Safety of Besivance™ (Besifloxacin Ophthalmic Suspension) 0.6% Compared to Vehicle

• Sponsor: Bausch & Lomb Incorporated (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01175590
• Collaborator: (none)
• Enrollment: 518
• Location: 1
• Arms: 2
• Duration (Months): 20
• Patients Per Site Per Month: 25.8

Study Details

Study Description

Brief Summary

The objective of this study is to evaluate the safety of Besivance (besifloxacin ophthalmic suspension, 0.6%) compared to vehicle.

Condition or Disease	Intervention/Treatment	Phase
Bacterial Conjunctivitis	Drug: Besivance; Drug: Vehicle	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 518 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Study to Evaluate the Safety of Besivance™ (Besifloxacin Ophthalmic Suspension) 0.6% Compared to Vehicle Following Three Times Daily(TID) Dosing for 7 Days
• Study Start Date: Jun 1, 2010
• Actual Primary Completion Date: Dec 1, 2011
• Actual Study Completion Date: Feb 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Besivance besifloxacin ophthalmic suspension 0.6%	Drug: Besivance; Ocular administration to affected eye for 7 days
Placebo Comparator: Vehicle Vehicle of Besivance	Drug: Vehicle; Vehicle of Besivance administered to affected eye for 7 days

Outcome Measures

Primary Outcome Measures

1. Ocular Treatment Emergent Adverse Events [At each visit - 7 days]

   Ocular Treatment-Emergent Adverse Events on the Study Eye

2. Non-Ocular Treatment-Emergent Adverse Events [7 days]

   Non-Ocular Treatment-Emergent Adverse Events on the Study Eye

Secondary Outcome Measures

1. Clinical Resolution [Day 8 (Visit 2)]

   The absence of both conjunctival discharge and bulbar conjunctival injection, after seven days of treatment. Participants with non-missing data

2. Clinical Resolution [Day 11 (Visit 3)]

   The absence of both conjunctival discharge and bulbar conjunctival injection, after seven days of treatment.

3. Microbial Eradication [Days 8 (Visit 2)]

   The absence of all accepted ocular bacterial species that were present at or above threshold at baseline, after seven days of treatment.

4. Microbial Eradication [Days 11 (Visit 3)]

   The absence of all accepted ocular bacterial species that were present at or above threshold at baseline, after seven days of treatment.

5. Microbial Outcome With Clinical Resolution [Day 8 (Visit 2)]

   At each follow-up visit for the accepted ocular bacterial species that were present at or above threshold at baseline

6. Microbial Outcome With Clinical Resolution [Day 11 (Visit 3)]

   At each follow-up visit for the accepted ocular bacterial species that were present at or above threshold at baseline

7. Individual Clinical Outcomes - Ocular Discharge [At day 1 (Vist 1)]

   ocular conjunctival discharge measured as absent, mild, moderate or severe

8. Individual Clinical Outcomes - Ocular Discharge [At day 8 (Vist 2)]

   ocular conjunctival discharge measured as absent, mild, moderate or severe

9. Individual Clinical Outcomes - Ocular Discharge [At day 11 (Vist 3)]

   ocular conjunctival discharge measured as absent, mild, moderate or severe

10. Individual Clinical Outcomes - Bulbar Injection [At day 1 (Vist 1)]

    Bulbar conjunctival injection measured as normal, mild, moderate or severe

11. Individual Clinical Outcomes - Bulbar Injection [At day 8 (Vist 2)]

    Bulbar conjunctival injection measured as normal, mild, moderate or severe

12. Individual Clinical Outcomes - Bulbar Injection [At day 11 (Vist 3)]

    Bulbar conjunctival injection measured as normal, mild, moderate or severe

Eligibility Criteria

Criteria

• Ages Eligible for Study: 1 Year and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Subjects must have a clinical diagnosis of acute bacterial conjunctivitis and exhibit purulent conjunctival discharge (crusty or sticky eyelids) and redness in at least one eye.

