Trial Outcomes & Findings for Pharmacodynamics of Tafluprost 0.0015% Eye Drops: a Comparison Between the Preserved and Unpreserved Formulation (NCT NCT00918346)

NCT ID: NCT00918346

Last Updated: 2010-12-28

Results Overview

IOPs at baseline: mean IOP values at four timepoints (worse eye)

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 43 participants
• Primary outcome timeframe: Baseline
• Results posted on: 2010-12-28

Participant Flow

At 2 centers in Germany, 1 center in Finland: 14 September 2005 first patient screened 08 November 2005 first patient randomized 05 April 2006 last patient completed

A total of 45 patients screened and 43 patients randomized. 2 screening failure patients: 1 withdrawn consent and 1 too low IOP (inclusion criterion 4).

Participant milestones

Measure	Preserved Formulation First, Then Unpreserved Formulation Tafluprost 0.0015% preserved formulation once daily for first 4 weeks, then unpreserved formulation (after washout)	Unpreserved Formulation First, Then Preserved Formulation Tafluprost 0.0015% unpreserved formulation once daily for first 4 weeks, then preserved formulation (after washout)
First Treatment Period (4 Weeks) STARTED	21	22
First Treatment Period (4 Weeks) COMPLETED	21	21
First Treatment Period (4 Weeks) NOT COMPLETED	0	1
Washout (at Least 4 Weeks) STARTED	21	21
Washout (at Least 4 Weeks) COMPLETED	21	21
Washout (at Least 4 Weeks) NOT COMPLETED	0	0
Second Treatment Period (4 Weeks) STARTED	21	21
Second Treatment Period (4 Weeks) COMPLETED	21	21
Second Treatment Period (4 Weeks) NOT COMPLETED	0	0
Post Study Period STARTED	21	21
Post Study Period COMPLETED	21	21
Post Study Period NOT COMPLETED	0	0

Reasons for withdrawal

Measure	Preserved Formulation First, Then Unpreserved Formulation Tafluprost 0.0015% preserved formulation once daily for first 4 weeks, then unpreserved formulation (after washout)	Unpreserved Formulation First, Then Preserved Formulation Tafluprost 0.0015% unpreserved formulation once daily for first 4 weeks, then preserved formulation (after washout)
First Treatment Period (4 Weeks) Lack of Efficacy	0	1

Baseline Characteristics

Pharmacodynamics of Tafluprost 0.0015% Eye Drops: a Comparison Between the Preserved and Unpreserved Formulation

Baseline characteristics by cohort

Measure	Entire Study Population n=43 Participants Includes all 43 randomized patients (86 eyes)
Age Continuous	65.3 years STANDARD_DEVIATION 10.1 • n=5 Participants
Sex: Female, Male Female	27 Participants n=5 Participants
Sex: Female, Male Male	16 Participants n=5 Participants
Race/Ethnicity, Customized Caucasian	43 participants n=5 Participants
Region of Enrollment Germany	32 participants n=5 Participants
Region of Enrollment Finland	11 participants n=5 Participants
Diagnosis - worse eyes Primary Open Angle Glaucoma	28 eyes n=5 Participants
Diagnosis - worse eyes Capsular Glaucoma	3 eyes n=5 Participants
Diagnosis - worse eyes Ocular Hypertension	12 eyes n=5 Participants
Central corneal thickness Right eye	548.7 micrometer STANDARD_DEVIATION 42.8 • n=5 Participants
Central corneal thickness Left eye	547.0 micrometer STANDARD_DEVIATION 45.4 • n=5 Participants

PRIMARY outcome

Timeframe: Baseline

Population: IOPs of all subjects who received preserved/unpreserved formulation

IOPs at baseline: mean IOP values at four timepoints (worse eye)

