iPERME: Evaluation Of Aqueous Humor Of Levofloxacin-Dexamethasone Eye Drops And Of Its Components In Patients Undergoing Cataract Surgery

• Sponsor: NTC srl (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03740659
• Collaborator: (none)
• Enrollment: 125
• Locations: 2
• Arms: 3
• Actual Duration (Months): 3.1
• Patients Per Site: 62.5
• Patients Per Site Per Month: 20.5

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the penetration of levofloxacin and dexamethasone 21-phosphate into the aqueous humour after ocular administration in combination or as single active ingredients.

Condition or Disease	Intervention/Treatment	Phase
Cataract	Drug: Levofloxacin + Dexamethasone; Drug: Levofloxacin; Drug: Dexamethasone	Phase 2

Detailed Description

In most cases, postoperative care after cataract surgery consists of antiinflammatory and antibacterial drug therapy. The use of an ophthalmic solution containing the combination of a steroid and an antibiotic is routinely used in clinical practice; however, treatment duration could favour the emergence of antibiotic resistance. The study treatment associating a broad-spectrum antibiotic with a highly effective corticosteroid that can be used for a short period of time (one week) is therefore of considerable interest.

The aim of this study is to measure the concentrations of levofloxacin and dexamethasone in the aqueous humour after topical application of the combined ophthalmic solution and its single components.

Study Design

• Study Type: Interventional
• Actual Enrollment: 125 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: A randomized, assessor-blinded, parallel-group study.A randomized, assessor-blinded, parallel-group study.
• Masking: Single (Outcomes Assessor)
• Masking Description: Single
• Primary Purpose: Other
• Official Title: Aqueous Humour Concentrations After Topical apPlication of combinEd Levofloxacin-dexamethasone Eye dRops and of Its Single Components: a randoMized, assEssor-blinded, Parallel-group Study in Patients Undergoing Cataract Surgery - iPERME
• Actual Study Start Date: Sep 4, 2018
• Actual Primary Completion Date: Dec 6, 2018
• Actual Study Completion Date: Dec 6, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Levofloxacin + Dexamethasone Levofloxacin 5 mg/ml + Dexamethasone 1 mg/ml (30 μl administered twice before Limbal paracentesis). Limbal paracentesis will be performed prior to cataract surgery.	Drug: Levofloxacin + Dexamethasone; Levofloxacin + Dexamethasone ophthalmic solution + dexamethasone 21-phosphate administered twice: 90(±15) min. and 60(±15) min. before limbal paracentesis.
Active Comparator: Levofloxacin Levofloxacin 5 mg/ml (30 μl administered twice before Limbal paracentesis). Limbal paracentesis will be performed prior to cataract surgery.	Drug: Levofloxacin; Levofloxacin ophthalmic solution (Oftaquix®) administered twice: 90 (±15) min. and 60 (±15) min. before limbal paracentesis).; Other Names: Oftaquix®
Active Comparator: Dexamethasone Dexamethasone 1.14 mg/ml (26 μl administered twice before Limbal paracentesis). Limbal paracentesis will be performed prior to cataract surgery.	Drug: Dexamethasone; Dexamethasone ophthalmic solution (Tamesad®) administered twice: 90 (±15) min. and 60 (±15) min. before Limbal paracentesis.; Other Names: Tamesad®

Outcome Measures

Primary Outcome Measures

1. Aqueous Humour Concentration of Levofloxacin [90±15 min after the first administration of the study treatments]

   Defined as the concentration of levofloxacin into the aqueous humour in all the three arms: Levofloxacin + Dexamethasone, Dexamethasone and Levofloxacin.The concentration of levofloxacin has been measured by LC tandem mass spectrometry.

2. Aqueous Humour Concentration of Dexamethasone 21-phosphate [90±15 min after the first administration of the study treatments]

   Defined as the concentration of dexamethasone 21-phosphate into the aqueous humour in all the three arms: Levofloxacin + Dexamethasone, Dexamethasone and Levofloxacin. The concentration of dexamethasone 21-phosphate has been measured by LC tandem mass spectrometry.

