E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
treatment of adult amblyopia - amblyopia due to myopic or hyperopic anisometropia, or, congenital esotropia. |
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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 | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10065008 |
E.1.2 | Term | Amblyopia unilateral |
E.1.2 | System Organ Class | 10015919 - Eye disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10015475 |
E.1.2 | Term | Esotropia |
E.1.2 | System Organ Class | 10015919 - Eye disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10042158 |
E.1.2 | Term | Strabismic amblyopia |
E.1.2 | System Organ Class | 10015919 - Eye disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10001906 |
E.1.2 | Term | Amblyopia |
E.1.2 | System Organ Class | 10015919 - Eye disorders |
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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 |
To determine the improvement in visual acuity in the amblyopic eye as measured by Early Treatment of Diabetic Retinopathy Study (ETDRS) chart after 10 weeks of medication (fluoxetine 20 mg) and computer software-based training combined with occlusion of the dominant eye. A clinically significant improvement is defined as a negative change of 0.2 logarithm of the minimum angle of resolution (logMAR) units (i.e. 10 characters on the ETDRS chart). |
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E.2.2 | Secondary objectives of the trial |
• improvement in visual acuity 3 months after treatment. • stability of the change in visual acuity during follow-up. • relative change in visual acuity after 10 weeks of treatment. • relative improvement in visual acuity 3 months after treatment • difference in relative change in visual acuity after 10 weeks of treatment • difference in relative change in visual acuity 3 months after treatment • change in contrast sensitivity in the amblyopic eye after 10 weeks of treatment • change in contrast sensitivity 3 months after treatment • stability of change in contrast sensitivity during follow-up • change in binocularity after 10 weeks of treatment • change in binocularity 3 months after treatment • stability of change in binocularity during follow-up • change in near vision and crowding after 10 weeks of treatment • change in near vision and crowding 3 months after treatment • stability of change in near vision and crowding during follow-up • safety of fluoxetine |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
NeuroImaging of adult patients with anisometropic amblyopia during Phase II double blind multicenter study. Protocol HP-AM2-002, dated 5 January 2011, version 01-00 Final.
Objectives: To evaluate the changes in cortical neuronal activity recorded by neuroimaging with magneto- and encephalography (M/EEG) after 10 weeks of treatment with fluoxetine, eye-shading and computer-based cognitive training in the main study (HP-AM2-001) |
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E.3 | Principal inclusion criteria |
1. Provide written informed consent, i.e. they must be willing and able to comply with the study procedures. 2. Male or female, aged 18-60 years (inclusive). 3. Diagnosed with amblyopia due to myopic or hyperopic anisometropia, or, congenital esotropia. 4. Visual acuity in the amblyopic eye ≥0.30 and <1.10 logMAR (at least one character on the ETDRS chart). 5. Visual acuity in the dominant eye ≤0.10 logMAR. 6. Anisometropia ≤4.25 diopters. 7. Judged to be otherwise healthy by the Investigator, based on medical history, brief physical examination, eye examination and clinical laboratory assessments. Patients with abnormal clinical laboratory values or who have other abnormal clinical findings that are judged by the Investigator not to be of clinical significance may be entered into the study. 6. Females of childbearing potential are eligible for the study provided (i) they have a negative urine pregnancy test at the screening visit and (ii) they agree to use adequate contraception (e.g. oral, depot or implanted hormonal contraception, intrauterine device, surgical sterilization or partner vasectomy) from the screening visit until at least 4 weeks after the last dose of study medication (Week 16).