Outcome measures

Measure	Preserved Formulation n=42 Participants tafluprost 0.0015% preserved formulation	Unpreserved Formulation n=43 Participants tafluprost 0.0015% unpreserved formulation
Intraocular Pressures (IOPs) at Baseline 8 o'clock	22.57 mmHg Standard Deviation 3.04	22.98 mmHg Standard Deviation 3.18
Intraocular Pressures (IOPs) at Baseline 12 o'clock	20.86 mmHg Standard Deviation 2.79	21.78 mmHg Standard Deviation 2.68
Intraocular Pressures (IOPs) at Baseline 16 o'clock	21.73 mmHg Standard Deviation 3.19	21.51 mmHg Standard Deviation 2.49
Intraocular Pressures (IOPs) at Baseline 20 o'clock	21.77 mmHg Standard Deviation 3.02	21.81 mmHg Standard Deviation 2.61

PRIMARY outcome

Timeframe: Week 1

Population: IOPs of all subjects who received preserved/unpreserved formulation

IOPs at week 1: mean IOP values at four timepoints (worse eye)

Outcome measures

Measure	Preserved Formulation n=42 Participants tafluprost 0.0015% preserved formulation	Unpreserved Formulation n=43 Participants tafluprost 0.0015% unpreserved formulation
Intraocular Pressures (IOPs) at Week 1 12 o'clock	15.77 mmHg Standard Deviation 1.60	15.72 mmHg Standard Deviation 1.92
Intraocular Pressures (IOPs) at Week 1 8 o'clock	16.43 mmHg Standard Deviation 2.11	16.21 mmHg Standard Deviation 2.70
Intraocular Pressures (IOPs) at Week 1 16 o'clock	16.23 mmHg Standard Deviation 1.73	15.83 mmHg Standard Deviation 1.99
Intraocular Pressures (IOPs) at Week 1 20 o'clock	16.26 mmHg Standard Deviation 2.20	16.16 mmHg Standard Deviation 2.08

PRIMARY outcome

Timeframe: Week 4

Population: IOPs of all subjects who received preserved/unpreserved formulation

IOPs at week 4: mean IOP values at four timepoints (worse eye)

Outcome measures

Measure	Preserved Formulation n=42 Participants tafluprost 0.0015% preserved formulation	Unpreserved Formulation n=43 Participants tafluprost 0.0015% unpreserved formulation
Intraocular Pressures (IOPs) at Week 4 8 o'clock	16.39 mmHg Standard Deviation 2.43	16.80 mmHg Standard Deviation 3.00
Intraocular Pressures (IOPs) at Week 4 12 o'clock	16.30 mmHg Standard Deviation 2.46	16.67 mmHg Standard Deviation 2.54
Intraocular Pressures (IOPs) at Week 4 16 o'clock	16.64 mmHg Standard Deviation 2.37	16.71 mmHg Standard Deviation 2.53
Intraocular Pressures (IOPs) at Week 4 20 o'clock	17.21 mmHg Standard Deviation 1.91	17.01 mmHg Standard Deviation 2.44

PRIMARY outcome

Timeframe: Baseline - Week 4

Population: Intention To Treat (ITT): randomized patients who received at least one dose of study medication and had at least one pharmacodynamic (IOP) measurement available.

Overall treatment difference at 4 weeks (unpreserved-preserved) evaluated using a repeated measurements analysis of covariance (RM ANCOVA) model.

Outcome measures

Measure	Preserved Formulation n=43 Participants tafluprost 0.0015% preserved formulation	Unpreserved Formulation tafluprost 0.0015% unpreserved formulation
Primary Pharmacodynamic Variable Intention to Treat Efficacy Dataset: Change From Baseline in the Overall Diurnal Intraocular Pressure (IOP) at Week 4 (Worse Eye)	0.01 mmHg Interval -0.46 to 0.49	—

PRIMARY outcome

Timeframe: Baseline - Week 4

Population: Per Protocol (PP): randomized patients who completed the study per protocol (i.e. excluded from PP is the discontinued patient and a patient with major protocol violation)

Overall treatment difference at 4 weeks (unpreserved-preserved) evaluated using a repeated measurments analysis of covariance (RM ANCOVA) model.

Outcome measures

Measure	Preserved Formulation n=41 Participants tafluprost 0.0015% preserved formulation	Unpreserved Formulation tafluprost 0.0015% unpreserved formulation
Primary Pharmacodynamic Variable Per Protocol Efficacy Dataset: Change From Baseline in the Overall Diurnal Intraocular Pressure (IOP) at Week 4 (Worse Eye)	-0.05 mmHg Interval -0.52 to 0.42	—

SECONDARY outcome

Timeframe: Baseline - Week 1

Population: ITT: randomized patients who received at least one dose of study medication and had at least one pharmacodynamic (IOP) measurement available.