3. Aqueous Humour Concentration of Dexamethasone [90±15 min after the first administration of the study treatments]

   Defined as the concentration of dexamethasone into the aqueous humour in all the three arms: Levofloxacin + Dexamethasone, Dexamethasone and Levofloxacin.The concentration of dexamethasone has been measured by LC tandem mass spectrometry.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 40 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Written informed consent

2. Male or female patients, aged ≥40 years

3. Patient undergoing phacoemulsification

4. Corneal thickness between 450 μm and 600 μm as measured by means of pachymetry

5. Corneal integrity confirmed by means of fluorescein test

6. Adequate pupil dilation assessed at screening

7. Female patients of childbearing potential must have a negative pregnancy test

8. Ability to fully understand all study procedures

Exclusion Criteria:

1. Corneal epithelium integrity not confirmed by fluorescein test

2. History of corneal disease or dystrophy

3. History of ocular trauma with corneal damage

4. History of acute ocular inflammation (including uveitis) in the 6 months prior to screening

5. Previous ocular surgery (including laser treatment)

6. Glaucoma

7. Treatment with an ophthalmic investigational drug in the 3 months prior to screening

8. Treatment with any topical ocular drug within 12 hours before start of cataract surgery other than study drugs and instillation of topical anaesthetic within 10 minutes before start of surgery

9. Treatment with any topical steroid or antibiotic drug in the 7 days prior to cataract surgery

10. Treatment with any systemic steroid or antibiotic drug in the 7 days prior to cataract surgery

11. Known hypersensitivity to levofloxacin, other fluoroquinolones or dexamethasone

12. Pregnant or lactating women

13. Patients who have received any investigational drug during the preceding 30 days or 5 times the plasma half-life, or who have previously participated in this trial

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	ASST Santi Paolo e Carlo di Milano - P.O. San Paolo di Milano	Milano	MI	Italy	20142
2	A.O.U. Pisana - P.O. di Cisanello	Pisa	PI	Italy	56124

Sponsors and Collaborators

• NTC srl

Investigators

• Principal Investigator: Marco Nardi, Prof., A.O.U. Pisana - P.O. di Cisanello

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Mar 21, 2018

More Information

Publications

None provided.

• Responsible Party: NTC srl
• ClinicalTrials.gov Identifier: NCT03740659
• Other Study ID Numbers: LevoDesa_05-2017
• First Posted: Nov 14, 2018
• Last Update Posted: Jul 7, 2020
• Last Verified: Jun 1, 2020

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Cataract; Levofloxacin; Ofloxacin; Dexamethasone; Dexamethasone acetate; BB 1101

Study Results

Participant Flow

Recruitment Details	Study Period: Date of first enrolment: 4 September 2018 Date study finalized (last patient last visit): 6 December 2018 Study centres: U.O. Oculistica Universitaria, Azienda Ospedaliera Universitaria Pisana, Presidio Ospedaliero di Cisanello, Pisa; Clinica Oculistica, Presidio Ospedale San Paolo, Milan.
Pre-assignment Detail	Planned sample size n.120; randomized patients n.125; screened patients n.133 (1 patient screened for both eyes).

Arm/Group Title	Levofloxacin + Dexamethasone	Levofloxacin	Dexamethasone
Arm/Group Description	Levofloxacin 0.5% + DSP 0.132% (w/v) eye drops (TEST product). One ml contains levofloxacin hemihydrate 5.12 mg, corresponding to 5 mg of levofloxacin, and DSP 1.32 mg, corresponding to 1 mg of dexamethasone. Administration route: ocular instillation Dose and regimen: two 30 μl doses 30 minutes apart, one 90 ± 15 minutes prior to surgery and the other 60 ± 15 minutes prior to surgery (each dose contains 150 μg anhydrous levofloxacin and 39.6 μg DSP).	Levofloxacin 0.5% eye drops (Oftaquix®). One ml contains 5,12 mg of levofloxacin hemihydrate equal to 5 mg of levofloxacin. Administration route: ocular instillation Dose and regimen: two 30 μl doses 30 minutes apart, one 90 ± 15 minutes prior to surgery and the other 60 ± 15 minutes prior to surgery (each dose contains 150 μg anhydrous levofloxacin).	Dexamethasone sodium phosphate 0.15% eye drops (Tamesad®). One ml contains 1.5 mg of DSP corresponding to 1.14 mg/ml of dexamethasone. Administration route: ocular instillation Dose and regimen: two 26 μl doses 30 minutes apart, one 90 ± 15 minutes prior to surgery and the other 60 ± 15 minutes prior to surgery (each dose containing 39 μg DSP).
Period Title: Overall Study
STARTED	42	42	41
COMPLETED	42	42	41
NOT COMPLETED	0	0	0

Baseline Characteristics

Arm/Group Title	Levofloxacin + Dexamethasone	Levofloxacin	Dexamethasone	Total
Arm/Group Description	Levofloxacin 0.5% + DSP 0.132% (w/v) eye drops (TEST product). One ml contains levofloxacin hemihydrate 5.12 mg, corresponding to 5 mg of levofloxacin, and DSP 1.32 mg, corresponding to 1 mg of dexamethasone. Administration route: ocular instillation Dose and regimen: two 30 μl doses 30 minutes apart, one 90 ± 15 minutes prior to surgery and the other 60 ± 15 minutes prior to surgery (each dose contains 150 μg anhydrous levofloxacin and 39.6 μg DSP).	Levofloxacin 0.5% eye drops (Oftaquix®). One ml contains 5,12 mg of levofloxacin hemihydrate equal to 5 mg of levofloxacin. Administration route: ocular instillation Dose and regimen: two 30 μl doses 30 minutes apart, one 90 ± 15 minutes prior to surgery and the other 60 ± 15 minutes prior to surgery (each dose contains 150 μg anhydrous levofloxacin).	Dexamethasone sodium phosphate 0.15% eye drops (Tamesad®). One ml contains 1.5 mg of DSP corresponding to 1.14 mg/ml of dexamethasone. Administration route: ocular instillation Dose and regimen: two 26 μl doses 30 minutes apart, one 90 ± 15 minutes prior to surgery and the other 60 ± 15 minutes prior to surgery (each dose containing 39 μg DSP).	Total of all reporting groups
Overall Participants	42	42	41	125
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	7 16.7%	4 9.5%	6 14.6%	17 13.6%
>=65 years	35 83.3%	38 90.5%	35 85.4%	108 86.4%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	72.45 (7.60)	75.38 (8.38)	74.59 (8.00)	74.14 (8.03)
Sex: Female, Male (Count of Participants)
Female	27 64.3%	21 50%	21 51.2%	69 55.2%
Male	15 35.7%	21 50%	20 48.8%	56 44.8%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%
Asian	0 0%	1 2.4%	1 2.4%	2 1.6%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%
Black or African American	0 0%	1 2.4%	0 0%	1 0.8%
White	42 100%	40 95.2%	40 97.6%	122 97.6%
More than one race	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
Italy	42 100%	42 100%	41 100%	125 100%

Outcome Measures

1. Primary Outcome

Title	Aqueous Humour Concentration of Levofloxacin
Description	Defined as the concentration of levofloxacin into the aqueous humour in all the three arms: Levofloxacin + Dexamethasone, Dexamethasone and Levofloxacin.The concentration of levofloxacin has been measured by LC tandem mass spectrometry.
Time Frame	90±15 min after the first administration of the study treatments

Outcome Measure Data

Analysis Population Description

Participants in all Arms/Groups were assessed for this Outcome Measure regardless of treatment type

