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Clinical Trial Results:
A Phase 3, Multi-center, Randomized, Double-Masked Study to Evaluate the Clinical Efficacy and Safety of SHP640 (PVP-Iodine 0.6% and Dexamethasone 0.1%) Ophthalmic Suspension Compared to Placebo in the Treatment of Bacterial Conjunctivitis

Summary
EudraCT number
 2016-003361-25
Trial protocol
 DE   EE   HU   ES   PL   AT   FR   GB   IT  
Global end of trial date
01 Oct 2018

Results information
Results version number
 v1(current)
This version publication date
10 Apr 2019
First version publication date
10 Apr 2019
Other versions

Trial information

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Trial identification
Sponsor protocol code
SHP640-303
Additional study identifiers
ISRCTN number
 -
US NCT number
 NCT03004924
WHO universal trial number (UTN)
 -
Sponsors
Sponsor organisation name
Shire
Sponsor organisation address
300 Shire Way, Lexington, United States, MA 02421
Public contact
Study Director, Shire, ClinicalTransparency@shire.com
Scientific contact
Study Director, Shire, ClinicalTransparency@shire.com
Paediatric regulatory details
Is trial part of an agreed paediatric investigation plan (PIP)
Yes
EMA paediatric investigation plan number(s)
 EMEA-001936-PIP01-16
Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
No
Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
Yes
Results analysis stage
Analysis stage
Final
Date of interim/final analysis
01 Oct 2018
Is this the analysis of the primary completion data?
No
Global end of trial reached?
Yes
Global end of trial date
01 Oct 2018
Was the trial ended prematurely?
No
General information about the trial
Main objective of the trial
The primary objective of this study was to evaluate the efficacy of SHP640 based on clinical resolution (defined as absence of bulbar conjunctival injection and ocular conjunctival discharge) compared with placebo in the treatment of subjects with bacterial conjunctivitis in the study eye on Day 5.
Protection of trial subjects
The study was conducted in accordance with applicable regulations, International Conference on Harmonisation (ICH), European Union (EU) Directive 2001/20/EC and its updates, and local ethical and legal requirements.
Background therapy
 -
Evidence for comparator
 -
Actual start date of recruitment
29 Mar 2017
Long term follow-up planned
No
Independent data monitoring committee (IDMC) involvement?
No
Population of trial subjects
Number of subjects enrolled per country
Country: Number of subjects enrolled
Australia: 9
Country: Number of subjects enrolled
Austria: 14
Country: Number of subjects enrolled
Canada: 1
Country: Number of subjects enrolled
Estonia: 21
Country: Number of subjects enrolled
France: 1
Country: Number of subjects enrolled
Hungary: 7
Country: Number of subjects enrolled
Israel: 14
Country: Number of subjects enrolled
Italy: 1
Country: Number of subjects enrolled
Poland: 2
Country: Number of subjects enrolled
Puerto Rico: 11
Country: Number of subjects enrolled
South Africa: 18
Country: Number of subjects enrolled
Spain: 11
Country: Number of subjects enrolled
United Kingdom: 3
Country: Number of subjects enrolled
United States: 640
Worldwide total number of subjects
753
EEA total number of subjects
60
Number of subjects enrolled per age group
In utero
0
Preterm newborn - gestational age
0
Newborns (0-27 days)
0
Infants and toddlers (28 days-23 months)
10
Children (2-11 years)
66
Adolescents (12-17 years)
27
Adults (18-64 years)
482
From 65 to 84 years
158
85 years and over
10

Subject disposition

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

Pre-assignment
Screening details
 A total of 1080 subjects were screened, of them 753 were randomized to treatment. One subject was randomized in error and therefore captured only in the intent-to-treat (ITT) population.

