Safety and Efficacy Assessment of Monoprost® in Comparison With Lumigan® 0.01 % and Lumigan® 0.03% Unit Dose

• Sponsor: Laboratoires Thea (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02017327
• Collaborator: (none)
• Enrollment: 379
• Location: 1
• Arms: 3
• Duration (Months): 31
• Patients Per Site Per Month: 12.2

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
Primary Open Angle Glaucoma; Ocular Hypertension	Drug: Monoprost; Drug: Lumigan 0.01%; Drug: Lumigan 0.03% Unit Dose	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 379 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Investigator)
• Primary Purpose: Treatment
• Official Title: Safety and Efficacy Assessment of Monoprost® in Comparison With Lumigan® 0.01% and Lumigan® 0.03% Unit Dose, in Patients With Primary Open Angle Glaucoma or Ocular Hypertension, Stabilized by Lumigan® 0.01% With Ocular Surface Intolerance
• Study Start Date: Dec 1, 2013
• Actual Primary Completion Date: Jul 1, 2016
• Actual Study Completion Date: Jul 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Monoprost 1 drop in each eye once daily at 9.00 pm (± 1 hour) for 3 months.	Drug: 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.; Other Names: Latanoprost 0.005%
Active Comparator: Lumigan 0.01% 1 drop in each eye once daily at 9.00 pm (± 1 hour) for 3 months.	Drug: Lumigan 0.01%; Lumigan® 0.01%: Bimatoprost eye drop solution is supplied in 3 ml multidose container.; Other Names: Bimatoprost 0.1mg/ml
Active Comparator: Lumigan 0.03% Unit Dose 1 drop in each eye once daily at 9.00 pm (± 1 hour) for 3 months.	Drug: 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.; Other Names: Bimatoprost 0.3mg/ML

Outcome Measures

Primary Outcome Measures

1. 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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts 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/ exclusion criteria

• Non-controlled diabetic patient.

• Known or suspected hypersensitivity to one of the components of the study product.

• Any medical or surgical history, disorder or disease such as acute or chronic severe organic disease: hepatic, endocrine, neoplastic, haematological; immunosuppressive, infectious diseases, severe psychiatric illness, relevant cardiovascular abnormalities, etc… and/or any complicating factor or structural abnormality, judged by the investigator to be incompatible with the study.

Specific exclusion criteria for women

• Pregnancy, lactation.

• Childbearing potential woman who is not using a reliable method of contraception (oral contraceptive, intra-uterine device, subcutaneous contraceptive implant, vaginal ring, patch) and is not surgically sterilised.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Laboratoires Théa	Clermont ferrand		France	63000

Sponsors and Collaborators

• Laboratoires Thea

Investigators

• Principal Investigator: Christophe Baudouin, Professor, Hopital des XV-XX

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Laboratoires Thea
• ClinicalTrials.gov Identifier: NCT02017327
• Other Study ID Numbers: LT2345-PIV-02/13; 2013-001250-10
• First Posted: Dec 20, 2013
• Last Update Posted: Apr 2, 2020
• Last Verified: Feb 1, 2020

• Additional relevant MeSH terms: Glaucoma; Glaucoma, Open-Angle; Ocular Hypertension; Hypertension; Bimatoprost; Latanoprost

Study Results

Participant Flow

Recruitment Details	patients were enrolled at medical clinics from Dec 2013 to July 2016
Pre-assignment Detail	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

Arm/Group Title	Monoprost	Lumigan 0.01% (Bimatoprost Eye Drop Solution)	Lumigan 0.03% UD (Bimatoprost Eye Drop Solution)
Arm/Group Description	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.	1 drop in each eye once daily at 9.00 pm (± 1 hour) for 3 months. 3-mL multidose containers	one drop in each eye once daily at 9.00 pm (± 1 hour) in the inferior conjunctival cul-de-sac from D0 to D84. 0.4-mL single-use low density polyethylene (LDPE) containers.
Period Title: Overall Study
STARTED	122	125	132
COMPLETED	106	113	117
NOT COMPLETED	16	12	15

Baseline Characteristics

Arm/Group Title	Monoprost	Lumigan 0.01%	Lumigan 0.03% Unit Dose	Total
Arm/Group Description	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.	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.	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.	Total of all reporting groups
Overall Participants	119	124	130	373
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	46 38.7%	44 35.5%	48 36.9%	138 37%
>=65 years	73 61.3%	80 64.5%	82 63.1%	235 63%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	67.5 (9.9)	67.4 (10.3)	68.3 (10)	67.7 (10.1)
Sex: Female, Male (Count of Participants)
Female	70 58.8%	70 56.5%	78 60%	218 58.4%
Male	49 41.2%	54 43.5%	52 40%	155 41.6%
Region of Enrollment (participants) [Number]
France	24 20.2%	25 20.2%	26 20%	75 20.1%
Germany	14 11.8%	12 9.7%	15 11.5%	41 11%
Spain	50 42%	52 41.9%	51 39.2%	153 41%
United Kingdom	21 17.6%	24 19.4%	26 20%	71 19%
Greece	10 8.4%	11 8.9%	12 9.2%	33 8.8%

Outcome Measures

1. Primary Outcome

Title	Safety With Respect to the Assessment of Conjunctival Hyperaemia in the Worse Eye
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Monoprost	Lumigan 0.01%	Lumigan 0.03% Unit Dose
Arm/Group Description	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.	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.	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.
Measure Participants	112	118	124
change at D84 -3	4 3.4%	1 0.8%	5 3.8%
change at D84 - 2	29 24.4%	13 10.5%	19 14.6%
change at D84 -1	47 39.5%	59 47.6%	42 32.3%
change at D84 0	29 24.4%	39 31.5%	38 29.2%
change at D84 +1	2 1.7%	6 4.8%	17 13.1%
change at D84 +2	0 0%	0 0%	1 0.8%
missing data	1 0.8%	0 0%	2 1.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Monoprost, Lumigan 0.03% Unit Dose
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Monoprost, Lumigan 0.01%
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0045
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

Adverse Events

Time Frame	3 months
Arm/Group Title	Monoprost		Lumigan 0.01%		Lumigan 0.03% Unit Dose
Arm/Group Description	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.		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.		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.
All Cause Mortality
	Monoprost		Lumigan 0.01%		Lumigan 0.03% Unit Dose
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Monoprost		Lumigan 0.01%		Lumigan 0.03% Unit Dose
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/119 (2.5%)		2/124 (1.6%)		2/130 (1.5%)
Cardiac disorders
myocardial infarction	0/119 (0%)	0	1/124 (0.8%)	1	0/130 (0%)	0
Musculoskeletal and connective tissue disorders
intervetebral disk protrusion	1/119 (0.8%)	1	0/124 (0%)	0	0/130 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
prostate cancer	1/119 (0.8%)	1	0/124 (0%)	0	0/130 (0%)	0
breast neoplasm	1/119 (0.8%)	1	0/124 (0%)	0	0/130 (0%)	0
metastatic colon cancer	0/119 (0%)	0	0/124 (0%)	0	1/130 (0.8%)	1
Renal and urinary disorders
ureterolithiasis	0/119 (0%)	0	0/124 (0%)	0	1/130 (0.8%)	1
Vascular disorders
hypotension	0/119 (0%)	0	1/124 (0.8%)	1	0/130 (0%)	0
Other (Not Including Serious) Adverse Events
	Monoprost		Lumigan 0.01%		Lumigan 0.03% Unit Dose
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/119 (0%)		0/124 (0%)		0/130 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

All the results of the Trial are the sole and exclusive property of THEA, and cannot be used in whatever form without prior written agreement of THEA.