• Subjects who are willing to discontinue contact lens wear for the duration of the study.

• Subjects who are able and willing to comply with all treatment and follow- up/study procedures.

Exclusion Criteria:

• Subjects who have any uncontrolled systemic disease or debilitating disease.

• Subjects with a known hypersensitivity or contraindications to Besivance, fluoroquinolones, or any of the ingredients in the study drugs.

• Subjects who are expected to require disallowed concurrent systemic or ocular therapy(either eye)during or prior to study start. (ie, NSAIDs, corticosteroids, mast cell stabilizers, antihistamines, decongestants or antimicrobial therapy)

• Subjects having ocular surgery (including laser surgery) in either eye within six weeks prior to entry into this study.

• Subjects with suspected viral or allergic conjunctivitis or any other disease conditions that could interfere with the efficacy and safety evaluations of the study medication.

• Subjects with suspected iritis.

• Subjects with a history of recurrent corneal erosion syndrome, either idiopathic or secondary to previous corneal trauma or dry eye syndrome.

• Subjects with any active ulcerative keratitis, specifically any epithelial loss greater than punctate keratitis.

• Subjects who are immune compromised.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Bausch & Lomb, Inc.	Rochester	New York	United States	14609

Sponsors and Collaborators

• Bausch & Lomb Incorporated

Investigators

• Study Director: Catherine Allaire, MD, Bausch & Lomb Incorporated

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Bausch & Lomb Incorporated
• ClinicalTrials.gov Identifier: NCT01175590
• Other Study ID Numbers: 631
• First Posted: Aug 5, 2010
• Last Update Posted: May 1, 2013
• Last Verified: Mar 1, 2013

• Additional relevant MeSH terms: Conjunctivitis, Bacterial; Conjunctivitis; Besifloxacin

Study Results

Participant Flow

Recruitment Details	First participant entered the study 6/22/2010 and the last participant visit was 12/12/2011. Twenty four sites in the United States participated in the study.
Pre-assignment Detail	518 participants with a clinical diagnosis of bacterial conjunctivitis were enrolled in the study, 496 completed the study; 518 participants were in Intent-to-Treat (ITT) population, 514 participants were in Safety population, and 299 participants were in modified Intent-to-Treat (mITT) population (Participants with positive culture at baseline).

Arm/Group Title	Besivance	Vehicle
Arm/Group Description	besifloxacin ophthalmic suspension 0.6% Besivance : Ocular administration to affected eye for 7 days	Vehicle of Besivance Vehicle : Vehicle of Besivance administered to affected eye for 7 days
Period Title: Overall Study
STARTED	347	171
Modified Intent to Treat Population	212	87
Safety Population	344	170
COMPLETED	335	161
NOT COMPLETED	12	10

Baseline Characteristics

Arm/Group Title	Besivance	Vehicle	Total
Arm/Group Description	besifloxacin ophthalmic suspension 0.6% Besivance : Ocular administration to affected eye for 7 days	Vehicle of Besivance Vehicle : Vehicle of Besivance administered to affected eye for 7 days	Total of all reporting groups
Overall Participants	347	171	518
Age, Customized (participants) [Number]
0-17 years	149 42.9%	62 36.3%	211 40.7%
18 - 49 years	106 30.5%	71 41.5%	177 34.2%
>=50 years	92 26.5%	38 22.2%	130 25.1%
Sex: Female, Male (Count of Participants)
Female	205 59.1%	95 55.6%	300 57.9%
Male	142 40.9%	76 44.4%	218 42.1%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	7 2%	3 1.8%	10 1.9%
Asian	5 1.4%	5 2.9%	10 1.9%
Native Hawaiian or Other Pacific Islander	0 0%	1 0.6%	1 0.2%
Black or African American	83 23.9%	40 23.4%	123 23.7%
White	213 61.4%	103 60.2%	316 61%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	39 11.2%	19 11.1%	58 11.2%