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E.4 | Principal exclusion criteria |
1. Diagnosed with other reasons for strabismus as the primary reason for amblyopia. 2. History of any amblyopia therapy in the 2 years before the screening visit. 3. Any eye surgery less than 6 months before the screening visit. 4. Observed off-fixation by ophthalmological examination (extra-foveal fixation) 5. Other ophthalmological pathologies that may affect the patient’s rehabilitation. 6. Pregnant, planning to become pregnant during the study, or breast feeding. 7. History of depressive illness or treatment with antidepressant medication within 6 months before the screening visit. 8. Use of psychiatric medication within 6 months before the screening visit. 9. Receipt of an experimental treatment for any disease within 4 weeks before the screening visit. 10. History or presence of illicit drug use or alcohol abuse. 11. History or presence of any medical or psychiatric condition or disease, or laboratory abnormality that, in the opinion of the Investigator, may place the patient at unacceptable risk or that could prevent the patient from completing the study. 12. Hypersensitivity to fluoxetine or any of its excipients. 13. Epilepsy or a history of seizures. 14. History of mania or hypomania. 15. Concomitant treatment with any of the following medications that are known to interact with fluoxetine: a. Monoamine oxidase inhibitor (MAOI) - less than 2 weeks after discontinuation of an irreversible MAOI, or, less than one day after discontinuation of a reversible MAOI-A. b. Phenytoin. c. Serotonergic drugs. d. Lithium or tryptophan. e. Drugs predominantly metabolized by CYP2D6 isoenzyme, e.g. flecainide, encainide, carbamazepine and tricyclic antidepressants. f. Oral anticoagulants. g. St John’s Wort (Hypericum perforatum). h. Benzodiazepines. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is the change from baseline (Week 0) to end of treatment (Week 10) in visual acuity in the amblyopic eye as measured by ETDRS chart. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Change from baseline (week 0) to end of treatment (10 weeks). |
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E.5.2 | Secondary end point(s) |
• Change from baseline (Week 0) to end of follow-up (Week 22) in visual acuity in the amblyopic eye as measured by ETDRS chart. • Change from end of treatment (Week 10) to end of follow-up (Week 22) in visual acuity in the amblyopic eye as measured by ETDRS chart. • Relative change (%) in visual acuity in the amblyopic eye from baseline (Week 0) to end of treatment (Week 10) as measured by ETDRS chart. • Relative change (%) in visual acuity in the amblyopic eye from baseline (Week 0) to end of follow-up (Week 22) as measured by ETDRS chart. • Difference between the dominant and amblyopic eye in relative change (%) in visual acuity from baseline (Week 0) to end of treatment (Week 10) as measured by ETDRS chart. • Difference between the dominant and amblyopic eye in relative change (%) in visual acuity from baseline (Week 0) to end of follow-up (Week 22) as measured by ETDRS chart. • Change from baseline (Week 0) to end of treatment (Week 10) in contrast sensitivity in the amblyopic eye as measured by Pelli Robson chart. • Change from baseline (Week 0) to end of follow-up (Week 22) in contrast sensitivity in the amblyopic eye as measured by Pelli-Robson chart. • Change from end of treatment (Week 10) to end of follow-up (Week 22) in contrast sensitivity in the ablyopic eye as measured by Pelli-Robson chart. • Change from baseline (Week 0) to end of treatment (Week 10) in binocularity as measured by Bagolini striated glass test. • Change from baseline (Week 0) to end of follow-up (Week 22) in binocularity as measured by Bagolini striated glass test. • Change from end of treatment (Week 10) to end of follow-up (Week 22) in binocularity as measured by Bagolini striated glass test. • Change from baseline (Week 0) to end of treatment (Week 10) in near vision and crowding as measured by Landolt C ring charts. • Change from baseline (Week 0) to end of follow-up (Week 22) in near vision and crowding as measured by Landolt C ring charts. • Change from end of treatment (Week 10) to end of follow-up (Week 22) in near vision and crowding as measured by Landolt C ring charts.
Safety Endpoints: • Changes from baseline (Week 0) to end of treatment (Week 10), end of weaning-off and washout (Week 14) and end of follow-up (Week 22) in adverse events (AEs), physical examination, vital signs and laboratory safety tests (Week 0, 10, 14). • Changes in ophthalmological examinations from baseline (Week 0) to end of follow-up (Week 22). |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Change from baseline (week 0) to end of treatment (week 10). Change from baseline (week 0) to end of follow-up (week 22). Change from end of treatment (week 10) to end of follow-up (week 22). Change in safety parameters from baseline (week 0), to end of treatment (week 10), end of wean-off (week 14) and end of follow-up (week 22). |
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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 | 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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
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) | 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
| 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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 4 |
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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End of the trial is when the last patient has completed visit 7 - follow-up, week 22 after randomisation. |
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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 | 2 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |