E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients who have been biopsied during an intracranial procedure due to suspected Normal Pressure Hydrocephalus (NPH) |
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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 | 10029773 |
E.1.2 | Term | Normal pressure hydrocephalus |
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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 level of association between the quantitative estimates of brain uptake of [18F]flutemetamol and the quantitative estimates of amyloid levels in biopsy samples (primary standard of truth [SOT]) previously obtained during intracranial pressure measurement in patients who have normal pressure hydrocephalus (NPH). The quantitative estimates of brain uptake of [18F]flutemetamol (standard uptake value ratios [SUVR]) will be made from the analysis of positron emission tomography (PET) images at a location on the contralateral brain hemisphere that corresponds to the biopsy site. |
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E.2.2 | Secondary objectives of the trial |
To determine the level of association between SUVR and the quantitative estimates of amyloid levels for the following regions: • Ipsilateral SUVR estimates compared to quantitative estimates of amyloid levels in the biopsy samples – primary SOT • Contralateral SUVR estimates compared to other quantitative estimates of amyloid levels in the biopsy samples – secondary SOT
To determine the levels of association between the blinded visual assessment of PET images (normal/abnormal amyloid levels) and the assessment of normal and abnormal amyloid levels from the quantitative estimates of amyloid levels in the biopsy samples. To determine the level of association between SUVR values determined from (18F]flutemetamol PET images and those determined from PET images made using 11C-labelled Pittsburgh Compound B ([11C]-PiB), in subjects who have undergone, or who will undergo, [11C]-PiB imaging independent of this study. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
(1) Informed consent has been signed and dated by the subject and/or the subjects’ legally acceptable representative, if applicable, in accordance with local regulations. (2) The subject is at least 50 years of age. (3) The subjects’ general health is adequate to comply with study procedures. (4) The subject has had a frontal lobe cortical biopsy adequate for the detection and quantitation of amyloid. (5) For women who are either surgically sterile (have had a documented bilateral oophorectomy and/or documented hysterectomy) or are postmenopausal (cessation of menses for more than 2 years), enrollment in the study without a pregnancy test at screening will be allowed. For women of childbearing potential, the results of a serum and urine human chorionic gonadotropin pregnancy test (with the result known on the day of and before Investigational Medicinal Product (IMP) administration) must be negative. |
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E.4 | Principal exclusion criteria |
(1) The subject has a contraindication for MRI or PET. (2) The subject is pregnant or lactating. (3) The subject has participated in any clinical study using an investigational agent within 30 days of dosing, with the exception of the PET tracer, 11C-labelled Pittsburgh Compound B ([11C]-PiB). (4) The subject has a known or suspected hypersensitivity/allergy to [18F]flutemetamol or to any of the excipients. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy endpoint will be the SUVR contralateral to and at the approximate level of the biopsy site. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Yes |
E.6.2 | Prophylaxis | Information not present in EudraCT |
E.6.3 | Therapy | Information not present in EudraCT |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Information not present in EudraCT |
E.6.7 | Pharmacodynamic | Information not present in EudraCT |
E.6.8 | Bioequivalence | Information not present in EudraCT |
E.6.9 | Dose response | Information not present in EudraCT |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | Information not present in EudraCT |
E.6.12 | Pharmacoeconomic | Information not present in EudraCT |
E.6.13 | Others | Information not present in EudraCT |
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 | No |
E.8.1.1 | Randomised | Information not present in EudraCT |
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 | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
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.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | No |
E.8.5.1 | Number of sites anticipated in the EEA | 1 |
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
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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 | 8 |
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 | 8 |
E.8.9.2 | In all countries concerned by the trial days | 0 |