Period 1
Period 1 title
Overall Study (overall period)
Is this the baseline period?
 Yes
Allocation method
Randomised - controlled
Blinding used
 Double blind
Roles blinded
 Investigator, Subject

Arms
Are arms mutually exclusive
Yes

Arm title
 SHP640
Arm description
 Subjects 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.
Arm type
 Experimental

Investigational medicinal product name
SHP640
Investigational medicinal product code
Other name
Pharmaceutical forms
Eye drops
Routes of administration
Ocular use
Dosage and administration details
Subjects administered 1 drop of SHP640 ophthalmic suspension in each eye QID.

Arm title
 PVP-I 0.6%
Arm description
 Subjects administered 1 drop of PVP-I 0.6% ophthalmic solution in each eye QID for 7 days.
Arm type
 Experimental

Investigational medicinal product name
PVP-I
Investigational medicinal product code
Other name
Pharmaceutical forms
Eye drops
Routes of administration
Ocular use
Dosage and administration details
Subjects administered 1 drop of PVP-I 0.6% ophthalmic solution in each eye QID.

Arm title
 Placebo
Arm description
 Subjects administered 1 drop of placebo ophthalmic solution in each eye QID for 7 days.
Arm type
 Placebo

Investigational medicinal product name
Placebo
Investigational medicinal product code
Other name
Pharmaceutical forms
Eye drops
Routes of administration
Ocular use
Dosage and administration details
Subjects administered 1 drop of placebo ophthalmic solution in each eye QID.

Number of subjects in period 1
SHP640 PVP-I 0.6% Placebo
Started
324
108
321
Completed
297
94
293
Not completed
27
14
28
     Withdrawal by parent/guardian
1
-
2
     Protocol deviation
4
-
1
     Physician decision
1
-
1
     Terminated by Sponsor
-
-
1
     Lack of efficacy
2
4
2
     Pregnancy
-
1
-
     Missed Study Visit
-
-
2
     Screen Failure
1
-
-
     Adverse event, non-fatal
6
5
10
     HSV1 Positive
1
-
-
     Consent withdrawn by subject
5
3
5
     Lost to follow-up
6
1
4

Baseline characteristics

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Baseline characteristics reporting groups
Reporting group title
SHP640
Reporting group description
 Subjects 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.

Reporting group title
PVP-I 0.6%
Reporting group description
 Subjects administered 1 drop of PVP-I 0.6% ophthalmic solution in each eye QID for 7 days.

Reporting group title
Placebo
Reporting group description
 Subjects administered 1 drop of placebo ophthalmic solution in each eye QID for 7 days.

Reporting group values
 SHP640 PVP-I 0.6% Placebo Total
Number of subjects
 324 108 321
Age categorical
Units: Subjects
Age continuous
Units: years
    arithmetic mean (standard deviation)
 44.2 ± 22.87 43.1 ± 23.03 44.7 ± 23.00 -
Gender categorical
Units: Subjects
    Female
 191 71 199 461
    Male
 133 37 122 292
Race/Ethnicity, Customized
Units: Subjects
    Ethnicity Hispanic or Latino
 62 30 87 179
    Ethnicity Not Hispanic or Latino
 254 76 230 560
    Ethnicity Not reported
 4 2 2 8
    Ethnicity Other
 4 0 2 6
Race/Ethnicity, Customized
Units: Subjects
    Race American Indian or Alaska Native
 0 1 3 4
    Race Asian
 12 0 8 20
    Race Black or African American
 54 18 54 126
    Race White
 250 88 250 588
    Race Native Hawaiian or Other Pacific Islander
 0 0 2 2
    Race Other
 6 1 4 11
    Race Multiple
 2 0 0 2

End points

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End points reporting groups
Reporting group title
SHP640
Reporting group description
 Subjects 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.

Reporting group title
PVP-I 0.6%
Reporting group description
 Subjects administered 1 drop of PVP-I 0.6% ophthalmic solution in each eye QID for 7 days.

Reporting group title
Placebo
Reporting group description
 Subjects administered 1 drop of placebo ophthalmic solution in each eye QID for 7 days.

