Bacterial Conjunctivitis
Conditions
Brief summary
The purpose of this study is to determine if an investigational treatment is effective compared with placebo and PVP-Iodine in the treatment of adults and children with bacterial conjunctivitis.
Interventions
DRUGSHP640
Instill 1 drop of SHP640 (povidone-iodine \[PVPI\] 0.6% and Dexamethasone 0.1%) ophthalmic suspension in each eye QID (with a minimum of 2 hours between doses) for 7 days.
DRUGPVP-I 0.6%
Instill 1 drop of PVP-I 0.6% ophthalmic solution in each eye 4 times QID (with a minimum of 2 hours between doses) for 7 days.
DRUGPlacebo
Instill 1 drop of placebo ophthalmic solution in each eye 4 times QID (with a minimum of 2 hours between doses) for 7 days.
Sponsors
Shire
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion criteria
* An understanding, ability, and willingness to fully comply with study procedures and restrictions (by the parent(s), guardian, or legally authorized representative, if applicable). * Ability to voluntarily provide written, signed, and dated (personally or via a parent(s), guardian, or legally authorized representative(s) informed consent (and assent, if applicable) to participate in the study. * Participants of any age at Visit 1 (Note: participants less than (\<) 3 months of age at Visit 1 must have been full-term, that is (ie,) greater than or equal to (\>=) 37 weeks gestational age at birth). * Have a negative AdenoPlus® test in both eyes within 24 hours of Visit 1 or at Visit 1. * Have a clinical diagnosis of suspected bacterial conjunctivitis in at least 1 eye confirmed by the presence of the following minimal clinical signs and symptoms in that same eye: 1. Report presence of signs and/or symptoms of bacterial conjunctivitis for less than or equal to (\<=) 4 days prior to Visit 1 2. Bulbar conjunctival injection: a grade of \>= 1 on 0-4 scale of Bulbar Conjunctival Injection Scale 3. Ocular conjunctival discharge: a grade of \>= 1 (mild) on a 0-3 scale of Ocular Conjunctival Discharge Scale * Be willing to discontinue contact lens wear for the duration of the study. * Have a Best Corrected Visual Acuity (BCVA) of 0.60 logMAR or better in each eye as measured using an Early Treatment Diabetic Retinopathy Study (ETDRS) chart. BCVA will be assessed by an age appropriate method in accordance with the AAP Policy Statement for Visual System Assessment in Infants, Children, and Young Adults by Pediatricians (Donahue and Baker, 2016; American Academy of Pediatrics, 2016). The policy statement recommends formal vision screening can begin at 3 years of age. VA measurements for children under the age of 3 will be done at the discretion of the investigator. If not done, child should be able to fixate on and follow a moving object, except participants \< 2 months of age who have not yet developed this ability. Participants \< 2 months will be enrolled at the discretion of investigator. * Male, or non-pregnant, non-lactating female who agrees to comply with any applicable contraceptive requirements of the protocol or females of non-childbearing potential.
Exclusion criteria
* Current or recurrent disease that could affect the action, absorption, or disposition of the investigational product, or clinical or laboratory assessments, per investigator's discretion. * Current or relevant history of physical or psychiatric illness, any medical disorder that may make the participant unlikely to fully complete the study, or any condition that presents undue risk from the investigational product or procedures. * Have known or suspected intolerance or hypersensitivity to the investigational product, closely related compounds, or any of the stated ingredients. * Prior enrollment in a FST-100 or SHP640 clinical study. * Participants who are employees, or immediate family members of employees (who are directly related to study conduct), at the investigational site. * Have a history of ocular surgical intervention within \<= 6 months prior to Visit 1 or planned for the period of the study. * Have a preplanned overnight hospitalization during the period of the study. * Have presence of any intraocular, corneal, or conjunctival ocular inflammation (example \[eg,\] uveitis, iritis, ulcerative keratitis, chronic blepharoconjunctivitis), other than bacterial conjunctivitis. * Have active or a history of ocular herpes. * Have at enrollment or within \<= 30 days of Visit 1, a clinical presentation more consistent with the diagnosis of non-infectious conjunctivitis (except presumed seasonal/perennial allergic conjunctivitis) or non-bacterial ocular infection (eg, viral, fungal, acanthamoebal, or other parasitic). Note: history or concomitant presence of presumed seasonal or perennial allergic conjunctivitis signs/symptoms is not exclusionary. * Neonates or infants (ie, participants less than 12 months of age) who have suspected or confirmed (based on the result of any test conducted prior to screening) conjunctivitis of gonococcal, chlamydial, herpetic or chemical origin. * Neonates or infants (ie, participants less than 12 months of age) whose birth mothers had any sexually transmitted disease within 1 month of delivery