The overall and time-wise, i.e. at 8:00, 12:00, 16:00 and 20:00, comparisons of IOP at week 1 (diurnal IOP and IOP value at given timepoint at 1 week minus corresponding value at baseline: unpreserved-preserved) were done using the RM ANCOVA model.

Outcome measures

Measure	Preserved Formulation n=43 Participants tafluprost 0.0015% preserved formulation	Unpreserved Formulation tafluprost 0.0015% unpreserved formulation
Overall and Time-wise Comparisons of IOP at Week 1 Overall	-0.27 mmHg Interval -0.73 to 0.19	—
Overall and Time-wise Comparisons of IOP at Week 1 Timepoint 8:00	-0.32 mmHg Interval -0.96 to 0.32	—
Overall and Time-wise Comparisons of IOP at Week 1 Timepoint 12:00	-0.25 mmHg Interval -0.89 to 0.4	—
Overall and Time-wise Comparisons of IOP at Week 1 Timepoint 16:00	-0.39 mmHg Interval -1.03 to 0.26	—
Overall and Time-wise Comparisons of IOP at Week 1 Timepoint 20:00	-0.13 mmHg Interval -0.77 to 0.52	—

SECONDARY outcome

Timeframe: Baseline - Week 4

Population: ITT: randomized patients who received at least one dose of study medication and had at least one pharmacodynamic (IOP) measurement available.

The time-wise, i.e. at 8:00, 12:00, 16:00 and 20:00, comparisons of IOP at week 4 (IOP value at given timepoint at 4 weeks minus corresponding value at baseline: unpreserved-preserved) were done using the RM ANCOVA model.

Outcome measures

Measure	Preserved Formulation n=43 Participants tafluprost 0.0015% preserved formulation	Unpreserved Formulation tafluprost 0.0015% unpreserved formulation
Change From Baseline in Time-wise IOPs at Week 4 Timepoint 8:00	0.24 mmHg Interval -0.51 to 0.98	—
Change From Baseline in Time-wise IOPs at Week 4 Timepoint 12:00	0.11 mmHg Interval -0.64 to 0.86	—
Change From Baseline in Time-wise IOPs at Week 4 Timepoint 16:00	0.00 mmHg Interval -0.74 to 0.75	—
Change From Baseline in Time-wise IOPs at Week 4 Timepoint 20:00	-0.30 mmHg Interval -1.04 to 0.45	—

