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Non-inferiority of PRO-067 Ophthalmic Solution vs GAAP Ofteno® in Glaucoma or Ocular Hypertension (COMPLIANCE)

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ClinicalTrials.gov Identifier: NCT02801617
Recruitment Status : Terminated (expiration time limit of recruitment)
First Posted : June 16, 2016
Results First Posted : October 28, 2019
Last Update Posted : October 28, 2019
Sponsor:
Information provided by (Responsible Party):
Laboratorios Sophia S.A de C.V.

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Crossover Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Conditions Primary Open Angle Glaucoma
Ocular Hypertension
Interventions Drug: PRO-067
Drug: GAAP Ofteno®
Enrollment 116
Recruitment Details The study raised 120 research subjects, only 116 were selected, 2 left the study before being evaluated for a total of 114. However, 7 subjects were eliminated by: closure of center 1, without monitoring 2, by loss of follow-up 2, non-compliance with inclusion criteria 1 and failure of scrutiny 1, leaving a total of 107 randomized research subjects
Pre-assignment Details  
Arm/Group Title Sequence 1 (PRO-067) Sequence 2 (GAAP Ofteno®)
Hide Arm/Group Description

study subjects will be allocated to receive PRO-067 QD for 30 days, after which they will be crossed over to the other medication (GAAP Ofteno®) for another 30 days. The Intraocular pressure-reducing effect of the medications will be assessed by the reduction in IOP after each medication compared to baseline.

Washout period: 21 hours

PRO-067: 1 drop QD during 30 days is a sterile ophthalmic solution formulated by Laboratorios Sophia S.A. de C.V.

GAAP Ofteno®: 1 drop QD during 30 days Active comparator, reference medication.

study subjects will be allocated to receive GAAP Ofteno® QD for 30 days, after which they will be crossed over to the other medication (PRO-067) for another 30 days. The Intraocular pressure-reducing effect of the medications will be assessed by the reduction in IOP after each medication compared to baseline.

Washout period: 21 hours

PRO-067: 1 drop QD during 30 days is a sterile ophthalmic solution formulated by Laboratorios Sophia S.A. de C.V.

GAAP Ofteno®: 1 drop QD during 30 days Active comparator, reference medication.

Period Title: Overall Study
Started 51 56
Completed 49 50
Not Completed 2 6
Reason Not Completed
Protocol Violation             2             6
Arm/Group Title Sequence 1 (PRO-067) Sequence 2 (GAAP Ofteno®) Total
Hide Arm/Group Description

60 study subjects will be allocated to receive PRO-067 QD for 30 days, after which they will be crossed over to the other medication (GAAP Ofteno®) for another 30 days. The Intraocular pressure-reducing effect of the medications will be assessed by the reduction in IOP after each medication compared to baseline.

Washout period: 21 hours

PRO-067: 1 drop QD during 30 days is a sterile ophthalmic solution formulated by Laboratorios Sophia S.A. de C.V.

GAAP Ofteno®: 1 drop QD during 30 days Active comparator, reference medication.

60 study subjects will be allocated to receive GAAP Ofteno® QD for 30 days, after which they will be crossed over to the other medication (PRO-067) for another 30 days. The Intraocular pressure-reducing effect of the medications will be assessed by the reduction in IOP after each medication compared to baseline.

Washout period: 21 hours

PRO-067: 1 drop QD during 30 days is a sterile ophthalmic solution formulated by Laboratorios Sophia S.A. de C.V.

GAAP Ofteno®: 1 drop QD during 30 days Active comparator, reference medication.

