Efficacy and Safety of PRO-148 Versus Systane®, in Patients With Mild to Moderate Dry Eye

• Sponsor: Laboratorios Sophia S.A de C.V. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01657253
• Collaborator: (none)
• Enrollment: 183
• Location: 1
• Arms: 2
• Duration (Months): 17
• Patients Per Site Per Month: 10.8

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate efficacy and safety of the ophthalmic solution PRO-148 in the ocular surface of patients with mild to moderate dry eye compared with ophthalmic solution Systane®

Condition or Disease	Intervention/Treatment	Phase
Dry Eye	Drug: PRO-148; Drug: Systane	Phase 3

Detailed Description

Dry eye is a multifactorial disease of the tears and ocular surface that results in symptoms of discomfort, visual disturbance, and tear film instability with potential damage to the ocular surface. Current treatment is heavily weighted toward supplementation, stimulation, or preservation of aqueous tears. Artificial tears are one of the primary treatments for dry eye; it is mainly palliative and focuses on reducing the symptoms of discomfort to improve quality of life for a patient.

A phase III randomized double-blind clinical trial will be conducted to evaluate efficacy and safety of the ophthalmic solution PRO-148 in the ocular surface of patients with mild to moderate dry eye compared with ophthalmic solution Systane®. Patients will be randomized to receive one of the treatments for 60 days. Efficacy and safety measures will be performed at baseline and at 60 days after treatment

Study Design

• Study Type: Interventional
• Actual Enrollment: 183 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Randomized, Double-blind, Phase III Clinical Trial to Evaluate the Efficacy and Safety of PRO-148 Versus Systane®, in Patients With Mild to Moderate Dry Eye
• Study Start Date: Nov 1, 2013
• Actual Primary Completion Date: Feb 1, 2015
• Actual Study Completion Date: Apr 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: PRO-148 PRO-148 containing: xanthan gum and sulphate chondroitin, ophthalmic solution doses: 1 drop in each eye, quarter in day	Drug: PRO-148; Instill 1 drop in each eye four times a day, for 60 days; Other Names: PRO-148 (xanthan gum and sulphate chondroitin)
Active Comparator: Systane® Systane containing: polyethylene glycol 400 0.4%, propylene glycol 0.3% and hydroxypropyl guar doses: 1 drop in each eye, quarter in day	Drug: Systane; Instill 1 drop in each eye four times a day, for 60 days; Other Names: polyethyleneglycol 400, propyleneglycol, hydroxypropyl guar

Outcome Measures

Primary Outcome Measures

1. Ocular Surface Disease Index (OSDI©) Questionnaire [Day 60]

   Ocular Surface Disease Index (OSDI©) questionnaire , consists of 12 questions divided in 3 groups, Each question has a value that can go from 0 to 4 points according to the severity of the case: 0.None of the time, 1. Some of the time, 2.Half of the time, 3.most of the time and 4 all of the time. The points of all the questions will be used in the following formula for converted to a score of 0-100 : (sum of scores) x 25 / (# of questions answered), where 0 represents normality or non-symptomatology and 100 the most severe case. Will be used to measure the symptoms of dry eye disease by obtaining baseline data and comparing them against the last visit.

Secondary Outcome Measures

1. Schirmer Test [Day 60]

   Change from Baseline in Schirmer test after 60 days of treatment Schirmer test It is the technique most used to measure aqueous and at the same time the simplest tear secretion. It is carried out as follows: Without applying anesthesia, the patient is placed somewhere without much illumination, without applying anesthesia, a strip of filter paper of approximately 30 mm is placed, of which, 5 mm must go in the joint Of the middle and outer third of the lower eyelid. The patient is instructed to look forward and to blink normally. After 5 minutes the strips are removed and the wetting is recorded in millimeters. A test less than or equal to 6 mm is diagnostic of aqueous deficiency.The mean of the revisions by group will be compared at the baseline and final visit.

2. Tear Film Break up Time [Day 60]

   Change from Baseline in Tear film break up time after 60 days of treatment Tear film breakup time is the elapsed time from blinking to the first occurrence of a dry area in the cornea, visualized with the help of fluorescein staining. Measurement of tear film breakup time will be performed as follows: Fluorescein is instilled in the eye, the patient is asked to blink three times to distribute the dye and then set the eye to the front and do not blink while the examiner observes the cornea with cobalt blue light, looking for an area of tear film rupture, which is manifested by the appearance of a black island within the fluorescein green film. Normally film breakup time is 10 seconds or more and the minimum register may be 1 second, Under 10 seconds is considered abnormal.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Mild to moderate dry eye patients based on the Report of International Dry Eye Workshop (DEWS)

• OSDI score between 12 and 45

• Provided informed consent

Exclusion Criteria:

• Patients with one blind eye

• Visual acuity of 20/100 or worst in any eye

• Patients with any active ocular disease that would interfere with study interpretation

• Patients in treatment with any medication that could interfere with the study, contraindication of any medication used in the protocol

• Patients with history of hypersensitivity or contraindication for any drug used in the study

• Contact lens users

• Pregnant patients, at risk of pregnancy or breastfeeding

• Patients without birth control treatment

• Patients who had participated in any clinical trial in the last 90 days

• Legal or mentally disabled patients who could not give informed consent

• Patients who do not provide informed consent

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Consultorio privado	Guadalajara	Jalisco	Mexico	44600

Sponsors and Collaborators

• Laboratorios Sophia S.A de C.V.

