Trial Outcomes & Findings for Treatment of Bacterial Conjunctivitis With SHP640 Compared to PVP-Iodine and Placebo (NCT NCT03004924)

NCT ID: NCT03004924

Last Updated: 2021-06-09

Results Overview

Clinical resolution was defined as absence (score=0) of bulbar conjunctival injection and ocular conjunctival discharge in the study eye. Bulbar conjunctival injection was assessed based on 0 (Normal conjunctival vascular pattern) - 4 (Markedly prominent, intense diffuse hyperemia) scale which used pictures from validated bulbar redness (VBR) scale. Ocular conjunctival discharge was assessed based on 0 (No evidence of discharge in conjunctiva) - 3 (Abundant quantity of mucopurulent or purulent discharge) scale. The study eye was defined as an eye with score of at least 1 for both ocular conjunctival discharge and bulbar conjunctival redness at baseline. Data analysis was performed in SHP640 and placebo reporting groups only but not in PVP-I 0.6%.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 753 participants
• Primary outcome timeframe: Day 5
• Results posted on: 2021-06-09

Participant Flow

Study was conducted at 121 centers in 14 countries between 29 Mar 2017 (first participant first visit) and 01 Oct 2018 (last participant last visit).

A total of 1080 participants were screened, of them 753 enrolled and randomized to treatment. One participant was randomized in error and therefore captured only in the intent-to-treat (ITT) population.

Participant milestones

Measure	SHP640 Participants administered 1 drop of SHP640 (povidone-iodine \[PVP-I\] 0.6 percent \[%\] and Dexamethasone 0.1%) ophthalmic suspension in each eye 4 times a day (QID) for 7 days.	PVP-I 0.6% Participants administered 1 drop of PVP-I 0.6% ophthalmic solution in each eye QID for 7 days.	Placebo Participants administered 1 drop of placebo ophthalmic solution in each eye QID for 7 days.
Overall Study STARTED	324	108	321
Overall Study COMPLETED	297	94	293
Overall Study NOT COMPLETED	27	14	28

Reasons for withdrawal

Measure	SHP640 Participants administered 1 drop of SHP640 (povidone-iodine \[PVP-I\] 0.6 percent \[%\] and Dexamethasone 0.1%) ophthalmic suspension in each eye 4 times a day (QID) for 7 days.	PVP-I 0.6% Participants administered 1 drop of PVP-I 0.6% ophthalmic solution in each eye QID for 7 days.	Placebo Participants administered 1 drop of placebo ophthalmic solution in each eye QID for 7 days.
Overall Study Adverse Event	6	5	10
Overall Study Protocol Violation	4	0	1
Overall Study Withdrawal by Subject	5	3	5
Overall Study Lost to Follow-up	6	1	4
Overall Study Lack of Efficacy	2	4	2
Overall Study Physician Decision	1	0	1
Overall Study Withdrawal by parent/guardian	1	0	2
Overall Study Screen Failure	1	0	0
Overall Study Pregnancy	0	1	0
Overall Study Terminated by Sponsor	0	0	1
Overall Study Missed Study Visit	0	0	2
Overall Study HSV1 Positive	1	0	0

Baseline Characteristics

Treatment of Bacterial Conjunctivitis With SHP640 Compared to PVP-Iodine and Placebo