Total of all reporting groups
Overall Number of Baseline Participants 51 56 107
Hide Baseline Analysis Population Description
the estradistic analysis was performed by protocol for the primary variable and by intention to treat in tolerability and adverse events.
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 51 participants 56 participants 107 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
30
  58.8%
32
  57.1%
62
  57.9%
>=65 years
21
  41.2%
24
  42.9%
45
  42.1%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 51 participants 56 participants 107 participants
Female
36
  70.6%
47
  83.9%
83
  77.6%
Male
15
  29.4%
9
  16.1%
24
  22.4%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Hispanic Number Analyzed 51 participants 56 participants 107 participants
51
 100.0%
56
 100.0%
107
 100.0%
1.Primary Outcome
Title Target Intraocular Pressure (TIOP)
Hide Description Target Intraocular Pressure (TIOP): Efficacy of experimental drug or active comparator to maintain the IOP in a range at which a patient is likely to remain stable or at which worsening of glaucoma will be slow enough that the risk of additional intervention is not justified.The upper limit of intraocular pressure is: TIOP + 2 mmHg. The measurement of the TIOP in each treatment period.
Time Frame the baseline visit (day 0), Cross Over Visit (day 30) and the final visit (day 60) for both sequences
Hide Outcome Measure Data
Hide Analysis Population Description
by Protocol
Arm/Group Title Sequence A (PRO-067- GAAP Ofteno®) Sequence B (GAAP Ofteno® - PRO-067)
Hide Arm/Group Description:

First Period. PRO-067: 1 drop QD (per day) during 30 days is a sterile ophthalmic solution formulated by Laboratorios Sophia S.A. de C.V.

Second period. GAAP Ofteno®: 1 drop QD during 30 days Active comparator, reference medication.

Fist Period. GAAP Ofteno®: 1 drop QD (per day) during 30 days Active comparator, reference medication.

Second Period. PRO-067: 1 drop QD during 30 days is a sterile ophthalmic solution formulated by Laboratorios Sophia S.A. de C.V.

Overall Number of Participants Analyzed 49 50
Mean (Standard Deviation)
Unit of Measure: mmHg
baseline visit 14.25  (2.37) 14.04  (2.43)
Cross over visit 13.85  (2.07) 13.92  (2.17)
final visit 13.99  (2.46) 14.07  (2.37)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Sequence A (PRO-067- GAAP Ofteno®)
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments it will be considered not inferior if they keep the IOP goal with differences of no more than 2 mmHg analysis by protocol
Statistical Test of Hypothesis P-Value 0.861
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Sequence B (GAAP Ofteno® - PRO-067)
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments it will be considered not inferior if they keep the TIOP with differences of no more than 2 mmHg
Statistical Test of Hypothesis P-Value 0.890
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
2.Primary Outcome
Title Number of Adverse Events.
Hide Description

the two periods of PRO-067 of each sequence were grouped as well as those of GAAP to form two comparative groups of adverse events in each intervention. (PRO-067 vs. GAAP ofteno).

The number of adverse events presented throughout the study was evaluated with each study drug to make the comparison between groups.

Time Frame it is evaluated from the baseline visit (day 1) to the security call (day 75)
Hide Outcome Measure Data
Hide Analysis Population Description
intention-to-treat (ITT), all those subjects who received at least one dose of the investigational drugs were considered for the statistical analysis, having a total of 107 cases by intention to treat.
Arm/Group Title PRO-067 GAAP Ofteno®
Hide Arm/Group Description:
PRO-067,QD (per day) for 60 days. Includes both periods of PRO-067 in sequence A and B.
GAAP Ofteno® QD (per day) for 60 days. Includes both periods of GAAP in sequence A and B.
Overall Number of Participants Analyzed 51 56
Measure Type: Number
Unit of Measure: adverse events
24 20
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection PRO-067, GAAP Ofteno®
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments intention-to-treat analysis (ITT)
Statistical Test of Hypothesis P-Value 0.329
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
3.Secondary Outcome
Title Percentage of Ocular Burning
Hide Description the ocular burning of the study subjects was evaluated, during the baseline, crossover and final visit, the variable was described as present or absent, according to the case, in both groups. A Pearson´s chi-square test is performed in the crossover and final visit to compare the end of periods 1 and 2 between both study sequences.
Time Frame at the basal visit (day 1) crossover visit (day 30) and final visit (day 60)
Hide Outcome Measure Data
Hide Analysis Population Description
analysis by protocol
Arm/Group Title Sequence 1 (PRO-067) Sequence 2 (GAAP Ofteno®)
Hide Arm/Group Description:

Study subjects will be allocated to receive:

PRO-067: 1 drop QD (per day) during 30 days after GAAP Ofteno®: 1 drop QD during 30 days

Study subjects will be allocated to receive:

GAAP Ofteno®: 1 drop QD (per day) during 30 days after PRO-067: 1 drop QD during 30 days

Overall Number of Participants Analyzed 49 50
Measure Type: Number
Unit of Measure: percentage of Ocular burning
basal visit 20.7 19.6
Crossover visit 03.8 25.0
Final visit 10.3 16.1
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Sequence 1 (PRO-067), Sequence 2 (GAAP Ofteno®)
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments it will be considered not inferior if they keep the percentage of ocular burning with differences of no more than 20%
Statistical Test of Hypothesis P-Value 0.388
Comments [Not Specified]
Method Chi-squared, Corrected
Comments [Not Specified]
4.Secondary Outcome
Title Percentage of Participants With Foreign Body Sensation
Hide Description The foreign body sensation will be measured as present / absent according to each case. A Pearson´s chi-square test is performed in the crossover and final visit to compare the end of periods 1 and 2 between both study sequences.
Time Frame basal visit (day 1), Crossover visit (day 30) and final visit (day 60)
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis by protocol
Arm/Group Title Sequence A (PRO-067- GAAP Ofteno®) Sequence B (GAAP Ofteno® - PRO-067)
Hide Arm/Group Description:

First Period. PRO-067: 1 drop QD (per day) during 30 days is a sterile ophthalmic solution formulated by Laboratorios Sophia S.A. de C.V.

Second period. GAAP Ofteno®: 1 drop QD during 30 days Active comparator, reference medication.

Fist Period. GAAP Ofteno®: 1 drop QD (per day) during 30 days Active comparator, reference medication.

Second Period. PRO-067: 1 drop QD during 30 days is a sterile ophthalmic solution formulated by Laboratorios Sophia S.A. de C.V.

Overall Number of Participants Analyzed 49 50
Measure Type: Number
Unit of Measure: percentage of patients with Foreign body
basal visit (day 1) 20.7 37.5
Crossover visit (day 30 24.1 30.4
final visit (day 60) 17.2 30.4
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Sequence A (PRO-067- GAAP Ofteno®), Sequence B (GAAP Ofteno® - PRO-067)
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments it will be considered not inferior if they keep the percentage of ocular burning with differences of no more than 20%
Statistical Test of Hypothesis P-Value 0.125
Comments [Not Specified]
Method Chi-squared, Corrected
Comments [Not Specified]
5.Secondary Outcome
Title Percentage of Participants With Tearing
Hide Description The tearing will be measured as present / absent according to each case. A Pearson´s chi-square test is performed in the crossover and final visit to compare the end of periods 1 and 2 between both study sequences.
Time Frame basal visit (day 1), Crossover visit (day 30) and final visit (day 60)
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis by protocol
Arm/Group Title Sequence A (PRO-067- GAAP Ofteno®) Sequence B (GAAP Ofteno® - PRO-067)
Hide Arm/Group Description:

First Period. PRO-067: 1 drop QD (per day) during 30 days is a sterile ophthalmic solution formulated by Laboratorios Sophia S.A. de C.V.

Second period. GAAP Ofteno®: 1 drop QD during 30 days Active comparator, reference medication.

Fist Period. GAAP Ofteno®: 1 drop QD (per day) during 30 days Active comparator, reference medication.