Primary: Number of Subjects With Clinical Resolution Among who Received SHP640 or Placebo on Day 5

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End point title
 Number of Subjects With Clinical Resolution Among who Received SHP640 or Placebo on Day 5 [1]
End point description
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. 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. Modified intent-to-treat (mITT) population included subjects who received at least one dose of investigational product and had a positive bacterial culture (presence of one or more bacterial species at or above pathological threshold) at baseline. Here, number of subjects analyzed refer to evaluable subjects at specified time points.
End point type
Primary
End point timeframe
Day 5
Notes
[1] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was planned to compare the efficacy between the SHP640 and placebo groups.
End point values
 SHP640 Placebo
Number of subjects analysed
220
222
Units: Subjects
    Subjects
111
95
Statistical analysis title
 Statistical analysis 1
Comparison groups
Placebo v SHP640
Number of subjects included in analysis
442
Analysis specification
Pre-specified
Analysis type
 superiority
P-value
 = 0.127
Method
 Fisher exact
Parameter type
 Difference in response rate
Point estimate
7.7
Confidence interval
     level
 95%
     sides
2-sided
     lower limit
 -1.6
     upper limit
 16.9

Secondary: Number of Subjects With Bacterial Eradication Among who Received SHP640 or Placebo on Day 5

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End point title
 Number of Subjects With Bacterial Eradication Among who Received SHP640 or Placebo on Day 5 [2]
End point description
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 subject. mITT population included subjects 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 subjects analyzed refer to the subjects evaluable for this outcome at specified time point.
End point type
Secondary
End point timeframe
Baseline, Day 5
Notes
[2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was planned to compare the efficacy between the SHP640 and placebo groups.
End point values
 SHP640 Placebo
Number of subjects analysed
217
218
Units: Subjects
    Subjects
94
102
Statistical analysis title
 Statistical analysis 1
Comparison groups
Placebo v SHP640
Number of subjects included in analysis
435
Analysis specification
Pre-specified
Analysis type
 superiority
P-value
 = 0.5
Method
 Fisher exact
Parameter type
 Difference in response rate
Point estimate
-3.5
Confidence interval
     level
 95%
     sides
2-sided
     lower limit
 -12.8
     upper limit
 5.9

Secondary: Number of Subjects With Clinical Resolution

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End point title
 Number of Subjects With Clinical Resolution
End point description
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. 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. mITT population included subjects who received at least one dose of investigational product and had a positive bacterial culture (presence of one or more bacterial species at or above pathological threshold) at baseline. in the study. Here, "n" refer to the subjects evaluable for this outcome at specified time point.
End point type
Secondary
End point timeframe
Day 3, 8 and 12
End point values
 SHP640 PVP-I 0.6% Placebo
Number of subjects analysed
223
76
227
Units: Subjects
    Day 3 (n=215,76,218)
39
6
39
    Day 8 (n=205,65,206)
148
39
133
    Day 12 (n=195,62,187)
150
47
154
No statistical analyses for this end point

Secondary: Number of Subjects With Bacterial Eradication

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End point title
 Number of Subjects With Bacterial Eradication
End point description
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 subject. mITT population included subjects 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, "n" refer to the subjects evaluable for this outcome at specified time point.
End point type
Secondary
End point timeframe
Day 3, 8 and 12
End point values
 SHP640 PVP-I 0.6% Placebo
Number of subjects analysed
223
76
227
Units: Subjects
    Day 3 (n=213,75,214)
76
33
79
    Day 8 (n=205,64,200)
85
25
87
    Day 12 (n=194,60,183)
83
21
82
No statistical analyses for this end point