Adverse Events

Preserved Formulation

Serious events: 0 serious events

Other events: 7 other events

Deaths: 0 deaths

Unpreserved Formulation

Serious events: 0 serious events

Other events: 11 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Preserved Formulation n=42 participants at risk Tafluprost 0.0015% preserved formulation once daily for 4 weeks	Unpreserved Formulation n=43 participants at risk Tafluprost 0.0015% unpreserved formulation once daily for first 4 weeks
Eye disorders Conjunctival hyperemia	4.8% 2/42 • Number of events 2 • Adverse event data was collected at Week 1 and Week 4 visits of treatment period I and II, as well as on last Post-study visit. Additionally, baseline symptoms were queried on Day 0 (=Baseline) visit of the two treatment periods. Patients were asked about ocular or non-ocular symptoms with a non-leading question, or they volunteered the information during a study visit. Also, any clinically significant signs observed by the investigator could be recorded as adverse events.	14.0% 6/43 • Number of events 6 • Adverse event data was collected at Week 1 and Week 4 visits of treatment period I and II, as well as on last Post-study visit. Additionally, baseline symptoms were queried on Day 0 (=Baseline) visit of the two treatment periods. Patients were asked about ocular or non-ocular symptoms with a non-leading question, or they volunteered the information during a study visit. Also, any clinically significant signs observed by the investigator could be recorded as adverse events.
Eye disorders Ocular hyperemia	0.00% 0/42 • Adverse event data was collected at Week 1 and Week 4 visits of treatment period I and II, as well as on last Post-study visit. Additionally, baseline symptoms were queried on Day 0 (=Baseline) visit of the two treatment periods. Patients were asked about ocular or non-ocular symptoms with a non-leading question, or they volunteered the information during a study visit. Also, any clinically significant signs observed by the investigator could be recorded as adverse events.	4.7% 2/43 • Number of events 2 • Adverse event data was collected at Week 1 and Week 4 visits of treatment period I and II, as well as on last Post-study visit. Additionally, baseline symptoms were queried on Day 0 (=Baseline) visit of the two treatment periods. Patients were asked about ocular or non-ocular symptoms with a non-leading question, or they volunteered the information during a study visit. Also, any clinically significant signs observed by the investigator could be recorded as adverse events.
Eye disorders Erythema of eyelid	2.4% 1/42 • Number of events 1 • Adverse event data was collected at Week 1 and Week 4 visits of treatment period I and II, as well as on last Post-study visit. Additionally, baseline symptoms were queried on Day 0 (=Baseline) visit of the two treatment periods. Patients were asked about ocular or non-ocular symptoms with a non-leading question, or they volunteered the information during a study visit. Also, any clinically significant signs observed by the investigator could be recorded as adverse events.	2.3% 1/43 • Number of events 1 • Adverse event data was collected at Week 1 and Week 4 visits of treatment period I and II, as well as on last Post-study visit. Additionally, baseline symptoms were queried on Day 0 (=Baseline) visit of the two treatment periods. Patients were asked about ocular or non-ocular symptoms with a non-leading question, or they volunteered the information during a study visit. Also, any clinically significant signs observed by the investigator could be recorded as adverse events.
Eye disorders Eye pruritus	2.4% 1/42 • Number of events 1 • Adverse event data was collected at Week 1 and Week 4 visits of treatment period I and II, as well as on last Post-study visit. Additionally, baseline symptoms were queried on Day 0 (=Baseline) visit of the two treatment periods. Patients were asked about ocular or non-ocular symptoms with a non-leading question, or they volunteered the information during a study visit. Also, any clinically significant signs observed by the investigator could be recorded as adverse events.	2.3% 1/43 • Number of events 1 • Adverse event data was collected at Week 1 and Week 4 visits of treatment period I and II, as well as on last Post-study visit. Additionally, baseline symptoms were queried on Day 0 (=Baseline) visit of the two treatment periods. Patients were asked about ocular or non-ocular symptoms with a non-leading question, or they volunteered the information during a study visit. Also, any clinically significant signs observed by the investigator could be recorded as adverse events.
Eye disorders Foreign body sensation	2.4% 1/42 • Number of events 1 • Adverse event data was collected at Week 1 and Week 4 visits of treatment period I and II, as well as on last Post-study visit. Additionally, baseline symptoms were queried on Day 0 (=Baseline) visit of the two treatment periods. Patients were asked about ocular or non-ocular symptoms with a non-leading question, or they volunteered the information during a study visit. Also, any clinically significant signs observed by the investigator could be recorded as adverse events.	2.3% 1/43 • Number of events 1 • Adverse event data was collected at Week 1 and Week 4 visits of treatment period I and II, as well as on last Post-study visit. Additionally, baseline symptoms were queried on Day 0 (=Baseline) visit of the two treatment periods. Patients were asked about ocular or non-ocular symptoms with a non-leading question, or they volunteered the information during a study visit. Also, any clinically significant signs observed by the investigator could be recorded as adverse events.
