Trial Outcomes & Findings for Circadian Rhythms of Aqueous Humor Dynamics in Humans (NCT NCT00572936)

NCT ID: NCT00572936

Last Updated: 2023-10-24

Results Overview

Intra-ocular Pressure was measured by applanation tonometry

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 30 participants
• Primary outcome timeframe: 2 weeks
• Results posted on: 2023-10-24

Participant Flow

One patient who was taking latanoprost for ocular hypertension did not have an IOP rise greater than 20mmHg after discontinuing treatment for up to 12 weeks. A second patient who initially expressed interest chose to withdraw from the study.

Participant milestones

Measure	Latanoprost/Dorzolamide/Timolol The participants received latanoprost at night and vehicle in the morning for two weeks, then 6 week washout, then Dorzolamide BID for two weeks, then 6 week washout, then Timolol BID for two weeks. The order in which the participants received the three different drugs was random.	Latanoprost/Timolol/Dorzolamide The participants received latanoprost at night and vehicle in the morning for two weeks, then 6 week washout, then Dorzolamide BID for two weeks, then 6 week washout, then Timolol BID for two weeks. The order in which the participants received the three different drugs was random.	Dorzolamide/Latanoprost/Timolol The participants received latanoprost at night and vehicle in the morning for two weeks, then 6 week washout, then Dorzolamide BID for two weeks, then 6 week washout, then Timolol BID for two weeks. The order in which the participants received the three different drugs was random.	Dorzolamide/Timolol/Latanoprost The participants received latanoprost at night and vehicle in the morning for two weeks, then 6 week washout, then Dorzolamide BID for two weeks, then 6 week washout, then Timolol BID for two weeks. The order in which the participants received the three different drugs was random.	Timolol/Dorzolamide/Latanoprost The participants received latanoprost at night and vehicle in the morning for two weeks, then 6 week washout, then Dorzolamide BID for two weeks, then 6 week washout, then Timolol BID for two weeks. The order in which the participants received the three different drugs was random.	Timolol/Latanoprost/Dorzolamide The participants received latanoprost at night and vehicle in the morning for two weeks, then 6 week washout, then Dorzolamide BID for two weeks, then 6 week washout, then Timolol BID for two weeks. The order in which the participants received the three different drugs was random.
First Intervention STARTED	4	4	5	5	5	5
First Intervention COMPLETED	4	4	5	5	5	5
First Intervention NOT COMPLETED	0	0	0	0	0	0
Second Intervention STARTED	4	3	4	5	4	5
Second Intervention COMPLETED	4	3	4	5	4	5
Second Intervention NOT COMPLETED	0	0	0	0	0	0
Third Intervention STARTED	4	3	4	5	3	5
Third Intervention COMPLETED	4	3	4	5	3	5
Third Intervention NOT COMPLETED	0	0	0	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Circadian Rhythms of Aqueous Humor Dynamics in Humans

Baseline characteristics by cohort

Measure	Latanoprost/Dorzolamide/Timolol n=30 Participants The participants received latanoprost at night and vehicle in the morning for two weeks, then 6 week washout, then Dorzolamide BID for two weeks, then 6 week washout, then Timolol BID for two weeks. The order in which the participants received the three different drugs was random.
Age, Continuous	59 years STANDARD_DEVIATION 11 • n=5 Participants
Sex: Female, Male Female	21 Participants n=5 Participants
Sex: Female, Male Male	9 Participants n=5 Participants

PRIMARY outcome

Timeframe: 2 weeks

Intra-ocular Pressure was measured by applanation tonometry

Outcome measures

Measure	Latanoprost n=28 Participants The participants received latanoprost 0.004% at night and vehicle in the morning for two weeks	Timolol n=24 Participants The participants received timolol 0.5% BID for two weeks	Dorzolamide n=26 Participants The participants received dorzolamide 2% BID for two weeks
Intraocular Pressure Daytime	17.6 mmHg Standard Deviation 3.7	16.4 mmHg Standard Deviation 2.3	20.2 mmHg Standard Deviation 4.8
Intraocular Pressure Night time	17.0 mmHg Standard Deviation 3.2	17.1 mmHg Standard Deviation 2.5	17.6 mmHg Standard Deviation 2.4

PRIMARY outcome

Timeframe: 2 weeks

aqueous flow measurements was calculated using fluorophotometry measurements.

Outcome measures

Measure	Latanoprost n=28 Participants The participants received latanoprost 0.004% at night and vehicle in the morning for two weeks	Timolol n=24 Participants The participants received timolol 0.5% BID for two weeks	Dorzolamide n=26 Participants The participants received dorzolamide 2% BID for two weeks
Aqueous Flow day time	2.09 μL/min Standard Deviation 0.71	1.57 μL/min Standard Deviation 0.44	1.75 μL/min Standard Deviation 0.54
Aqueous Flow night time	1.1 μL/min Standard Deviation 0.38	1.1 μL/min Standard Deviation 0.38	1.1 μL/min Standard Deviation 0.38