or any history of genital herpes. * Presence of nasolacrimal duct obstruction at Visit 1 (Day 1). * Presence of any significant ophthalmic condition (eg, Retinopathy of Prematurity, congenital cataract, congenital glaucoma) or other congenital disorder with ophthalmic involvement that could affect study variables. * Be a known intraocular pressure (IOP) steroid responder, have a known history or current diagnosis of glaucoma or be a glaucoma suspect. * Have any known clinically significant optic nerve defects. * Have a history of recurrent corneal erosion syndrome, either idiopathic or secondary to previous corneal trauma or dry eye syndrome; presence of corneal epithelial defect or any significant corneal opacity at Visit 1. * Presence of significant, active condition in the posterior segment that requires invasive treatment (eg, intravitreal treatment with vascular endothelial growth factor inhibitors or corticosteroids) and may progress during the study participation period. * Have used any topical ocular or systemic antibiotics within \<= 7 days of enrollment. * Have used any topical ocular non-steroidal anti-inflammatory drugs within \<= 1 day of enrollment. * Have used any topical ophthalmic steroids in the last \<= 14 days. * Have used any systemic corticosteroid agents within \<= 14 days of Day 1. Stable (initiated \>= 30 days prior to enrollment) use of inhaled and nasal corticosteroids is allowed, given no anticipated change in dose for the duration of the study. Topical dermal steroids are allowed except in the periocular area. * Have used non-corticosteroid immunosuppressive agents within \<= 14 days of Day 1. * Have used any topical ophthalmic products, including tear substitutes, and over-the-counter preparations such as lid scrubs, within 2 hours of Visit 1 and be unable to discontinue all topical ophthalmic products for the duration of the study. Use of hot or cold compresses is also not permitted during the study. * Have any significant ocular disease (eg, Sjogren's syndrome) or any uncontrolled systemic disease or debilitating disease (eg, cardiovascular disease, hypertension, sexually transmitted diseases/infections, diabetes, or cystic fibrosis) that may affect the study parameters, per investigator's discretion. * Any known history of immunodeficiency disorder or known active conditions predisposing to immunodeficiency, such as human immunodeficiency virus, hepatitis B or C, evidence of active hepatitis A (anti-hepatitis A virus immunoglobulin M), or organ or bone marrow transplantation. * Within 30 days prior to the first dose of investigational product: 1. Have used an investigational product or device, or 2. Have been enrolled in a clinical study (including vaccine studies) that, in the investigator's opinion, may impact this Shire-sponsored study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Clinical Resolution Among Who Received SHP640 or Placebo on Day 5 | Day 5 | 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%. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Bacterial Eradication Among Who Received SHP640 or Placebo on Day 5 | Baseline, Day 5 | 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%. |
| Number of Participants With Clinical Resolution | Day 3, 8 and 12 | 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. |
| Ocular Conjunctival Discharge Score | Day 3, 5, 8 and 12 | 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. |
| Number of Participants With Bacterial Eradication | Day 3, 8 and 12 | 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. |
| Bulbar Conjunctival Injection Score | Day 3, 5, 8 and 12 | 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. |
| Change From Baseline in the Bulbar Conjunctival Injection Score | Baseline, Day 3, 5, 8 and 12 | 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. |
| Change From Baseline in the Ocular Conjunctival Discharge Score | Baseline, Day 3, 5, 8 and 12 | 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. |
| Global Clinical Score | Day 3, 5, 8 and 12 | 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. |
| Change From Baseline in the Global Clinical Score | Baseline, Day 3, 5, 8 and 12 | 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. |
| Number of Participants With Modified Clinical Resolution | Day 3, 5, 8 and 12 | 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. |
| Number of Participants With Expanded Clinical Resolution | Day 3, 5, 8 and 12 | 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. |
| Time to Clinical Resolution | Baseline to Day 12 | 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. |
| Number of Participants Who Used Rescue Medication | Baseline to Day 12 | 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. |
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) | From start of study drug administration up to 14 days | 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. |
Countries
Australia, Austria, Canada, Estonia, France, Hungary, Israel, Italy, Poland, Puerto Rico, South Africa, Spain, United States
Participant flow
Recruitment details
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).
