Ocular Hypertension, Open Angle Glaucoma
Conditions
Brief summary
To evaluate if preservative free cosopt is well tolerated in patients with Open angle glaucoma (OAG) or Ocular hypertension (OH) with dry eyes.
Interventions
dorzolamide hydrochloride (2%)/ timolol maleate (0.5%) Preservative free twice a day (BID), for 8 weeks of treatment
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Adult patient with newly diagnosed and untreated for open-angle glaucoma or ocular hypertension with an Intra-ocular Pressure (IOP) of \> 27 mm Hg (in at least one eye) and a baseline GSS SYMP-6 total score of 75 or less * Patient is male or a female who is highly unlikely to conceive * Patient has been recently diagnosed and is presently untreated for open-angle glaucoma or ocular hypertension with an IOP of at least 27 mm Hg in at least one eye (patient's worse eye) * Patient already diagnosed with open-angle glaucoma or ocular hypertension and untreated for at least 30 days are eligible for the study if they have an IOP of 27 mm Hg or more in at least one eye
Exclusion criteria
* A history of any illness that, in the opinion of the investigator, might confound the results of the study or pose additional risk by administering preservative free dorzolamide-timolol (preservative-free Cosopt®) * The presence of any fundus pathology likely to change during the study or to influence IOP (background of diabetic retinopathy is permitted) * Any contraindication to the use of preservative-free Cosopt® including: * bronchospasm, including bronchial asthma or a history of bronchial asthma or chronic obstructive pulmonary disease, sinus bradycardia, second or third degree AV block, cardiac failure (grade III and IV), cardiogenic shock, severe renal impairment (serum creatinine \> 150 umol/L or creatinine clearance \< 30 ml/min) * Patient on: * carbonic anhydrase inhibitor, concomitant systemic or dermatological medication known to affect the IOP, e.g. clonidine, corticosteroids, oral beta-blocking agents. patient on a non-glaucoma medication that contains a preservative agent, i.e. benzalkonium chloride, benzododecinium bromide or stabilized oxychloro complex * Patient with hypersensitivity to any component of preservative free dorzolamide-timolol (preservative-free Cosopt®)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Glaucoma Symptom Scale (GSS)-SYMP-6 Score | Baseline to week 8 | GSS-SYMP-6 measures 6 non-visual adverse symptoms related to glaucoma medications, with 10 5-point Likert scale questions. Score ranges between 0 and 100, lower scores indicating higher symptoms severity. Change equals post-baseline value minus baseline. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Patient's Global Satisfaction | Week 8 | At week 8, patients were asked to complete a single question describing how satisfied they were regarding with their medication, on a 5-level scale: very satisfied, satisfied, neither satisfied or dissatisfied, dissatisfied, very dissatisfied. |
| Physician's Global Satisfaction | Week 8 | At week 8, physicians were asked to complete a single question describing how satisfied they were regarding their patient's treatment, on a 5-level scale: very satisfied, satisfied, neither satisfied or dissatisfied, dissatisfied, very dissatisfied. |
| Change in Intra-ocular Pressure (IOP) for Worse Eye From Baseline to Week 4 and From Baseline to Week 8, in Patients Receiving Preservative-free Dorzolamide-timolol | Baseline to Week 4 and from Baseline to Week 8 | IOP measurements using Goldmann applanation tonometry, performed by a masked physician two hours after patient was administered study medication. Change is computed as week 4 (or week 8) value minus baseline value. |
Participant flow
Recruitment details
First patient in: MAY-23-2007 Last patient out: OCT-15-2008 Total number of sites: 28 sites in Canada. (Study performed in Canada only).
Participants by arm
| Arm | Count |
|---|---|
| Preservative-free Dorzolamide-timolol (COSOPT®) subjects received preservative-free dorzolamide-timolol (COSOPT®) administered one drop in the affected eye two times daily
The number of patients analyzed (n=176) differs from the initial tables because 2 patients withdrew consent and for whom no data were available at subsequent visits (only baseline characteristircs were available). | 178 |
| Total | 178 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | cancel all appointments, no rebooking | 1 |
| Overall Study | did not complete course of treatment | 1 |
| Overall Study | inclement weather | 1 |
| Overall Study | Lost to Follow-up | 3 |
| Overall Study | Withdrawal by Subject | 2 |
Baseline characteristics
| Characteristic | Preservative-free Dorzolamide-timolol (COSOPT®) |
|---|---|
| Age, Continuous | 65.6 years STANDARD_DEVIATION 12.1 |
| Sex: Female, Male Female | 90 Participants |
| Sex: Female, Male Male | 88 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 0 |
| serious Total, serious adverse events | 3 / 178 |
Outcome results
Primary
Change in Glaucoma Symptom Scale (GSS)-SYMP-6 Score
GSS-SYMP-6 measures 6 non-visual adverse symptoms related to glaucoma medications, with 10 5-point Likert scale questions. Score ranges between 0 and 100, lower scores indicating higher symptoms severity. Change equals post-baseline value minus baseline.