Second Period. PRO-067: 1 drop QD during 30 days is a sterile ophthalmic solution formulated by Laboratorios Sophia S.A. de C.V.

Overall Number of Participants Analyzed 49 50
Measure Type: Number
Unit of Measure: percentage of patients with tearing
Basal visit (day 1) 8.6 5.4
Crossover visit (day 30) 8.6 10.7
Final visit (day 60) 3.4 7.1
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Sequence A (PRO-067- GAAP Ofteno®), Sequence B (GAAP Ofteno® - PRO-067)
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments it will be considered not inferior if they keep the percentage of ocular burning with differences of no more than 20%
Statistical Test of Hypothesis P-Value 0.434
Comments [Not Specified]
Method Chi-squared, Corrected
Comments [Not Specified]
6.Secondary Outcome
Title Percentage of Participants With Chemosis
Hide Description The chemosis will be measured as present / absent according to each case. A Pearson´s chi-square test is performed in the crossover and final visit to compare the end of periods 1 and 2 between both study sequences.
Time Frame basal visit (day 1), Crossover visit (day 30) and final visit (day 60)
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis by protocol
Arm/Group Title Sequence A (PRO-067- GAAP Ofteno®) Sequence B (GAAP Ofteno® - PRO-067)
Hide Arm/Group Description:

First Period. PRO-067: 1 drop QD (per day) during 30 days is a sterile ophthalmic solution formulated by Laboratorios Sophia S.A. de C.V.

Second period. GAAP Ofteno®: 1 drop QD during 30 days Active comparator, reference medication.

Fist Period. GAAP Ofteno®: 1 drop QD (per day) during 30 days Active comparator, reference medication.

Second Period. PRO-067: 1 drop QD during 30 days is a sterile ophthalmic solution formulated by Laboratorios Sophia S.A. de C.V.

Overall Number of Participants Analyzed 49 50
Measure Type: Number
Unit of Measure: percentage of patients with chemosis
basal visit (day 1) 3.4 7.1
Crossover visit (day 30) 0 0
final visit (day 60) 0 0
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Sequence A (PRO-067- GAAP Ofteno®), Sequence B (GAAP Ofteno® - PRO-067)
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments it will be considered not inferior if they keep the percentage of ocular burning with differences of no more than 20%
Statistical Test of Hypothesis P-Value 0
Comments [Not Specified]
Method Chi-squared, Corrected
Comments [Not Specified]
7.Secondary Outcome
Title Percentage of Participants With Hyperemia
Hide Description the hyperemia of the study subjects was evaluated, during the baseline, crossover and final visit, the variable was described as a scale of: absent, very mild, mild, moderate and severe, according to the case, in both groups. A Pearson´s chi-square test is performed in the crossover and final visit to compare the end of periods 1 and 2 between both study sequences.
Time Frame basal visit (day 1), Crossover visit (day 30) and final visit (day 60)
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis by protocol
Arm/Group Title Sequence A (PRO-067- GAAP Ofteno®) Sequence B (GAAP Ofteno® - PRO-067)
Hide Arm/Group Description:

First Period. PRO-067: 1 drop QD (per day) during 30 days is a sterile ophthalmic solution formulated by Laboratorios Sophia S.A. de C.V.

Second period. GAAP Ofteno®: 1 drop QD during 30 days Active comparator, reference medication.

Fist Period. GAAP Ofteno®: 1 drop QD (per day) during 30 days Active comparator, reference medication.

Second Period. PRO-067: 1 drop QD during 30 days is a sterile ophthalmic solution formulated by Laboratorios Sophia S.A. de C.V.