Pre-assignment details
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.
Participants by arm
| Arm | Count |
|---|---|
| SHP640 Participants administered 1 drop of SHP640 ophthalmic suspension in each eye QID for 7 days. | 324 |
| PVP-I 0.6% Participants administered 1 drop of PVP-I 0.6% ophthalmic solution in each eye QID for 7 days. | 108 |
| Placebo Participants administered 1 drop of placebo ophthalmic solution in each eye QID for 7 days. | 321 |
| Total | 753 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 6 | 5 | 10 |
| Overall Study | HSV1 Positive | 1 | 0 | 0 |
| Overall Study | Lack of Efficacy | 2 | 4 | 2 |
| Overall Study | Lost to Follow-up | 6 | 1 | 4 |
| Overall Study | Missed Study Visit | 0 | 0 | 2 |
| Overall Study | Physician Decision | 1 | 0 | 1 |
| Overall Study | Pregnancy | 0 | 1 | 0 |
| Overall Study | Protocol Violation | 4 | 0 | 1 |
| Overall Study | Screen Failure | 1 | 0 | 0 |
| Overall Study | Terminated by Sponsor | 0 | 0 | 1 |
| Overall Study | Withdrawal by parent/guardian | 1 | 0 | 2 |
| Overall Study | Withdrawal by Subject | 5 | 3 | 5 |
Baseline characteristics
| Characteristic | SHP640 | Total | Placebo | PVP-I 0.6% |
|---|---|---|---|---|
| Age, Continuous | 44.2 Years STANDARD_DEVIATION 22.87 | 44.3 Years STANDARD_DEVIATION 22.92 | 44.7 Years STANDARD_DEVIATION 23 | 43.1 Years STANDARD_DEVIATION 23.03 |
| Race/Ethnicity, Customized Ethnicity Hispanic or Latino | 62 Participants | 179 Participants | 87 Participants | 30 Participants |
| Race/Ethnicity, Customized Ethnicity Not Hispanic or Latino | 254 Participants | 560 Participants | 230 Participants | 76 Participants |
| Race/Ethnicity, Customized Ethnicity Not reported | 4 Participants | 8 Participants | 2 Participants | 2 Participants |
| Race/Ethnicity, Customized Ethnicity Other | 4 Participants | 6 Participants | 2 Participants | 0 Participants |
| Race/Ethnicity, Customized Race American Indian or Alaska Native | 0 Participants | 4 Participants | 3 Participants | 1 Participants |
| Race/Ethnicity, Customized Race Asian | 12 Participants | 20 Participants | 8 Participants | 0 Participants |
| Race/Ethnicity, Customized Race Black or African American | 54 Participants | 126 Participants | 54 Participants | 18 Participants |
| Race/Ethnicity, Customized Race Multiple | 2 Participants | 2 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Race Native Hawaiian or Other Pacific Islander | 0 Participants | 2 Participants | 2 Participants | 0 Participants |
| Race/Ethnicity, Customized Race Other | 6 Participants | 11 Participants | 4 Participants | 1 Participants |
| Race/Ethnicity, Customized Race White | 250 Participants | 588 Participants | 250 Participants | 88 Participants |
| Sex: Female, Male Female | 191 Participants | 461 Participants | 199 Participants | 71 Participants |
| Sex: Female, Male Male | 133 Participants | 292 Participants | 122 Participants | 37 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 323 | 0 / 108 | 0 / 321 |
| other Total, other adverse events | 67 / 323 | 26 / 108 | 7 / 321 |
| serious Total, serious adverse events | 0 / 323 | 0 / 108 | 0 / 321 |
Outcome results
Primary
Number of Participants With Clinical Resolution Among Who Received SHP640 or Placebo on Day 5
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%.
Time frame: 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.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| SHP640 | Number of Participants With Clinical Resolution Among Who Received SHP640 or Placebo on Day 5 | 111 Participants |
| PVP-I 0.6% | Number of Participants With Clinical Resolution Among Who Received SHP640 or Placebo on Day 5 | 0 Participants |
| Placebo | Number of Participants With Clinical Resolution Among Who Received SHP640 or Placebo on Day 5 | 95 Participants |
p-value: 0.12795% CI: [-1.6, 16.9]Fisher Exact
Secondary
Bulbar Conjunctival Injection Score
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.