Baseline characteristics by cohort

Measure	SHP640 n=324 Participants Participants administered 1 drop of SHP640 ophthalmic suspension in each eye QID for 7 days.	PVP-I 0.6% n=108 Participants Participants administered 1 drop of PVP-I 0.6% ophthalmic solution in each eye QID for 7 days.	Placebo n=321 Participants Participants administered 1 drop of placebo ophthalmic solution in each eye QID for 7 days.	Total n=753 Participants Total of all reporting groups
Age, Continuous	44.2 Years STANDARD_DEVIATION 22.87 • n=5 Participants	43.1 Years STANDARD_DEVIATION 23.03 • n=7 Participants	44.7 Years STANDARD_DEVIATION 23.00 • n=5 Participants	44.3 Years STANDARD_DEVIATION 22.92 • n=4 Participants
Sex: Female, Male Female	191 Participants n=5 Participants	71 Participants n=7 Participants	199 Participants n=5 Participants	461 Participants n=4 Participants
Sex: Female, Male Male	133 Participants n=5 Participants	37 Participants n=7 Participants	122 Participants n=5 Participants	292 Participants n=4 Participants
Race/Ethnicity, Customized Ethnicity · Hispanic or Latino	62 Participants n=5 Participants	30 Participants n=7 Participants	87 Participants n=5 Participants	179 Participants n=4 Participants
Race/Ethnicity, Customized Ethnicity · Not Hispanic or Latino	254 Participants n=5 Participants	76 Participants n=7 Participants	230 Participants n=5 Participants	560 Participants n=4 Participants
Race/Ethnicity, Customized Ethnicity · Not reported	4 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants	8 Participants n=4 Participants
Race/Ethnicity, Customized Ethnicity · Other	4 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants	6 Participants n=4 Participants
Race/Ethnicity, Customized Race · American Indian or Alaska Native	0 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants	4 Participants n=4 Participants
Race/Ethnicity, Customized Race · Asian	12 Participants n=5 Participants	0 Participants n=7 Participants	8 Participants n=5 Participants	20 Participants n=4 Participants
Race/Ethnicity, Customized Race · Black or African American	54 Participants n=5 Participants	18 Participants n=7 Participants	54 Participants n=5 Participants	126 Participants n=4 Participants
Race/Ethnicity, Customized Race · White	250 Participants n=5 Participants	88 Participants n=7 Participants	250 Participants n=5 Participants	588 Participants n=4 Participants
Race/Ethnicity, Customized Race · Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants	2 Participants n=4 Participants
Race/Ethnicity, Customized Race · Other	6 Participants n=5 Participants	1 Participants n=7 Participants	4 Participants n=5 Participants	11 Participants n=4 Participants
Race/Ethnicity, Customized Race · Multiple	2 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	2 Participants n=4 Participants

PRIMARY outcome

Timeframe: Day 5

Population: Modified intent-to-treat (mITT) population included participants who received at least one dose of investigational product (IP) and had a positive bacterial culture (presence of one or more bacterial species at or above pathological threshold) at baseline in the study. Analysis was done in SHP640 and placebo reporting groups only.

Clinical resolution was defined as absence (score=0) of bulbar conjunctival injection and ocular conjunctival discharge in the study eye. Bulbar conjunctival injection was assessed based on 0 (Normal conjunctival vascular pattern) - 4 (Markedly prominent, intense diffuse hyperemia) scale which used pictures from validated bulbar redness (VBR) scale. Ocular conjunctival discharge was assessed based on 0 (No evidence of discharge in conjunctiva) - 3 (Abundant quantity of mucopurulent or purulent discharge) scale. The study eye was defined as an eye with score of at least 1 for both ocular conjunctival discharge and bulbar conjunctival redness at baseline. Data analysis was performed in SHP640 and placebo reporting groups only but not in PVP-I 0.6%.

Outcome measures

Measure	PVP-I 0.6% Participants administered 1 drop of PVP-I 0.6% ophthalmic solution in each eye QID for 7 days.	SHP640 n=220 Participants Participants administered 1 drop of SHP640 (povidone-iodine \[PVP-I\] 0.6 percent \[%\] and Dexamethasone 0.1%) ophthalmic suspension in each eye 4 times a day (QID) for 7 days.	Placebo n=222 Participants Participants administered 1 drop of placebo ophthalmic solution in each eye QID for 7 days.
Number of Participants With Clinical Resolution Among Who Received SHP640 or Placebo on Day 5	0 Participants	111 Participants	95 Participants

SECONDARY outcome

Timeframe: Baseline, Day 5

Population: mITT population included participants who received at least one dose of IP and had a positive bacterial culture (presence of one or more bacterial species at or above pathological threshold) at baseline in the study. Here, the number of participants analyzed refer to the participants evaluable for this outcome at specified time point.

Bacterial eradication was defined as absence of all bacterial species present at or above pathological threshold at baseline in the study eye. Bacterial species were identified by Matrix Assisted Laser Desorption/Ionization-Time of Flight Mass Spectrometry, using their unique protein patterns. Pathological threshold for individual bacterial species was based on colony-forming unit (CFU)/mL threshold levels established by Cagle and modified by Leibowitz for different ocular bacterial species found in the specimens collected from each participant. Data analysis was performed in SHP640 and placebo reporting groups only but not in PVP-I 0.6%.