Time frame: Baseline to week 8
Population: 176 patients qualified for inclusion in the intent to treat (ITT) analysis and completed the first visit. Observations on GSS-SYMP-6 were available for 114 and 111 patients at week 4 and 8 respectively
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Preservative-free Dorzolamide-timolol (COSOPT®) Week 4 | Change in Glaucoma Symptom Scale (GSS)-SYMP-6 Score | 1.7 Units on a Scale | Standard Deviation 16.8 |
| Preservative-free Dorzolamide-timolol (COSOPT®) Week 8 | Change in Glaucoma Symptom Scale (GSS)-SYMP-6 Score | 3.2 Units on a Scale | Standard Deviation 20.2 |
Comparison: The change is the post-baseline value minus the baseline value.~Null Hypothesis: change in GSS-SYMP-6 score = 7p-value: 0.00195% CI: [-0.6, 7]t-test, 2 sided
Comparison: The change is the post-baseline value minus the baseline value.~Null Hypothesis: change in GSS-SYMP-6 = 0p-value: 0.09795% CI: [-0.6, 7]t-test, 2 sided
Other Pre-specified
Change in Intra-ocular Pressure (IOP) for Worse Eye From Baseline to Week 4 and From Baseline to Week 8, in Patients Receiving Preservative-free Dorzolamide-timolol
IOP measurements using Goldmann applanation tonometry, performed by a masked physician two hours after patient was administered study medication. Change is computed as week 4 (or week 8) value minus baseline value.
Time frame: Baseline to Week 4 and from Baseline to Week 8
Population: 176 patients qualified for inclusion in the intent to treat (ITT) analysis and completed the first visit. Observations on IOP were available for 164 and 166 patients at week 4 and 8 respectively
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Preservative-free Dorzolamide-timolol (COSOPT®) Week 4 | Change in Intra-ocular Pressure (IOP) for Worse Eye From Baseline to Week 4 and From Baseline to Week 8, in Patients Receiving Preservative-free Dorzolamide-timolol | -11.7 mm Hg | Standard Deviation 5.1 |
| Preservative-free Dorzolamide-timolol (COSOPT®) Week 8 | Change in Intra-ocular Pressure (IOP) for Worse Eye From Baseline to Week 4 and From Baseline to Week 8, in Patients Receiving Preservative-free Dorzolamide-timolol | -11.5 mm Hg | Standard Deviation 5.3 |
Comparison: The change is the post-baseline value minus the baseline value.~Null Hypothesis: change in IOP = -4p-value: <0.00195% CI: [-12.3, -10.7]t-test, 2 sided
Comparison: The change is the post-baseline value minus the baseline value.~Null Hypothesis: change in IOP = 0p-value: <0.00195% CI: [-12.3, -10.7]t-test, 2 sided
Other Pre-specified
Patient's Global Satisfaction
At week 8, patients were asked to complete a single question describing how satisfied they were regarding with their medication, on a 5-level scale: very satisfied, satisfied, neither satisfied or dissatisfied, dissatisfied, very dissatisfied.
Time frame: Week 8
Population: 178 - number of patients that signed the consent form and received at least one dose of study medication. The number of patients analyzed (n=176) differs from the initial tables because 2 patients withdrew consent and for whom no data were available at subsequent visits (only baseline characteristics were available).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Preservative-free Dorzolamide-timolol (COSOPT®) Week 4 | Patient's Global Satisfaction | Very Satisfied | 79 Participants |
| Preservative-free Dorzolamide-timolol (COSOPT®) Week 4 | Patient's Global Satisfaction | Satisfied | 65 Participants |
| Preservative-free Dorzolamide-timolol (COSOPT®) Week 4 | Patient's Global Satisfaction | Neither Satisfied or Dissatisfied | 11 Participants |
| Preservative-free Dorzolamide-timolol (COSOPT®) Week 4 | Patient's Global Satisfaction | Dissatisfied | 6 Participants |
| Preservative-free Dorzolamide-timolol (COSOPT®) Week 4 | Patient's Global Satisfaction | Very Dissatisfied | 3 Participants |
| Preservative-free Dorzolamide-timolol (COSOPT®) Week 4 | Patient's Global Satisfaction | Missing | 6 Participants |
Other Pre-specified
Physician's Global Satisfaction
At week 8, physicians were asked to complete a single question describing how satisfied they were regarding their patient's treatment, on a 5-level scale: very satisfied, satisfied, neither satisfied or dissatisfied, dissatisfied, very dissatisfied.
Time frame: Week 8
Population: 178 - number of patients that signed the consent form and received at least one dose of study medication. The number of patients analyzed (n=176) differs from the initial tables because 2 patients withdrew consent and for whom no data were available at subsequent visits (only baseline characteristics were available).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Preservative-free Dorzolamide-timolol (COSOPT®) Week 4 | Physician's Global Satisfaction | Missing | 3 Participants |
| Preservative-free Dorzolamide-timolol (COSOPT®) Week 4 | Physician's Global Satisfaction | Very Satisfied | 130 Participants |
| Preservative-free Dorzolamide-timolol (COSOPT®) Week 4 | Physician's Global Satisfaction | Satisfied | 52 Participants |
| Preservative-free Dorzolamide-timolol (COSOPT®) Week 4 | Physician's Global Satisfaction | Neither Satisfied or Dissatisfied | 5 Participants |
| Preservative-free Dorzolamide-timolol (COSOPT®) Week 4 | Physician's Global Satisfaction | Dissatisfied | 5 Participants |
| Preservative-free Dorzolamide-timolol (COSOPT®) Week 4 | Physician's Global Satisfaction | Very Dissatisfied | 2 Participants |