Clinical Trial Results:
An Exploratory Study to Assess the 24-hour Intraocular Pressure (IOP) Lowering Characteristics, Duration of Action and Safety of DE-126 ophthalmic solution 0.002% versus Latanoprost ophthalmic solution 0.005% in Subjects with Primary Open Angle Glaucoma or Ocular Hypertension

Trial information Top of page
Trial identification
Sponsor protocol code	012603SA
Additional study identifiers
ISRCTN number	-
US NCT number	-
WHO universal trial number (UTN)	-
Sponsors
Sponsor organisation name	Santen S.A.S.
Sponsor organisation address	1 Rue Pierre Fontaine, Genavenir IV, Evry cedex, France, F-91058
Public contact	Responsible Physician, Santen Oy, +358 405012416, auli.ropo@santen.com
Scientific contact	Responsible Physician, Santen Oy, +358 405012416, auli.ropo@santen.com
Paediatric regulatory details
Is trial part of an agreed paediatric investigation plan (PIP)	No
Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?	No
Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?	No
Results analysis stage
Analysis stage	Final
Date of interim/final analysis	30 Mar 2023
Is this the analysis of the primary completion data?	Yes
Primary completion date	09 Jan 2023
Global end of trial reached?	Yes
Global end of trial date	09 Jan 2023
Was the trial ended prematurely?	No
General information about the trial
Main objective of the trial	To compare the 24h IOP lowering characteristics of DE-126 ophthalmic solution 0.002% with latanoprost ophthalmic solution 0.005%, both given once daily in the evening for 3 months+1d.
Protection of trial subjects	The Informed Consent Form was written in compliance with US Title 21 CFR Part 50, ICH guidelines, and other national regulations as appropriate. Site-specific versions are on file with Santen, Inc. and are available upon request.
Background therapy	-
Evidence for comparator	-
Actual start date of recruitment	30 Jun 2021
Long term follow-up planned	No
Independent data monitoring committee (IDMC) involvement?	No
Population of trial subjects
Number of subjects enrolled per country
Country: Number of subjects enrolled	Austria: 5
Country: Number of subjects enrolled	Germany: 8
Country: Number of subjects enrolled	Greece: 20
Worldwide total number of subjects	33
EEA total number of subjects	33
Number of subjects enrolled per age group
In utero	0
Preterm newborn - gestational age < 37 wk	0
Newborns (0-27 days)	0
Infants and toddlers (28 days-23 months)	0
Children (2-11 years)	0
Adolescents (12-17 years)	0
Adults (18-64 years)	16
From 65 to 84 years	17
85 years and over	0

Trial information Top of page

Subject disposition Top of page
Recruitment
Recruitment details	-
Pre-assignment
Screening details	A total of 47 subjects were enrolled into the study (signed informed consent) of whom 33 were randomized. 14 subjects were considered screen failure. 1 subject in the DE-126 group had a fatal outcome following complications related to COVID-19.
Period 1
Period 1 title	Single-Masked treatment Period (overall period)
Is this the baseline period?	Yes
Allocation method	Randomised - controlled
Blinding used	Single blind
Roles blinded	Investigator [1]
Arms
Are arms mutually exclusive	Yes
Arm title	DE-126
Arm description	0.002% DE-126 Aqueous solution containing 0.02 mg/mL DE-126, and water for injections.
Arm type	Experimental
Investigational medicinal product name	PF DE-126 ophthalmic solution 0.002%
Investigational medicinal product code
Other name
Pharmaceutical forms	Eye drops
Routes of administration	Ophthalmic use
Dosage and administration details	DE-126 0.002%, dosed once daily in the evening, was identified as the optimal dose among the 4 concentrations evaluated in both US and Japanese subjects with POAG or OHT, with respect to IOP lowering and safety profile.
Arm title	Latanoprost
Arm description	0.005% Latanoprost Aqueous solution containing the active ingredient, latanoprost 0.05 mg/mL, water for injections.
Arm type	Active comparator
Investigational medicinal product name	Latanoprost ophthalmic solution 0.005% (Xalatan®)
Investigational medicinal product code
Other name
Pharmaceutical forms	Eye drops
Routes of administration	Ophthalmic use
Dosage and administration details	For latanoprost, the study dosing regimen was consistent with the current Xalatan labeling recommendation.
Notes [1] - The roles blinded appear inconsistent with a simple blinded trial. Justification: The study was a single-masked study with investigators involved in the conduct of the study masked from the study treatment.
Number of subjects in period 1 DE-126 Latanoprost Started 17 16 Completed 16 16 Not completed 1 0      Adverse event, serious fatal 1 -

