Glaucoma
Conditions
Brief summary
To assess the effectiveness of latanoprost 0.005% ophthalmic solution dosed once-daily and timolol 0.5% dosed twice-daily in paediatric subjects of 18 years of age or under who are diagnosed with glaucoma.
Interventions
DRUGTimolol
Timolol 0.5% dosed twice-daily
DRUGlatanoprost
Latanoprost 0.005% ophthalmic solution dosed once-daily
Sponsors
Pfizer's Upjohn has merged with Mylan to form Viatris Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
36 Weeks to 18 Years
Healthy volunteers
No
Inclusion criteria
* Male or female of 18 years of age or under * Diagnosis of glaucoma * IOP of 22 mmHg or above in at least 1 eye
Exclusion criteria
* Require surgery for acute angle closure * Have had prior cyclodestructive procedures * Have a history of ocular trauma or surgery in either eye within 3 months of the baseline visit
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Reduction From Baseline in Mean IOP at Week 12, Last Observation Carried Forward (LOCF) | Baseline, Week 12 | Calculated as Baseline IOP minus Week 12 IOP, LOCF. IOP measured using 1 of 3 methods: Goldmann applanation tonometry (preferred method, if feasible), Perkins tonometry, or TonoPen. IOP was measured twice and if the measurements were less than or equal to (≤) 2 millimeters of mercury (mmHg) of each other, the mean of the 2 readings was recorded as the IOP at that time point. Otherwise, a third IOP measurement was taken and the median IOP recorded. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Reduction From Baseline in Mean IOP at Week 4 | Baseline, Week 4 | Calculated as Baseline IOP minus Week 4 IOP (observed). IOP measured using 1 of 3 methods: Goldmann applanation tonometry (preferred method, if feasible), Perkins tonometry, or TonoPen. IOP was measured twice and if the measurements were ≤ 2 mmHg of each other, the mean of the 2 readings was recorded as the IOP at that time point. Otherwise, a third IOP measurement was taken and the median IOP recorded. |
| Reduction From Baseline in Mean IOP at Week 12 (Observed) | Baseline, Week 12 | Calculated as Baseline IOP minus Week 12 IOP (observed). IOP measured using 1 of 3 methods: Goldmann applanation tonometry (preferred method, if feasible), Perkins tonometry, or TonoPen. IOP was measured twice and if the measurements were ≤ 2 mmHg of each other, the mean of the 2 readings was recorded as the IOP at that time point. Otherwise, a third IOP measurement was taken and the median IOP recorded. |
| Mean IOP at Baseline | Baseline | IOP measured using 1 of 3 methods: Goldmann applanation tonometry (preferred method, if feasible), Perkins tonometry, or TonoPen. IOP was measured twice and if the measurements were ≤ 2 mmHg of each other, the mean of the 2 readings was recorded as the IOP at that time point. Otherwise, a third IOP measurement was taken and the median IOP recorded. |
| Mean IOP at Week 1 | Week 1 | IOP measured using 1 of 3 methods: Goldmann applanation tonometry (preferred method, if feasible), Perkins tonometry, or TonoPen. IOP was measured twice and if the measurements were ≤ 2 mmHg of each other, the mean of the 2 readings was recorded as the IOP at that time point. Otherwise, a third IOP measurement was taken and the median IOP recorded. |
| Reduction From Baseline in Mean IOP at Week 1 | Baseline, Week 1 | Calculated as Baseline IOP minus Week 1 IOP (observed). IOP measured using 1 of 3 methods: Goldmann applanation tonometry (preferred method, if feasible), Perkins tonometry, or TonoPen. IOP was measured twice and if the measurements were ≤ 2 mmHg of each other, the mean of the 2 readings was recorded as the IOP at that time point. Otherwise, a third IOP measurement was taken and the median IOP recorded. |
| Mean IOP at Week 12 | Week 12 | IOP measured using 1 of 3 methods: Goldmann applanation tonometry (preferred method, if feasible), Perkins tonometry, or TonoPen. IOP was measured twice and if the measurements were ≤ 2 mmHg of each other, the mean of the 2 readings was recorded as the IOP at that time point. Otherwise, a third IOP measurement was taken and the median IOP recorded. |