PRIMARY outcome

Timeframe: 2 weeks

central corneal thickness was measured by ultrasound pachymetry

Outcome measures

Measure	Latanoprost n=28 Participants The participants received latanoprost 0.004% at night and vehicle in the morning for two weeks	Timolol n=24 Participants The participants received timolol 0.5% BID for two weeks	Dorzolamide n=26 Participants The participants received dorzolamide 2% BID for two weeks
Central Corneal Thickness day time	564 μm Standard Deviation 40	568 μm Standard Deviation 43	564 μm Standard Deviation 44
Central Corneal Thickness night time	585 μm Standard Deviation 46	586 μm Standard Deviation 45	582 μm Standard Deviation 43

PRIMARY outcome

Timeframe: 2 weeks

Anterior chamber volume was measured by A-scan ultrasound biometry, daytime

Outcome measures

Measure	Latanoprost n=28 Participants The participants received latanoprost 0.004% at night and vehicle in the morning for two weeks	Timolol n=24 Participants The participants received timolol 0.5% BID for two weeks	Dorzolamide n=26 Participants The participants received dorzolamide 2% BID for two weeks
Anterior Chamber Volume	191 μL Standard Deviation 45	191 μL Standard Deviation 33	198 μL Standard Deviation 38

PRIMARY outcome

Timeframe: 2 weeks

blood pressure was measured by sphygmomanometry

Outcome measures

Measure	Latanoprost n=28 Participants The participants received latanoprost 0.004% at night and vehicle in the morning for two weeks	Timolol n=24 Participants The participants received timolol 0.5% BID for two weeks	Dorzolamide n=26 Participants The participants received dorzolamide 2% BID for two weeks
Blood Pressure systolic day time	136 mmHg Standard Deviation 20	138 mmHg Standard Deviation 22	139 mmHg Standard Deviation 19
Blood Pressure systolic night time	143 mmHg Standard Deviation 17	136 mmHg Standard Deviation 15	138 mmHg Standard Deviation 17
Blood Pressure diastolic day time	78 mmHg Standard Deviation 12	81 mmHg Standard Deviation 12	83 mmHg Standard Deviation 11
Blood Pressure diastolic night time	83 mmHg Standard Deviation 11	79 mmHg Standard Deviation 11	82 mmHg Standard Deviation 12

PRIMARY outcome

Timeframe: 2 weeks

Episcleral venous pressure was measured by venomenometry

Outcome measures

Measure	Latanoprost n=28 Participants The participants received latanoprost 0.004% at night and vehicle in the morning for two weeks	Timolol n=24 Participants The participants received timolol 0.5% BID for two weeks	Dorzolamide n=26 Participants The participants received dorzolamide 2% BID for two weeks
Episcleral Venous Pressure	9.4 mmHg Standard Deviation 1.4	9.6 mmHg Standard Deviation 1.3	9.4 mmHg Standard Deviation 1.0

PRIMARY outcome

Timeframe: 2 weeks

outflow facility was calculated using fluorophotometry and tonography

Outcome measures

Measure	Latanoprost n=28 Participants The participants received latanoprost 0.004% at night and vehicle in the morning for two weeks	Timolol n=24 Participants The participants received timolol 0.5% BID for two weeks	Dorzolamide n=26 Participants The participants received dorzolamide 2% BID for two weeks
Outflow Facility day time fluorophotometry	0.23 µL/min per mm Hg Standard Deviation 0.18	0.23 µL/min per mm Hg Standard Deviation 0.12	0.21 µL/min per mm Hg Standard Deviation 0.11
Outflow Facility daytime tonography	0.22 µL/min per mm Hg Standard Deviation 0.10	0.18 µL/min per mm Hg Standard Deviation 0.08	0.20 µL/min per mm Hg Standard Deviation 0.08
Outflow Facility night tonography	0.21 µL/min per mm Hg Standard Deviation 0.11	0.17 µL/min per mm Hg Standard Deviation 0.08	0.18 µL/min per mm Hg Standard Deviation 0.08

PRIMARY outcome

Timeframe: 2 weeks

uvescleral outflow was calulated using goldmann equation

Outcome measures

Measure	Latanoprost n=28 Participants The participants received latanoprost 0.004% at night and vehicle in the morning for two weeks	Timolol n=24 Participants The participants received timolol 0.5% BID for two weeks	Dorzolamide n=26 Participants The participants received dorzolamide 2% BID for two weeks
Uvescleral Outflow day time fluorophotometry	0.43 µL/min per mm Hg Standard Deviation 1.64	-0.16 µL/min per mm Hg Standard Deviation 1.13	0.14 µL/min per mm Hg Standard Deviation 1.21
Uvescleral Outflow daytime tonography	0.90 µL/min per mm Hg Standard Deviation 1.46	0.70 µL/min per mm Hg Standard Deviation 1.52	0.58 µL/min per mm Hg Standard Deviation 1.62
Uvescleral Outflow night tonography	0.26 µL/min per mm Hg Standard Deviation 1.10	0.50 µL/min per mm Hg Standard Deviation 1.38	0.12 µL/min per mm Hg Standard Deviation 1.45

Adverse Events

Latanoprost

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Dorzolamide

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Timolol

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Carol Toris, PhD

University of Nebraska Medical Center

Phone: 402-559-1852

Email: ctoris@unmc.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place