Subject disposition Top of page

Baseline characteristics Top of page
Baseline characteristics reporting groups
Reporting group title	DE-126
Reporting group description	0.002% DE-126 Aqueous solution containing 0.02 mg/mL DE-126, and water for injections.
Reporting group title	Latanoprost
Reporting group description	0.005% Latanoprost Aqueous solution containing the active ingredient, latanoprost 0.05 mg/mL, water for injections.
Reporting group values DE-126 Latanoprost Total Number of subjects 17 16 33 Age categorical Units: Subjects     In utero 0 0 0     Preterm newborn infants (gestational age < 37 wks) 0 0 0     Newborns (0-27 days) 0 0 0     Infants and toddlers (28 days-23 months) 0 0 0     Children (2-11 years) 0 0 0     Adolescents (12-17 years) 0 0 0     Adults (18-64 years) 7 9 16     From 65-84 years 10 7 17     85 years and over 0 0 0 Age continuous Units: years     arithmetic mean (standard deviation) 62.6 ( 13.16 ) 64.6 ( 8.17 ) - Gender categorical Units: Subjects     Female 7 11 18     Male 10 5 15 Race Units: Subjects     White 17 16 33     Black or African American 0 0 0     Asian 0 0 0     American Indian or Alaska Native 0 0 0     Native Hawaiian or Other Pacific Islander 0 0 0     Not Reported 0 0 0     Unknown 0 0 0     Multiple 0 0 0 Ethnicity Units: Subjects     Hispanic or Latino 0 0 0     Not Hispanic or Latino 17 16 33     Unknown 0 0 0

Baseline characteristics Top of page

End points Top of page
End points reporting groups
Reporting group title	DE-126
Reporting group description	0.002% DE-126 Aqueous solution containing 0.02 mg/mL DE-126, and water for injections.
Reporting group title	Latanoprost
Reporting group description	0.005% Latanoprost Aqueous solution containing the active ingredient, latanoprost 0.05 mg/mL, water for injections.

End points Top of page

Primary: 24-hour mean IOP at Month 3 Top of page
End point title	24-hour mean IOP at Month 3
End point description	24hr mean IOP at Month 3
End point type	Primary
End point timeframe	The primary efficacy endpoint evaluated the study eye 24-hour mean IOP at Month 3, measured at 4h (24:00), 8h (04:00), 12h (08:00), 16h (12:00), 20h (16:00), and 24h (20:00) after the last dose given the previous night at 20:00.
End point values DE-126 Latanoprost Number of subjects analysed 16 16 Units: mmHg     arithmetic mean (standard error) 17.31 ( 0.783 ) 18.19 ( 0.604 )
Statistical analysis title	Mean 24-Hour IOP at Month 3
Statistical analysis description	DE-126 v Latanoprost
Comparison groups	DE-126 v Latanoprost
Number of subjects included in analysis	32
Analysis specification	Pre-specified
Analysis type	other [1]
Method
Parameter type	Mean difference (final values)
Point estimate	0
Confidence interval
level	95%
sides	2-sided
lower limit	-2.89
upper limit	1.14
Notes [1] - This is an exploratory study, and no hypothesis testing was performed.

Primary: 24-hour mean IOP at Month 3 Top of page

Secondary: Mean 24-Hour IOP at Week 6 Top of page
End point title	Mean 24-Hour IOP at Week 6
End point description	24-hour mean IOP at Week 6.
End point type	Secondary
End point timeframe	The study eye 24-hour mean IOP at Week 6, measured at 4h (24:00), 8h (04:00), 12h (08:00), 16h (12:00), 20h (16:00), and 24h (20:00) after the last dose given the previous night at 20:00 was summarized for the analysis of the first secondary endpoint.
End point values DE-126 Latanoprost Number of subjects analysed 17 16 Units: mmHg     arithmetic mean (standard error) 17.38 ( 0.763 ) 18.53 ( 0.769 )
No statistical analyses for this end point