| Percentage of Participants With Greater Than or Equal to (≥) 15% IOP Reduction From Baseline at Both Weeks 4 and 12 | Baseline, Week 4, and Week 12 | Participants with ≥15% IOP reduction from baseline at both Week 4 and Week 12. Calculated as (post baseline IOP minus baseline IOP) divided by IOP, multiplied by 100%. IOP measured using 1 of 3 methods: Goldmann applanation tonometry (preferred method, if feasible), Perkins tonometry, or TonoPen. IOP was measured twice and if the measurements were ≤ 2 mmHg of each other, the mean of the 2 readings was recorded as the IOP at that time point. Otherwise, a third IOP measurement was taken and the median IOP recorded. |
| Percentage of Participants Discontinuing Therapy Due to a Drug-related Adverse Experience | Baseline through Week 12 | An investigator's causality assessment was the determination of whether there existed a reasonable possibility that the investigational product caused or contributed to an adverse event (AE). If the investigator did not know whether or not investigational product caused the event, then the event was handled as related to investigational product for reporting purposes. |
| Mean IOP at Week 4 | Week 4 | IOP measured using 1 of 3 methods: Goldmann applanation tonometry (preferred method, if feasible), Perkins tonometry, or TonoPen. IOP was measured twice and if the measurements were ≤ 2 mmHg of each other, the mean of the 2 readings was recorded as the IOP at that time point. Otherwise, a third IOP measurement was taken and the median IOP recorded. |
Countries
Belgium, Colombia, Czechia, France, Germany, India, Italy, Philippines, Poland, Portugal, Romania, Russia, Serbia, Slovakia, Slovenia, South Africa, Spain, Ukraine, United Kingdom, United States
Participant flow
Pre-assignment details
Randomization was stratified by age, diagnosis (congenital glaucoma \[PCG\] or non-congenital glaucoma \[non-PCG\], and intraocular pressure \[IOP\]) of the study eye at baseline.
Participants by arm
| Arm | Count |
|---|---|
| Timolol Timolol maleate ophthalmic solution; 1 drop of timolol 0.5% (or optionally 0.25% for participants younger than 3 years old) at approximately 8 AM and again at approximately 8 PM . | 69 |
| Latanoprost Latanoprost ophthalmic solution and vehicle; 1 drop of vehicle daily at approximately 8 AM and 1 drop (latanoprost 0.005%) daily at approximately 8 PM. | 68 |
| Total | 137 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 4 | 1 |
| Overall Study | Lack of Efficacy | 3 | 0 |
| Overall Study | Not treated | 1 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 3 |
Baseline characteristics
| Characteristic | Total | Latanoprost | Timolol |
|---|---|---|---|
| Age, Customized 0 to < 3 years | 34 Participants | 17 Participants | 17 Participants |
| Age, Customized 12 to 18 years | 48 Participants | 25 Participants | 23 Participants |
| Age, Customized 3 to less than (<) 12 years | 55 Participants | 26 Participants | 29 Participants |
| Sex: Female, Male Female | 71 Participants | 34 Participants | 37 Participants |
| Sex: Female, Male Male | 66 Participants | 34 Participants | 32 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 20 / 69 | 12 / 68 |
| serious Total, serious adverse events | 7 / 69 | 2 / 68 |
Outcome results
Primary
Reduction From Baseline in Mean IOP at Week 12, Last Observation Carried Forward (LOCF)
Calculated as Baseline IOP minus Week 12 IOP, LOCF. IOP measured using 1 of 3 methods: Goldmann applanation tonometry (preferred method, if feasible), Perkins tonometry, or TonoPen. IOP was measured twice and if the measurements were less than or equal to (≤) 2 millimeters of mercury (mmHg) of each other, the mean of the 2 readings was recorded as the IOP at that time point. Otherwise, a third IOP measurement was taken and the median IOP recorded.