Secondary: Bulbar Conjunctival Injection Score

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End point title
 Bulbar Conjunctival Injection Score
End point description
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. mITT population included subjects 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, "n" refer to the subjects evaluable for this outcome at specified time point.
End point type
Secondary
End point timeframe
Day 3, 5, 8 and 12
End point values
 SHP640 PVP-I 0.6% Placebo
Number of subjects analysed
223
76
227
Units: Score on a scale
arithmetic mean (standard deviation)
    Day 3 (n=216,76,218)
1.0 ± 0.84
1.3 ± 0.90
1.1 ± 0.86
    Day 5 (n=207,65,209)
0.5 ± 0.77
0.7 ± 0.88
0.7 ± 0.80
    Day 8 (n=205,65,206)
0.3 ± 0.64
0.4 ± 0.61
0.4 ± 0.61
    Day 12 (n=196,62,187)
0.2 ± 0.56
0.2 ± 0.47
0.2 ± 0.48
No statistical analyses for this end point

Secondary: Change From Baseline in the Bulbar Conjunctival Injection Score

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End point title
 Change From Baseline in the Bulbar Conjunctival Injection Score
End point description
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. mITT population included subjects 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, "n" refer to the subjects evaluable for this outcome at specified time point.
End point type
Secondary
End point timeframe
Baseline, Day 3, 5, 8 and 12
End point values
 SHP640 PVP-I 0.6% Placebo
Number of subjects analysed
223
76
227
Units: Score on a scale
arithmetic mean (standard deviation)
    Day 3 (n=216,76,218)
-1.0 ± 0.77
-0.8 ± 0.76
-0.9 ± 0.76
    Day 5 (n=207,65,209)
-1.5 ± 0.87
-1.3 ± 0.99
-1.3 ± 0.85
    Day 8 (n=205,65,206)
-1.8 ± 0.91
-1.6 ± 0.86
-1.6 ± 0.81
    Day 12 (n=196,62,187)
-1.8 ± 0.89
-1.8 ± 0.74
-1.8 ± 0.82
No statistical analyses for this end point

Secondary: Ocular Conjunctival Discharge Score

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End point title
 Ocular Conjunctival Discharge Score
End point description
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. mITT population included subjects 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, "n" refer to the subjects evaluable for this outcome at specified time point.
End point type
Secondary
End point timeframe
Day 3, 5, 8 and 12
End point values
 SHP640 PVP-I 0.6% Placebo
Number of subjects analysed
223
76
227
Units: Score on a scale
arithmetic mean (standard deviation)
    Day 3 (n=215,76,218)
0.7 ± 0.73
0.8 ± 0.74
0.7 ± 0.76
    Day 5 (n=206,65,209)
0.3 ± 0.57
0.2 ± 0.44
0.4 ± 0.60
    Day 8 (n=205,65,206)
0.1 ± 0.43
0.1 ± 0.31
0.2 ± 0.47
    Day 12 (n=195,62,187)
0.1 ± 0.49
0.0 ± 0.22
0.1 ± 0.28
No statistical analyses for this end point

Secondary: Change From Baseline in the Ocular Conjunctival Discharge Score

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End point title
 Change From Baseline in the Ocular Conjunctival Discharge Score
End point description
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. mITT population included subjects 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, "n" refer to the subjects evaluable for this outcome at specified time point.
End point type
Secondary
End point timeframe
Baseline, Day 3, 5, 8 and 12
End point values
 SHP640 PVP-I 0.6% Placebo
Number of subjects analysed
223
76
227
Units: Score on a scale
arithmetic mean (standard deviation)
    Day 3 (n=215,76,218)
-0.9 ± 0.77
-0.8 ± 0.67
-0.9 ± 0.85
    Day 5 (n=206,65,209)
-1.4 ± 0.74
-1.4 ± 0.75
-1.3 ± 0.75
    Day 8 (n=205,65,206)
-1.5 ± 0.71
-1.5 ± 0.73
-1.4 ± 0.74
    Day 12 (n=195,62,187)
-1.5 ± 0.76
-1.6 ± 0.71
-1.6 ± 0.73
No statistical analyses for this end point