Outcome measures

Measure	PVP-I 0.6% Participants administered 1 drop of PVP-I 0.6% ophthalmic solution in each eye QID for 7 days.	SHP640 n=217 Participants Participants administered 1 drop of SHP640 (povidone-iodine \[PVP-I\] 0.6 percent \[%\] and Dexamethasone 0.1%) ophthalmic suspension in each eye 4 times a day (QID) for 7 days.	Placebo n=218 Participants Participants administered 1 drop of placebo ophthalmic solution in each eye QID for 7 days.
Number of Participants With Bacterial Eradication Among Who Received SHP640 or Placebo on Day 5	0 Participants	94 Participants	102 Participants

SECONDARY outcome

Timeframe: Day 3, 8 and 12

Population: mITT population included participants who received at least one dose of IP and had a positive bacterial culture (presence of one or more bacterial species at or above pathological threshold) at baseline in the study. Here, the number of participants analyzed refer to the participants evaluable for this outcome at specified time point.

Clinical resolution was defined as absence (score=0) of bulbar conjunctival injection and ocular conjunctival discharge in the study eye. Bulbar conjunctival injection was assessed based on 0 (Normal conjunctival vascular pattern) - 4 (Markedly prominent, intense diffuse hyperemia) scale which used pictures from VBR scale. Ocular conjunctival discharge was assessed based on 0 (No evidence of discharge in conjunctiva) - 3 (Abundant quantity of mucopurulent or purulent discharge) scale. The study eye was defined as an eye with score of atleast 1 for both ocular conjunctival discharge and bulbar conjunctival redness at baseline.

Outcome measures

Measure	PVP-I 0.6% n=76 Participants Participants administered 1 drop of PVP-I 0.6% ophthalmic solution in each eye QID for 7 days.	SHP640 n=223 Participants Participants administered 1 drop of SHP640 (povidone-iodine \[PVP-I\] 0.6 percent \[%\] and Dexamethasone 0.1%) ophthalmic suspension in each eye 4 times a day (QID) for 7 days.	Placebo n=227 Participants Participants administered 1 drop of placebo ophthalmic solution in each eye QID for 7 days.
Number of Participants With Clinical Resolution Day 3	6 Participants	39 Participants	39 Participants
Number of Participants With Clinical Resolution Day 8	39 Participants	148 Participants	133 Participants
Number of Participants With Clinical Resolution Day 12	47 Participants	150 Participants	154 Participants

SECONDARY outcome

Timeframe: Day 3, 8 and 12

Population: mITT population included participants who received at least one dose of IP and had a positive bacterial culture (presence of one or more bacterial species at or above pathological threshold) at baseline in the study.

Bacterial eradication was defined as absence of all bacterial species present at or above pathological threshold at baseline in the study eye. Bacterial species were identified by Matrix Assisted Laser Desorption/Ionization-Time of Flight Mass Spectrometry, using their unique protein patterns. Pathological threshold for individual bacterial species was based on CFU/mL threshold levels established by Cagle and modified by Leibowitz for different ocular bacterial species found in the specimens collected from each participant.

Outcome measures

Measure	PVP-I 0.6% n=76 Participants Participants administered 1 drop of PVP-I 0.6% ophthalmic solution in each eye QID for 7 days.	SHP640 n=223 Participants Participants administered 1 drop of SHP640 (povidone-iodine \[PVP-I\] 0.6 percent \[%\] and Dexamethasone 0.1%) ophthalmic suspension in each eye 4 times a day (QID) for 7 days.	Placebo n=227 Participants Participants administered 1 drop of placebo ophthalmic solution in each eye QID for 7 days.
Number of Participants With Bacterial Eradication Day 3	33 Participants	76 Participants	79 Participants
Number of Participants With Bacterial Eradication Day 8	25 Participants	85 Participants	87 Participants
Number of Participants With Bacterial Eradication Day 12	21 Participants	83 Participants	82 Participants

SECONDARY outcome

Timeframe: Day 3, 5, 8 and 12

Population: mITT population included participants who received at least one dose of IP and had a positive bacterial culture (presence of one or more bacterial species at or above pathological threshold) at baseline in the study. Here, the number of participants analyzed refer to the participants evaluable for this outcome at specified time point.

