Preservative-free Tafluprost/Timolol Fixed Combination: Morning vs Evening Dosing (TTFC)

A 3-month Study Investigating the 24-hour Efficacy With the Preservative-free Tafluprost/Timolol Fixed Combination Dosed Morning, or Evening in Subjects With Open-angle Glaucoma Insufficiently Controlled With Latanoprost Monotherapy

The ideal dosing for preservative-free tafluprost/timolol fixed combination remains to be elucidated. The present study compared the 24-hour intraocular pressure efficacy obtained with tafluprost/timolol given once in the evening with placebo once in the morning, versus that with the same fixed combination administered once in the morning with placebo given once in the evening in consecutive patients with open-angle glaucoma insufficiently controlled with branded, or generic latanoprost monotherapy.

Study Overview

• Status: Completed
• Conditions: Glaucoma, Open-Angle
• Intervention / Treatment: Drug: Tafluprost/timolol fixed combination

Detailed Description

Prospective, observer-masked, placebo-controlled, crossover, comparison in consecutive open-angle glaucoma patients, insufficiently controlled with preserved latanoprost monotherapy (mean 24-hr IOP greater than 20 mmHg). Patients were randomized to either morning (08:00), or evening (20:00) preservative-free tafluprost/timolol fixed combination for 3 months and then were crossed over. After each treatment period patients underwent habitual 24-hour intraocular pressure monitoring with Goldmann tonometry in the sitting position (at 10:00, 14:00, 18:00 and 22:00) and Perkins tonometry in the supine position (at 02:00 and 06:00).

Primary Study Objective: Mean 24-hour efficacy with both dosing regimens of tafluprost/timolol fixed combination versus latanoprost monotherapy.

Secondary Study Objectives

1. Mean efficacy with the evening dosing of tafluprost/timolol compared with the morning-dosed tafluprost/timolol fixed combination at each time point measured.
2. Mean daytime and mean nighttime IOP control with the two dosing regimens.
3. Mean peak and fluctuation of 24-hour pressure with the evening and the morning dosing of the fixed combination.

• Study Type: Interventional
• Enrollment (Actual): 42
• Phase: Phase 4

Contacts and Locations

Study Locations

• Greece
  • Makedonia
    • Thessaloníki, Makedonia, Greece, 54636
      • 1st University Department of Ophthalmology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. age between 21-85 years;
2. mild to moderate glaucomatous disc damage and visual field loss (less than -12 dB mean deviation visual field loss attributed to glaucoma and 0.8 or better vertical cup-to-disc ratio);
3. visual acuity greater than 0.1 in the study eye;
4. open anterior chamber angles;
5. in each patient the diagnosis of open-angle glaucoma will be made by the principal investigator based on the European Glaucoma Society criteria;
6. study patients will have to demonstrate a reliable visual field (at least two visual fields with less than 20% fixation losses, false positives, or negatives);
7. patient should understand the study instructions and to be willing to attend all follow-up appointments and should be willing to comply with study medication usage.

Exclusion Criteria:

1. previous history of less than 10% IOP decrease on any IOP-lowering medication;
2. evidence of concurrent conjunctivitis, keratitis, or uveitis in either eye;
3. history of inadequate adherence; intolerance, or contraindication to either prostaglandins, β-blockers, dorzolamide, or benzalconium chloride (BAK);
4. severe ocular surface disease, intraocular conventional or laser surgery in the study eye (within 6 months prior to enrolment);
5. previous history of ocular trauma;
6. use of corticosteroids (within 3 months before the enrolment) and use of contact lenses;
7. patients will also be excluded if on baseline exam they show clinical evidence of inflammation, signs of ocular infection (except blepharitis), signs of any corneal abnormality that will affect subsequent IOP measurements;
8. unwillingness to participate in the trial;
9. females of childbearing potential or lactating mothers.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Tafluprost/timolol with PM dosing; Therapy with Tafluprost/timolol fixed combination drops dosed PM (20:00)	Drug: Tafluprost/timolol fixed combination; Evaluation of 24-hour pressure control with tafluprost/timolol given in the evening or morning; Other Names: Taptiqom
Active Comparator: Tafluprost/timolol with AM dosing; Therapy with Tafluprost/timolol fixed combination drops dosed AM (08:00)	Drug: Tafluprost/timolol fixed combination; Evaluation of 24-hour pressure control with tafluprost/timolol given in the evening or morning; Other Names: Taptiqom

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean 24-hour pressure control with Tafluprost/timolol fixed combination dosed morning or evening	24-hour efficacy documented after each period of therapy	3-month study

Collaborators and Investigators

• Sponsor: Aristotle University Of Thessaloniki
• Collaborators: Santen Oy
• Investigators: Study Director: Theodoros Giannopoulos, MD, Aristotle University

Publications and helpful links

General Publications

• Konstas AG, Katsanos A, Athanasopoulos GP, Voudouragkaki IC, Panagiotou ES, Pagkalidou E, Haidich AB, Giannoulis DA, Spathi E, Giannopoulos T, Katz LJ. Preservative-free tafluprost/timolol fixed combination: comparative 24-h efficacy administered morning or evening in open-angle glaucoma patients. Expert Opin Pharmacother. 2018 Dec;19(18):1981-1988. doi: 10.1080/14656566.2018.1534958. Epub 2018 Oct 17.

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2017
• Primary Completion (Actual): April 1, 2018
• Study Completion (Actual): July 1, 2018

Study Registration Dates

• First Submitted: July 20, 2018
• First Submitted That Met QC Criteria: July 27, 2018
• First Posted (Actual): August 2, 2018

Study Record Updates

• Last Update Posted (Actual): December 17, 2020
• Last Update Submitted That Met QC Criteria: December 16, 2020
• Last Verified: December 1, 2020

More Information

Terms related to this study

• Keywords: tafluprost/timolol fixed combination, 24-hour IOP control
• Additional Relevant MeSH Terms: Eye Diseases; Ocular Hypertension; Glaucoma; Glaucoma, Open-Angle; Physiological Effects of Drugs; Adrenergic beta-Antagonists; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Antihypertensive Agents; Timolol
• Other Study ID Numbers: 433

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No