Primary Open Angle Glaucoma, Ocular Hypertension
Conditions
Brief summary
Primary objective: The primary objective is to demonstrate the superiority of Monoprost® versus Lumigan® 0.01% and Lumigan® 0.03% Unit Dose in term of safety with respect to the assessment of conjunctival hyperaemia in the worse eye at Day 84. The conjunctival hyperaemia will be scored using the MacMonnies photographic scale (0 to 5).
Interventions
DRUGMonoprost
Monoprost®: Latanoprost 0.005% ophthalmic preparation is a sterile unpreserved oil-based solution for topical ophthalmic use. It is supplied in 0.30 ml single use polyethylene containers. The batch numbers and reanalysis dates will be stated in the certificate of analysis.
DRUGLumigan 0.01%
Lumigan® 0.01%: Bimatoprost eye drop solution is supplied in 3 ml multidose container.
DRUGLumigan 0.03% Unit Dose
Lumigan® 0.03% Unit Dose: Bimatoprost eye drop solution is supplied in 0.4 ml single use low density polyethylene (LDPE) containers.
Sponsors
Laboratoires Thea
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Male or female aged ≥18 years old. * Written informed consent. * Association of the 3 following criteria: 1. Both eyes have primary open angle glaucoma or ocular hypertension already treated and controlled by mono-therapy of Lumigan® 0.01% since at least 3 months (according to European Glaucoma Society guidelines). 2. Intra Ocular Pressure ≤ 18 mm Hg in both eyes. 3. With local intolerance signs in at least one eye defined by the association of: 3.1 Hyperaemia = Grade (2) or (3) or (4) following the photographic MacMonnies scale. And 3.2.1 Presence of at least 2 symptoms with a level of severity ≥ 1 (= mild or moderate or severe) among the following 5 symptoms: irritation/burning, itching, tearing, eye dryness sensation, foreign body sensation. And/Or 3.2.2 Presence of at least 2 signs with a level of severity ≥ 1 (= mild or moderate or severe) among the following 3 signs: superficial punctate keratitis, blepharitis, eyelid skin darkness.
Exclusion criteria
* \- Presence of at least one severe objective sign among the following: * Global ocular staining with Oxford (0-15) grading scheme \>12. * Blepharitis (Grade 4: Very severe, i.e. eczematiform lesion). * Any ocular hypertension other than primary ocular hypertension or primary chronic open angle glaucoma (such as congenital, angle closure glaucoma, secondary glaucoma). * Visual field not performed or not available within the 6 months before inclusion visit. * Fundus not performed or not available within the 6 months before inclusion visit. * Advanced stage of glaucoma: * Absolute defect in the ten degrees central point of the visual field. * Severe visual field loss according to the investigator's best judgement. * Risk of visual field worsening as a consequence of participation in the trial according to the investigator's best judgement. * Best far corrected visual acuity ≤ 1/10. * History of trauma, infection, inflammation within the 3 months before inclusion visit. * Ongoing or known history of ocular allergy and/or uveitis and/or viral infection. * Severe dry eye (defined by severe epithelial erosions of the cornea and/or use of dry eye medication with a frequency exceeding 8 instillations / day). * Corneal ulceration. * Palpebral abnormalities not related to medical treatment study and incompatible with a good evaluation. * Any abnormality preventing accurate assessment e.g. reliable tonometry measurement, visual field examination. Systemic/non ophthalmic/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety With Respect to the Assessment of Conjunctival Hyperaemia in the Worse Eye | Day 84 | The primary endpoint is the change from baseline of conjunctival hyperaemia assessed on MacMonnies' 6 point ordinal scale, in the worse eye at the D84 visit. The primary statistical hypothesis tested is that Monoprost® is superior to Lumigan® 0.03% Unit Dose with regard to this primary endpoint, i.e. that in the worse eye the decrease from baseline in the MacMonnies 6 point ordinal scale is greater in the Monoprost® treated group than in the Lumigan® 0.03% Unit Dose group at the Day 84 visit. The conjunctival hyperaemia will be scored using the McMonnies photographic scale (0 to 5). The minimum score is 0 corresponding to a low hyperaemia and the maximum score is 5 corresponding to a higher hyperaemia. The Rows represent the number of participants with a change from Baseline to D84 corresponding to * decrease of 3 points * decrease of 2 points * no change, * increase of 2 points * increase of 1 point on Mc Monnies scale |
Countries
France
Participant flow
Recruitment details
patients were enrolled at medical clinics from Dec 2013 to July 2016
Pre-assignment details
the number of patients enrolled in 379 but as the primary Endpoint is Safety, the Baseline population is based on the safety Set and it corresponds to 373 patients
Participants by arm
| Arm | Count |
|---|---|
| Monoprost 1 drop in each eye once daily at 9.00 pm (± 1 hour) for 3 months.