Bulbar conjunctival injection was assessed based on 0 (Normal conjunctival vascular pattern) - 4 (Markedly prominent, intense diffuse hyperemia) scale which used pictures from VBR scale.

Outcome measures

Measure	PVP-I 0.6% n=76 Participants Participants administered 1 drop of PVP-I 0.6% ophthalmic solution in each eye QID for 7 days.	SHP640 n=223 Participants Participants administered 1 drop of SHP640 (povidone-iodine \[PVP-I\] 0.6 percent \[%\] and Dexamethasone 0.1%) ophthalmic suspension in each eye 4 times a day (QID) for 7 days.	Placebo n=227 Participants Participants administered 1 drop of placebo ophthalmic solution in each eye QID for 7 days.
Bulbar Conjunctival Injection Score Day 3	1.3 Score on a scale Standard Deviation 0.90	1.0 Score on a scale Standard Deviation 0.84	1.1 Score on a scale Standard Deviation 0.86
Bulbar Conjunctival Injection Score Day 5	0.7 Score on a scale Standard Deviation 0.88	0.5 Score on a scale Standard Deviation 0.77	0.7 Score on a scale Standard Deviation 0.80
Bulbar Conjunctival Injection Score Day 8	0.4 Score on a scale Standard Deviation 0.61	0.3 Score on a scale Standard Deviation 0.64	0.4 Score on a scale Standard Deviation 0.61
Bulbar Conjunctival Injection Score Day 12	0.2 Score on a scale Standard Deviation 0.47	0.2 Score on a scale Standard Deviation 0.56	0.2 Score on a scale Standard Deviation 0.48

SECONDARY outcome

Timeframe: Baseline, Day 3, 5, 8 and 12

Population: mITT population included participants who received at least one dose of IP and had a positive bacterial culture (presence of one or more bacterial species at or above pathological threshold) at baseline in the study. Here, the number of participants analyzed refer to the participants evaluable for this outcome at specified time point.

Bulbar conjunctival injection was assessed based on 0 (Normal conjunctival vascular pattern) - 4 (Markedly prominent, intense diffuse hyperemia) scale which used pictures from VBR scale.

Outcome measures

Measure	PVP-I 0.6% n=76 Participants Participants administered 1 drop of PVP-I 0.6% ophthalmic solution in each eye QID for 7 days.	SHP640 n=223 Participants Participants administered 1 drop of SHP640 (povidone-iodine \[PVP-I\] 0.6 percent \[%\] and Dexamethasone 0.1%) ophthalmic suspension in each eye 4 times a day (QID) for 7 days.	Placebo n=227 Participants Participants administered 1 drop of placebo ophthalmic solution in each eye QID for 7 days.
Change From Baseline in the Bulbar Conjunctival Injection Score Day 3	-0.8 Score on a scale Standard Deviation 0.76	-1.0 Score on a scale Standard Deviation 0.77	-0.9 Score on a scale Standard Deviation 0.76
Change From Baseline in the Bulbar Conjunctival Injection Score Day 5	-1.3 Score on a scale Standard Deviation 0.99	-1.5 Score on a scale Standard Deviation 0.87	-1.3 Score on a scale Standard Deviation 0.85
Change From Baseline in the Bulbar Conjunctival Injection Score Day 8	-1.6 Score on a scale Standard Deviation 0.86	-1.8 Score on a scale Standard Deviation 0.91	-1.6 Score on a scale Standard Deviation 0.81
Change From Baseline in the Bulbar Conjunctival Injection Score Day 12	-1.8 Score on a scale Standard Deviation 0.74	-1.8 Score on a scale Standard Deviation 0.89	-1.8 Score on a scale Standard Deviation 0.82

SECONDARY outcome

Timeframe: Day 3, 5, 8 and 12

Population: mITT population included participants who received at least one dose of IP and had a positive bacterial culture (presence of one or more bacterial species at or above pathological threshold) at baseline in the study. Here, the number of participants analyzed refer to the participants evaluable for this outcome at specified time point.

Ocular conjunctival discharge was assessed based on a 0 (No evidence of discharge in the conjunctiva) - 3 (Abundant quantity of mucopurulent or purulent discharge) scale.