Time frame: Baseline, Week 12
Population: Per Protocol (PP) Population: participants with no major protocol violations who received at least 1 week of study medication and had at least Week 1 IOP measurements. LOCF.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Timolol | Reduction From Baseline in Mean IOP at Week 12, Last Observation Carried Forward (LOCF) | 5.72 mmHg | Standard Error 0.81 |
| Latanoprost | Reduction From Baseline in Mean IOP at Week 12, Last Observation Carried Forward (LOCF) | 7.18 mmHg | Standard Error 0.81 |
Comparison: Null hypothesis: latanoprost inferior to timolol (0.5 percent \[%\] optionally 0.25% for participants younger than 3 years). Power calculation: assuming common standard deviation (7 mmHg), 110 participants have 84% power to demonstrate latanoprost not inferior to timolol within 3 mmHg margin, assuming latanoprost has 1 mmHg reduction more than timolol in mean change from baseline IOP.95% CI: [-0.81, 3.74]
Secondary
Mean IOP at Baseline
IOP measured using 1 of 3 methods: Goldmann applanation tonometry (preferred method, if feasible), Perkins tonometry, or TonoPen. IOP was measured twice and if the measurements were ≤ 2 mmHg of each other, the mean of the 2 readings was recorded as the IOP at that time point. Otherwise, a third IOP measurement was taken and the median IOP recorded.
Time frame: Baseline
Population: PP
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Timolol | Mean IOP at Baseline | 27.8 mmHg | Standard Deviation 6.18 |
| Latanoprost | Mean IOP at Baseline | 27.3 mmHg | Standard Deviation 5.46 |
Secondary
Mean IOP at Week 1
IOP measured using 1 of 3 methods: Goldmann applanation tonometry (preferred method, if feasible), Perkins tonometry, or TonoPen. IOP was measured twice and if the measurements were ≤ 2 mmHg of each other, the mean of the 2 readings was recorded as the IOP at that time point. Otherwise, a third IOP measurement was taken and the median IOP recorded.
Time frame: Week 1
Population: PP
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Timolol | Mean IOP at Week 1 | 21.7 mmHg | Standard Deviation 7.99 |
| Latanoprost | Mean IOP at Week 1 | 20.6 mmHg | Standard Deviation 6.38 |
Secondary
Mean IOP at Week 12
IOP measured using 1 of 3 methods: Goldmann applanation tonometry (preferred method, if feasible), Perkins tonometry, or TonoPen. IOP was measured twice and if the measurements were ≤ 2 mmHg of each other, the mean of the 2 readings was recorded as the IOP at that time point. Otherwise, a third IOP measurement was taken and the median IOP recorded.
Time frame: Week 12
Population: Evaluable participants in PP
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Timolol | Mean IOP at Week 12 | 19.8 mmHg | Standard Deviation 3.5 |
| Latanoprost | Mean IOP at Week 12 | 19.2 mmHg | Standard Deviation 5.87 |
Secondary
Mean IOP at Week 4
IOP measured using 1 of 3 methods: Goldmann applanation tonometry (preferred method, if feasible), Perkins tonometry, or TonoPen. IOP was measured twice and if the measurements were ≤ 2 mmHg of each other, the mean of the 2 readings was recorded as the IOP at that time point. Otherwise, a third IOP measurement was taken and the median IOP recorded.
Time frame: Week 4
Population: Evaluable participants in PP
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Timolol | Mean IOP at Week 4 | 21.5 mmHg | Standard Deviation 7.49 |
| Latanoprost | Mean IOP at Week 4 | 20.1 mmHg | Standard Deviation 6.82 |
Secondary
Percentage of Participants Discontinuing Therapy Due to a Drug-related Adverse Experience
An investigator's causality assessment was the determination of whether there existed a reasonable possibility that the investigational product caused or contributed to an adverse event (AE). If the investigator did not know whether or not investigational product caused the event, then the event was handled as related to investigational product for reporting purposes.
