| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated | | Patients diagnosed with ocular hypertension or open-angle glaucoma (primary open-angle glaucoma [POAG], capsular glaucoma or pigmentary glaucoma). | |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 12.1 | | E.1.2 | Level | LLT | | E.1.2 | Classification code | 10030043 | | E.1.2 | Term | Ocular hypertension | |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 12.1 | | E.1.2 | Level | LLT | | E.1.2 | Classification code | 10036719 | | E.1.2 | Term | Primary open angle glaucoma | |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 12.1 | | E.1.2 | Level | LLT | | E.1.2 | Classification code | 10035015 | | E.1.2 | Term | Pigmentary glaucoma | |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 12.1 | | E.1.2 | Level | LLT | | E.1.2 | Classification code | 10037118 | | E.1.2 | Term | Pseudoexfoliation glaucoma | |
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial | The objective of this study is to compare the efficacy and safety of the preservative-free FDC of tafluprost 0.0015% and timolol 0.5% eye drops to concomitant administration of preservative-free tafluprost 0.0015% and preservative-free timolol 0.5%.
Primary Efficacy Variable:
o Change from baseline in the average diurnal IOP at 6 months
The primary objective of the study is to demonstrate that after a 6-month treatment period the preservative-free FDC administered once daily is non-inferior to concomitant administration of tafluprost 0.0015% once daily and timolol 0.5% twice daily in patients with open-angle glaucoma (OAG) or ocular hypertension (OH). | |
| E.2.2 | Secondary objectives of the trial | Secondary Efficacy Variables
o Proportion of responders (e.g. a decrease of IOP of 20% or more or an IOP level of 16 mmHg or less) at 6 months
o Change from baseline in the average diurnal IOP at 2 weeks, 6 weeks and 3 months
o Change from baseline in timewise IOPs (at 8:00, 10:00, 16:00) at 2 weeks, 6 weeks, 3 months and 6 months
Evaluation of safety and tolerability of the FDC vs concomitant administration of tafluprost and timolol:
oAdverse events
oVisual acuity
oCentral corneal thickness
oConjunctival redness
oBiomicroscopy
oOphthalmoscopy
oVisual field examination
oResting blood pressure and heart rate
oOverall drop discomfort
| |
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria | Patients of any race and either sex meeting all of the following criteria:
1.Aged 18 years or more
2.A diagnosis of ocular hypertension or open-angle glaucoma (either POAG, capsular glaucoma or pigmentary glaucoma) in one or both eyes
3.Clinical need for additional IOP lowering medication as judged by the investigator and an untreated (after washout if applicable) IOP of ≥23 mmHg at the 8:00 measurement at baseline in one or both eyes
4.Patients on prior glaucoma medication must have following minimum washout:
•≥4 weeks for ß-adrenergic antagonists (ß-blockers)
•≥4 weeks for prostamides or prostaglandin analogues
•≥3 weeks for α-adrenergic agonists (α-agonists)
•≥7 days for carbonic anhydrase inhibitors (CAIs)
•≥5 days for miotics
5.A best corrected ETDRS visual acuity score of +0.6 logMAR or better in both eyes (i.e. monocular patients are not eligible)
6.Are willing to follow instructions
7.Have provided a written informed consent
| |
| E.4 | Principal exclusion criteria | 1.Females who are pregnant, nursing or planning pregnancy, or females of childbearing potential who are not using a reliable method of contraception
2.Anterior chamber angle in either eye to be treated less than grade 2 according to Schaffer classification as measured by gonioscopy
3.Any corneal abnormality or other condition preventing reliable applanation tonometry in the treated eyes, including prior refractive eye surgery
4.IOP greater than 36 mmHg at any time point in either eye at Screening or Baseline visits
5.Diagnosis of angle-closure glaucoma or secondary glaucoma other than capsular or pigmentary glaucoma in either eye
6.Suspected contraindication to tafluprost or timolol therapy;
a.hypersensitivity to tafluprost/timolol or any of the excipients
b.low heart rate of <50 bpm (at Screening visit) or clinically relevant low blood pressure for age, chronic obstructive pulmonary disease, bronchial asthma, strong tendency to bronchospasm, certain cardiac arrhythmias, the most common of which are second or third degree AV block and bradycardia, or uncontrolled congestive heart failure
c.also for washout medication Azopt® (use of which is judged by the investigator): hypersensitivity to brinzolamide or any of the excipients, known hypersensitivity to sulphonamide, severe renal insufficiency or hyperchloraemic acidosis
7.Glaucoma filtration surgery or any other ocular surgery (including ocular laser procedures) within 6 months prior to Screening in eye(s) to be treated with study medication
8.Use of contact lenses at Screening or during the study
9.Advanced visual field defect in either eye or anticipated progression during the study as judged by the investigator
10.Inability to safely discontinue the use of ocular hypotensive medications during the washout period
11.Any ocular (e.g. aphakia, pseudophakia with torn posterior lens capsule or anterior chamber lenses, known risk factors for cystoid macular oedema or iritis/uveitis), systemic or psychiatric disease/condition (e.g. uncontrolled arterial hypertension, diabetes) that may put the patient at a significant risk or may confound the study results or may interfere significantly with the patient’s participation in the study as judged by the investigator
12.Change of an existing chronic therapy that could substantially affect the IOP or the study outcomes within 30 days prior to Visit 1, or anticipated change in such therapy during the study
13.Current alcohol or drug abuse
14.Current participation in another clinical trial involving an investigational drug/device, or participation in such a trial within the last 30 days | |
| E.5 End points |
| E.5.1 | Primary end point(s) | Change from baseline in the average diurnal intraocular pressure (IOP) at 6 months.
Diurnal IOP measurements will be performed at 8:00 (+/- 1 h), 10:00 (+/- 1 h) and 16:00 (+/- 1 h)
The primary evaluation of IOP will be based on the worse eye. | |
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Yes |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| E.8.3 | The trial involves single site in the Member State concerned | No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 5 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 35 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | No |
| E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
| E.8.7 | Trial has a data monitoring committee | No |
| E.8.8 | Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial | | As stated in the protocol | |
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 1 |
| E.8.9.1 | In the Member State concerned months | 4 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 1 |
| E.8.9.2 | In all countries concerned by the trial months | 4 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