Outcome measures

Measure	PVP-I 0.6% n=76 Participants Participants administered 1 drop of PVP-I 0.6% ophthalmic solution in each eye QID for 7 days.	SHP640 n=223 Participants Participants administered 1 drop of SHP640 (povidone-iodine \[PVP-I\] 0.6 percent \[%\] and Dexamethasone 0.1%) ophthalmic suspension in each eye 4 times a day (QID) for 7 days.	Placebo n=227 Participants Participants administered 1 drop of placebo ophthalmic solution in each eye QID for 7 days.
Ocular Conjunctival Discharge Score Day 3	0.8 Score on a scale Standard Deviation 0.74	0.7 Score on a scale Standard Deviation 0.73	0.7 Score on a scale Standard Deviation 0.76
Ocular Conjunctival Discharge Score Day 5	0.2 Score on a scale Standard Deviation 0.44	0.3 Score on a scale Standard Deviation 0.57	0.4 Score on a scale Standard Deviation 0.60
Ocular Conjunctival Discharge Score Day 8	0.1 Score on a scale Standard Deviation 0.31	0.1 Score on a scale Standard Deviation 0.43	0.2 Score on a scale Standard Deviation 0.47
Ocular Conjunctival Discharge Score Day 12	0.0 Score on a scale Standard Deviation 0.22	0.1 Score on a scale Standard Deviation 0.49	0.1 Score on a scale Standard Deviation 0.28

SECONDARY outcome

Timeframe: Baseline, Day 3, 5, 8 and 12

Population: mITT population included participants who received at least one dose of IP and had a positive bacterial culture (presence of one or more bacterial species at or above pathological threshold) at baseline in the study. Here, the number of participants analyzed refer to the participants evaluable for this outcome at specified time point.

Ocular conjunctival discharge was assessed based on a 0 (No evidence of discharge in the conjunctiva) - 3 (Abundant quantity of mucopurulent or purulent discharge) scale.

Outcome measures

Measure	PVP-I 0.6% n=76 Participants Participants administered 1 drop of PVP-I 0.6% ophthalmic solution in each eye QID for 7 days.	SHP640 n=223 Participants Participants administered 1 drop of SHP640 (povidone-iodine \[PVP-I\] 0.6 percent \[%\] and Dexamethasone 0.1%) ophthalmic suspension in each eye 4 times a day (QID) for 7 days.	Placebo n=227 Participants Participants administered 1 drop of placebo ophthalmic solution in each eye QID for 7 days.
Change From Baseline in the Ocular Conjunctival Discharge Score Day 3	-0.8 Score on a scale Standard Deviation 0.67	-0.9 Score on a scale Standard Deviation 0.77	-0.9 Score on a scale Standard Deviation 0.85
Change From Baseline in the Ocular Conjunctival Discharge Score Day 5	-1.4 Score on a scale Standard Deviation 0.75	-1.4 Score on a scale Standard Deviation 0.74	-1.3 Score on a scale Standard Deviation 0.75
Change From Baseline in the Ocular Conjunctival Discharge Score Day 8	-1.5 Score on a scale Standard Deviation 0.73	-1.5 Score on a scale Standard Deviation 0.71	-1.4 Score on a scale Standard Deviation 0.74
Change From Baseline in the Ocular Conjunctival Discharge Score Day 12	-1.6 Score on a scale Standard Deviation 0.71	-1.5 Score on a scale Standard Deviation 0.76	-1.6 Score on a scale Standard Deviation 0.73

SECONDARY outcome

Timeframe: Day 3, 5, 8 and 12

Population: mITT population included participants who received at least one dose of IP and had a positive bacterial culture (presence of one or more bacterial species at or above pathological threshold) at baseline in the study. Here, the number of participants analyzed refer to the participants evaluable for this outcome at specified time point.

Global clinical score was defined as the sum of bulbar conjunctival injection and ocular conjunctival discharge scores. Bulbar conjunctival injection was assessed based on 0 (Normal conjunctival vascular pattern) - 4 (Markedly prominent, intense diffuse hyperemia) scale which used pictures from VBR scale. Ocular conjunctival discharge was assessed based on 0 (No evidence of discharge in conjunctiva) - 3 (Abundant quantity of mucopurulent or purulent discharge) scale. The study eye was defined as an eye with a score of at least 1 for both ocular conjunctival discharge and bulbar conjunctival redness at baseline.

