E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Neovascular age-related macular degeneration |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10025409 |
E.1.2 | Term | Macular degeneration |
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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 systemic and local safety and tolerability of repeat topical ocular doses of pazopanib when administered daily to adult subjects with CNV due to neovascular AMD |
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E.2.2 | Secondary objectives of the trial |
• To determine the effect of repeat topical ocular doses of pazopanib on visual acuity when administered daily to adult subjects with CNV due to neovascular AMD. • To determine the impact of repeat topical ocular doses of pazopanib on central retinal lesion thickness and retinal morphology • To determine the impact of repeat topical ocular doses of pazopanib on CNV size and lesion size and characteristics |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Subjects who participated in Phase IIa study MD7108240 and who did not experience AMD disease progression requiring rescue therapy during pazopanib treatment or require discontinuation of pazopanib eye drops for safety reasons. 2. Best-corrected ETDRS visual acuity in the study eye of 23 letters (20/320 or 4/63) or better at screening. 3. QTcB or QTcF < 450msec; or QTc < 480msec in subjects with Bundle Branch Block. 4. Subject is willing and able to return for all study visits, and is willing and able to comply with all protocol requirements and procedures. 5. Subject is capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form. If the subject is unable to read the consent form due to visual impairment then the consent must be read to the subject verbatim by person administering the consent, a family member or legally acceptable representative. If the subject is unable to provide written informed consent due to visual impairment, then written informed consent on behalf of the subject must be provided by a legally acceptable representative. (Note: Consent by legally acceptable representative is allowed where this is in accordance with local laws, regulations and ethics committee policy.)
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E.4 | Principal exclusion criteria |
1. Anterior segment and vitreous abnormalities in the study eye that would preclude adequate observation of the fundus for photographs, fluorescein angiography and OCT. 2. Vitreous, subretinal or retinal hemorrhage in the study eye that is unrelated to AMD. 3. Intraocular surgery in the study eye within 3 months of dosing. 4. Use of topical ocular medications (other than pazopanib) in the study eye within 7 days of first dose of investigational product or expected use of topical ocular medications during the treatment period, with the exception of artificial tears. 5. Current use of medications known to be toxic to the retina, lens or optic nerve (e.g. desferoximine, chloroquine/hydrochloroquine, chlorpromazine, phenothiazines, tamoxifen, nicotinic acid, and ethambutol). 6. An unwillingness to refrain from wearing contact lenses starting from the screening visit, through the follow-up visit 7. ALT or AST above the upper limit of normal or total bilirubin ≥ 1.5 times the upper limit of normal at baseline. Note: Laboratory tests outside of the normal range may be repeated at the discretion of the Investigator. 8. Medical history or condition: • Uncontrolled Diabetes Mellitus, with hemoglobin A1c (HbA1c) > 10%. • Myocardial infarction or stroke within 6 months of screening. • Active bleeding disorder. • Major surgery within 1 month of screening. • Hepatic impairment. 9. Uncontrolled hypertension, based on criteria provided in Section 7.2.2. Note: Initiation or adjustment of antihypertensive medications is permitted prior to study entry provided the referenced criteria are met. 10. Use of prohibited medications listed in Section 9.2 within the restricted timeframe relative to the first dose of study medication. 11. A condition or situation which, in the opinion of the investigator, may result in significant risk to the subject, confound the study results or interfere significantly with participation.
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E.5 End points |
E.5.1 | Primary end point(s) |
Safety and tolerability endpoints include ophthalmic examinations, vital signs (heart rate and blood pressure), clinical laboratory (including LFT monitoring), and adverse event reporting |
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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 | No |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Information not present in EudraCT |
E.7.1.1 | First administration to humans | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | Information not present in EudraCT |
E.7.4 | Therapeutic use (Phase IV) | Information not present in EudraCT |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
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
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 9 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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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 trial is last visit of the last subject |
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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 | 0 |
E.8.9.1 | In the Member State concerned months | 12 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 12 |
E.8.9.2 | In all countries concerned by the trial days | 0 |