Time frame: Baseline through Week 12
Population: Intent to treat (ITT) population: all participants who were randomized into the study and received at least 1 dose of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Timolol | Percentage of Participants Discontinuing Therapy Due to a Drug-related Adverse Experience | 1.4 Percentage of particpants |
| Latanoprost | Percentage of Participants Discontinuing Therapy Due to a Drug-related Adverse Experience | 0 Percentage of particpants |
Secondary
Percentage of Participants With Greater Than or Equal to (≥) 15% IOP Reduction From Baseline at Both Weeks 4 and 12
Participants with ≥15% IOP reduction from baseline at both Week 4 and Week 12. Calculated as (post baseline IOP minus baseline IOP) divided by IOP, multiplied by 100%. IOP measured using 1 of 3 methods: Goldmann applanation tonometry (preferred method, if feasible), Perkins tonometry, or TonoPen. IOP was measured twice and if the measurements were ≤ 2 mmHg of each other, the mean of the 2 readings was recorded as the IOP at that time point. Otherwise, a third IOP measurement was taken and the median IOP recorded.
Time frame: Baseline, Week 4, and Week 12
Population: Evaluable participants in PP
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Timolol | Percentage of Participants With Greater Than or Equal to (≥) 15% IOP Reduction From Baseline at Both Weeks 4 and 12 | 52 Percentage of participants |
| Latanoprost | Percentage of Participants With Greater Than or Equal to (≥) 15% IOP Reduction From Baseline at Both Weeks 4 and 12 | 60 Percentage of participants |
p-value: 0.3315Cochran-Mantel-Haenszel
Secondary
Reduction From Baseline in Mean IOP at Week 1
Calculated as Baseline IOP minus Week 1 IOP (observed). IOP measured using 1 of 3 methods: Goldmann applanation tonometry (preferred method, if feasible), Perkins tonometry, or TonoPen. IOP was measured twice and if the measurements were ≤ 2 mmHg of each other, the mean of the 2 readings was recorded as the IOP at that time point. Otherwise, a third IOP measurement was taken and the median IOP recorded.
Time frame: Baseline, Week 1
Population: PP
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Timolol | Reduction From Baseline in Mean IOP at Week 1 | 6.02 mmHg | Standard Error 0.83 |
| Latanoprost | Reduction From Baseline in Mean IOP at Week 1 | 6.70 mmHg | Standard Error 0.84 |
95% CI: [-1.66, 3.02]
Secondary
Reduction From Baseline in Mean IOP at Week 12 (Observed)
Calculated as Baseline IOP minus Week 12 IOP (observed). IOP measured using 1 of 3 methods: Goldmann applanation tonometry (preferred method, if feasible), Perkins tonometry, or TonoPen. IOP was measured twice and if the measurements were ≤ 2 mmHg of each other, the mean of the 2 readings was recorded as the IOP at that time point. Otherwise, a third IOP measurement was taken and the median IOP recorded.
Time frame: Baseline, Week 12
Population: Evaluable participants in PP
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Timolol | Reduction From Baseline in Mean IOP at Week 12 (Observed) | 6.96 mmHg | Standard Error 0.68 |
| Latanoprost | Reduction From Baseline in Mean IOP at Week 12 (Observed) | 7.75 mmHg | Standard Error 0.66 |
95% CI: [-1.1, 2.67]
Secondary
Reduction From Baseline in Mean IOP at Week 4
Calculated as Baseline IOP minus Week 4 IOP (observed). IOP measured using 1 of 3 methods: Goldmann applanation tonometry (preferred method, if feasible), Perkins tonometry, or TonoPen. IOP was measured twice and if the measurements were ≤ 2 mmHg of each other, the mean of the 2 readings was recorded as the IOP at that time point. Otherwise, a third IOP measurement was taken and the median IOP recorded.
Time frame: Baseline, Week 4
Population: Evaluable participants in PP
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Timolol | Reduction From Baseline in Mean IOP at Week 4 | 5.37 mmHg | Standard Error 0.94 |
| Latanoprost | Reduction From Baseline in Mean IOP at Week 4 | 6.99 mmHg | Standard Error 0.92 |
95% CI: [-1, 4.25]