Investigators

• Study Director: Leopoldo M Baiza-Durán, MD, Laboratorios Sophia S.A de C.V.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Laboratorios Sophia S.A de C.V.
• ClinicalTrials.gov Identifier: NCT01657253
• Other Study ID Numbers: SOPH148-0512/III
• First Posted: Aug 6, 2012
• Last Update Posted: Dec 15, 2017
• Last Verified: May 1, 2017

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Additional relevant MeSH terms: Dry Eye Syndromes; Keratoconjunctivitis Sicca

Study Results

Participant Flow

Recruitment Details	Recruitment period started since february 2014 to january 2015. sites of research: Private Medical Office, Ophthalmology Hospitals (nationals and internationals) Patients with: mild to moderate Dry eye age > 18 year old OSDI between 12 and 45 TBUT ≤ 10 seconds Schirmer test ≤ 10mm
Pre-assignment Detail	183 patients were enrolled at baseline, however, only 148 ended the period of intervention and 35 were excluded or deleted by different reasons.

Arm/Group Title	PRO-148	Systane®
Arm/Group Description	PRO-148 containing: xanthan gum and sulphate chondroitin, ophthalmic solution doses: 1 drop in each eye, quarter in day PRO-148: Instill 1 drop in each eye four times a day, for 60 days	Systane containing: polyethylene glycol 400 0.4%, propylene glycol 0.3% and hydroxypropyl guar doses: 1 drop in each eye, quarter in day Systane: Instill 1 drop in each eye four times a day, for 60 days
Period Title: Overall Study
STARTED	93	90
COMPLETED	76	72
NOT COMPLETED	17	18

Baseline Characteristics

Arm/Group Title	PRO-148	Systane®	Total
Arm/Group Description	PRO-148 containing: xanthan gum and sulphate chondroitin, ophthalmic solution doses: 1 drop in each eye, quarter in day PRO-148: Instill 1 drop in each eye four times a day, for 60 days	Systane containing: polyethylene glycol 400 0.4%, propylene glycol 0.3% and hydroxypropyl guar doses: 1 drop in each eye, quarter in day Systane: Instill 1 drop in each eye four times a day, for 60 days	Total of all reporting groups
Overall Participants	93	90	183
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	48.3 (16.0)	45.3 (13.8)	46.8 (14.9)
Sex: Female, Male (Count of Participants)
Female	67 72%	65 72.2%	132 72.1%
Male	26 28%	25 27.8%	51 27.9%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	93 100%	90 100%	183 100%
Not Hispanic or Latino	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
Mexico	59 63.4%	63 70%	122 66.7%
Chile	17 18.3%	15 16.7%	32 17.5%
Colombia	17 18.3%	12 13.3%	29 15.8%

Outcome Measures

1. Primary Outcome

Title	Ocular Surface Disease Index (OSDI©) Questionnaire
Description	Ocular Surface Disease Index (OSDI©) questionnaire , consists of 12 questions divided in 3 groups, Each question has a value that can go from 0 to 4 points according to the severity of the case: 0.None of the time, 1. Some of the time, 2.Half of the time, 3.most of the time and 4 all of the time. The points of all the questions will be used in the following formula for converted to a score of 0-100 : (sum of scores) x 25 / (# of questions answered), where 0 represents normality or non-symptomatology and 100 the most severe case. Will be used to measure the symptoms of dry eye disease by obtaining baseline data and comparing them against the last visit.
Time Frame	Day 60

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	PRO-148	Systane®
Arm/Group Description	PRO-148 containing: xanthan gum and sulphate chondroitin, ophthalmic solution doses: 1 drop in each eye, quarter in day PRO-148: Instill 1 drop in each eye four times a day, for 60 days	Systane containing: polyethylene glycol 400 0.4%, propylene glycol 0.3% and hydroxypropyl guar doses: 1 drop in each eye, quarter in day Systane: Instill 1 drop in each eye four times a day, for 60 days
Measure Participants	76	72
Measure eyes	152	144
baseline values	19.3 (7.4)	19.3 (7.5)
final values	7.3 (5.9)	7.9 (8.2)

