) and Vehicle (8:00; no active DE-117 ingredient) QD DE-117 Ophthalmic Solution QD: DE-117 ophthalmic solution QD and Vehicle (no active DE-117 ingredient) QD add one drop in each eye
Measure Participants	48	50
Least Squares Mean (Standard Error) [mmHg]	17.77 (0.45)	18.35 (0.43)

6. Primary Outcome

Title	Intraocular Pressure (IOP) at Week 6
Description	Intraocular pressure (IOP), the fluid pressure inside the eye, was mea...
Time Frame	16:00 at week 6

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Test Arm: DE-117 BID	Drug Arm: DE-117 QD
Arm/Group Description	DE-117 Ophthalmic Solution BID Twice daily (20:00 and 8:00) DE-117 Ophthalmic Solution BID: DE-117 ophthalmic solution BID twice Daily (20:00 and 8:00) add one drop in each eye	DE-117 Ophthalmic Solution QD (20:00) and Vehicle (8:00; no active DE-117 ingredient) QD DE-117 Ophthalmic Solution QD: DE-117 ophthalmic solution QD and Vehicle (no active DE-117 ingredient) QD add one drop in each eye
Measure Participants	48	50
Least Squares Mean (Standard Error) [mmHg]	17.30 (0.45)	17.66 (0.43)

7. Secondary Outcome

Title	Mean Diurnal Intraocular Pressure (IOP)
Description	Intraocular pressure (IOP), the fluid pressure inside the eye, was measured by applanation tonometry in millimeters mercury (mmHg).
Time Frame	6 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Test Arm: DE-117 BID	Drug Arm: DE-117 QD
Arm/Group Description	DE-117 Ophthalmic Solution BID Twice daily (20:00 and 8:00) DE-117 Ophthalmic Solution BID: DE-117 ophthalmic solution BID twice Daily (20:00 and 8:00) add one drop in each eye	DE-117 Ophthalmic Solution QD (20:00) and Vehicle (8:00; no active DE-117 ingredient) QD DE-117 Ophthalmic Solution QD: DE-117 ophthalmic solution QD and Vehicle (no active DE-117 ingredient) QD add one drop in each eye
Measure Participants	48	50
Least Squares Mean (Standard Error) [mmHg]	17.77 (0.43)	18.37 (0.41)

Adverse Events

Time Frame	All SAEs were collected from the signing of the Inform Consent Form until the subject withdrew or completed the scheduled exit visit at Week 6.
Arm/Group Title	Test Arm: DE-117 BID		Drug Arm: DE-117 QD
Arm/Group Description	DE-117 Ophthalmic Solution BID Twice daily (20:00 and 8:00) DE-117 Ophthalmic Solution BID: DE-117 ophthalmic solution BID twice Daily (20:00 and 8:00) add one drop in each eye		DE-117 Ophthalmic Solution QD (20:00) and Vehicle (8:00; no active DE-117 ingredient) QD DE-117 Ophthalmic Solution QD: DE-117 ophthalmic solution QD and Vehicle (no active DE-117 ingredient) QD add one drop in each eye
All Cause Mortality
	Test Arm: DE-117 BID		Drug Arm: DE-117 QD
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/48 (0%)		0/50 (0%)
Serious Adverse Events
	Test Arm: DE-117 BID		Drug Arm: DE-117 QD
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/48 (0%)		1/50 (2%)
Hepatobiliary disorders
Cholelithiasis	0/48 (0%)	0	1/50 (2%)	1
Other (Not Including Serious) Adverse Events
	Test Arm: DE-117 BID		Drug Arm: DE-117 QD
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	20/48 (41.7%)		7/50 (14%)
Blood and lymphatic system disorders
Anaemia	0/48 (0%)	0	1/50 (2%)	1
Eye disorders
Conjunctival hyperaemia	6/48 (12.5%)	7	0/50 (0%)	0
Ocular hyperaemia	5/48 (10.4%)	5	1/50 (2%)	1
Accommodation disorder	1/48 (2.1%)	1	0/50 (0%)	0
Corneal pigmentation	1/48 (2.1%)	1	0/50 (0%)	0
Eye pain	1/48 (2.1%)	1	1/50 (2%)	1
Eye pruritus	1/48 (2.1%)	1	0/50 (0%)	0
Glare	1/48 (2.1%)	1	0/50 (0%)	0
Iridocyclitis	1/48 (2.1%)	1	0/50 (0%)	0
Iritis	1/48 (2.1%)	1	0/50 (0%)	0
Ocular discomfort	1/48 (2.1%)	1	0/50 (0%)	0
Photophobia	1/48 (2.1%)	1	2/50 (4%)	2
Vision blurred	1/48 (2.1%)	1	0/50 (0%)	0
Visual impairment	1/48 (2.1%)	1	1/50 (2%)	1
Punctate keratitis	0/48 (0%)	0	1/50 (2%)	1
Gastrointestinal disorders
Nausea	1/48 (2.1%)	1	0/50 (0%)	0
Infections and infestations
Upper respiratory tract infection	1/48 (2.1%)	1	0/50 (0%)	0
Injury, poisoning and procedural complications
Upper limb fracture	1/48 (2.1%)	1	0/50 (0%)	0
Investigations
Vital dye staining cornea present	2/48 (4.2%)	3	1/50 (2%)	2
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Myelodysplastic syndrome	0/48 (0%)	0	1/50 (2%)	1
Nervous system disorders
Headache	1/48 (2.1%)	1	2/50 (4%)	2
Product Issues
Device dislocation	1/48 (2.1%)	1	0/50 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

Site/Investigator is not permitted to publish results communications without Santen's consent until after a period of sixty (60 days) for Santen review/comment. Santen may request removal of any Confidential Information (other than Study results) from manuscripts or materials prior to submission or presentation. At Santen's request Site/Investigator has to withhold any publication if there is a patentable invention until such time as Santen is able to secure adequate patent protection.