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SHP640 | Bulbar Conjunctival Injection Score | Day 3 | 1.0 Score on a scale | Standard Deviation 0.84 |
| SHP640 | Bulbar Conjunctival Injection Score | Day 5 | 0.5 Score on a scale | Standard Deviation 0.77 |
| SHP640 | Bulbar Conjunctival Injection Score | Day 8 | 0.3 Score on a scale | Standard Deviation 0.64 |
| SHP640 | Bulbar Conjunctival Injection Score | Day 12 | 0.2 Score on a scale | Standard Deviation 0.56 |
| PVP-I 0.6% | Bulbar Conjunctival Injection Score | Day 12 | 0.2 Score on a scale | Standard Deviation 0.47 |
| PVP-I 0.6% | Bulbar Conjunctival Injection Score | Day 3 | 1.3 Score on a scale | Standard Deviation 0.9 |
| PVP-I 0.6% | Bulbar Conjunctival Injection Score | Day 8 | 0.4 Score on a scale | Standard Deviation 0.61 |
| PVP-I 0.6% | Bulbar Conjunctival Injection Score | Day 5 | 0.7 Score on a scale | Standard Deviation 0.88 |
| Placebo | Bulbar Conjunctival Injection Score | Day 12 | 0.2 Score on a scale | Standard Deviation 0.48 |
| Placebo | Bulbar Conjunctival Injection Score | Day 5 | 0.7 Score on a scale | Standard Deviation 0.8 |
| Placebo | Bulbar Conjunctival Injection Score | Day 8 | 0.4 Score on a scale | Standard Deviation 0.61 |
| Placebo | Bulbar Conjunctival Injection Score | Day 3 | 1.1 Score on a scale | Standard Deviation 0.86 |
Secondary
Change From Baseline in the Bulbar Conjunctival Injection Score
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.
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SHP640 | Change From Baseline in the Bulbar Conjunctival Injection Score | Day 3 | -1.0 Score on a scale | Standard Deviation 0.77 |
| SHP640 | Change From Baseline in the Bulbar Conjunctival Injection Score | Day 5 | -1.5 Score on a scale | Standard Deviation 0.87 |
| SHP640 | Change From Baseline in the Bulbar Conjunctival Injection Score | Day 8 | -1.8 Score on a scale | Standard Deviation 0.91 |
| SHP640 | Change From Baseline in the Bulbar Conjunctival Injection Score | Day 12 | -1.8 Score on a scale | Standard Deviation 0.89 |
| PVP-I 0.6% | Change From Baseline in the Bulbar Conjunctival Injection Score | Day 12 | -1.8 Score on a scale | Standard Deviation 0.74 |
| PVP-I 0.6% | Change From Baseline in the Bulbar Conjunctival Injection Score | Day 3 | -0.8 Score on a scale | Standard Deviation 0.76 |
| PVP-I 0.6% | Change From Baseline in the Bulbar Conjunctival Injection Score | Day 8 | -1.6 Score on a scale | Standard Deviation 0.86 |
| PVP-I 0.6% | Change From Baseline in the Bulbar Conjunctival Injection Score | Day 5 | -1.3 Score on a scale | Standard Deviation 0.99 |
| Placebo | Change From Baseline in the Bulbar Conjunctival Injection Score | Day 12 | -1.8 Score on a scale | Standard Deviation 0.82 |
| Placebo | Change From Baseline in the Bulbar Conjunctival Injection Score | Day 5 | -1.3 Score on a scale | Standard Deviation 0.85 |
| Placebo | Change From Baseline in the Bulbar Conjunctival Injection Score | Day 8 | -1.6 Score on a scale | Standard Deviation 0.81 |
| Placebo | Change From Baseline in the Bulbar Conjunctival Injection Score | Day 3 | -0.9 Score on a scale | Standard Deviation 0.76 |
Secondary
Change From Baseline in the Global Clinical Score
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.
