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

Sponsor

National University of Malaysia (Other)

Overall Status

Unknown status

CT.gov ID

NCT04214821

Collaborator

Santen Pharmaceutical Co., Ltd. (Industry)

128

Enrollment

Locations

Arms

31.2

Anticipated Duration (Months)

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Endophthalmitis	Drug: Levofloxacin Ophthalmic Solution Drug: Moxifloxacin Ophthalmic Solution	Phase 1/Phase 2

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.

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

128 participants

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.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.

Masking:

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

Primary Purpose:

Prevention

Official Title:

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

Actual Study Start Date :

Sep 23, 2019

Anticipated Primary Completion Date :

Aug 1, 2021

Anticipated Study Completion Date :

May 1, 2022

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Levofloxacin -1 hour group 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.	Drug: Levofloxacin Ophthalmic Solution 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 Names: Cravit 1.5%
Active Comparator: Levofloxacin-2 hour group 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.	Drug: Levofloxacin Ophthalmic Solution 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 Names: Cravit 1.5%
Active Comparator: Levofloxacin-4 hour group 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.	Drug: Levofloxacin Ophthalmic Solution 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 Names: Cravit 1.5%
Active Comparator: Levofloxacin-6 hour group 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	Drug: Levofloxacin Ophthalmic Solution 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 Names: Cravit 1.5%
Active Comparator: Moxifloxacin-1 hour group 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.	Drug: Moxifloxacin Ophthalmic Solution 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 Names: Vigamox 0.5%
Active Comparator: Moxifloxacin-2 hour group 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.	Drug: Moxifloxacin Ophthalmic Solution 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 Names: Vigamox 0.5%
Active Comparator: Moxifloxacin-4 hour group 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.	Drug: Moxifloxacin Ophthalmic Solution 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 Names: Vigamox 0.5%
Active Comparator: Moxifloxacin-6 hour group 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.	Drug: Moxifloxacin Ophthalmic Solution 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 Names: Vigamox 0.5%

Outcome Measures

Primary Outcome Measures

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]
A compartmental analysis will be carried out. Data for the pooled aqueous and vitreous humor concentrations in each of the treatment groups, n, mean, SD, median, and coefficient of variation, and range values for each time point will be calculated. Since each patient contributed to this pooled non-compartmental analysis at a specified time point, Maximum Plasma Concentration (Cmax), and time to Cmax (Tmax) will be determined by direct observation.
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]
A compartmental analysis will be carried out. Data for the pooled aqueous and vitreous humor concentrations in each of the treatment groups, n, mean, SD, median, and coefficient of variation, and range values for each time point will be calculated. Since each patient contributed to this pooled non-compartmental analysis at a specified time point, a representative Area under the plasma concentration versus time curve (AUC0-6) will be determined by direct observation. The median AUC0-6 calculation will be performed using the linear trapezoid method.
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]
The mean concentration vs time of last drop (i.e. AUC) will be plotted for both levofloxacin 1.5% and moxofloxacin 0.5% in aqueous and vitreous fluids. A Kruskal-Wallis non-parametric one-way analysis of variance (ANOVA) will be used to detect differences between the concentrations in each treatment arm at various time points.