Outcome measures

Measure	PVP-I 0.6% n=76 Participants Participants administered 1 drop of PVP-I 0.6% ophthalmic solution in each eye QID for 7 days.	SHP640 n=223 Participants Participants administered 1 drop of SHP640 (povidone-iodine \[PVP-I\] 0.6 percent \[%\] and Dexamethasone 0.1%) ophthalmic suspension in each eye 4 times a day (QID) for 7 days.	Placebo n=227 Participants Participants administered 1 drop of placebo ophthalmic solution in each eye QID for 7 days.
Global Clinical Score Day 3	2.1 Score on a scale Standard Deviation 1.39	1.7 Score on a scale Standard Deviation 1.37	1.9 Score on a scale Standard Deviation 1.42
Global Clinical Score Day 5	0.9 Score on a scale Standard Deviation 1.19	0.8 Score on a scale Standard Deviation 1.18	1.0 Score on a scale Standard Deviation 1.18
Global Clinical Score Day 8	0.5 Score on a scale Standard Deviation 0.77	0.4 Score on a scale Standard Deviation 0.93	0.6 Score on a scale Standard Deviation 0.93
Global Clinical Score Day 12	0.3 Score on a scale Standard Deviation 0.55	0.4 Score on a scale Standard Deviation 0.90	0.3 Score on a scale Standard Deviation 0.67

SECONDARY outcome

Timeframe: Baseline, Day 3, 5, 8 and 12

Population: mITT population included participants who received at least one dose of IP and had a positive bacterial culture (presence of one or more bacterial species at or above pathological threshold) at baseline in the study. Here, the number of participants analyzed refer to the participants evaluable for this outcome at specified time point.

Global clinical score was defined as the sum of bulbar conjunctival injection and ocular conjunctival discharge scores. Bulbar conjunctival injection was assessed based on 0 (Normal conjunctival vascular pattern) - 4 (Markedly prominent, intense diffuse hyperemia) scale which used pictures from VBR scale. Ocular conjunctival discharge was assessed based on 0 (No evidence of discharge in conjunctiva) - 3 (Abundant quantity of mucopurulent or purulent discharge) scale. The study eye was defined as an eye with a score of at least 1 for both ocular conjunctival discharge and bulbar conjunctival redness at baseline.

Outcome measures

Measure	PVP-I 0.6% n=76 Participants Participants administered 1 drop of PVP-I 0.6% ophthalmic solution in each eye QID for 7 days.	SHP640 n=223 Participants Participants administered 1 drop of SHP640 (povidone-iodine \[PVP-I\] 0.6 percent \[%\] and Dexamethasone 0.1%) ophthalmic suspension in each eye 4 times a day (QID) for 7 days.	Placebo n=227 Participants Participants administered 1 drop of placebo ophthalmic solution in each eye QID for 7 days.
Change From Baseline in the Global Clinical Score Day 3	-1.6 Score on a scale Standard Deviation 1.22	-1.9 Score on a scale Standard Deviation 1.28	-1.8 Score on a scale Standard Deviation 1.30
Change From Baseline in the Global Clinical Score Day 5	-2.8 Score on a scale Standard Deviation 1.47	-2.9 Score on a scale Standard Deviation 1.27	-2.6 Score on a scale Standard Deviation 1.31
Change From Baseline in the Global Clinical Score Day 8	-3.2 Score on a scale Standard Deviation 1.25	-3.2 Score on a scale Standard Deviation 1.36	-3.1 Score on a scale Standard Deviation 1.25
Change From Baseline in the Global Clinical Score Day 12	-3.4 Score on a scale Standard Deviation 1.06	-3.3 Score on a scale Standard Deviation 1.38	-3.3 Score on a scale Standard Deviation 1.23

SECONDARY outcome

Timeframe: Day 3, 5, 8 and 12

Population: mITT population included participants who received at least one dose of IP and had a positive bacterial culture (presence of one or more bacterial species at or above pathological threshold) at baseline in the study. Here, the number of participants analyzed refer to the participants evaluable for this outcome at specified time point.