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SHP640 | Change From Baseline in the Global Clinical Score | Day 3 | -1.9 Score on a scale | Standard Deviation 1.28 |
| SHP640 | Change From Baseline in the Global Clinical Score | Day 5 | -2.9 Score on a scale | Standard Deviation 1.27 |
| SHP640 | Change From Baseline in the Global Clinical Score | Day 8 | -3.2 Score on a scale | Standard Deviation 1.36 |
| SHP640 | Change From Baseline in the Global Clinical Score | Day 12 | -3.3 Score on a scale | Standard Deviation 1.38 |
| PVP-I 0.6% | Change From Baseline in the Global Clinical Score | Day 12 | -3.4 Score on a scale | Standard Deviation 1.06 |
| PVP-I 0.6% | Change From Baseline in the Global Clinical Score | Day 3 | -1.6 Score on a scale | Standard Deviation 1.22 |
| PVP-I 0.6% | Change From Baseline in the Global Clinical Score | Day 8 | -3.2 Score on a scale | Standard Deviation 1.25 |
| PVP-I 0.6% | Change From Baseline in the Global Clinical Score | Day 5 | -2.8 Score on a scale | Standard Deviation 1.47 |
| Placebo | Change From Baseline in the Global Clinical Score | Day 12 | -3.3 Score on a scale | Standard Deviation 1.23 |
| Placebo | Change From Baseline in the Global Clinical Score | Day 5 | -2.6 Score on a scale | Standard Deviation 1.31 |
| Placebo | Change From Baseline in the Global Clinical Score | Day 8 | -3.1 Score on a scale | Standard Deviation 1.25 |
| Placebo | Change From Baseline in the Global Clinical Score | Day 3 | -1.8 Score on a scale | Standard Deviation 1.3 |
Secondary
Change From Baseline in the Ocular Conjunctival Discharge Score
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.
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SHP640 | Change From Baseline in the Ocular Conjunctival Discharge Score | Day 3 | -0.9 Score on a scale | Standard Deviation 0.77 |
| SHP640 | Change From Baseline in the Ocular Conjunctival Discharge Score | Day 5 | -1.4 Score on a scale | Standard Deviation 0.74 |
| SHP640 | Change From Baseline in the Ocular Conjunctival Discharge Score | Day 8 | -1.5 Score on a scale | Standard Deviation 0.71 |
| SHP640 | Change From Baseline in the Ocular Conjunctival Discharge Score | Day 12 | -1.5 Score on a scale | Standard Deviation 0.76 |
| PVP-I 0.6% | Change From Baseline in the Ocular Conjunctival Discharge Score | Day 12 | -1.6 Score on a scale | Standard Deviation 0.71 |
| PVP-I 0.6% | Change From Baseline in the Ocular Conjunctival Discharge Score | Day 3 | -0.8 Score on a scale | Standard Deviation 0.67 |
| PVP-I 0.6% | Change From Baseline in the Ocular Conjunctival Discharge Score | Day 8 | -1.5 Score on a scale | Standard Deviation 0.73 |
| PVP-I 0.6% | Change From Baseline in the Ocular Conjunctival Discharge Score | Day 5 | -1.4 Score on a scale | Standard Deviation 0.75 |
| Placebo | Change From Baseline in the Ocular Conjunctival Discharge Score | Day 12 | -1.6 Score on a scale | Standard Deviation 0.73 |
| Placebo | Change From Baseline in the Ocular Conjunctival Discharge Score | Day 5 | -1.3 Score on a scale | Standard Deviation 0.75 |
| Placebo | Change From Baseline in the Ocular Conjunctival Discharge Score | Day 8 | -1.4 Score on a scale | Standard Deviation 0.74 |
| Placebo | Change From Baseline in the Ocular Conjunctival Discharge Score | Day 3 | -0.9 Score on a scale | Standard Deviation 0.85 |
Secondary
Global Clinical Score
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.
