MK0507A Clinical Study in Patients With Glaucoma and Ocular Hypertension

This study has been completed.

Sponsor:

Information provided by:

Merck

ClinicalTrials.gov Identifier:

NCT00449956

First received: March 19, 2007

Last updated: April 20, 2010

Last verified: April 2010

History of Changes

Results First Received: January 23, 2009

Study Type:	Interventional
Study Design:	Allocation: Randomized; Endpoint Classification: Safety/Efficacy Study; Intervention Model: Parallel Assignment; Masking: Double Blind (Subject, Investigator); Primary Purpose: Treatment
Condition:	Glaucoma
Interventions:	Drug: dorzolamide hydrochloride (+) timolol maleate Drug: Comparator: timolol maleate Drug: Comparator: dorzolamide hydrochloride

Participant Flow

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Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Phase III. Studied period: April 9, 2007 (date study therapy started for the first subject) to February 16, 2008 (the last subject’s last visit stipulated in study protocol). Study was conducted at 67 clinical sites.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Outpatients with primary open angle glaucoma (broad definition) and/or ocular hypertension received 4-week timolol 0.5% monotherapy in the wash-out period before the study randomization.

Reporting Groups

	Description
MK0507A (Dorzolamide 1.0% / Timolol 0.5% Combination)	MK0507A (Dorzolamide 1.0% / Timolol 0.5% combination), one drop per dose twice daily to the study eye.
Timolol 0.5%	Timolol 0.5%, one drop per dose twice daily to the study eye.
Concomitant (Dorzolamide 1.0% / Timolol 0.5%)	Concomitant (Dorzolamide 1.0%, one drop per dose three times daily to the study eye / Timolol 0.5%, one drop per dose twice daily to the study eye).

Participant Flow: Overall Study

	MK0507A (Dorzolamide 1.0% / Timolol 0.5% Combination)	Timolol 0.5%	Concomitant (Dorzolamide 1.0% / Timolol 0.5%)
STARTED	189	92	193
COMPLETED	179	88	184
NOT COMPLETED	10	4	9
Adverse Event	7	1	6
Lack of Efficacy	0	0	1
Protocol Violation	1	1	1
Withdrawal by Subject	0	1	0
Physician Decision	2	1	1

Baseline Characteristics

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Reporting Groups

	Description
MK0507A (Dorzolamide 1.0% / Timolol 0.5% Combination)	MK0507A (Dorzolamide 1.0% / Timolol 0.5% combination), one drop per dose twice daily to the study eye.
Timolol 0.5%	Timolol 0.5%, one drop per dose twice daily to the study eye.
Concomitant (Dorzolamide 1.0% / Timolol 0.5%)	Concomitant (Dorzolamide 1.0%, one drop per dose three times daily to the study eye / Timolol 0.5%, one drop per dose twice daily to the study eye).
Total	Total of all reporting groups

Baseline Measures

	MK0507A (Dorzolamide 1.0% / Timolol 0.5% Combination)	Timolol 0.5%	Concomitant (Dorzolamide 1.0% / Timolol 0.5%)	Total
Number of Participants [units: participants]	189	92	193	474
Age [units: Years] Mean ± Standard Deviation	63.2 ± 10.8	61.3 ± 11.6	62.3 ± 12.7	62.4 ± 11.7
Age, Customized [units: participants]
<65 years	92	50	102	244
>=65 years	97	42	91	230
Gender [units: participants]
Female	104	43	98	245
Male	85	49	95	229
Diagnosis [units: participants]
Open-angle glaucoma	107	51	90	248
Normal-tension glaucoma	8	6	4	18
Ocular hypertension	74	35	99	208
Intraocular pressure (IOP) at Hour 2 [units: mmHg] Mean ± Standard Deviation	20.54 ± 2.07	20.23 ± 1.85	20.38 ± 2.31	20.42 ± 2.13

Outcome Measures

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1. Primary:

Change in Intraocular Pressure (IOP) From Baseline at 8 Weeks [ Time Frame: 8 weeks ]

Measure Type	Primary
Measure Title	Change in Intraocular Pressure (IOP) From Baseline at 8 Weeks
Measure Description	Change from baseline to 8 weeks in Intraocular Pressure (IOP) assessed 2 hours after ocular instillation (at Hour 2)
Time Frame	8 weeks
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Last observed value during the 8-week treatment period was used in the Full Analysis Set (FAS).

Reporting Groups

	Description
MK0507A (Dorzolamide 1.0% / Timolol 0.5% Combination)	MK0507A (Dorzolamide 1.0% / Timolol 0.5% combination), one drop per dose twice daily to the study eye.
Timolol 0.5%	Timolol 0.5%, one drop per dose twice daily to the study eye.
Concomitant (Dorzolamide 1.0% / Timolol 0.5%)	Concomitant (Dorzolamide 1.0%, one drop per dose three times daily to the study eye / Timolol 0.5%, one drop per dose twice daily to the study eye).

Measured Values

	MK0507A (Dorzolamide 1.0% / Timolol 0.5% Combination)	Timolol 0.5%	Concomitant (Dorzolamide 1.0% / Timolol 0.5%)
Number of Participants Analyzed [units: participants]	185	90	188
Change in Intraocular Pressure (IOP) From Baseline at 8 Weeks [units: mmHg] Least Squares Mean ( 95% Confidence Interval )	-2.50 ( -2.86 to -2.15 )	-1.82 ( -2.33 to -1.31 )	-2.78 ( -3.13 to -2.43 )

Statistical Analysis 1 for Change in Intraocular Pressure (IOP) From Baseline at 8 Weeks

Groups ^[1]	MK0507A (Dorzolamide 1.0% / Timolol 0.5% Combination) vs. Timolol 0.5%
Mean Difference (Final Values) ^[2]	-0.68
95% Confidence Interval	( -1.30 to -0.06 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Other relevant estimation information:
	An analysis of covariance model with a factor for treatment and time-matched baseline as a covariate was used to compute 95% confidence intervals.