Modified clinical resolution was defined as a global clinical score of 0 or 1. Global clinical score was defined as the sum of bulbar conjunctival injection and ocular conjunctival discharge scores. Global clinical score was defined as the sum of bulbar conjunctival injection and ocular conjunctival discharge scores. Bulbar conjunctival injection was assessed based on 0 (Normal conjunctival vascular pattern) - 4 (Markedly prominent, intense diffuse hyperemia) scale which used pictures from VBR scale. Ocular conjunctival discharge was assessed based on 0 (No evidence of discharge in conjunctiva) - 3 (Abundant quantity of mucopurulent or purulent discharge) scale.

Outcome measures

Measure	PVP-I 0.6% n=76 Participants Participants administered 1 drop of PVP-I 0.6% ophthalmic solution in each eye QID for 7 days.	SHP640 n=223 Participants Participants administered 1 drop of SHP640 (povidone-iodine \[PVP-I\] 0.6 percent \[%\] and Dexamethasone 0.1%) ophthalmic suspension in each eye 4 times a day (QID) for 7 days.	Placebo n=227 Participants Participants administered 1 drop of placebo ophthalmic solution in each eye QID for 7 days.
Number of Participants With Modified Clinical Resolution Day 3	28 Participants	100 Participants	93 Participants
Number of Participants With Modified Clinical Resolution Day 5	48 Participants	166 Participants	143 Participants
Number of Participants With Modified Clinical Resolution Day 8	59 Participants	189 Participants	175 Participants
Number of Participants With Modified Clinical Resolution Day 12	59 Participants	182 Participants	173 Participants

SECONDARY outcome

Timeframe: Day 3, 5, 8 and 12

Population: mITT population included participants who received at least one dose of IP and had a positive bacterial culture (presence of one or more bacterial species at or above pathological threshold) at baseline in the study. Here, the number of participants analyzed refer to the participants evaluable for this outcome at specified time point.

Expanded clinical resolution was defined as a global clinical score of 0, 1, or 2 with neither injection nor discharge having a score of 2. Global clinical score was defined as the sum of bulbar conjunctival injection and ocular conjunctival discharge scores. Bulbar conjunctival injection was assessed based on 0 (Normal conjunctival vascular pattern) - 4 (Markedly prominent, intense diffuse hyperemia) scale which used pictures from VBR scale. Ocular conjunctival discharge was assessed based on 0 (No evidence of discharge in conjunctiva) - 3 (Abundant quantity of mucopurulent or purulent discharge) scale.

Outcome measures

Measure	PVP-I 0.6% n=76 Participants Participants administered 1 drop of PVP-I 0.6% ophthalmic solution in each eye QID for 7 days.	SHP640 n=226 Participants Participants administered 1 drop of SHP640 (povidone-iodine \[PVP-I\] 0.6 percent \[%\] and Dexamethasone 0.1%) ophthalmic suspension in each eye 4 times a day (QID) for 7 days.	Placebo n=227 Participants Participants administered 1 drop of placebo ophthalmic solution in each eye QID for 7 days.
Number of Participants With Expanded Clinical Resolution Day 3	46 Participants	155 Participants	154 Participants
Number of Participants With Expanded Clinical Resolution Day 5	54 Participants	185 Participants	171 Participants
Number of Participants With Expanded Clinical Resolution Day 8	63 Participants	193 Participants	192 Participants
Number of Participants With Expanded Clinical Resolution Day 12	61 Participants	185 Participants	181 Participants

SECONDARY outcome

Timeframe: Baseline to Day 12

Population: mITT population included participants who received at least one dose of IP and had a positive bacterial culture (presence of one or more bacterial species at or above pathological threshold) at baseline in the study.

Clinical resolution was defined as absence (score of 0) of bulbar conjunctival injection and ocular conjunctival discharge in the study eye. Bulbar conjunctival injection was assessed based on 0 (Normal conjunctival vascular pattern) - 4 (Markedly prominent, intense diffuse hyperemia) scale which used pictures from VBR scale. Ocular conjunctival discharge was assessed based on 0 (No evidence of discharge in conjunctiva) - 3 (Abundant quantity of mucopurulent or purulent discharge) scale. Time to clinical resolution defined as the date on which a participant first reached clinical resolution minus the date of first dose of investigational product, plus 1.