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SHP640 | Global Clinical Score | Day 3 | 1.7 Score on a scale | Standard Deviation 1.37 |
| SHP640 | Global Clinical Score | Day 5 | 0.8 Score on a scale | Standard Deviation 1.18 |
| SHP640 | Global Clinical Score | Day 8 | 0.4 Score on a scale | Standard Deviation 0.93 |
| SHP640 | Global Clinical Score | Day 12 | 0.4 Score on a scale | Standard Deviation 0.9 |
| PVP-I 0.6% | Global Clinical Score | Day 12 | 0.3 Score on a scale | Standard Deviation 0.55 |
| PVP-I 0.6% | Global Clinical Score | Day 3 | 2.1 Score on a scale | Standard Deviation 1.39 |
| PVP-I 0.6% | Global Clinical Score | Day 8 | 0.5 Score on a scale | Standard Deviation 0.77 |
| PVP-I 0.6% | Global Clinical Score | Day 5 | 0.9 Score on a scale | Standard Deviation 1.19 |
| Placebo | Global Clinical Score | Day 12 | 0.3 Score on a scale | Standard Deviation 0.67 |
| Placebo | Global Clinical Score | Day 5 | 1.0 Score on a scale | Standard Deviation 1.18 |
| Placebo | Global Clinical Score | Day 8 | 0.6 Score on a scale | Standard Deviation 0.93 |
| Placebo | Global Clinical Score | Day 3 | 1.9 Score on a scale | Standard Deviation 1.42 |
Secondary
Number of Participants Who Used Rescue Medication
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.
Time frame: 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.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| SHP640 | Number of Participants Who Used Rescue Medication | 2 Participants |
| PVP-I 0.6% | Number of Participants Who Used Rescue Medication | 3 Participants |
| Placebo | Number of Participants Who Used Rescue Medication | 4 Participants |
Secondary
Number of Participants With Bacterial Eradication
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.
Time frame: 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.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| SHP640 | Number of Participants With Bacterial Eradication | Day 8 | 85 Participants |
| SHP640 | Number of Participants With Bacterial Eradication | Day 3 | 76 Participants |
| SHP640 | Number of Participants With Bacterial Eradication | Day 12 | 83 Participants |
| PVP-I 0.6% | Number of Participants With Bacterial Eradication | Day 8 | 25 Participants |
| PVP-I 0.6% | Number of Participants With Bacterial Eradication | Day 3 | 33 Participants |
| PVP-I 0.6% | Number of Participants With Bacterial Eradication | Day 12 | 21 Participants |
| Placebo | Number of Participants With Bacterial Eradication | Day 3 | 79 Participants |
| Placebo | Number of Participants With Bacterial Eradication | Day 12 | 82 Participants |
| Placebo | Number of Participants With Bacterial Eradication | Day 8 | 87 Participants |
Secondary
Number of Participants With Bacterial Eradication Among Who Received SHP640 or Placebo on Day 5
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%.
Time frame: 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.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| SHP640 | Number of Participants With Bacterial Eradication Among Who Received SHP640 or Placebo on Day 5 | 94 Participants |
| PVP-I 0.6% | Number of Participants With Bacterial Eradication Among Who Received SHP640 or Placebo on Day 5 | 0 Participants |
| Placebo | Number of Participants With Bacterial Eradication Among Who Received SHP640 or Placebo on Day 5 | 102 Participants |
p-value: 0.595% CI: [-12.8, 5.9]Fisher Exact
Secondary
Number of Participants With Clinical Resolution
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.
Time frame: 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.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| SHP640 | Number of Participants With Clinical Resolution | Day 8 | 148 Participants |
| SHP640 | Number of Participants With Clinical Resolution | Day 3 | 39 Participants |
| SHP640 | Number of Participants With Clinical Resolution | Day 12 | 150 Participants |
| PVP-I 0.6% | Number of Participants With Clinical Resolution | Day 8 | 39 Participants |
| PVP-I 0.6% | Number of Participants With Clinical Resolution | Day 3 | 6 Participants |
| PVP-I 0.6% | Number of Participants With Clinical Resolution | Day 12 | 47 Participants |
| Placebo | Number of Participants With Clinical Resolution | Day 3 | 39 Participants |
| Placebo | Number of Participants With Clinical Resolution | Day 12 | 154 Participants |
| Placebo | Number of Participants With Clinical Resolution | Day 8 | 133 Participants |
Secondary
Number of Participants With Expanded Clinical Resolution
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.