Secondary: Global Clinical Score

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End point title
 Global Clinical Score
End point description
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. 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. mITT population included subjects 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, "n" refer to the subjects evaluable for this outcome at specified time point.
End point type
Secondary
End point timeframe
Day 3, 5, 8 and 12
End point values
 SHP640 PVP-I 0.6% Placebo
Number of subjects analysed
223
76
227
Units: Score on a scale
arithmetic mean (standard deviation)
    Day 3 (n=215,76,218)
1.7 ± 1.37
2.1 ± 1.39
1.9 ± 1.42
    Day 5 (n=206,65,209)
0.8 ± 1.18
0.9 ± 1.19
1.0 ± 1.18
    Day 8 (n=205,65,206)
0.4 ± 0.93
0.5 ± 0.77
0.6 ± 0.93
    Day 12 (n=195,62,187)
0.4 ± 0.90
0.3 ± 0.55
0.3 ± 0.67
No statistical analyses for this end point

Secondary: Change From Baseline in the Global Clinical Score

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End point title
 Change From Baseline in the Global Clinical Score
End point description
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. 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. mITT population included subjects 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, "n" refer to the subjects evaluable for this outcome at specified time point.
End point type
Secondary
End point timeframe
Baseline, Day 3, 5, 8 and 12
End point values
 SHP640 PVP-I 0.6% Placebo
Number of subjects analysed
223
76
227
Units: Score on a scale
arithmetic mean (standard deviation)
    Day 3 (n=215,76,218)
-1.9 ± 1.28
-1.6 ± 1.22
-1.8 ± 1.30
    Day 5 (n=206,65,209)
-2.9 ± 1.27
-2.8 ± 1.47
-2.6 ± 1.31
    Day 8 (n=205,65,206)
-3.2 ± 1.36
-3.2 ± 1.25
-3.1 ± 1.25
    Day 12 (n=195,62,187)
-3.3 ± 1.38
-3.4 ± 1.06
-3.3 ± 1.23
No statistical analyses for this end point

Secondary: Number of Subjects With Modified Clinical Resolution

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End point title
 Number of Subjects With Modified Clinical Resolution
End point description
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. mITT population included subjects 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, "n" refer to the subjects evaluable for this outcome at specified time point.
End point type
Secondary
End point timeframe
Day 3, 5, 8 and 12
End point values
 SHP640 PVP-I 0.6% Placebo
Number of subjects analysed
223
76
227
Units: Subjects
    Day 3 (n=215,76,218)
100
28
93
    Day 5 (n=206,65,209)
166
48
143
    Day 8 (n=205,65,206)
189
59
175
    Day 12 (n=195,62,187)
182
59
173
No statistical analyses for this end point

Secondary: Number of Subjects With Expanded Clinical Resolution

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End point title
 Number of Subjects With Expanded Clinical Resolution
End point description
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. mITT population included subjects 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, "n" refer to the subjects evaluable for this outcome at specified time point.
End point type
Secondary
End point timeframe
Day 3, 5, 8 and 12
End point values
 SHP640 PVP-I 0.6% Placebo
Number of subjects analysed
226
76
227
Units: Subjects
    Day 3 (n=215,76,218)
155
46
154
    Day 5 (n=206,65,209)
185
54
171
    Day 8 (n=205,65,206)
193
63
192
    Day 12 (n=195,62,187)
185
61
181
No statistical analyses for this end point

Secondary: Time to Clinical Resolution

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End point title
 Time to Clinical Resolution
End point description
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 subject first reached clinical resolution minus the date of first dose of investigational product, plus 1. mITT population included subjects 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.
End point type
Secondary
End point timeframe
Baseline to Day 12
End point values
 SHP640 PVP-I 0.6% Placebo
Number of subjects analysed
223
76
227
Units: Days
median (confidence interval 95%)
    Days
5 (5.0 to 8.0)
6 (5.0 to 8.0)
8 (5.0 to 8.0)
No statistical analyses for this end point