Outcome Measures

1. Primary Outcome

Title	Ocular Treatment Emergent Adverse Events
Description	Ocular Treatment-Emergent Adverse Events on the Study Eye
Time Frame	At each visit - 7 days

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	Besivance	Vehicle
Arm/Group Description	besifloxacin ophthalmic suspension 0.6% Besivance : Ocular administration to affected eye for 7 days	Vehicle of Besivance Vehicle : Vehicle of Besivance administered to affected eye for 7 days
Measure Participants	344	170
Measure eyes	344	170
Conjunctivitis	3	3
Blepharitis	1	1
Conjunctival Oedema	1	1
Erythema of Eyelid	2	0
Punctate Keratitis	1	1
Conjunctival Haemorrhage	1	0
Conjunctivitis Allergic	0	1
Corneal Infiltrates	1	0
Dacryocystitis	1	0
Eye Pain	1	0
Lacrimation Increased	1	0
Scleritis	0	1
Instillation Site Reaction	2	1
Instillation Site Erythema	1	0
Instillation Site Irritation	0	1
Instillation Site Pain	1	0
Pain	0	1
Herpes Dermatitis	1	0
Post-Traumatic Pain	0	1
Corneal Staining	1	0

2. Secondary Outcome

Title	Clinical Resolution
Description	The absence of both conjunctival discharge and bulbar conjunctival injection, after seven days of treatment. Participants with non-missing data
Time Frame	Day 8 (Visit 2)

Outcome Measure Data

Analysis Population Description

Study eye for the mITT population

Arm/Group Title	Besivance	Vehicle
Arm/Group Description	besifloxacin ophthalmic suspension 0.6% Besivance : Ocular administration to affected eye for 7 days	Vehicle of Besivance Vehicle : Vehicle of Besivance administered to affected eye for 7 days
Measure Participants	206	83
Measure eyes	206	83
Number [eyes]	112	46

3. Secondary Outcome

Title	Clinical Resolution
Description	The absence of both conjunctival discharge and bulbar conjunctival injection, after seven days of treatment.
Time Frame	Day 11 (Visit 3)

Outcome Measure Data

Analysis Population Description

Study eye for the mITT population

Arm/Group Title	Besivance	Vehicle
Arm/Group Description	besifloxacin ophthalmic suspension 0.6% Besivance : Ocular administration to affected eye for 7 days	Vehicle of Besivance Vehicle : Vehicle of Besivance administered to affected eye for 7 days
Measure Participants	204	84
Number [eyes]	169	68

4. Secondary Outcome

Title	Microbial Eradication
Description	The absence of all accepted ocular bacterial species that were present at or above threshold at baseline, after seven days of treatment.
Time Frame	Days 8 (Visit 2)

Outcome Measure Data

Analysis Population Description

Study Eye, Modified Intent-to-Treat Population

Arm/Group Title	Besivance	Vehicle
Arm/Group Description	besifloxacin ophthalmic suspension 0.6% Besivance : Ocular administration to affected eye for 7 days	Vehicle of Besivance Vehicle : Vehicle of Besivance administered to affected eye for 7 days
Measure Participants	206	80
Measure eyes	206	80
Number [eyes]	172	36

5. Secondary Outcome

Title	Microbial Eradication
Description	The absence of all accepted ocular bacterial species that were present at or above threshold at baseline, after seven days of treatment.
Time Frame	Days 11 (Visit 3)

Outcome Measure Data

Analysis Population Description

Study Eye, Modified Intent-to-Treat Population

Arm/Group Title	Besivance	Vehicle
Arm/Group Description	besifloxacin ophthalmic suspension 0.6% Besivance : Ocular administration to affected eye for 7 days	Vehicle of Besivance Vehicle : Vehicle of Besivance administered to affected eye for 7 days
Measure Participants	200	83
Measure eyes	200	83
Number [eyes]	169	48