Monoprost: Monoprost®: Latanoprost 0.005% ophthalmic preparation is a sterile unpreserved oil-based solution for topical ophthalmic use. It is supplied in 0.30 ml single use polyethylene containers. The batch numbers and reanalysis dates will be stated in the certificate of analysis. | 119 |
| Lumigan 0.01% 1 drop in each eye once daily at 9.00 pm (± 1 hour) for 3 months.
Lumigan 0.01%: Lumigan® 0.01%: Bimatoprost eye drop solution is supplied in 3 ml multidose container. | 124 |
| Lumigan 0.03% Unit Dose 1 drop in each eye once daily at 9.00 pm (± 1 hour) for 3 months.
Lumigan 0.03% Unit Dose: Lumigan® 0.03% Unit Dose: Bimatoprost eye drop solution is supplied in 0.4 ml single use low density polyethylene (LDPE) containers. | 130 |
| Total | 373 |
Baseline characteristics
| Characteristic | Monoprost | Lumigan 0.01% | Lumigan 0.03% Unit Dose | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 73 Participants | 80 Participants | 82 Participants | 235 Participants |
| Age, Categorical Between 18 and 65 years | 46 Participants | 44 Participants | 48 Participants | 138 Participants |
| Age, Continuous | 67.5 years STANDARD_DEVIATION 9.9 | 67.4 years STANDARD_DEVIATION 10.3 | 68.3 years STANDARD_DEVIATION 10 | 67.7 years STANDARD_DEVIATION 10.1 |
| Region of Enrollment France | 24 participants | 25 participants | 26 participants | 75 participants |
| Region of Enrollment Germany | 14 participants | 12 participants | 15 participants | 41 participants |
| Region of Enrollment Greece | 10 participants | 11 participants | 12 participants | 33 participants |
| Region of Enrollment Spain | 50 participants | 52 participants | 51 participants | 153 participants |
| Region of Enrollment United Kingdom | 21 participants | 24 participants | 26 participants | 71 participants |
| Sex: Female, Male Female | 70 Participants | 70 Participants | 78 Participants | 218 Participants |
| Sex: Female, Male Male | 49 Participants | 54 Participants | 52 Participants | 155 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 119 | 0 / 124 | 0 / 130 |
| serious Total, serious adverse events | 3 / 119 | 2 / 124 | 2 / 130 |
Outcome results
Primary
Safety With Respect to the Assessment of Conjunctival Hyperaemia in the Worse Eye
The primary endpoint is the change from baseline of conjunctival hyperaemia assessed on MacMonnies' 6 point ordinal scale, in the worse eye at the D84 visit. The primary statistical hypothesis tested is that Monoprost® is superior to Lumigan® 0.03% Unit Dose with regard to this primary endpoint, i.e. that in the worse eye the decrease from baseline in the MacMonnies 6 point ordinal scale is greater in the Monoprost® treated group than in the Lumigan® 0.03% Unit Dose group at the Day 84 visit. The conjunctival hyperaemia will be scored using the McMonnies photographic scale (0 to 5). The minimum score is 0 corresponding to a low hyperaemia and the maximum score is 5 corresponding to a higher hyperaemia. The Rows represent the number of participants with a change from Baseline to D84 corresponding to * decrease of 3 points * decrease of 2 points * no change, * increase of 2 points * increase of 1 point on Mc Monnies scale
Time frame: Day 84
Population: the primary analysis was performed in the mSAF.(All randomised patients of the Safety set with at least one eligible eye and with any safety information on treatment.)