Secondary: Number of Subjects who Used Rescue Medication

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End point title
 Number of Subjects who Used Rescue Medication
End point description
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. mITT population included subjects 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.
End point type
Secondary
End point timeframe
Baseline to Day 12
End point values
 SHP640 PVP-I 0.6% Placebo
Number of subjects analysed
223
76
227
Units: Subjects
    Subjects
2
3
4
No statistical analyses for this end point

Secondary: Number of Subjects with Treatment-emergent Adverse Events (TEAEs)

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End point title
 Number of Subjects with Treatment-emergent Adverse Events (TEAEs)
End point description
An adverse event (AE) was any untoward medical occurrence in a clinical investigation subject 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. Safety population included all subjects who received at least one dose of investigational product.
End point type
Secondary
End point timeframe
From start of study drug administration up to 14 days
End point values
 SHP640 PVP-I 0.6% Placebo
Number of subjects analysed
323
108
321
Units: Subjects
    Subjects
106
43
61
No statistical analyses for this end point

Adverse events

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Adverse events information
Timeframe for reporting adverse events
From start of study drug administration up to 14 days
Assessment type
 Non-systematic
Dictionary used for adverse event reporting
Dictionary name
 MedDRA
Dictionary version
19.1
Reporting groups
Reporting group title
SHP640
Reporting group description
 Subjects administered 1 drop of SHP640 ophthalmic suspension in each eye QID for 7 days.

Reporting group title
Placebo
Reporting group description
 Subjects administered 1 drop of placebo ophthalmic solution in each eye QID for 7 days.

Reporting group title
PVP-I 0.6%
Reporting group description
 Subjects administered 1 drop of PVP-I 0.6% ophthalmic solution in each eye QID for 7 days.

Serious adverse events
 SHP640 Placebo PVP-I 0.6%
Total subjects affected by serious adverse events
     subjects affected / exposed
0 / 323 (0.00%)
0 / 321 (0.00%)
0 / 108 (0.00%)
     number of deaths (all causes)
0
0
0
     number of deaths resulting from adverse events
0
0
0
Frequency threshold for reporting non-serious adverse events: 5%
Non-serious adverse events
 SHP640 Placebo PVP-I 0.6%
Total subjects affected by non serious adverse events
     subjects affected / exposed
67 / 323 (20.74%)
7 / 321 (2.18%)
26 / 108 (24.07%)
General disorders and administration site conditions
Instillation site pain
     subjects affected / exposed
67 / 323 (20.74%)
7 / 321 (2.18%)
26 / 108 (24.07%)
     occurrences all number
68
7
26

More information

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Substantial protocol amendments (globally)
Were there any global substantial amendments to the protocol? Yes
Date
Amendment
28 Nov 2016
Aligned clinical strategy and language across the SHP640 adenoviral and bacterial conjunctivitis programs and updated the assessments and inclusion and exclusion criteria.
15 Feb 2017
- Added the Middle East and Africa to the list of regions participating in the study. - Added the discontinuation of subjects less than 2 months old who tested positive for the presence of chlamydia or gonorrhea. - Added the discontinuation of subjects who tested positive for HSV in either eye at baseline and added testing for HSV by qPCR in all subjects at baseline.
13 Dec 2017
- Added windows for Study Visit 2, 4, and 5, and changed the window for the inclusion criterion relating to bacterial conjunctivitis. - Clarified the exclusion criterion relating to a clinical presentation more consistent with the diagnosis of non-infectious conjunctivitis. - Removed the exclusion criterion relating to subjects with a known history of elevated intraocular pressure >21 mmHg. - Clarified the safety follow up to be conducted for subjects who tested positive for HSV in either eye.
31 Jul 2018
- Increased the planned number of subjects to be randomized and the number of study sites, to ensure the target number of subjects in the mITT population would be achieved.

Interruptions (globally)
Were there any global interruptions to the trial? No

Limitations and caveats
Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
None reported

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