Trial Outcomes & Findings for Non-inferiority of PRO-067 Ophthalmic Solution vs GAAP Ofteno® in Glaucoma or Ocular Hypertension (NCT NCT02801617)

Last Updated: 2024-07-05

Results Overview

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.

Recruitment status

TERMINATED

Study phase

PHASE3

Target enrollment

116 participants

Primary outcome timeframe

the baseline visit (day 0), Cross Over Visit (day 30) and the final visit (day 60) for both sequences

Results posted on

2024-07-05

Participant Flow

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

Participant milestones

Participant milestones
Measure	Sequence 1 (PRO-067) 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.	Sequence 2 (GAAP Ofteno®) 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.
Overall Study STARTED	51	56
Overall Study COMPLETED	49	50
Overall Study NOT COMPLETED	2	6

Reasons for withdrawal

Reasons for withdrawal
Measure	Sequence 1 (PRO-067) 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.	Sequence 2 (GAAP Ofteno®) 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.
Overall Study Protocol Violation	2	6

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Sequence 1 (PRO-067) n=51 Participants 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.	Sequence 2 (GAAP Ofteno®) n=56 Participants 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 n=107 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Age, Categorical Between 18 and 65 years	30 Participants n=99 Participants	32 Participants n=107 Participants	62 Participants n=206 Participants
Age, Categorical >=65 years	21 Participants n=99 Participants	24 Participants n=107 Participants	45 Participants n=206 Participants
Sex: Female, Male Female	36 Participants n=99 Participants	47 Participants n=107 Participants	83 Participants n=206 Participants
Sex: Female, Male Male	15 Participants n=99 Participants	9 Participants n=107 Participants	24 Participants n=206 Participants
Race/Ethnicity, Customized Hispanic	51 Participants n=99 Participants	56 Participants n=107 Participants	107 Participants n=206 Participants

PRIMARY outcome

Timeframe: the baseline visit (day 0), Cross Over Visit (day 30) and the final visit (day 60) for both sequences

Population: by Protocol

Outcome measures

Outcome measures
Measure	Sequence A (PRO-067- GAAP Ofteno®) n=49 Participants 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.	Sequence B (GAAP Ofteno® - PRO-067) n=50 Participants 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.
Target Intraocular Pressure (TIOP) baseline visit	14.25 mmHg Standard Deviation 2.37	14.04 mmHg Standard Deviation 2.43
Target Intraocular Pressure (TIOP) Cross over visit	13.85 mmHg Standard Deviation 2.07	13.92 mmHg Standard Deviation 2.17
Target Intraocular Pressure (TIOP) final visit	13.99 mmHg Standard Deviation 2.46	14.07 mmHg Standard Deviation 2.37

PRIMARY outcome

Timeframe: it is evaluated from the baseline visit (day 1) to the security call (day 75)

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Sequence A (PRO-067- GAAP Ofteno®) n=51 Participants 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.	Sequence B (GAAP Ofteno® - PRO-067) n=56 Participants 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.
Number of Adverse Events.	24 adverse events	20 adverse events

SECONDARY outcome

Timeframe: at the basal visit (day 1) crossover visit (day 30) and final visit (day 60)

Population: analysis by protocol

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.

Outcome measures

Outcome measures
Measure	Sequence A (PRO-067- GAAP Ofteno®) n=49 Participants 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.	Sequence B (GAAP Ofteno® - PRO-067) n=50 Participants 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.
Percentage of Ocular Burning basal visit	20.7 percentage of Ocular burning	19.6 percentage of Ocular burning
Percentage of Ocular Burning Crossover visit	03.8 percentage of Ocular burning	25.0 percentage of Ocular burning
Percentage of Ocular Burning Final visit	10.3 percentage of Ocular burning	16.1 percentage of Ocular burning

SECONDARY outcome

Timeframe: basal visit (day 1), Crossover visit (day 30) and final visit (day 60)

Population: Analysis by protocol

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.

Outcome measures

Outcome measures
Measure	Sequence A (PRO-067- GAAP Ofteno®) n=49 Participants 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.	Sequence B (GAAP Ofteno® - PRO-067) n=50 Participants 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.
Percentage of Participants With Foreign Body Sensation basal visit (day 1)	20.7 percentage of patients with Foreign body	37.5 percentage of patients with Foreign body
Percentage of Participants With Foreign Body Sensation Crossover visit (day 30	24.1 percentage of patients with Foreign body	30.4 percentage of patients with Foreign body
Percentage of Participants With Foreign Body Sensation final visit (day 60)	17.2 percentage of patients with Foreign body	30.4 percentage of patients with Foreign body

SECONDARY outcome

Timeframe: basal visit (day 1), Crossover visit (day 30) and final visit (day 60)

Population: Analysis by protocol

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.

