The Pharmacokinetics of Topical Levofloxacin 1.5% vs Topical Moxifloxacin 0.5%

The Pharmacokinetics of Topical Levofloxacin 1.5% vs Topical Moxifloxacin 0.5%

Sponsors

Lead Sponsor: National University of Malaysia

Collaborator: Santen Pharmaceutical Co., Ltd.

Source National University of Malaysia
Brief Summary

Endophthalmitis is defined as intraocular inflammatory disorder affecting the vitreous cavity that can result from exogenous or endogenous spread of infecting organisms into the eye. Patients presents with reduced or blurred vision, red eye, pain, and lid swelling. Endophthalmitis can progress into panophthalmitis, corneal infiltration and perforation, and finally phthisis bulbi. For exogenous endopthalmitis, the intraocular inflammation occurs due to a breach of the ocular compartment. The infectious agent indirectly introduced into the eye. This usually happens after intraocular surgery such as cataract surgery, vitrectomy, glaucoma filtration surgery, intravitreal injections, and other causes include penetrating ocular trauma or from adjacent periocular tissue. Several prophylactic measures have been taken to reduce the incidence of post-operative endopthalmitis post-cataract surgery, this includes the use of pre-operative topical levofloxacin, intracameral cefuroxime, and providone iodine as ocular surface preparation.The proposed study is to evaluate the pharmacokinetic parameters of Levofloxacin 1.5% vs Moxifloxacin 0.5% aqueous and vitreous fluid after topical administration on the anterior segment parameters.

Detailed Description

This is a prospective, double - blinded randomized clinical trial conducted in University Kebangsaan Malaysia Medical Centre (UKMMC) where there are two intervention arms. All patients from Ophthalmology Clinic in UKM Medical Centre from September 2019 till December 2021 will be involved in this study. Patients who fulfill the inclusion criteria will be included in this study. All eligible subjects will be asked to sign an informed consent.

The qualified patients will be randomized on a 1:1 ratio into each treatment arm. Qualified eyes were further randomized into one of four subgroups, which specified the time between the last drop of study medication and the time of aqueous and vitreous humor sample collection (i.e., 1-, 2-, 4-, and 6-hour subgroups- about 32 patients per subgroup-: 16 Levofloxacin, 16 Moxifloxacin.

For 3 days prior to the day of the elective vitrectomy surgery, subjects will instill exactly one drop of study medication into their operative eye four times daily. On the day of surgery (visit 2, day 4), patients will receive their final drop of study medication administered by trained study personnel at the study site.

Samples of aqueous (0.1 ml), and vitreous (0.2 ml) humour were taken simultaneously from the same patient at the commencement of surgery by paracentesis using a 30-gauge needle on a tuberculin syringe. All samples will be stored at -80°C as soon as possible until the concentrations of the drug will be measured.

Measurements for moxifloxacin and levofloxacin concentrations in aqueous fluid will be determined using HPLC with UV detection, which is currently undergoing method development and validation at the Faculty of Pharmacy, UKM. Measurements for moxifloxacin and levofloxacin concentrations in vitreous fluid will be outsourced to a laboratory at the Centre for Research and Instrument Management (CRIM) in UKM, due to the high sensitivity required to determine the drugs' concentrations in vitreous fluid.

A compartmental analysis will be carried out using AUC0-6, Cmax, and time to Cmax (Tmax) will be determined by direct observation. The median AUC0-6 calculation will be performed using the linear trapezoid method. A Kruskal-Wallis nonparametric one-way analysis of variance (ANOVA) will be used to detect differences between the concentrations in each treatment arm at various time points. A p value of <0.05 is considered statistically significant. Data management and statistical analysis will be performed using the PKNCA package in R and SPSS ver 23.0, whichever deemed suitable.

Overall Status Recruiting
Start Date September 23, 2019
Completion Date August 2021
Primary Completion Date August 2020
Phase Phase 1/Phase 2
Study Type Interventional
Primary Outcome
Measure Time Frame
Comparison of volume of distribution (Maximum Plasma Concentration) of Levofloxacin 1.5% vs Moxifloxacin 0.5% in the aqueous and vitreous fluid. Throughout study completion, an average of 2 years
Comparison of volume of distribution (Area under the plasma concentration versus time curve) of Levofloxacin 1.5% vs Moxifloxacin 0.5% in the aqueous and vitreous fluid. Throughout study completion, an average of 2 years
Comparison of concentration of Levofloxacin 1.5% and Moxifloxacin 0.5% in the aqueous and vitreous fluid. Throughout study completion, an average of 2 years
Enrollment 128
Condition
Intervention

Intervention Type: Drug

Intervention Name: Levofloxacin Ophthalmic Solution

Description: Levofloxacin hydrate, an aqueous ophthalmic solution, to be given one drop at a time, 4 times daily for 3 days pre-operatively and one drop on the day of operation.

Other Name: Cravit 1.5%

Intervention Type: Drug

Intervention Name: Moxifloxacin Ophthalmic Solution

Description: Moxifloxacin hydrochloride, an aqueous ophthalmic solution, to be given one drop at a time, 4 times daily for 3 days pre-operatively and one drop on the day of operation.