Time frame: 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.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| SHP640 | Number of Participants With Expanded Clinical Resolution | Day 3 | 155 Participants |
| SHP640 | Number of Participants With Expanded Clinical Resolution | Day 5 | 185 Participants |
| SHP640 | Number of Participants With Expanded Clinical Resolution | Day 8 | 193 Participants |
| SHP640 | Number of Participants With Expanded Clinical Resolution | Day 12 | 185 Participants |
| PVP-I 0.6% | Number of Participants With Expanded Clinical Resolution | Day 12 | 61 Participants |
| PVP-I 0.6% | Number of Participants With Expanded Clinical Resolution | Day 3 | 46 Participants |
| PVP-I 0.6% | Number of Participants With Expanded Clinical Resolution | Day 8 | 63 Participants |
| PVP-I 0.6% | Number of Participants With Expanded Clinical Resolution | Day 5 | 54 Participants |
| Placebo | Number of Participants With Expanded Clinical Resolution | Day 12 | 181 Participants |
| Placebo | Number of Participants With Expanded Clinical Resolution | Day 5 | 171 Participants |
| Placebo | Number of Participants With Expanded Clinical Resolution | Day 8 | 192 Participants |
| Placebo | Number of Participants With Expanded Clinical Resolution | Day 3 | 154 Participants |
Secondary
Number of Participants With Modified Clinical Resolution
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.
Time frame: 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.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| SHP640 | Number of Participants With Modified Clinical Resolution | Day 3 | 100 Participants |
| SHP640 | Number of Participants With Modified Clinical Resolution | Day 5 | 166 Participants |
| SHP640 | Number of Participants With Modified Clinical Resolution | Day 8 | 189 Participants |
| SHP640 | Number of Participants With Modified Clinical Resolution | Day 12 | 182 Participants |
| PVP-I 0.6% | Number of Participants With Modified Clinical Resolution | Day 12 | 59 Participants |
| PVP-I 0.6% | Number of Participants With Modified Clinical Resolution | Day 3 | 28 Participants |
| PVP-I 0.6% | Number of Participants With Modified Clinical Resolution | Day 8 | 59 Participants |
| PVP-I 0.6% | Number of Participants With Modified Clinical Resolution | Day 5 | 48 Participants |
| Placebo | Number of Participants With Modified Clinical Resolution | Day 12 | 173 Participants |
| Placebo | Number of Participants With Modified Clinical Resolution | Day 5 | 143 Participants |
| Placebo | Number of Participants With Modified Clinical Resolution | Day 8 | 175 Participants |
| Placebo | Number of Participants With Modified Clinical Resolution | Day 3 | 93 Participants |
Secondary
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
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.
Time frame: 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.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| SHP640 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 106 Participants |
| PVP-I 0.6% | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 43 Participants |
| Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 61 Participants |
Secondary
Ocular Conjunctival Discharge Score
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.
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SHP640 | Ocular Conjunctival Discharge Score | Day 3 | 0.7 Score on a scale | Standard Deviation 0.73 |
| SHP640 | Ocular Conjunctival Discharge Score | Day 5 | 0.3 Score on a scale | Standard Deviation 0.57 |
| SHP640 | Ocular Conjunctival Discharge Score | Day 8 | 0.1 Score on a scale | Standard Deviation 0.43 |
| SHP640 | Ocular Conjunctival Discharge Score | Day 12 | 0.1 Score on a scale | Standard Deviation 0.49 |
| PVP-I 0.6% | Ocular Conjunctival Discharge Score | Day 12 | 0.0 Score on a scale | Standard Deviation 0.22 |
| PVP-I 0.6% | Ocular Conjunctival Discharge Score | Day 3 | 0.8 Score on a scale | Standard Deviation 0.74 |
| PVP-I 0.6% | Ocular Conjunctival Discharge Score | Day 8 | 0.1 Score on a scale | Standard Deviation 0.31 |
| PVP-I 0.6% | Ocular Conjunctival Discharge Score | Day 5 | 0.2 Score on a scale | Standard Deviation 0.44 |
| Placebo | Ocular Conjunctival Discharge Score | Day 12 | 0.1 Score on a scale | Standard Deviation 0.28 |
| Placebo | Ocular Conjunctival Discharge Score | Day 5 | 0.4 Score on a scale | Standard Deviation 0.6 |
| Placebo | Ocular Conjunctival Discharge Score | Day 8 | 0.2 Score on a scale | Standard Deviation 0.47 |
| Placebo | Ocular Conjunctival Discharge Score | Day 3 | 0.7 Score on a scale | Standard Deviation 0.76 |
Secondary
Time to Clinical Resolution
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.
Time frame: 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| SHP640 | Time to Clinical Resolution | 5 Days |
| PVP-I 0.6% | Time to Clinical Resolution | 6 Days |
| Placebo | Time to Clinical Resolution | 8 Days |