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Monoprost | Safety With Respect to the Assessment of Conjunctival Hyperaemia in the Worse Eye | change at D84 - 2 | 29 Participants |
| Monoprost | Safety With Respect to the Assessment of Conjunctival Hyperaemia in the Worse Eye | change at D84 +1 | 2 Participants |
| Monoprost | Safety With Respect to the Assessment of Conjunctival Hyperaemia in the Worse Eye | change at D84 0 | 29 Participants |
| Monoprost | Safety With Respect to the Assessment of Conjunctival Hyperaemia in the Worse Eye | change at D84 -3 | 4 Participants |
| Monoprost | Safety With Respect to the Assessment of Conjunctival Hyperaemia in the Worse Eye | missing data | 1 Participants |
| Monoprost | Safety With Respect to the Assessment of Conjunctival Hyperaemia in the Worse Eye | change at D84 +2 | 0 Participants |
| Monoprost | Safety With Respect to the Assessment of Conjunctival Hyperaemia in the Worse Eye | change at D84 -1 | 47 Participants |
| Lumigan 0.01% | Safety With Respect to the Assessment of Conjunctival Hyperaemia in the Worse Eye | change at D84 0 | 39 Participants |
| Lumigan 0.01% | Safety With Respect to the Assessment of Conjunctival Hyperaemia in the Worse Eye | change at D84 -3 | 1 Participants |
| Lumigan 0.01% | Safety With Respect to the Assessment of Conjunctival Hyperaemia in the Worse Eye | change at D84 - 2 | 13 Participants |
| Lumigan 0.01% | Safety With Respect to the Assessment of Conjunctival Hyperaemia in the Worse Eye | change at D84 -1 | 59 Participants |
| Lumigan 0.01% | Safety With Respect to the Assessment of Conjunctival Hyperaemia in the Worse Eye | change at D84 +1 | 6 Participants |
| Lumigan 0.01% | Safety With Respect to the Assessment of Conjunctival Hyperaemia in the Worse Eye | change at D84 +2 | 0 Participants |
| Lumigan 0.01% | Safety With Respect to the Assessment of Conjunctival Hyperaemia in the Worse Eye | missing data | 0 Participants |
| Lumigan 0.03% Unit Dose | Safety With Respect to the Assessment of Conjunctival Hyperaemia in the Worse Eye | change at D84 +1 | 17 Participants |
| Lumigan 0.03% Unit Dose | Safety With Respect to the Assessment of Conjunctival Hyperaemia in the Worse Eye | change at D84 - 2 | 19 Participants |
| Lumigan 0.03% Unit Dose | Safety With Respect to the Assessment of Conjunctival Hyperaemia in the Worse Eye | missing data | 2 Participants |
| Lumigan 0.03% Unit Dose | Safety With Respect to the Assessment of Conjunctival Hyperaemia in the Worse Eye | change at D84 +2 | 1 Participants |
| Lumigan 0.03% Unit Dose | Safety With Respect to the Assessment of Conjunctival Hyperaemia in the Worse Eye | change at D84 0 | 38 Participants |
| Lumigan 0.03% Unit Dose | Safety With Respect to the Assessment of Conjunctival Hyperaemia in the Worse Eye | change at D84 -1 | 42 Participants |
| Lumigan 0.03% Unit Dose | Safety With Respect to the Assessment of Conjunctival Hyperaemia in the Worse Eye | change at D84 -3 | 5 Participants |
p-value: <0.0001Cochran-Mantel-Haenszel
p-value: 0.0045Cochran-Mantel-Haenszel