Arm/Group Title	Levofloxacin + Dexamethasone	Levofloxacin	Dexamethasone
Arm/Group Description	Levofloxacin 0.5% + DSP 0.132% (w/v) eye drops (TEST product). One ml contains levofloxacin hemihydrate 5.12 mg, corresponding to 5 mg of levofloxacin, and DSP 1.32 mg, corresponding to 1 mg of dexamethasone. Administration route: ocular instillation Dose and regimen: two 30 μl doses 30 minutes apart, one 90 ± 15 minutes prior to surgery and the other 60 ± 15 minutes prior to surgery (each dose contains 150 μg anhydrous levofloxacin and 39.6 μg DSP).	Levofloxacin 0.5% eye drops (Oftaquix®). One ml contains 5,12 mg of levofloxacin hemihydrate equal to 5 mg of levofloxacin. Administration route: ocular instillation Dose and regimen: two 30 μl doses 30 minutes apart, one 90 ± 15 minutes prior to surgery and the other 60 ± 15 minutes prior to surgery (each dose contains 150 μg anhydrous levofloxacin).	Dexamethasone sodium phosphate 0.15% eye drops (Tamesad®). One ml contains 1.5 mg of DSP corresponding to 1.14 mg/ml of dexamethasone. Administration route: ocular instillation Dose and regimen: two 26 μl doses 30 minutes apart, one 90 ± 15 minutes prior to surgery and the other 60 ± 15 minutes prior to surgery (each dose containing 39 μg DSP).
Measure Participants	42	42	41
Mean (95% Confidence Interval) [nmol/mL]	1.970	2.151	0

2. Primary Outcome

Title	Aqueous Humour Concentration of Dexamethasone 21-phosphate
Description	Defined as the concentration of dexamethasone 21-phosphate into the aqueous humour in all the three arms: Levofloxacin + Dexamethasone, Dexamethasone and Levofloxacin. The concentration of dexamethasone 21-phosphate has been measured by LC tandem mass spectrometry.
Time Frame	90±15 min after the first administration of the study treatments

Outcome Measure Data

Analysis Population Description

Participants in all Arms/Groups were assessed for this Outcome Measure regardless of treatment type

Arm/Group Title	Levofloxacin + Dexamethasone	Levofloxacin	Dexamethasone
Arm/Group Description	Levofloxacin 0.5% + DSP 0.132% (w/v) eye drops (TEST product). One ml contains levofloxacin hemihydrate 5.12 mg, corresponding to 5 mg of levofloxacin, and DSP 1.32 mg, corresponding to 1 mg of dexamethasone. Administration route: ocular instillation Dose and regimen: two 30 μl doses 30 minutes apart, one 90 ± 15 minutes prior to surgery and the other 60 ± 15 minutes prior to surgery (each dose contains 150 μg anhydrous levofloxacin and 39.6 μg DSP).	Levofloxacin 0.5% eye drops (Oftaquix®). One ml contains 5,12 mg of levofloxacin hemihydrate equal to 5 mg of levofloxacin. Administration route: ocular instillation Dose and regimen: two 30 μl doses 30 minutes apart, one 90 ± 15 minutes prior to surgery and the other 60 ± 15 minutes prior to surgery (each dose contains 150 μg anhydrous levofloxacin).	Dexamethasone sodium phosphate 0.15% eye drops (Tamesad®). One ml contains 1.5 mg of DSP corresponding to 1.14 mg/ml of dexamethasone. Administration route: ocular instillation Dose and regimen: two 26 μl doses 30 minutes apart, one 90 ± 15 minutes prior to surgery and the other 60 ± 15 minutes prior to surgery (each dose containing 39 μg DSP).
Measure Participants	42	42	41
Mean (95% Confidence Interval) [nmol/mL]	0	0	0

3. Primary Outcome

Title	Aqueous Humour Concentration of Dexamethasone
Description	Defined as the concentration of dexamethasone into the aqueous humour in all the three arms: Levofloxacin + Dexamethasone, Dexamethasone and Levofloxacin.The concentration of dexamethasone has been measured by LC tandem mass spectrometry.
Time Frame	90±15 min after the first administration of the study treatments