6. Primary Outcome

Title	Non-Ocular Treatment-Emergent Adverse Events
Description	Non-Ocular Treatment-Emergent Adverse Events on the Study Eye
Time Frame	7 days

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	Besivance	Vehicle
Arm/Group Description	besifloxacin ophthalmic suspension 0.6% Besivance : Ocular administration to affected eye for 7 days	Vehicle of Besivance Vehicle : Vehicle of Besivance administered to affected eye for 7 days
Measure Participants	344	170
Ear Pain	1	0
Dysgeusia	1	0
Pyrexia	1	0
Nasopharyngitis	2	1
Bronchitis	0	1
Gastroenteritis, Viral	0	1
Otitis Media	1	0
Upper Respiratory Tract Infection	1	0

7. Secondary Outcome

Title	Microbial Outcome With Clinical Resolution
Description	At each follow-up visit for the accepted ocular bacterial species that were present at or above threshold at baseline
Time Frame	Day 8 (Visit 2)

Outcome Measure Data

Analysis Population Description

Modified Intent-to-Treat Population

Arm/Group Title	Besivance	Vehicle
Arm/Group Description	besifloxacin ophthalmic suspension 0.6% Besivance : Ocular administration to affected eye for 7 days	Vehicle of Besivance Vehicle : Vehicle of Besivance administered to affected eye for 7 days
Measure Participants	206	80
Clinical Resolution with Microbial Eradication	96	22
Clinical Resolution with no Microbial Eradication	16	24
No Clinical Resolution with Microbial Eradication	76	14
No Clinical Resolution no Microbial Eradication	18	20

8. Secondary Outcome

Title	Microbial Outcome With Clinical Resolution
Description	At each follow-up visit for the accepted ocular bacterial species that were present at or above threshold at baseline
Time Frame	Day 11 (Visit 3)

Outcome Measure Data

Analysis Population Description

Modified Intent-to-Treat Population

Arm/Group Title	Besivance	Vehicle
Arm/Group Description	besifloxacin ophthalmic suspension 0.6% Besivance : Ocular administration to affected eye for 7 days	Vehicle of Besivance Vehicle : Vehicle of Besivance administered to affected eye for 7 days
Measure Participants	200	83
Measure eyes	200	83
Clinical Resolution with Microbial Eradication	143	42
Clinical Resolution with no Microbial Eradication	23	25
No Clinical Resolution with Microbial Eradication	26	6
No Clinical Resolution no Microbial Eradication	8	10

9. Secondary Outcome

Title	Individual Clinical Outcomes - Ocular Discharge
Description	ocular conjunctival discharge measured as absent, mild, moderate or severe
Time Frame	At day 1 (Vist 1)

Outcome Measure Data

Analysis Population Description

Baseline-Designated Study Eye (Modified Intent-to- Treat Population)

Arm/Group Title	Besivance	Vehicle
Arm/Group Description	besifloxacin ophthalmic suspension 0.6% Besivance : Ocular administration to affected eye for 7 days	Vehicle of Besivance Vehicle : Vehicle of Besivance administered to affected eye for 7 days
Measure Participants	212	87
Measure eyes	212	87
Absent	0	0
Mild	94	38
Moderate	106	44
Severe	12	5

10. Secondary Outcome

Title	Individual Clinical Outcomes - Ocular Discharge
Description	ocular conjunctival discharge measured as absent, mild, moderate or severe
Time Frame	At day 8 (Vist 2)

Outcome Measure Data

Analysis Population Description

Baseline-Designated Study Eye (Modified Intent-to- Treat Population)

Arm/Group Title	Besivance	Vehicle
Arm/Group Description	besifloxacin ophthalmic suspension 0.6% Besivance : Ocular administration to affected eye for 7 days	Vehicle of Besivance Vehicle : Vehicle of Besivance administered to affected eye for 7 days
Measure Participants	206	83
Measure eyes	206	83
Absent	155	61
Mild	42	18
Moderate	8	4
Severe	1	0

