Trial Outcomes & Findings for Non-inferiority of PRO-122 Ophthalmic Solution vs KRYTANTEK Ofteno® in Glaucoma or Ocular Hypertension (CONFORTK) (NCT NCT03257813)

Last Updated: 2019-12-09

Results Overview

Intraocular pressure, Unit: Millimeters of mercury (mmHg) type of variable: Continuous, Measurement method: Goldman applanation tonometry. Normal intraocular pressure 11-21 mmHg. The change between the IOP of both groups was compared (sequence 1 versus sequence 2) of the data obtained at the end of each period (day 30 and day 60).

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

60 participants

Primary outcome timeframe

Change from Baseline intraocular pressure at day 30 and 60.

Results posted on

2019-12-09

Participant Flow

Participant milestones

Participant milestones
Measure	Group A In group A, therapy with Krytantek Ofteno® will be continued for 30 days, in which the subject will be retested and switched to a PRO-122 solution which will be used for 30 days until the 60th day, The final visit. PRO-122: 1 drop every 12 hours for 30 days of alternating treatment with 30 days Krytantek Ofteno®: 1 drop every 12 hours for 30 days of alternating treatment with 30 days	Group B In group B, therapy with Krytantek Ofteno® will be suspended and changes for PRO-122 for 30 days, in which the subject will be retested and later switched to Krytantek Ofteno® solution which will be used for 30 days until the 60th day, The final visit. PRO-122: 1 drop every 12 hours for 30 days of alternating treatment with 30 days Krytantek Ofteno®: 1 drop every 12 hours for 30 days of alternating treatment with 30 days
Overall Study STARTED	30	30
Overall Study COMPLETED	24	27
Overall Study NOT COMPLETED	6	3

Reasons for withdrawal

Reasons for withdrawal
Measure	Group A In group A, therapy with Krytantek Ofteno® will be continued for 30 days, in which the subject will be retested and switched to a PRO-122 solution which will be used for 30 days until the 60th day, The final visit. PRO-122: 1 drop every 12 hours for 30 days of alternating treatment with 30 days Krytantek Ofteno®: 1 drop every 12 hours for 30 days of alternating treatment with 30 days	Group B In group B, therapy with Krytantek Ofteno® will be suspended and changes for PRO-122 for 30 days, in which the subject will be retested and later switched to Krytantek Ofteno® solution which will be used for 30 days until the 60th day, The final visit. PRO-122: 1 drop every 12 hours for 30 days of alternating treatment with 30 days Krytantek Ofteno®: 1 drop every 12 hours for 30 days of alternating treatment with 30 days
Overall Study Protocol Violation	6	3

Baseline Characteristics

Non-inferiority of PRO-122 Ophthalmic Solution vs KRYTANTEK Ofteno® in Glaucoma or Ocular Hypertension (CONFORTK)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Group A n=30 Participants In group A, therapy with Krytantek Ofteno® will be continued for 30 days, in which the subject will be retested and switched to a PRO-122 solution which will be used for 30 days until the 60th day, The final visit. PRO-122: 1 drop every 12 hours for 30 days of alternating treatment with 30 days Krytantek Ofteno®: 1 drop every 12 hours for 30 days of alternating treatment with 30 days	Group B n=30 Participants In group B, therapy with Krytantek Ofteno® will be suspended and changes for PRO-122 for 30 days, in which the subject will be retested and later switched to Krytantek Ofteno® solution which will be used for 30 days until the 60th day, The final visit. PRO-122: 1 drop every 12 hours for 30 days of alternating treatment with 30 days Krytantek Ofteno®: 1 drop every 12 hours for 30 days of alternating treatment with 30 days	Total n=60 Participants Total of all reporting groups
Age, Continuous	68.43 years STANDARD_DEVIATION 8.86 • n=5 Participants	64.37 years STANDARD_DEVIATION 12.84 • n=7 Participants	66.44 years STANDARD_DEVIATION 11.17 • n=5 Participants
Sex: Female, Male Female	24 Participants n=5 Participants	21 Participants n=7 Participants	45 Participants n=5 Participants
Sex: Female, Male Male	6 Participants n=5 Participants	9 Participants n=7 Participants	15 Participants n=5 Participants
Race/Ethnicity, Customized hispanic	30 Participants n=5 Participants	30 Participants n=7 Participants	60 Participants n=5 Participants

PRIMARY outcome

Timeframe: Change from Baseline intraocular pressure at day 30 and 60.

