Trial Outcomes & Findings for Preservative-Free Tafluprost (MK-2452) for the Treatment of Open-Angle Glaucoma or Ocular Hypertension (MK-2452-002) (NCT NCT01254604)

Results Overview

IOP was measured at baseline, Week 2 and Week 4 using a Goldmann applanation tonometer. At each of these visits, IOP measurement was performed at 0800, 1000 and 1600 hours. At each IOP assessment time point during a visit, 2 consecutive IOP measurements were made. If these 2 measurements differed by ≤2 mmHg, then the average of the 2 IOP values was recorded. If the 2 measurements differed by \>2 mmHg, then a third measurement was obtained and the median of these 3 measurements was recorded. The IOP value for a visit (e.g., Week 4) was the mean of the values recorded at the 3 time points during the visit. For each participant, one "study eye" was identified for data summarization and analysis for this primary efficacy outcome measure. The "study eye" was the eye with the higher (i.e., "worse") IOP at baseline, or if both eyes had the same baseline IOP value, the right eye was designated the "study eye." Change from baseline in IOP at Week 4 = Week 4 IOP value - baseline IOP value.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

190 participants

Primary outcome timeframe

Baseline and Week 4

Results posted on

2018-09-20

Participant Flow

Participant milestones

Participant milestones
Measure	Tafluprost One drop of preservative-free vehicle (contains no active drug) per eye in the morning, and one drop of preservative-free tafluprost (0.0015%) per eye in the evening for four weeks.	Timolol One drop of preservative-free timolol maleate (0.05%) per eye twice daily (morning and evening) for four weeks.
Overall Study STARTED	95	95
Overall Study Treated	93	94
Overall Study COMPLETED	87	86
Overall Study NOT COMPLETED	8	9

Reasons for withdrawal

Reasons for withdrawal
Measure	Tafluprost One drop of preservative-free vehicle (contains no active drug) per eye in the morning, and one drop of preservative-free tafluprost (0.0015%) per eye in the evening for four weeks.	Timolol One drop of preservative-free timolol maleate (0.05%) per eye twice daily (morning and evening) for four weeks.
Overall Study Lost to Follow-up	1	1
Overall Study Protocol Violation	2	2
Overall Study Withdrawal by Subject	2	4
Overall Study Adverse Event	3	2

Baseline Characteristics

Preservative-Free Tafluprost (MK-2452) for the Treatment of Open-Angle Glaucoma or Ocular Hypertension (MK-2452-002)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Tafluprost n=93 Participants One drop of preservative-free vehicle (contains no active drug) per eye in the morning, and one drop of preservative-free tafluprost (0.0015%) per eye in the evening for four weeks.	Timolol n=94 Participants One drop of preservative-free timolol maleate (0.05%) per eye twice daily (morning and evening) for four weeks.	Total n=187 Participants Total of all reporting groups
Age, Continuous	56.7 years STANDARD_DEVIATION 11.54 • n=5 Participants	54.9 years STANDARD_DEVIATION 13.42 • n=7 Participants	55.8 years STANDARD_DEVIATION 12.52 • n=5 Participants
Sex: Female, Male Female	34 Participants n=5 Participants	22 Participants n=7 Participants	56 Participants n=5 Participants
Sex: Female, Male Male	59 Participants n=5 Participants	72 Participants n=7 Participants	131 Participants n=5 Participants
Intraocular Pressure (IOP) - Study Eye	24.8 mmHg STANDARD_DEVIATION 3.0 • n=5 Participants	24.9 mmHg STANDARD_DEVIATION 2.6 • n=7 Participants	24.9 mmHg STANDARD_DEVIATION 2.8 • n=5 Participants

PRIMARY outcome

Timeframe: Baseline and Week 4

Population: Per Protocol population: Participants who received at least one dose of study drug, had at least one efficacy measurement available for an analysis endpoint and did not have any protocol violations that may substantially affect the results of the primary efficacy endpoint

IOP was measured at baseline, Week 2 and Week 4 using a Goldmann applanation tonometer. At each of these visits, IOP measurement was performed at 0800, 1000 and 1600 hours. At each IOP assessment time point during a visit, 2 consecutive IOP measurements were made. If these 2 measurements differed by ≤2 mmHg, then the average of the 2 IOP values was recorded. If the 2 measurements differed by \>2 mmHg, then a third measurement was obtained and the median of these 3 measurements was recorded. The IOP value for a visit (e.g., Week 4) was the mean of the values recorded at the 3 time points during the visit. For each participant, one "study eye" was identified for data summarization and analysis for this primary efficacy outcome measure. The "study eye" was the eye with the higher (i.e., "worse") IOP at baseline, or if both eyes had the same baseline IOP value, the right eye was designated the "study eye." Change from baseline in IOP at Week 4 = Week 4 IOP value - baseline IOP value.

Outcome measures

Outcome measures
Measure	Tafluprost n=84 Participants One drop of preservative-free vehicle (contains no active drug) per eye in the morning, and one drop of preservative-free tafluprost (0.0015%) per eye in the evening for four weeks.	Timolol n=83 Participants One drop of preservative-free timolol maleate (0.05%) per eye twice daily (morning and evening) for four weeks.
Mean Diurnal IOP Change From Baseline at Week 4 - Study Eye	-8.3 mmHg Interval -9.0 to -7.6	-6.6 mmHg Interval -7.3 to -5.9

PRIMARY outcome

Timeframe: Up to 14 days after Week 4 visit

Population: APaT population

An AE is any unfavorable and unintended change in the structure, function or chemistry of the body temporally associated with study drug administration, whether or not considered related to the study drug. Participants with one or more AEs during the study are counted once in this summary.