Other Name: Vigamox 0.5%

Eligibility

Criteria:

Inclusion Criteria:

- All patients planned for vitrectomy for macula hole , ERM, RD surgery

- Age 18 and above

- Not on any topical medication

Exclusion Criteria:

- Patients with underlying ocular surface disease

- Fluoroquinolone allergy

Gender: All

Minimum Age: 18 Years

Maximum Age: N/A

Healthy Volunteers: No

Overall Official
Last Name Role Affiliation
Wan Haslina Wan Abdul Halim, M.D Study Chair Department of Ophthalmology, UKM Medical Centre
Overall Contact

Last Name: Wan Haslina Wan Abdul Halim, M.D

Phone: +6019-6679633

Email: [email protected]

Location
Facility: Status: Contact: Investigator:
UKM Medical Centre | Cheras, Kuala Lumpur, 56000, Malaysia Recruiting Wan Haslina Wan Abdul Halim, M.D +6019-6679633 [email protected] Wan Haslina Wan Abdul Halim, M.D Principal Investigator Norshamsiah Md Din, M.D Sub-Investigator Mae-Lynn Catherine Bastion, M.D Sub-Investigator Mushawiahti Mustapha, M.D Sub-Investigator Othmaliza Othman, M.D Sub-Investigator Norashikin Maslan Sub-Investigator
Faculty of Pharmacy, National University of Malaysia | Kuala Lumpur, Wilayah Persekutuan, 50300, Malaysia Enrolling by invitation
Location Countries

Malaysia

Verification Date

December 2019

Responsible Party

Type: Principal Investigator

Investigator Affiliation: National University of Malaysia

Investigator Full Name: Wan Haslina Wan Abdul Halim

Investigator Title: Consultant Ophthalmologist-Cornea And Anterior Segment

Keywords
Has Expanded Access No
Condition Browse
Number Of Arms 8
Arm Group

Label: Levofloxacin -1 hour group

Type: Active Comparator

Description: Levofloxacin hydrate, an aqueous ophthalmic solution, to be given one drop at a time, 4 times daily (8am, 12pm, 4pm, 8pm) for 3 days prior to the surgery. On the day of surgery, there will be 1-hour gap between last drop of study medication and the time of aqueous and vitreous humor sample collection.

Label: Levofloxacin-2 hour group

Type: Active Comparator

Description: Levofloxacin hydrate, an aqueous ophthalmic solution, to be given one drop at a time, 4 times daily (8am, 12pm, 4pm, 8pm) for 3 days prior to the surgery. On the day of surgery, there will be 2-hour gap between last drop of study medication and the time of aqueous and vitreous humor sample collection.

Label: Levofloxacin-4 hour group

Type: Active Comparator

Description: Levofloxacin hydrate, an aqueous ophthalmic solution, to be given one drop at a time, 4 times daily (8am, 12pm, 4pm, 8pm) for 3 days prior to the surgery. On the day of surgery, there will be 4-hour gap between last drop of study medication and the time of aqueous and vitreous humor sample collection.

Label: Levofloxacin-6 hour group

Type: Active Comparator

Description: Levofloxacin hydrate, an aqueous ophthalmic solution, to be given one drop at a time, 4 times daily (8am, 12pm, 4pm, 8pm) for 3 days prior to the surgery. On the day of surgery, there will be 6-hour gap between last drop of study medication and the time of aqueous and vitreous humor sample collection

Label: Moxifloxacin-1 hour group

Type: Active Comparator

Description: Moxifloxacin hydrochloride, an aqueous ophthalmic solution, to be given one drop at a time, 4 times daily (8am, 12pm, 4pm, 8pm) for 3 days prior to the surgery. On the day of surgery, there will be 1-hour gap between last drop of study medication and the time of aqueous and vitreous humor sample collection.

Label: Moxifloxacin-2 hour group

Type: Active Comparator

Description: Moxifloxacin hydrochloride, an aqueous ophthalmic solution, to be given one drop at a time, 4 times daily (8am, 12pm, 4pm, 8pm) for 3 days prior to the surgery. On the day of surgery, there will be 2-hour gap between last drop of study medication and the time of aqueous and vitreous humor sample collection.

Label: Moxifloxacin-4 hour group

Type: Active Comparator

Description: Moxifloxacin hydrochloride, an aqueous ophthalmic solution, to be given one drop at a time, 4 times daily (8am, 12pm, 4pm, 8pm) for 3 days prior to the surgery. On the day of surgery, there will be 4-hour gap between last drop of study medication and the time of aqueous and vitreous humor sample collection.

Label: Moxifloxacin-6 hour group

Type: Active Comparator

Description: Moxifloxacin hydrochloride, an aqueous ophthalmic solution, to be given one drop at a time, 4 times daily (8am, 12pm, 4pm, 8pm) for 3 days prior to the surgery. On the day of surgery, there will be 6-hour gap between last drop of study medication and the time of aqueous and vitreous humor sample collection.

Study Design Info

Allocation: Randomized

Intervention Model: Parallel Assignment

Intervention Model Description: The qualified patients will be randomized on a 1:1 ratio into each treatment arm. Qualified eyes were further randomized into one of four subgroups, which specified the time between the last drop of study medication and the time of aqueous and vitreous humor sample collection (i.e., 1-, 2-, 4-, and 6-hour subgroups- about 32 patients per subgroup. Within each subgroups, there will be 16 of Levofloxacin group and 16 of Moxifloxacin group.

Primary Purpose: Prevention

Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Source: ClinicalTrials.gov