Population: the statistical analysis was carried out taking into account each eye as a case number, therefore, each research subject could provide 2 cases.

Outcome measures

Outcome measures
Measure	Sequence A n=48 eyes First Period: PRO-122: 1 drop every 12 hours for 30 days of alternating treatment with 30 days Second Period: Krytantek Ofteno®: 1 drop every 12 hours for 30 days of alternating treatment with 30 days	Sequence B n=54 eyes First Period: Krytantek Ofteno®: 1 drop every 12 hours for 30 days of alternating treatment with 30 days Second Period: PRO-122: 1 drop every 12 hours for 30 days of alternating treatment with 30 days
Intraocular Pressure (IOP) basal visit (day 1)	13.60 mmHg Standard Deviation 2.9	12.13 mmHg Standard Deviation 1.8
Intraocular Pressure (IOP) Crossover visit (day 30)	13.19 mmHg Standard Deviation 3.2	11.80 mmHg Standard Deviation 2.1
Intraocular Pressure (IOP) Final visit (day 60)	12.60 mmHg Standard Deviation 3.0	11.24 mmHg Standard Deviation 1.6

SECONDARY outcome

Timeframe: Visual Acuity at Baseline (day 1) crossover visit (day 30) and final visit (day 60)

Population: the statistical analysis was carried out taking into account each eye as a case number, therefore, each research subject could provide 2 cases.

The VA will be evaluated basally, without refractive correction with the Snellen chart. A Snellen chart is placed at a standard distance: 20 ft. At this distance, the symbols on the line representing "normal" acuity subtend. This line, designated 20/20 is the smallest line that a person with normal acuity can read at a distance of 20fs. the scale consists of 11 lines of letters of different size, the size of the letter gives a fractional value according to the visual acuity of the patient, the value is inversely proportional to the visual acuity, if the denominator is greater the visual acuity will be less. Line 1: 20/200 Line 2: 20/100, Line 3: 20/70, line 4: 20/50, line 5: 20/40, Line 6: 20/30, line 7: 20/25, Line 8: 20/20, line 9: 20/15, line 10: 20/13, line 11: 20/10. the differences between groups in the basal, cross over and final visit will be evaluated.

Outcome measures

Outcome measures
Measure	Sequence A n=30 Participants First Period: PRO-122: 1 drop every 12 hours for 30 days of alternating treatment with 30 days Second Period: Krytantek Ofteno®: 1 drop every 12 hours for 30 days of alternating treatment with 30 days	Sequence B n=30 Participants First Period: Krytantek Ofteno®: 1 drop every 12 hours for 30 days of alternating treatment with 30 days Second Period: PRO-122: 1 drop every 12 hours for 30 days of alternating treatment with 30 days
Visual Acuity (VA) basal visit (day 1)	38.31 score on a scale Standard Error 3.577	39.48 score on a scale Standard Error 3.742
Visual Acuity (VA) Crossover visit (day 30)	36.85 score on a scale Standard Error 3.806	40.43 score on a scale Standard Error 3.753
Visual Acuity (VA) Final visit (day 60)	38.98 score on a scale Standard Error 3.717	35.50 score on a scale Standard Error 3.402

OTHER_PRE_SPECIFIED outcome

Timeframe: 75 days, includes the security call

Population: the statistical analysis was carried out taking into account each eye as a case number, therefore, each research subject could provide 2 cases. statistical analysis by intention to treat (ITT)

The presence of adverse events by percentage between groups will be evaluated. the scale is present or absent.

Outcome measures

Outcome measures
Measure	Sequence A n=120 eyes First Period: PRO-122: 1 drop every 12 hours for 30 days of alternating treatment with 30 days Second Period: Krytantek Ofteno®: 1 drop every 12 hours for 30 days of alternating treatment with 30 days	Sequence B n=120 eyes First Period: Krytantek Ofteno®: 1 drop every 12 hours for 30 days of alternating treatment with 30 days Second Period: PRO-122: 1 drop every 12 hours for 30 days of alternating treatment with 30 days
Adverse Events mild	55.6 percentage of adverse events	18.2 percentage of adverse events
Adverse Events moderate	44.4 percentage of adverse events	72.7 percentage of adverse events
Adverse Events severe	0 percentage of adverse events	9.1 percentage of adverse events

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline (day 1) crossover visit (day 30) and final visit (day 60)

Population: the statistical analysis was carried out taking into account each eye as a case number, therefore, each research subject could provide 2 cases.

the conjunctival hyperemia will be evaluated by the presence or absence of it and the percentage of affected by group will be reported.