Statistical Analysis 2 for Change in Intraocular Pressure (IOP) From Baseline at 8 Weeks

Groups ^[1]	MK0507A (Dorzolamide 1.0% / Timolol 0.5% Combination) vs. Concomitant (Dorzolamide 1.0% / Timolol 0.5%)
Non-Inferiority/Equivalence Test ^[2]	Yes
Mean Difference (Final Values) ^[3]	0.28
95% Confidence Interval	( -0.22 to 0.78 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Details of power calculation, definition of non-inferiority margin, and other key parameters:
	Non-inferiority margin = 1.2 mmHg
[3]	Other relevant estimation information:
	An analysis of covariance model with a factor for treatment and time-matched baseline as a covariate was used to compute 95% confidence intervals.

2. Secondary:

Percent Change From Baseline in Intraocular Pressure (IOP) at 8 Weeks [ Time Frame: 8 Weeks ]

Measure Type	Secondary
Measure Title	Percent Change From Baseline in Intraocular Pressure (IOP) at 8 Weeks
Measure Description	Percent Change from baseline to 8 weeks in Intraocular Pressure (IOP) assessed 2 hours after ocular instillation (at Hour 2)
Time Frame	8 Weeks
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Last observed value during the 8-week treatment period was used in the FAS.

Reporting Groups

	Description
MK0507A (Dorzolamide 1.0% / Timolol 0.5% Combination)	MK0507A (Dorzolamide 1.0% / Timolol 0.5% combination), one drop per dose twice daily to the study eye.
Timolol 0.5%	Timolol 0.5%, one drop per dose twice daily to the study eye.
Concomitant (Dorzolamide 1.0% / Timolol 0.5%)	Concomitant (Dorzolamide 1.0%, one drop per dose three times daily to the study eye / Timolol 0.5%, one drop per dose twice daily to the study eye).

Measured Values

	MK0507A (Dorzolamide 1.0% / Timolol 0.5% Combination)	Timolol 0.5%	Concomitant (Dorzolamide 1.0% / Timolol 0.5%)
Number of Participants Analyzed [units: participants]	185	90	188
Percent Change From Baseline in Intraocular Pressure (IOP) at 8 Weeks [units: Percent Change] Least Squares Mean ( 95% Confidence Interval )	-11.99 ( -13.69 to -10.28 )	-8.74 ( -11.18 to -6.30 )	-13.46 ( -15.15 to -11.77 )

No statistical analysis provided for Percent Change From Baseline in Intraocular Pressure (IOP) at 8 Weeks

3. Secondary:

Percent Change From Baseline in Outflow Pressure Reduction Rate at 8 Weeks [ Time Frame: 8 weeks ]

Measure Type	Secondary
Measure Title	Percent Change From Baseline in Outflow Pressure Reduction Rate at 8 Weeks
Measure Description	Percent Change from baseline to 8 weeks in Outflow Pressure Reduction Rate assessed 2 hours after ocular instillation (at Hour 2)
Time Frame	8 weeks
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Last observed value during the 8-week treatment period was used in the FAS.

Reporting Groups

	Description
MK0507A (Dorzolamide 1.0% / Timolol 0.5% Combination)	MK0507A (Dorzolamide 1.0% / Timolol 0.5% combination), one drop per dose twice daily to the study eye.
Timolol 0.5%	Timolol 0.5%, one drop per dose twice daily to the study eye.
Concomitant (Dorzolamide 1.0% / Timolol 0.5%)	Concomitant (Dorzolamide 1.0%, one drop per dose three times daily to the study eye / Timolol 0.5%, one drop per dose twice daily to the study eye).

Measured Values

	MK0507A (Dorzolamide 1.0% / Timolol 0.5% Combination)	Timolol 0.5%	Concomitant (Dorzolamide 1.0% / Timolol 0.5%)
Number of Participants Analyzed [units: participants]	185	90	188
Percent Change From Baseline in Outflow Pressure Reduction Rate at 8 Weeks [units: Percent Change] Least Squares Mean ( 95% Confidence Interval )	23.47 ( 20.07 to 26.88 )	17.17 ( 12.29 to 22.05 )	26.75 ( 23.37 to 30.12 )

No statistical analysis provided for Percent Change From Baseline in Outflow Pressure Reduction Rate at 8 Weeks

Serious Adverse Events

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Other Adverse Events

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More Information

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Certain Agreements:

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

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

The agreement is:

	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed. Restriction Description: Merck agreements may vary with individual investigators, but will not prohibit any investigator from publishing. Merck supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.

Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.

Results Point of Contact:

Name/Title: Senior Vice President, Clinical and Quantitative Sciences
Organization: Merck Sharp & Dohme Corp
phone: 1-800-672-6372

No publications provided

Responsible Party:	Executive Vice President, Clinical and Quantitative Sciences, Merck Sharp & Dohme Corp
ClinicalTrials.gov Identifier:	NCT00449956 History of Changes
Other Study ID Numbers:	2007_011, MK0507A-149
Study First Received:	March 19, 2007
Results First Received:	January 23, 2009
Last Updated:	April 20, 2010
Health Authority:	Japan: Pharmaceuticals and Medical Devices Agency

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