2. Secondary Outcome

Title	Schirmer Test
Description	Change from Baseline in Schirmer test after 60 days of treatment Schirmer test It is the technique most used to measure aqueous and at the same time the simplest tear secretion. It is carried out as follows: Without applying anesthesia, the patient is placed somewhere without much illumination, without applying anesthesia, a strip of filter paper of approximately 30 mm is placed, of which, 5 mm must go in the joint Of the middle and outer third of the lower eyelid. The patient is instructed to look forward and to blink normally. After 5 minutes the strips are removed and the wetting is recorded in millimeters. A test less than or equal to 6 mm is diagnostic of aqueous deficiency.The mean of the revisions by group will be compared at the baseline and final visit.
Time Frame	Day 60

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	PRO-148	Systane®
Arm/Group Description	PRO-148 containing: xanthan gum and sulphate chondroitin, ophthalmic solution doses: 1 drop in each eye, quarter in day PRO-148: Instill 1 drop in each eye four times a day, for 60 days	Systane containing: polyethylene glycol 400 0.4%, propylene glycol 0.3% and hydroxypropyl guar doses: 1 drop in each eye, quarter in day Systane: Instill 1 drop in each eye four times a day, for 60 days
Measure Participants	76	72
Measure eyes	152	144
baseline values	6.4 (2.2)	6.5 (2.5)
final values	11.0 (6.6)	10.5 (5.6)

3. Secondary Outcome

Title	Tear Film Break up Time
Description	Change from Baseline in Tear film break up time after 60 days of treatment Tear film breakup time is the elapsed time from blinking to the first occurrence of a dry area in the cornea, visualized with the help of fluorescein staining. Measurement of tear film breakup time will be performed as follows: Fluorescein is instilled in the eye, the patient is asked to blink three times to distribute the dye and then set the eye to the front and do not blink while the examiner observes the cornea with cobalt blue light, looking for an area of tear film rupture, which is manifested by the appearance of a black island within the fluorescein green film. Normally film breakup time is 10 seconds or more and the minimum register may be 1 second, Under 10 seconds is considered abnormal.
Time Frame	Day 60

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	PRO-148	Systane®
Arm/Group Description	PRO-148 containing: xanthan gum and sulphate chondroitin, ophthalmic solution doses: 1 drop in each eye, quarter in day PRO-148: Instill 1 drop in each eye four times a day, for 60 days	Systane containing: polyethylene glycol 400 0.4%, propylene glycol 0.3% and hydroxypropyl guar doses: 1 drop in each eye, quarter in day Systane: Instill 1 drop in each eye four times a day, for 60 days
Measure Participants	76	72
Measure eyes	152	144
baseline values	5.5 (2.1)	5.2 (2.0)
final values	7.4 (2.9)	7.4 (2.7)

Adverse Events

Time Frame	The evaluation of serious and no serious adverse events was done during 15 months
Adverse Event Reporting Description	in each clinical visit, the ophthalmologist completed the case report and the adverse events format
Arm/Group Title	PRO-148		Systane®
Arm/Group Description	PRO-148 containing: xanthan gum and sulphate chondroitin, ophthalmic solution doses: 1 drop in each eye, quarter in day PRO-148: Instill 1 drop in each eye four times a day, for 60 days		Systane containing: polyethylene glycol 400 0.4%, propylene glycol 0.3% and hydroxypropyl guar doses: 1 drop in each eye, quarter in day Systane: Instill 1 drop in each eye four times a day, for 60 days
All Cause Mortality
	PRO-148		Systane®
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	PRO-148		Systane®
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/93 (0%)		1/90 (1.1%)
Cardiac disorders
heart attack	0/93 (0%)	0	1/90 (1.1%)	1
Other (Not Including Serious) Adverse Events
	PRO-148		Systane®
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	14/93 (15.1%)		5/90 (5.6%)
Eye disorders
Conjunctivitis	5/93 (5.4%)	5	0/90 (0%)	0
ocular burning sensation	3/93 (3.2%)	3	0/90 (0%)	0
Pruritus	2/93 (2.2%)	2	0/90 (0%)	0
Red eye	1/93 (1.1%)	1	0/90 (0%)	0
Change in the visual acuity	0/93 (0%)	0	1/90 (1.1%)	1
Musculoskeletal and connective tissue disorders
Back spasm	0/93 (0%)	0	1/90 (1.1%)	1
Lower back pain	1/93 (1.1%)	1	0/90 (0%)	0
Respiratory, thoracic and mediastinal disorders
rhinitis	1/93 (1.1%)	1	3/90 (3.3%)	3
Surgical and medical procedures
Dental extraction	1/93 (1.1%)	1	0/90 (0%)	0

Limitations/Caveats

The study was performed according to the clinical protocol.

More Information

Certain Agreements

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

All the information is confidential and exclusive property of the sponsor. Information can be revealed only to my staff and regulatory agencies or ethics committee. All the information from this protocol is confidential and exclusive property of the sponsor, it can not be revealed without written consent from the sponsor.