Eye disorders Anterior chamber cell	0.00% 0/42 • Adverse event data was collected at Week 1 and Week 4 visits of treatment period I and II, as well as on last Post-study visit. Additionally, baseline symptoms were queried on Day 0 (=Baseline) visit of the two treatment periods. Patients were asked about ocular or non-ocular symptoms with a non-leading question, or they volunteered the information during a study visit. Also, any clinically significant signs observed by the investigator could be recorded as adverse events.	2.3% 1/43 • Number of events 1 • Adverse event data was collected at Week 1 and Week 4 visits of treatment period I and II, as well as on last Post-study visit. Additionally, baseline symptoms were queried on Day 0 (=Baseline) visit of the two treatment periods. Patients were asked about ocular or non-ocular symptoms with a non-leading question, or they volunteered the information during a study visit. Also, any clinically significant signs observed by the investigator could be recorded as adverse events.
Eye disorders Blepharitis	0.00% 0/42 • Adverse event data was collected at Week 1 and Week 4 visits of treatment period I and II, as well as on last Post-study visit. Additionally, baseline symptoms were queried on Day 0 (=Baseline) visit of the two treatment periods. Patients were asked about ocular or non-ocular symptoms with a non-leading question, or they volunteered the information during a study visit. Also, any clinically significant signs observed by the investigator could be recorded as adverse events.	2.3% 1/43 • Number of events 1 • Adverse event data was collected at Week 1 and Week 4 visits of treatment period I and II, as well as on last Post-study visit. Additionally, baseline symptoms were queried on Day 0 (=Baseline) visit of the two treatment periods. Patients were asked about ocular or non-ocular symptoms with a non-leading question, or they volunteered the information during a study visit. Also, any clinically significant signs observed by the investigator could be recorded as adverse events.
Eye disorders Eye pain	0.00% 0/42 • Adverse event data was collected at Week 1 and Week 4 visits of treatment period I and II, as well as on last Post-study visit. Additionally, baseline symptoms were queried on Day 0 (=Baseline) visit of the two treatment periods. Patients were asked about ocular or non-ocular symptoms with a non-leading question, or they volunteered the information during a study visit. Also, any clinically significant signs observed by the investigator could be recorded as adverse events.	2.3% 1/43 • Number of events 1 • Adverse event data was collected at Week 1 and Week 4 visits of treatment period I and II, as well as on last Post-study visit. Additionally, baseline symptoms were queried on Day 0 (=Baseline) visit of the two treatment periods. Patients were asked about ocular or non-ocular symptoms with a non-leading question, or they volunteered the information during a study visit. Also, any clinically significant signs observed by the investigator could be recorded as adverse events.
Eye disorders Lacrimation increased	0.00% 0/42 • Adverse event data was collected at Week 1 and Week 4 visits of treatment period I and II, as well as on last Post-study visit. Additionally, baseline symptoms were queried on Day 0 (=Baseline) visit of the two treatment periods. Patients were asked about ocular or non-ocular symptoms with a non-leading question, or they volunteered the information during a study visit. Also, any clinically significant signs observed by the investigator could be recorded as adverse events.	2.3% 1/43 • Number of events 1 • Adverse event data was collected at Week 1 and Week 4 visits of treatment period I and II, as well as on last Post-study visit. Additionally, baseline symptoms were queried on Day 0 (=Baseline) visit of the two treatment periods. Patients were asked about ocular or non-ocular symptoms with a non-leading question, or they volunteered the information during a study visit. Also, any clinically significant signs observed by the investigator could be recorded as adverse events.
Eye disorders Punctate keratitis	0.00% 0/42 • Adverse event data was collected at Week 1 and Week 4 visits of treatment period I and II, as well as on last Post-study visit. Additionally, baseline symptoms were queried on Day 0 (=Baseline) visit of the two treatment periods. Patients were asked about ocular or non-ocular symptoms with a non-leading question, or they volunteered the information during a study visit. Also, any clinically significant signs observed by the investigator could be recorded as adverse events.	2.3% 1/43 • Number of events 1 • Adverse event data was collected at Week 1 and Week 4 visits of treatment period I and II, as well as on last Post-study visit. Additionally, baseline symptoms were queried on Day 0 (=Baseline) visit of the two treatment periods. Patients were asked about ocular or non-ocular symptoms with a non-leading question, or they volunteered the information during a study visit. Also, any clinically significant signs observed by the investigator could be recorded as adverse events.