Overall Number of Participants Analyzed 49 50
Measure Type: Number
Unit of Measure: percentage of patients with hyperemia
Basal Visit Very Mild 53.4 50.0
Basal Visit Mild 41.4 43.9
Basal Visit Moderate 5.2 4.4
Cross Over Visit Very Mild 60.3 51.8
Cross Over Visit Mild 37.9 44.6
Cross Over Visit Moderate 1.7 3.6
Final visit Very Mild 67.2 69.6
Final Visit Mild 32.8 23.2
Final Visit Moderate 0 7.1
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Sequence A (PRO-067- GAAP Ofteno®), Sequence B (GAAP Ofteno® - PRO-067)
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments it will be considered not inferior if they keep the percentage of ocular burning with differences of no more than 20%
Statistical Test of Hypothesis P-Value 0.039
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Time Frame Adverse events were monitored during 75 days, from the baseline visit (day 1) to the safety call (day 75)
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title PRO-067 GAAP Ofteno®
Hide Arm/Group Description PRO-067,QD for 60 days. Includes both periods of PRO-067 in sequence A and B. GAAP Ofteno®, QD for 60 days. Includes both periods of PRO-067 in sequence A and B.
All-Cause Mortality
PRO-067 GAAP Ofteno®
Affected / at Risk (%) Affected / at Risk (%)
Total   0/51 (0.00%)      0/56 (0.00%)    
Hide Serious Adverse Events
PRO-067 GAAP Ofteno®
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/51 (0.00%)      0/56 (0.00%)    
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
PRO-067 GAAP Ofteno®
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   24/51 (47.06%)      20/56 (35.71%)    
Ear and labyrinth disorders     
vertigo *  1/51 (1.96%)  1 0/56 (0.00%)  0
Endocrine disorders     
hypercholesterolemia *  0/51 (0.00%)  0 1/56 (1.79%)  1
Eye disorders     
Conjuntivitis *  2/51 (3.92%)  2 5/56 (8.93%)  5
subconjunctival hemorrhage *  1/51 (1.96%)  1 3/56 (5.36%)  3
spasm orbicularis oculi *  1/51 (1.96%)  1 0/56 (0.00%)  0
Gastrointestinal disorders     
gastritis *  1/51 (1.96%)  1 0/56 (0.00%)  0
constipation *  0/51 (0.00%)  0 3/56 (5.36%)  3
dental process *  0/51 (0.00%)  0 2/56 (3.57%)  2
General disorders     
headache *  3/51 (5.88%)  3 1/56 (1.79%)  1
Sleep disorder *  1/51 (1.96%)  1 0/56 (0.00%)  0
Musculoskeletal and connective tissue disorders     
low back pain *  1/51 (1.96%)  1 0/56 (0.00%)  0
ankle bruise *  1/51 (1.96%)  1 0/56 (0.00%)  0
Renal and urinary disorders     
urinary tract infection *  3/51 (5.88%)  3 1/56 (1.79%)  1
Respiratory, thoracic and mediastinal disorders     
rhinopharyngitis *  4/51 (7.84%)  4 3/56 (5.36%)  3
pneumonia *  1/51 (1.96%)  1 0/56 (0.00%)  0
Skin and subcutaneous tissue disorders     
itching *  2/51 (3.92%)  2 0/56 (0.00%)  0
Vascular disorders     
arterial hypertension *  1/51 (1.96%)  1 1/56 (1.79%)  1
venous insufficiency *  1/51 (1.96%)  1 0/56 (0.00%)  0
*
Indicates events were collected by non-systematic assessment
The limitations of this study were its short duration (60 days) and the size of the groups that was reduced.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
 
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Dr. Oscar Olvera
Organization: Laboratorios Sophia
Phone: (33) 3001 4200 ext 1074
EMail: oscar.olvera@sophia.com.mx
Layout table for additonal information
Responsible Party: Laboratorios Sophia S.A de C.V.
ClinicalTrials.gov Identifier: NCT02801617    
Other Study ID Numbers: SOPH067-0914/III
First Submitted: June 13, 2016
First Posted: June 16, 2016
Results First Submitted: February 1, 2018
Results First Posted: October 28, 2019
Last Update Posted: October 28, 2019