Outcome measures

Outcome measures
Measure	Sequence A (PRO-067- GAAP Ofteno®) n=49 Participants 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.	Sequence B (GAAP Ofteno® - PRO-067) n=50 Participants 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.
Percentage of Participants With Tearing Basal visit (day 1)	8.6 percentage of patients with tearing	5.4 percentage of patients with tearing
Percentage of Participants With Tearing Crossover visit (day 30)	8.6 percentage of patients with tearing	10.7 percentage of patients with tearing
Percentage of Participants With Tearing Final visit (day 60)	3.4 percentage of patients with tearing	7.1 percentage of patients with tearing

SECONDARY outcome

Timeframe: basal visit (day 1), Crossover visit (day 30) and final visit (day 60)

Population: Analysis by protocol

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.

Outcome measures

Outcome measures
Measure	Sequence A (PRO-067- GAAP Ofteno®) n=49 Participants 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.	Sequence B (GAAP Ofteno® - PRO-067) n=50 Participants 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.
Percentage of Participants With Chemosis basal visit (day 1)	3.4 percentage of patients with chemosis	7.1 percentage of patients with chemosis
Percentage of Participants With Chemosis Crossover visit (day 30)	0 percentage of patients with chemosis	0 percentage of patients with chemosis
Percentage of Participants With Chemosis final visit (day 60)	0 percentage of patients with chemosis	0 percentage of patients with chemosis

SECONDARY outcome

Timeframe: basal visit (day 1), Crossover visit (day 30) and final visit (day 60)

Population: Analysis by protocol

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.

Outcome measures

Outcome measures
Measure	Sequence A (PRO-067- GAAP Ofteno®) n=49 Participants 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.	Sequence B (GAAP Ofteno® - PRO-067) n=50 Participants 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.
Percentage of Participants With Hyperemia Basal Visit Moderate	5.2 percentage of patients with hyperemia	4.4 percentage of patients with hyperemia
Percentage of Participants With Hyperemia Cross Over Visit Very Mild	60.3 percentage of patients with hyperemia	51.8 percentage of patients with hyperemia
Percentage of Participants With Hyperemia Cross Over Visit Moderate	1.7 percentage of patients with hyperemia	3.6 percentage of patients with hyperemia
Percentage of Participants With Hyperemia Final visit Very Mild	67.2 percentage of patients with hyperemia	69.6 percentage of patients with hyperemia
Percentage of Participants With Hyperemia Basal Visit Very Mild	53.4 percentage of patients with hyperemia	50.0 percentage of patients with hyperemia
Percentage of Participants With Hyperemia Basal Visit Mild	41.4 percentage of patients with hyperemia	43.9 percentage of patients with hyperemia
Percentage of Participants With Hyperemia Cross Over Visit Mild	37.9 percentage of patients with hyperemia	44.6 percentage of patients with hyperemia
Percentage of Participants With Hyperemia Final Visit Mild	32.8 percentage of patients with hyperemia	23.2 percentage of patients with hyperemia
Percentage of Participants With Hyperemia Final Visit Moderate	0 percentage of patients with hyperemia	7.1 percentage of patients with hyperemia

Adverse Events

PRO-067

Serious events: 0 serious events

Other events: 24 other events

Deaths: 0 deaths

GAAP Ofteno®

Serious events: 0 serious events

Other events: 20 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Dr. Oscar Olvera