Eye disorders Vision blurred	2.4% 1/42 • Number of events 1 • Adverse event data was collected at Week 1 and Week 4 visits of treatment period I and II, as well as on last Post-study visit. Additionally, baseline symptoms were queried on Day 0 (=Baseline) visit of the two treatment periods. Patients were asked about ocular or non-ocular symptoms with a non-leading question, or they volunteered the information during a study visit. Also, any clinically significant signs observed by the investigator could be recorded as adverse events.	0.00% 0/43 • Adverse event data was collected at Week 1 and Week 4 visits of treatment period I and II, as well as on last Post-study visit. Additionally, baseline symptoms were queried on Day 0 (=Baseline) visit of the two treatment periods. Patients were asked about ocular or non-ocular symptoms with a non-leading question, or they volunteered the information during a study visit. Also, any clinically significant signs observed by the investigator could be recorded as adverse events.
Eye disorders Asthenopia	0.00% 0/42 • Adverse event data was collected at Week 1 and Week 4 visits of treatment period I and II, as well as on last Post-study visit. Additionally, baseline symptoms were queried on Day 0 (=Baseline) visit of the two treatment periods. Patients were asked about ocular or non-ocular symptoms with a non-leading question, or they volunteered the information during a study visit. Also, any clinically significant signs observed by the investigator could be recorded as adverse events.	2.3% 1/43 • Number of events 1 • Adverse event data was collected at Week 1 and Week 4 visits of treatment period I and II, as well as on last Post-study visit. Additionally, baseline symptoms were queried on Day 0 (=Baseline) visit of the two treatment periods. Patients were asked about ocular or non-ocular symptoms with a non-leading question, or they volunteered the information during a study visit. Also, any clinically significant signs observed by the investigator could be recorded as adverse events.
Eye disorders Conjunctival haemorrhage	0.00% 0/42 • Adverse event data was collected at Week 1 and Week 4 visits of treatment period I and II, as well as on last Post-study visit. Additionally, baseline symptoms were queried on Day 0 (=Baseline) visit of the two treatment periods. Patients were asked about ocular or non-ocular symptoms with a non-leading question, or they volunteered the information during a study visit. Also, any clinically significant signs observed by the investigator could be recorded as adverse events.	2.3% 1/43 • Number of events 1 • Adverse event data was collected at Week 1 and Week 4 visits of treatment period I and II, as well as on last Post-study visit. Additionally, baseline symptoms were queried on Day 0 (=Baseline) visit of the two treatment periods. Patients were asked about ocular or non-ocular symptoms with a non-leading question, or they volunteered the information during a study visit. Also, any clinically significant signs observed by the investigator could be recorded as adverse events.
Eye disorders Dry eye	0.00% 0/42 • Adverse event data was collected at Week 1 and Week 4 visits of treatment period I and II, as well as on last Post-study visit. Additionally, baseline symptoms were queried on Day 0 (=Baseline) visit of the two treatment periods. Patients were asked about ocular or non-ocular symptoms with a non-leading question, or they volunteered the information during a study visit. Also, any clinically significant signs observed by the investigator could be recorded as adverse events.	2.3% 1/43 • Number of events 1 • Adverse event data was collected at Week 1 and Week 4 visits of treatment period I and II, as well as on last Post-study visit. Additionally, baseline symptoms were queried on Day 0 (=Baseline) visit of the two treatment periods. Patients were asked about ocular or non-ocular symptoms with a non-leading question, or they volunteered the information during a study visit. Also, any clinically significant signs observed by the investigator could be recorded as adverse events.
Injury, poisoning and procedural complications Superficial injury of eye	2.4% 1/42 • Number of events 1 • Adverse event data was collected at Week 1 and Week 4 visits of treatment period I and II, as well as on last Post-study visit. Additionally, baseline symptoms were queried on Day 0 (=Baseline) visit of the two treatment periods. Patients were asked about ocular or non-ocular symptoms with a non-leading question, or they volunteered the information during a study visit. Also, any clinically significant signs observed by the investigator could be recorded as adverse events.	0.00% 0/43 • Adverse event data was collected at Week 1 and Week 4 visits of treatment period I and II, as well as on last Post-study visit. Additionally, baseline symptoms were queried on Day 0 (=Baseline) visit of the two treatment periods. Patients were asked about ocular or non-ocular symptoms with a non-leading question, or they volunteered the information during a study visit. Also, any clinically significant signs observed by the investigator could be recorded as adverse events.