Outcome measures

Outcome measures
Measure	Sequence A n=49 eyes First Period: PRO-122: 1 drop every 12 hours for 30 days of alternating treatment with 30 days Second Period: Krytantek Ofteno®: 1 drop every 12 hours for 30 days of alternating treatment with 30 days	Sequence B n=60 eyes First Period: Krytantek Ofteno®: 1 drop every 12 hours for 30 days of alternating treatment with 30 days Second Period: PRO-122: 1 drop every 12 hours for 30 days of alternating treatment with 30 days
Conjunctival Hyperemia basal visit (day 1)	39.6 percentage of eyes	11.1 percentage of eyes
Conjunctival Hyperemia Crossover visit (day 30)	37.5 percentage of eyes	25.9 percentage of eyes
Conjunctival Hyperemia Final visit (day 60)	20.8 percentage of eyes	13.0 percentage of eyes

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline (day 1) crossover visit (day 30) and final visit (day 60)

Population: the statistical analysis was carried out taking into account each eye as a case number, therefore, each research subject could provide 2 cases.

Chemosis: qualitative ordinal variable, will be evaluated by the presence or absence of it and the percentage of affected by group will be reported.

Outcome measures

Outcome measures
Measure	Sequence A n=49 eyes First Period: PRO-122: 1 drop every 12 hours for 30 days of alternating treatment with 30 days Second Period: Krytantek Ofteno®: 1 drop every 12 hours for 30 days of alternating treatment with 30 days	Sequence B n=50 eyes First Period: Krytantek Ofteno®: 1 drop every 12 hours for 30 days of alternating treatment with 30 days Second Period: PRO-122: 1 drop every 12 hours for 30 days of alternating treatment with 30 days
Chemosis basal visit (day 1)	0 percentage of chemosis	3.7 percentage of chemosis
Chemosis Crossover visit (day 30)	0 percentage of chemosis	3.7 percentage of chemosis
Chemosis Final visit (day 60)	0 percentage of chemosis	0 percentage of chemosis

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline (day 1) crossover visit (day 30) and final visit (day 60)

Population: the statistical analysis was carried out taking into account each eye as a case number, therefore, each research subject could provide 2 cases.

Eye ocular burning will be evaluated by the presence or absence of it and the number of affected by group will be reported.

Outcome measures

Outcome measures
Measure	Sequence A n=49 eyes First Period: PRO-122: 1 drop every 12 hours for 30 days of alternating treatment with 30 days Second Period: Krytantek Ofteno®: 1 drop every 12 hours for 30 days of alternating treatment with 30 days	Sequence B n=50 eyes First Period: Krytantek Ofteno®: 1 drop every 12 hours for 30 days of alternating treatment with 30 days Second Period: PRO-122: 1 drop every 12 hours for 30 days of alternating treatment with 30 days
Eye Burning basal visit (day 1)	16 number of eye burning	18 number of eye burning
Eye Burning Crossover visit (day 30)	12 number of eye burning	18 number of eye burning
Eye Burning Final visit (day 60)	14 number of eye burning	19 number of eye burning

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline (day 1) crossover visit (day 30) and final visit (day 60)

Population: the statistical analysis was carried out taking into account each eye as a case number, therefore, each research subject could provide 2 cases.