Outcome measures

Outcome measures
Measure	Tafluprost n=93 Participants One drop of preservative-free vehicle (contains no active drug) per eye in the morning, and one drop of preservative-free tafluprost (0.0015%) per eye in the evening for four weeks.	Timolol n=94 Participants One drop of preservative-free timolol maleate (0.05%) per eye twice daily (morning and evening) for four weeks.
Number of Participants With an Adverse Event (AE)	28 participants	32 participants

PRIMARY outcome

Timeframe: Up to Week 4

Population: APaT population

An AE is any unfavorable and unintended change in the structure, function or chemistry of the body temporally associated with study drug administration, whether or not considered related to the study drug. Participants who discontinued study drug treatment due to an AE are counted once in this summary.

Outcome measures

Outcome measures
Measure	Tafluprost n=93 Participants One drop of preservative-free vehicle (contains no active drug) per eye in the morning, and one drop of preservative-free tafluprost (0.0015%) per eye in the evening for four weeks.	Timolol n=94 Participants One drop of preservative-free timolol maleate (0.05%) per eye twice daily (morning and evening) for four weeks.
Number of Participants Who Discontinued Study Drug Due to an AE	3 participants	2 participants

SECONDARY outcome

Timeframe: Baseline and Week 4

Population: Per Protocol population: Participants who received at least one dose of study drug, had at least one efficacy measurement available for an analysis endpoint and did not have any protocol violations that may substantially affect the results of the primary efficacy endpoint

IOP was measured at baseline, Week 2 and Week 4 using a Goldmann applanation tonometer. At each of these visits, IOP measurement was performed at 0800, 1000 and 1600 hours. At each IOP assessment time point during a visit, 2 consecutive IOP measurements were made. If these 2 measurements differed by ≤2 mmHg, then the average of the 2 IOP values was recorded. If the 2 measurements differed by \>2 mmHg, then a third measurement was obtained and the median of these 3 measurements was recorded. The IOP value for a visit (e.g., Week 4) was the mean of the values recorded at the 3 time points during the visit. For each participant, one "study eye" was identified for data summarization and analysis. The "study eye" was the eye with the higher (i.e., "worse") IOP at baseline, or if both eyes had the same baseline IOP value, the right eye was designated the "study eye." Percent reduction in IOP at Week 4 = (\[baseline IOP value - Week 4 IOP value\]/Baseline IOP value)\*100.

Outcome measures

Outcome measures
Measure	Tafluprost n=84 Participants One drop of preservative-free vehicle (contains no active drug) per eye in the morning, and one drop of preservative-free tafluprost (0.0015%) per eye in the evening for four weeks.	Timolol n=83 Participants One drop of preservative-free timolol maleate (0.05%) per eye twice daily (morning and evening) for four weeks.
Number of Participants With ≥25% Reduction in IOP From Baseline to Week 4 - Study Eye	65 participants	48 participants

Adverse Events

Tafluprost

Serious events: 0 serious events

Other events: 19 other events

Deaths: 0 deaths

Timolol

Serious events: 1 serious events

Other events: 15 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Tafluprost n=93 participants at risk One drop of preservative-free vehicle (contains no active drug) per eye in the morning, and one drop of preservative-free tafluprost (0.0015%) per eye in the evening for four weeks.	Timolol n=94 participants at risk One drop of preservative-free timolol maleate (0.05%) per eye twice daily (morning and evening) for four weeks.
Injury, poisoning and procedural complications subdural hematoma	0.00% 0/93 • Up to 14 days after Week 4 visit	1.1% 1/94 • Number of events 1 • Up to 14 days after Week 4 visit

Other adverse events

Other adverse events
Measure	Tafluprost n=93 participants at risk One drop of preservative-free vehicle (contains no active drug) per eye in the morning, and one drop of preservative-free tafluprost (0.0015%) per eye in the evening for four weeks.	Timolol n=94 participants at risk One drop of preservative-free timolol maleate (0.05%) per eye twice daily (morning and evening) for four weeks.
Eye disorders Conjunctivitis	9.7% 9/93 • Number of events 11 • Up to 14 days after Week 4 visit	9.6% 9/94 • Number of events 10 • Up to 14 days after Week 4 visit
Eye disorders Eye irritation	6.5% 6/93 • Number of events 6 • Up to 14 days after Week 4 visit	5.3% 5/94 • Number of events 6 • Up to 14 days after Week 4 visit
Eye disorders Eye pruritus	7.5% 7/93 • Number of events 8 • Up to 14 days after Week 4 visit	3.2% 3/94 • Number of events 3 • Up to 14 days after Week 4 visit
Eye disorders Ocular hyperaemia	6.5% 6/93 • Number of events 8 • Up to 14 days after Week 4 visit	3.2% 3/94 • Number of events 3 • Up to 14 days after Week 4 visit

Additional Information

Senior Vice President, Global Clinical Development

Merck Sharp & Dohme Corp.

Phone: 1-800-672-6372

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Investigator may publish results for his/her study site after publication of results of entire multicenter trial, or after public disclosure of the results online if a multicenter manuscript is not planned. Sponsor must be able to review all proposed results communications regarding study 60 days prior to submission for publication/presentation. Information identified by the Sponsor as confidential must be deleted prior to submission.
Publication restrictions are in place

Restriction type: OTHER