E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Eye Diseases [C11] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 16.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10057889 |
E.1.2 | Term | Graves' ophthalmopathy |
E.1.2 | System Organ Class | 100000004853 |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary research question is whether the prostaglandin analogue eye drop preparation, Bimatoprost (PGF2-alpha), routinely used for glaucoma, is effective in reducing eyeball protrusion in patients with thyroid eye disease (TED).
TED is a chronic debilitating disease which can be complicated by sight loss in severe cases. A particular distressing feature of TED is protrusion of the eyeballs (proptosis) which occurs from increased fat accumulation and inflammation behind the eye. Proptosis causes a disfiguring appearance of the eyes which is a source of psychological distress and impaired quality of life in patients with TED. Currently available treatments for TED are unsatisfactory and established therapies which specifically reduce proptosis without involving major surgery are lacking. There is emerging evidence to suggest that prostaglandin analogue eye drops such as Bimatoprost may have a beneficial role in the treatment of TED but this has not been investigated in a controll |
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E.2.2 | Secondary objectives of the trial |
1. Change in quality of life scores on the TED quality of life questionnaire (GO-QOL) 2. Change in intraocular pressures 3. Side effect profiles of bimatoprost in TED patients during the study 4. Health economic consumption
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Stable TED with no reported change in proptosis for at least 6 months 2. Clinical activity score <3 3. Proptosis (subjective unilateral proptosis confirmed by asymmetry in exophthalmometry of >2mm OR greater than 20 mm on exophthalmometry measurement in one eye) 4. Euthyroid (FT3 and FT4 in the reference range). 5. If female, must be using a reliable form of contraception during the trial, e.g. oral contraceptive and condom, intra-uterine device (IUD) and condom, diaphragm with spermicide and condom. |
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E.4 | Principal exclusion criteria |
1. Age <18 yrs 2. Dysthyroid optic neuropathy unless previously treated 3. Pregnancy or lactation 4. Previous Corneal Herpes Simplex infection 5. On therapy for glaucoma or intraocular hypertension 6. Less than 6 months from prior steroid use 7. Aphakia, pseudophakia with torn posterior lens capsule or anterior chamber lenses 8. Patient with risk factors for cystoid macular oedema, iritis or uveitis 9. Severe Asthma (risk of severe allergic reaction to medication). 10. Previous allergy to Bimatoprost or preservative.
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint of this study will be comparison of the change in exophthalmometry readings over the two 3-month treatment periods. A reduction in proptosis of >2 mm more in the active treatment period than in the placebo period will be considered clinically significant for each patient. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Time point: 0, 3, 5 and 8 months visit. |
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E.5.2 | Secondary end point(s) |
1. Change in quality of life scores on the TED quality of life questionnaire (GO-QOL) 2. Change in intraocular pressures 3. Side effect profiles of bimatoprost in TED patients during the study 4. Health economic consumption |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Time point: 0, 3, 5, 8 and 10 months visit. |
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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 | Yes |
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 | Yes |
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) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
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 | No |
E.8.1.6 | Cross over | Yes |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
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 | No |
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
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The last visit of the last participant. |
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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 | 9 |
E.8.9.1 | In the Member State concerned days | 29 |
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 | 9 |
E.8.9.2 | In all countries concerned by the trial days | 29 |