Tearing will be evaluated by the presence or absence of it and the number of affected by group will be reported

Outcome measures

Outcome measures
Measure	Sequence A n=49 eyes First Period: PRO-122: 1 drop every 12 hours for 30 days of alternating treatment with 30 days Second Period: Krytantek Ofteno®: 1 drop every 12 hours for 30 days of alternating treatment with 30 days	Sequence B n=50 eyes First Period: Krytantek Ofteno®: 1 drop every 12 hours for 30 days of alternating treatment with 30 days Second Period: PRO-122: 1 drop every 12 hours for 30 days of alternating treatment with 30 days
Number of Eyes With Tearing basal visit (day 1)	9 eyes	2 eyes
Number of Eyes With Tearing Crossover visit (day 30)	8 eyes	9 eyes
Number of Eyes With Tearing Final visit (day 60)	7 eyes	9 eyes

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline (day 1) crossover visit (day 30) and final visit (day 60)

Population: the statistical analysis was carried out taking into account each eye as a case number, therefore, each research subject could provide 2 cases.

Foreign body sensation will be evaluated by the presence or absence of it and the number of affected by group will be reported.

Outcome measures

Outcome measures
Measure	Sequence A n=30 Participants First Period: PRO-122: 1 drop every 12 hours for 30 days of alternating treatment with 30 days Second Period: Krytantek Ofteno®: 1 drop every 12 hours for 30 days of alternating treatment with 30 days	Sequence B n=30 Participants First Period: Krytantek Ofteno®: 1 drop every 12 hours for 30 days of alternating treatment with 30 days Second Period: PRO-122: 1 drop every 12 hours for 30 days of alternating treatment with 30 days
Number of Eyes With Foreign Body Sensation basal visit (day 1)	14 eyes	14 eyes
Number of Eyes With Foreign Body Sensation Crossover visit (day 30)	14 eyes	16 eyes
Number of Eyes With Foreign Body Sensation Final visit (day 60)	5 eyes	7 eyes

Adverse Events

PRO-122

Serious events: 0 serious events

Other events: 12 other events

Deaths: 0 deaths

Krytantek Ofteno®

Serious events: 1 serious events

Other events: 8 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	PRO-122 n=60 participants at risk All adverse events that occurred with the product under investigation PRO-122 were collected regardless of the sequence in which they participated. The 30 participants of both sequences received at least one dose of PRO-122, therefore 60 subjects exposed in this group are considered.	Krytantek Ofteno® n=60 participants at risk All adverse events that occurred with the product under investigation Krytantek Ofteno® were collected regardless of the sequence in which they participated. The 30 participants of both sequences received at least one dose of Krytantek Ofteno®, therefore 60 subjects exposed in this group are considered.
Gastrointestinal disorders acute gastritis	0.00% 0/60 • 2 months The study's e-CRF was designed to collect adverse events for each research product separately. The sequence or crossing of the products under investigation was not considered for the report of adverse events because it can be detected at what time the event occurs and directly link it to the product that was being administered at the same time.	1.7% 1/60 • Number of events 1 • 2 months The study's e-CRF was designed to collect adverse events for each research product separately. The sequence or crossing of the products under investigation was not considered for the report of adverse events because it can be detected at what time the event occurs and directly link it to the product that was being administered at the same time.

Other adverse events

Additional Information

Dr. Ricardo Llamas (clinical safety pharmacologist)