11. Secondary Outcome

Title	Individual Clinical Outcomes - Ocular Discharge
Description	ocular conjunctival discharge measured as absent, mild, moderate or severe
Time Frame	At day 11 (Vist 3)

Outcome Measure Data

Analysis Population Description

Baseline-Designated Study Eye (Modified Intent-to- Treat Population)

Arm/Group Title	Besivance	Vehicle
Arm/Group Description	besifloxacin ophthalmic suspension 0.6% Besivance : Ocular administration to affected eye for 7 days	Vehicle of Besivance Vehicle : Vehicle of Besivance administered to affected eye for 7 days
Measure Participants	204	84
Measure eyes	204	84
Absent	187	77
Mild	12	6
Moderate	4	1
Severe	1	0

12. Secondary Outcome

Title	Individual Clinical Outcomes - Bulbar Injection
Description	Bulbar conjunctival injection measured as normal, mild, moderate or severe
Time Frame	At day 1 (Vist 1)

Outcome Measure Data

Analysis Population Description

Baseline-Designated Study Eye (Modified Intent-to- Treat Population)

Arm/Group Title	Besivance	Vehicle
Arm/Group Description	besifloxacin ophthalmic suspension 0.6% Besivance : Ocular administration to affected eye for 7 days	Vehicle of Besivance Vehicle : Vehicle of Besivance administered to affected eye for 7 days
Measure Participants	212	87
Measure eyes	212	87
Normal	0	0
Mild	110	44
Moderate	83	37
Severe	19	6

13. Secondary Outcome

Title	Individual Clinical Outcomes - Bulbar Injection
Description	Bulbar conjunctival injection measured as normal, mild, moderate or severe
Time Frame	At day 8 (Vist 2)

Outcome Measure Data

Analysis Population Description

Baseline-Designated Study Eye (Modified Intent-to- Treat Population)

Arm/Group Title	Besivance	Vehicle
Arm/Group Description	besifloxacin ophthalmic suspension 0.6% Besivance : Ocular administration to affected eye for 7 days	Vehicle of Besivance Vehicle : Vehicle of Besivance administered to affected eye for 7 days
Measure Participants	206	83
Measure eyes	206	83
Normal	142	57
Mild	56	23
Moderate	7	3
Severe	1	0

14. Secondary Outcome

Title	Individual Clinical Outcomes - Bulbar Injection
Description	Bulbar conjunctival injection measured as normal, mild, moderate or severe
Time Frame	At day 11 (Vist 3)

Outcome Measure Data

Analysis Population Description

Baseline-Designated Study Eye (Modified Intent-to- Treat Population)

Arm/Group Title	Besivance	Vehicle
Arm/Group Description	besifloxacin ophthalmic suspension 0.6% Besivance : Ocular administration to affected eye for 7 days	Vehicle of Besivance Vehicle : Vehicle of Besivance administered to affected eye for 7 days
Measure Participants	204	84
Measure eyes	204	84
Normal	182	72
Mild	18	11
Moderate	4	1
Severe	0	0

Adverse Events

Time Frame	11 days
Arm/Group Title	Besivance		Vehicle
Arm/Group Description	besifloxacin ophthalmic suspension 0.6% Besivance : Ocular administration to affected eye for 7 days		Vehicle of Besivance Vehicle : Vehicle of Besivance administered to affected eye for 7 days
All Cause Mortality
	Besivance		Vehicle
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Besivance		Vehicle
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/347 (0%)		0/171 (0%)
Other (Not Including Serious) Adverse Events
	Besivance		Vehicle
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/347 (0%)		0/171 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The results of the study may be published or presented by the Investigator(s) after the review by, and in consultation and agreement with the Sponsor, and such that confidential or proprietary information is not disclosed. Prior to publication or presentation, a copy of the final text should be forwarded by the Investigator(s) to the Sponsor or its designee, for comment.