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

October 12, 2020 updated by: Wan Haslina Wan Abdul Halim, National University of Malaysia
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.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Anticipated)

128

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Malaysia
    • Kuala Lumpur
      • Cheras, Kuala Lumpur, Malaysia, 56000
        • Recruiting
        • UKM Medical Centre
        • Contact:
        • Principal Investigator:
          • Wan Haslina Wan Abdul Halim, M.D
        • Sub-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
    • Wilayah Persekutuan
      • Kuala Lumpur, Wilayah Persekutuan, Malaysia, 50300
        • Enrolling by invitation
        • Faculty of Pharmacy, National University of Malaysia

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / 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: 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: 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-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%

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Comparison of volume of distribution (Maximum Plasma Concentration) of Levofloxacin 1.5% vs Moxifloxacin 0.5% in the aqueous and vitreous fluid.
Time Frame: 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.
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.
Time Frame: 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.
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.
Time Frame: 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.
Throughout study completion, an average of 2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National University of Malaysia

Collaborators

Santen Pharmaceutical Co., Ltd.

Investigators

  • Study Chair: Wan Haslina Wan Abdul Halim, M.D, Department of Ophthalmology, UKM Medical Centre

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 23, 2019

Primary Completion (Anticipated)

August 1, 2021

Study Completion (Anticipated)

May 1, 2022

Study Registration Dates

First Submitted

December 10, 2019

First Submitted That Met QC Criteria

December 29, 2019

First Posted (Actual)

January 2, 2020

Study Record Updates

Last Update Posted (Actual)

October 14, 2020

Last Update Submitted That Met QC Criteria

October 12, 2020

Last Verified

December 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • FF-2019-315

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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