Laboratorios Sophia

Phone: 3001 4200

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: OTHER

Measure	PRO-122 n=60 participants at risk All adverse events that occurred with the product under investigation PRO-122 were collected regardless of the sequence in which they participated. The 30 participants of both sequences received at least one dose of PRO-122, therefore 60 subjects exposed in this group are considered.	Krytantek Ofteno® n=60 participants at risk All adverse events that occurred with the product under investigation Krytantek Ofteno® were collected regardless of the sequence in which they participated. The 30 participants of both sequences received at least one dose of Krytantek Ofteno®, therefore 60 subjects exposed in this group are considered.
General disorders headache	3.3% 2/60 • Number of events 2 • 2 months The study's e-CRF was designed to collect adverse events for each research product separately. The sequence or crossing of the products under investigation was not considered for the report of adverse events because it can be detected at what time the event occurs and directly link it to the product that was being administered at the same time.	0.00% 0/60 • 2 months The study's e-CRF was designed to collect adverse events for each research product separately. The sequence or crossing of the products under investigation was not considered for the report of adverse events because it can be detected at what time the event occurs and directly link it to the product that was being administered at the same time.
General disorders Meniere syndrome exacerbated	1.7% 1/60 • Number of events 1 • 2 months The study's e-CRF was designed to collect adverse events for each research product separately. The sequence or crossing of the products under investigation was not considered for the report of adverse events because it can be detected at what time the event occurs and directly link it to the product that was being administered at the same time.	0.00% 0/60 • 2 months The study's e-CRF was designed to collect adverse events for each research product separately. The sequence or crossing of the products under investigation was not considered for the report of adverse events because it can be detected at what time the event occurs and directly link it to the product that was being administered at the same time.
Ear and labyrinth disorders vertigo	1.7% 1/60 • Number of events 1 • 2 months The study's e-CRF was designed to collect adverse events for each research product separately. The sequence or crossing of the products under investigation was not considered for the report of adverse events because it can be detected at what time the event occurs and directly link it to the product that was being administered at the same time.	0.00% 0/60 • 2 months The study's e-CRF was designed to collect adverse events for each research product separately. The sequence or crossing of the products under investigation was not considered for the report of adverse events because it can be detected at what time the event occurs and directly link it to the product that was being administered at the same time.
Skin and subcutaneous tissue disorders atopic dermatitis	1.7% 1/60 • Number of events 1 • 2 months The study's e-CRF was designed to collect adverse events for each research product separately. The sequence or crossing of the products under investigation was not considered for the report of adverse events because it can be detected at what time the event occurs and directly link it to the product that was being administered at the same time.	0.00% 0/60 • 2 months The study's e-CRF was designed to collect adverse events for each research product separately. The sequence or crossing of the products under investigation was not considered for the report of adverse events because it can be detected at what time the event occurs and directly link it to the product that was being administered at the same time.
Respiratory, thoracic and mediastinal disorders rhinopharyngitis	6.7% 4/60 • Number of events 4 • 2 months The study's e-CRF was designed to collect adverse events for each research product separately. The sequence or crossing of the products under investigation was not considered for the report of adverse events because it can be detected at what time the event occurs and directly link it to the product that was being administered at the same time.	1.7% 1/60 • Number of events 1 • 2 months The study's e-CRF was designed to collect adverse events for each research product separately. The sequence or crossing of the products under investigation was not considered for the report of adverse events because it can be detected at what time the event occurs and directly link it to the product that was being administered at the same time.
Eye disorders allergic Blepharokeratoconjunctivitis	3.3% 2/60 • Number of events 2 • 2 months The study's e-CRF was designed to collect adverse events for each research product separately. The sequence or crossing of the products under investigation was not considered for the report of adverse events because it can be detected at what time the event occurs and directly link it to the product that was being administered at the same time.	0.00% 0/60 • 2 months The study's e-CRF was designed to collect adverse events for each research product separately. The sequence or crossing of the products under investigation was not considered for the report of adverse events because it can be detected at what time the event occurs and directly link it to the product that was being administered at the same time.
Gastrointestinal disorders pharyngitis tonsillitis	3.3% 2/60 • Number of events 2 • 2 months The study's e-CRF was designed to collect adverse events for each research product separately. The sequence or crossing of the products under investigation was not considered for the report of adverse events because it can be detected at what time the event occurs and directly link it to the product that was being administered at the same time.	1.7% 1/60 • Number of events 1 • 2 months The study's e-CRF was designed to collect adverse events for each research product separately. The sequence or crossing of the products under investigation was not considered for the report of adverse events because it can be detected at what time the event occurs and directly link it to the product that was being administered at the same time.