Gastrointestinal disorders Nausea	2.4% 1/42 • Number of events 1 • Adverse event data was collected at Week 1 and Week 4 visits of treatment period I and II, as well as on last Post-study visit. Additionally, baseline symptoms were queried on Day 0 (=Baseline) visit of the two treatment periods. Patients were asked about ocular or non-ocular symptoms with a non-leading question, or they volunteered the information during a study visit. Also, any clinically significant signs observed by the investigator could be recorded as adverse events.	0.00% 0/43 • Adverse event data was collected at Week 1 and Week 4 visits of treatment period I and II, as well as on last Post-study visit. Additionally, baseline symptoms were queried on Day 0 (=Baseline) visit of the two treatment periods. Patients were asked about ocular or non-ocular symptoms with a non-leading question, or they volunteered the information during a study visit. Also, any clinically significant signs observed by the investigator could be recorded as adverse events.
Musculoskeletal and connective tissue disorders Pain in extremity	0.00% 0/42 • Adverse event data was collected at Week 1 and Week 4 visits of treatment period I and II, as well as on last Post-study visit. Additionally, baseline symptoms were queried on Day 0 (=Baseline) visit of the two treatment periods. Patients were asked about ocular or non-ocular symptoms with a non-leading question, or they volunteered the information during a study visit. Also, any clinically significant signs observed by the investigator could be recorded as adverse events.	2.3% 1/43 • Number of events 1 • Adverse event data was collected at Week 1 and Week 4 visits of treatment period I and II, as well as on last Post-study visit. Additionally, baseline symptoms were queried on Day 0 (=Baseline) visit of the two treatment periods. Patients were asked about ocular or non-ocular symptoms with a non-leading question, or they volunteered the information during a study visit. Also, any clinically significant signs observed by the investigator could be recorded as adverse events.
Musculoskeletal and connective tissue disorders Osteoporosis	2.4% 1/42 • Number of events 1 • Adverse event data was collected at Week 1 and Week 4 visits of treatment period I and II, as well as on last Post-study visit. Additionally, baseline symptoms were queried on Day 0 (=Baseline) visit of the two treatment periods. Patients were asked about ocular or non-ocular symptoms with a non-leading question, or they volunteered the information during a study visit. Also, any clinically significant signs observed by the investigator could be recorded as adverse events.	0.00% 0/43 • Adverse event data was collected at Week 1 and Week 4 visits of treatment period I and II, as well as on last Post-study visit. Additionally, baseline symptoms were queried on Day 0 (=Baseline) visit of the two treatment periods. Patients were asked about ocular or non-ocular symptoms with a non-leading question, or they volunteered the information during a study visit. Also, any clinically significant signs observed by the investigator could be recorded as adverse events.
Musculoskeletal and connective tissue disorders Tendonitis	2.4% 1/42 • Number of events 1 • Adverse event data was collected at Week 1 and Week 4 visits of treatment period I and II, as well as on last Post-study visit. Additionally, baseline symptoms were queried on Day 0 (=Baseline) visit of the two treatment periods. Patients were asked about ocular or non-ocular symptoms with a non-leading question, or they volunteered the information during a study visit. Also, any clinically significant signs observed by the investigator could be recorded as adverse events.	0.00% 0/43 • Adverse event data was collected at Week 1 and Week 4 visits of treatment period I and II, as well as on last Post-study visit. Additionally, baseline symptoms were queried on Day 0 (=Baseline) visit of the two treatment periods. Patients were asked about ocular or non-ocular symptoms with a non-leading question, or they volunteered the information during a study visit. Also, any clinically significant signs observed by the investigator could be recorded as adverse events.

Additional Information

Auli Ropo

Santen Oy

Phone: +358405012416

Email: auli.ropo@santen.fi

Results disclosure agreements

• Principal investigator is a sponsor employee The sponsor respects the investigators' wish to publish results of the study, and will not unnecessarily restrict the spreading of information of scientific interest. However, the study may involve confidential information affecting the company's business, such as aspects related to patent application. Therefore, the investigators agree to allow the sponsor to review any manuscripts and to negotiate timing and forum of publication.
• Publication restrictions are in place

Restriction type: OTHER