Outcome measures

Measure	PVP-I 0.6% n=76 Participants Participants administered 1 drop of PVP-I 0.6% ophthalmic solution in each eye QID for 7 days.	SHP640 n=223 Participants Participants administered 1 drop of SHP640 (povidone-iodine \[PVP-I\] 0.6 percent \[%\] and Dexamethasone 0.1%) ophthalmic suspension in each eye 4 times a day (QID) for 7 days.	Placebo n=227 Participants Participants administered 1 drop of placebo ophthalmic solution in each eye QID for 7 days.
Time to Clinical Resolution	6 Days Interval 5.0 to 8.0	5 Days Interval 5.0 to 8.0	8 Days Interval 5.0 to 8.0

SECONDARY outcome

Timeframe: Baseline to Day 12

Population: mITT population included participants who received at least one dose of IP and had a positive bacterial culture (presence of one or more bacterial species at or above pathological threshold) at baseline in the study. Here, the number of participants analyzed refer to the participants evaluable for this outcome at specified time point.

Rescue treatment with a licensed antibiotic according to the local standard of care was provided to participants if, in the judgment of the investigator, there was no clinical improvement or worsening of their condition to an extent that it would be in the best interest of the participant treated with an alternate therapy for safety reasons.

Outcome measures

Measure	PVP-I 0.6% n=76 Participants Participants administered 1 drop of PVP-I 0.6% ophthalmic solution in each eye QID for 7 days.	SHP640 n=223 Participants Participants administered 1 drop of SHP640 (povidone-iodine \[PVP-I\] 0.6 percent \[%\] and Dexamethasone 0.1%) ophthalmic suspension in each eye 4 times a day (QID) for 7 days.	Placebo n=227 Participants Participants administered 1 drop of placebo ophthalmic solution in each eye QID for 7 days.
Number of Participants Who Used Rescue Medication	3 Participants	2 Participants	4 Participants

SECONDARY outcome

Timeframe: From start of study drug administration up to 14 days

Population: Safety population included all participants who received at least one dose of investigational product.

An adverse event (AE) was any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. Any AE that occured after the first dose of investigational product instillation was considered a TEAE.

Outcome measures

Measure	PVP-I 0.6% n=108 Participants Participants administered 1 drop of PVP-I 0.6% ophthalmic solution in each eye QID for 7 days.	SHP640 n=323 Participants Participants administered 1 drop of SHP640 (povidone-iodine \[PVP-I\] 0.6 percent \[%\] and Dexamethasone 0.1%) ophthalmic suspension in each eye 4 times a day (QID) for 7 days.	Placebo n=321 Participants Participants administered 1 drop of placebo ophthalmic solution in each eye QID for 7 days.
Number of Participants With Treatment-emergent Adverse Events (TEAEs)	43 Participants	106 Participants	61 Participants

Adverse Events

SHP640

Serious events: 0 serious events

Other events: 67 other events

Deaths: 0 deaths

PVP-I 0.6%

Serious events: 0 serious events

Other events: 26 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 7 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	SHP640 n=323 participants at risk Participants administered 1 drop of SHP640 ophthalmic suspension in each eye QID for 7 days.	PVP-I 0.6% n=108 participants at risk Participants administered 1 drop of PVP-I 0.6% ophthalmic solution in each eye QID for 7 days.	Placebo n=321 participants at risk Participants administered 1 drop of placebo ophthalmic solution in each eye QID for 7 days.
General disorders Instillation site pain	20.7% 67/323 • Number of events 68 • From start of study drug administration up to 14 days. One participant was randomized in error and therefore captured in the ITT population, but not in the Safety Population.	24.1% 26/108 • Number of events 26 • From start of study drug administration up to 14 days. One participant was randomized in error and therefore captured in the ITT population, but not in the Safety Population.	2.2% 7/321 • Number of events 7 • From start of study drug administration up to 14 days. One participant was randomized in error and therefore captured in the ITT population, but not in the Safety Population.

Additional Information

Study Director

Shire

Phone: +1 866 842 5335

Email: ClinicalTransparency@shire.com

Results disclosure agreements

• Principal investigator is a sponsor employee If a multicenter publication is not submitted within twelve (12) months after conclusion, abandonment or termination of the Study at all sites, or after Sponsor confirms there shall be no multicenter Study publication, the Institution and/or such Principal Investigator may publish the results from the Institution site individually.
• Publication restrictions are in place

Restriction type: OTHER