Laboratorios Sophia

Phone: (33) 3001 4200

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: OTHER

Measure	PRO-067 n=51 participants at risk PRO-067,QD for 60 days. Includes both periods of PRO-067 in sequence A and B.	GAAP Ofteno® n=56 participants at risk GAAP Ofteno®, QD for 60 days. Includes both periods of PRO-067 in sequence A and B.
Eye disorders Conjuntivitis	3.9% 2/51 • Number of events 2 • Adverse events were monitored during 75 days, from the baseline visit (day 1) to the safety call (day 75)	8.9% 5/56 • Number of events 5 • Adverse events were monitored during 75 days, from the baseline visit (day 1) to the safety call (day 75)
Skin and subcutaneous tissue disorders itching	3.9% 2/51 • Number of events 2 • Adverse events were monitored during 75 days, from the baseline visit (day 1) to the safety call (day 75)	0.00% 0/56 • Adverse events were monitored during 75 days, from the baseline visit (day 1) to the safety call (day 75)
Gastrointestinal disorders gastritis	2.0% 1/51 • Number of events 1 • Adverse events were monitored during 75 days, from the baseline visit (day 1) to the safety call (day 75)	0.00% 0/56 • Adverse events were monitored during 75 days, from the baseline visit (day 1) to the safety call (day 75)
Musculoskeletal and connective tissue disorders low back pain	2.0% 1/51 • Number of events 1 • Adverse events were monitored during 75 days, from the baseline visit (day 1) to the safety call (day 75)	0.00% 0/56 • Adverse events were monitored during 75 days, from the baseline visit (day 1) to the safety call (day 75)
Renal and urinary disorders urinary tract infection	5.9% 3/51 • Number of events 3 • Adverse events were monitored during 75 days, from the baseline visit (day 1) to the safety call (day 75)	1.8% 1/56 • Number of events 1 • Adverse events were monitored during 75 days, from the baseline visit (day 1) to the safety call (day 75)
Ear and labyrinth disorders vertigo	2.0% 1/51 • Number of events 1 • Adverse events were monitored during 75 days, from the baseline visit (day 1) to the safety call (day 75)	0.00% 0/56 • Adverse events were monitored during 75 days, from the baseline visit (day 1) to the safety call (day 75)
Respiratory, thoracic and mediastinal disorders rhinopharyngitis	7.8% 4/51 • Number of events 4 • Adverse events were monitored during 75 days, from the baseline visit (day 1) to the safety call (day 75)	5.4% 3/56 • Number of events 3 • Adverse events were monitored during 75 days, from the baseline visit (day 1) to the safety call (day 75)
Gastrointestinal disorders constipation	0.00% 0/51 • Adverse events were monitored during 75 days, from the baseline visit (day 1) to the safety call (day 75)	5.4% 3/56 • Number of events 3 • Adverse events were monitored during 75 days, from the baseline visit (day 1) to the safety call (day 75)
General disorders headache	5.9% 3/51 • Number of events 3 • Adverse events were monitored during 75 days, from the baseline visit (day 1) to the safety call (day 75)	1.8% 1/56 • Number of events 1 • Adverse events were monitored during 75 days, from the baseline visit (day 1) to the safety call (day 75)
Respiratory, thoracic and mediastinal disorders pneumonia	2.0% 1/51 • Number of events 1 • Adverse events were monitored during 75 days, from the baseline visit (day 1) to the safety call (day 75)	0.00% 0/56 • Adverse events were monitored during 75 days, from the baseline visit (day 1) to the safety call (day 75)
Eye disorders subconjunctival hemorrhage	2.0% 1/51 • Number of events 1 • Adverse events were monitored during 75 days, from the baseline visit (day 1) to the safety call (day 75)	5.4% 3/56 • Number of events 3 • Adverse events were monitored during 75 days, from the baseline visit (day 1) to the safety call (day 75)
General disorders Sleep disorder	2.0% 1/51 • Number of events 1 • Adverse events were monitored during 75 days, from the baseline visit (day 1) to the safety call (day 75)	0.00% 0/56 • Adverse events were monitored during 75 days, from the baseline visit (day 1) to the safety call (day 75)
Vascular disorders arterial hypertension	2.0% 1/51 • Number of events 1 • Adverse events were monitored during 75 days, from the baseline visit (day 1) to the safety call (day 75)	1.8% 1/56 • Number of events 1 • Adverse events were monitored during 75 days, from the baseline visit (day 1) to the safety call (day 75)
Musculoskeletal and connective tissue disorders ankle bruise	2.0% 1/51 • Number of events 1 • Adverse events were monitored during 75 days, from the baseline visit (day 1) to the safety call (day 75)	0.00% 0/56 • Adverse events were monitored during 75 days, from the baseline visit (day 1) to the safety call (day 75)
Gastrointestinal disorders dental process	0.00% 0/51 • Adverse events were monitored during 75 days, from the baseline visit (day 1) to the safety call (day 75)	3.6% 2/56 • Number of events 2 • Adverse events were monitored during 75 days, from the baseline visit (day 1) to the safety call (day 75)
Eye disorders spasm orbicularis oculi	2.0% 1/51 • Number of events 1 • Adverse events were monitored during 75 days, from the baseline visit (day 1) to the safety call (day 75)	0.00% 0/56 • Adverse events were monitored during 75 days, from the baseline visit (day 1) to the safety call (day 75)
Endocrine disorders hypercholesterolemia	0.00% 0/51 • Adverse events were monitored during 75 days, from the baseline visit (day 1) to the safety call (day 75)	1.8% 1/56 • Number of events 1 • Adverse events were monitored during 75 days, from the baseline visit (day 1) to the safety call (day 75)
Vascular disorders venous insufficiency	2.0% 1/51 • Number of events 1 • Adverse events were monitored during 75 days, from the baseline visit (day 1) to the safety call (day 75)	0.00% 0/56 • Adverse events were monitored during 75 days, from the baseline visit (day 1) to the safety call (day 75)