Secondary: Mean 24-Hour IOP at Week 6 Top of page

Secondary: Mean Diurnal IOP at Week 6 Top of page
End point title	Mean Diurnal IOP at Week 6
End point description
End point type	Secondary
End point timeframe	Mean diurnal IOP reflected IOP measurement values for the 08:00, 12:00, 16:00 and 20:00 hour timepoints.
End point values DE-126 Latanoprost Number of subjects analysed 17 16 Units: mmHg arithmetic mean (standard error)     Mean diurnal IOP 17.28 ( 0.774 ) 18.40 ( 0.771 )
No statistical analyses for this end point

Secondary: Mean Diurnal IOP at Week 6 Top of page

Secondary: Mean Diurnal IOP at Month 3 Top of page
End point title	Mean Diurnal IOP at Month 3
End point description
End point type	Secondary
End point timeframe	Mean diurnal IOP reflected IOP measurement values for the 08:00, 12:00, 16:00 and 20:00 hour timepoints.
End point values DE-126 Latanoprost Number of subjects analysed 16 16 Units: mmHg arithmetic mean (standard error)     Mean diurnal IOP 17.55 ( 0.737 ) 18.06 ( 0.598 )
No statistical analyses for this end point

Secondary: Mean Diurnal IOP at Month 3 Top of page

Adverse events Top of page
Adverse events information
Timeframe for reporting adverse events	Adverse events in this study were collected irrespective of their relationship to the clinical study, following informed consent and until subject withdrawal or study exit.
Assessment type	Systematic
Dictionary used for adverse event reporting
Dictionary name	MedDRA
Dictionary version	23.1
Reporting groups
Reporting group title	0.002% DE-126
Reporting group description	-
Reporting group title	0.005% Latanoprost
Reporting group description	-
Serious adverse events 0.002% DE-126 0.005% Latanoprost Total subjects affected by serious adverse events      subjects affected / exposed 2 / 17 (11.76%) 0 / 16 (0.00%)      number of deaths (all causes) 1 0      number of deaths resulting from adverse events 0 0 Musculoskeletal and connective tissue disorders Osteoarthritis      subjects affected / exposed 1 / 17 (5.88%) 0 / 16 (0.00%)      occurrences causally related to treatment / all 0 / 1 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 Infections and infestations COVID-19 pneumonia      subjects affected / exposed 1 / 17 (5.88%) 0 / 16 (0.00%)      occurrences causally related to treatment / all 0 / 1 0 / 0      deaths causally related to treatment / all 0 / 1 0 / 0
Frequency threshold for reporting non-serious adverse events: 0%
Non-serious adverse events 0.002% DE-126 0.005% Latanoprost Total subjects affected by non serious adverse events      subjects affected / exposed 10 / 17 (58.82%) 11 / 16 (68.75%) Injury, poisoning and procedural complications Corneal abrasion      subjects affected / exposed 1 / 17 (5.88%) 0 / 16 (0.00%)      occurrences all number 1 0 General disorders and administration site conditions Instillation site pain      subjects affected / exposed 2 / 17 (11.76%) 2 / 16 (12.50%)      occurrences all number 2 2 Immune system disorders Seasonal allergy      subjects affected / exposed 0 / 17 (0.00%) 1 / 16 (6.25%)      occurrences all number 0 1 Eye disorders Abnormal sensation in eye      subjects affected / exposed 2 / 17 (11.76%) 2 / 16 (12.50%)      occurrences all number 2 2 Ocular hyperaemia      subjects affected / exposed 3 / 17 (17.65%) 1 / 16 (6.25%)      occurrences all number 3 1 Eye pruritus      subjects affected / exposed 0 / 17 (0.00%) 3 / 16 (18.75%)      occurrences all number 0 3 Eye pain      subjects affected / exposed 1 / 17 (5.88%) 1 / 16 (6.25%)      occurrences all number 1 1 Foreign body sensation in eyes      subjects affected / exposed 2 / 17 (11.76%) 0 / 16 (0.00%)      occurrences all number 1 1 Eyelid oedema      subjects affected / exposed 0 / 17 (0.00%) 1 / 16 (6.25%)      occurrences all number 0 1 Vision blurred      subjects affected / exposed 0 / 17 (0.00%) 1 / 16 (6.25%)      occurrences all number 0 1 Visual impairment      subjects affected / exposed 0 / 17 (0.00%) 1 / 16 (6.25%)      occurrences all number 0 1

Adverse events Top of page

More information Top of page
Substantial protocol amendments (globally)
Were there any global substantial amendments to the protocol? No
Interruptions (globally)
Were there any global interruptions to the trial? No
Limitations and caveats
Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
None reported

More information Top of page