Musculoskeletal and connective tissue disorders maxillary traumatism	1.7% 1/60 • Number of events 1 • 2 months The study's e-CRF was designed to collect adverse events for each research product separately. The sequence or crossing of the products under investigation was not considered for the report of adverse events because it can be detected at what time the event occurs and directly link it to the product that was being administered at the same time.	0.00% 0/60 • 2 months The study's e-CRF was designed to collect adverse events for each research product separately. The sequence or crossing of the products under investigation was not considered for the report of adverse events because it can be detected at what time the event occurs and directly link it to the product that was being administered at the same time.
Eye disorders bacterial conjunctivitis	1.7% 1/60 • Number of events 1 • 2 months The study's e-CRF was designed to collect adverse events for each research product separately. The sequence or crossing of the products under investigation was not considered for the report of adverse events because it can be detected at what time the event occurs and directly link it to the product that was being administered at the same time.	1.7% 1/60 • Number of events 1 • 2 months The study's e-CRF was designed to collect adverse events for each research product separately. The sequence or crossing of the products under investigation was not considered for the report of adverse events because it can be detected at what time the event occurs and directly link it to the product that was being administered at the same time.
Musculoskeletal and connective tissue disorders ankle pain	1.7% 1/60 • Number of events 1 • 2 months The study's e-CRF was designed to collect adverse events for each research product separately. The sequence or crossing of the products under investigation was not considered for the report of adverse events because it can be detected at what time the event occurs and directly link it to the product that was being administered at the same time.	0.00% 0/60 • 2 months The study's e-CRF was designed to collect adverse events for each research product separately. The sequence or crossing of the products under investigation was not considered for the report of adverse events because it can be detected at what time the event occurs and directly link it to the product that was being administered at the same time.
Eye disorders Dotted Keratopathy	0.00% 0/60 • 2 months The study's e-CRF was designed to collect adverse events for each research product separately. The sequence or crossing of the products under investigation was not considered for the report of adverse events because it can be detected at what time the event occurs and directly link it to the product that was being administered at the same time.	5.0% 3/60 • Number of events 3 • 2 months The study's e-CRF was designed to collect adverse events for each research product separately. The sequence or crossing of the products under investigation was not considered for the report of adverse events because it can be detected at what time the event occurs and directly link it to the product that was being administered at the same time.
Gastrointestinal disorders stomach flu	1.7% 1/60 • Number of events 1 • 2 months The study's e-CRF was designed to collect adverse events for each research product separately. The sequence or crossing of the products under investigation was not considered for the report of adverse events because it can be detected at what time the event occurs and directly link it to the product that was being administered at the same time.	0.00% 0/60 • 2 months The study's e-CRF was designed to collect adverse events for each research product separately. The sequence or crossing of the products under investigation was not considered for the report of adverse events because it can be detected at what time the event occurs and directly link it to the product that was being administered at the same time.
Musculoskeletal and connective tissue disorders low back pain	1.7% 1/60 • Number of events 1 • 2 months The study's e-CRF was designed to collect adverse events for each research product separately. The sequence or crossing of the products under investigation was not considered for the report of adverse events because it can be detected at what time the event occurs and directly link it to the product that was being administered at the same time.	0.00% 0/60 • 2 months The study's e-CRF was designed to collect adverse events for each research product separately. The sequence or crossing of the products under investigation was not considered for the report of adverse events because it can be detected at what time the event occurs and directly link it to the product that was being administered at the same time.
Gastrointestinal disorders intestinal amebiasis	0.00% 0/60 • 2 months The study's e-CRF was designed to collect adverse events for each research product separately. The sequence or crossing of the products under investigation was not considered for the report of adverse events because it can be detected at what time the event occurs and directly link it to the product that was being administered at the same time.	1.7% 1/60 • Number of events 1 • 2 months The study's e-CRF was designed to collect adverse events for each research product separately. The sequence or crossing of the products under investigation was not considered for the report of adverse events because it can be detected at what time the event occurs and directly link it to the product that was being administered at the same time.
Cardiac disorders sinus bradycardia	0.00% 0/60 • 2 months The study's e-CRF was designed to collect adverse events for each research product separately. The sequence or crossing of the products under investigation was not considered for the report of adverse events because it can be detected at what time the event occurs and directly link it to the product that was being administered at the same time.	1.7% 1/60 • Number of events 1 • 2 months The study's e-CRF was designed to collect adverse events for each research product separately. The sequence or crossing of the products under investigation was not considered for the report of adverse events because it can be detected at what time the event occurs and directly link it to the product that was being administered at the same time.
Gastrointestinal disorders peptic acid disease	0.00% 0/60 • 2 months The study's e-CRF was designed to collect adverse events for each research product separately. The sequence or crossing of the products under investigation was not considered for the report of adverse events because it can be detected at what time the event occurs and directly link it to the product that was being administered at the same time.	1.7% 1/60 • Number of events 1 • 2 months The study's e-CRF was designed to collect adverse events for each research product separately. The sequence or crossing of the products under investigation was not considered for the report of adverse events because it can be detected at what time the event occurs and directly link it to the product that was being administered at the same time.