Outcome Measure Data

Analysis Population Description

Participants in all Arms/Groups were assessed for this Outcome Measure regardless of treatment type

Arm/Group Title	Levofloxacin + Dexamethasone	Levofloxacin	Dexamethasone
Arm/Group Description	Levofloxacin 0.5% + DSP 0.132% (w/v) eye drops (TEST product). One ml contains levofloxacin hemihydrate 5.12 mg, corresponding to 5 mg of levofloxacin, and DSP 1.32 mg, corresponding to 1 mg of dexamethasone. Administration route: ocular instillation Dose and regimen: two 30 μl doses 30 minutes apart, one 90 ± 15 minutes prior to surgery and the other 60 ± 15 minutes prior to surgery (each dose contains 150 μg anhydrous levofloxacin and 39.6 μg DSP).	Levofloxacin 0.5% eye drops (Oftaquix®). One ml contains 5,12 mg of levofloxacin hemihydrate equal to 5 mg of levofloxacin. Administration route: ocular instillation Dose and regimen: two 30 μl doses 30 minutes apart, one 90 ± 15 minutes prior to surgery and the other 60 ± 15 minutes prior to surgery (each dose contains 150 μg anhydrous levofloxacin).	Dexamethasone sodium phosphate 0.15% eye drops (Tamesad®). One ml contains 1.5 mg of DSP corresponding to 1.14 mg/ml of dexamethasone. Administration route: ocular instillation Dose and regimen: two 26 μl doses 30 minutes apart, one 90 ± 15 minutes prior to surgery and the other 60 ± 15 minutes prior to surgery (each dose containing 39 μg DSP).
Measure Participants	42	42	41
Mean (95% Confidence Interval) [nmol/mL]	0.030	0	0.042

Adverse Events

Time Frame	From baseline to the study completion, approximately 2 hours
Arm/Group Title	Levofloxacin + Dexamethasone		Levofloxacin		Dexamethasone
Arm/Group Description	Levofloxacin 0.5% + DSP 0.132% (w/v) eye drops (TEST product). One ml contains levofloxacin hemihydrate 5.12 mg, corresponding to 5 mg of levofloxacin, and DSP 1.32 mg, corresponding to 1 mg of dexamethasone. Administration route: ocular instillation Dose and regimen: two 30 μl doses 30 minutes apart, one 90 ± 15 minutes prior to surgery and the other 60 ± 15 minutes prior to surgery (each dose contains 150 μg anhydrous levofloxacin and 39.6 μg DSP).		Levofloxacin 0.5% eye drops (Oftaquix®). One ml contains 5,12 mg of levofloxacin hemihydrate equal to 5 mg of levofloxacin. Administration route: ocular instillation Dose and regimen: two 30 μl doses 30 minutes apart, one 90 ± 15 minutes prior to surgery and the other 60 ± 15 minutes prior to surgery (each dose contains 150 μg anhydrous levofloxacin).		Dexamethasone sodium phosphate 0.15% eye drops (Tamesad®). One ml contains 1.5 mg of DSP corresponding to 1.14 mg/ml of dexamethasone. Administration route: ocular instillation Dose and regimen: two 26 μl doses 30 minutes apart, one 90 ± 15 minutes prior to surgery and the other 60 ± 15 minutes prior to surgery (each dose containing 39 μg DSP).
All Cause Mortality
	Levofloxacin + Dexamethasone		Levofloxacin		Dexamethasone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/42 (0%)		0/42 (0%)		0/41 (0%)
Serious Adverse Events
	Levofloxacin + Dexamethasone		Levofloxacin		Dexamethasone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/42 (0%)		0/42 (0%)		0/41 (0%)
Other (Not Including Serious) Adverse Events
	Levofloxacin + Dexamethasone		Levofloxacin		Dexamethasone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/42 (0%)		0/42 (0%)		1/41 (2.4%)
Eye disorders
Mild Mydriasis	0/42 (0%)	0	0/42 (0%)	0	1/41 (2.4%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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