E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated | Subjects with possible Dementia with Lewy Bodies (DLB) who may or may not also fulfil the criteria for Alzheimers Disease (AD) | |
E.1.1.1 | Medical condition in easily understood language | Patients with diagnosis of dementia and suggestion of Dementia with Lewy Bodies (DLB) | |
E.1.1.2 | Therapeutic area | Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Diagnosis [E01] |
MedDRA Classification |
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 evaluate the impact of DaTSCAN imaging on dementia diagnostic category and confidence in diagnosis in subjects with an uncertain diagnosis of Dementia with Lewy Bodies (possible DLB) | |
E.2.2 | Secondary objectives of the trial | To demonstrate that the use of DaTSCAN improves confidence in diagnosis in these subjects. | |
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria | (1) Male or female 55 years of age or older. (2) Mini-Mental State Examination (MMSE) between 10 and 28. (3) Subjects with Possible DLB as defined by the International Consensus Criteria (dementia +1 core feature or 1 or more suggestive features), who may or may not also fulfil criteria for AD. (4) The subject and a legally acceptable representative (e.g., the subject’s carer) are able and willing to comply with study procedures and signed and dated informed consent is obtained from each. (5) The subject and a legally authorised representative are able to co-operate with the protocol and involvement would not adversely affect subject care, in the opinion of the investigator. (6) Women who are surgically sterile (have had documented oophorectomy and/or documented hysterectomy) or are postmenopausal (cessation of menses for more than 1 year) will be allowed to enrol in the study without a pregnancy test at screening. | |
E.4 | Principal exclusion criteria | (1) Having an established/certain clinical diagnosis of Probable DLB or non-DLB form of dementia. (2) Parkinsonism >1 year prior to onset of dementia. (3) Severe extrapyramidal symptoms (Unified Parkinson’s Disease Rating Scale, Part 3 [UPDRS-III] >30) or Parkinson’s disease dementia. (4) Known/suspected significant vascular pathology with multiple or strategic infarcts or vascular pathology in the striatum/basal ganglia as shown preferably by previous magnetic resonance imaging (MRI) or computed tomography (CT) examination. If MRI is not available prior to baseline and there is no contraindication, the subject will have to undergo an MRI scan during the course of the study to confirm that no significant vascular pathology is present. If an MRI is not clinically feasible, cerebral CT imaging within 6 months prior to baseline or during the study is also acceptable. (5) Symptoms suggestive of multiple system atrophy, corticobasal degeneration, progressive supranuclear palsy, or Huntington’s disease. (6) Persistent severe mental illness including depression, schizophrenia and schizoaffective illness. (7) Normal pressure hydrocephalus. (8) Use of any concomitant medication that is known or suspected to interact with striatal uptake through direct competition with binding of DaTSCAN to the DaT that could not be discontinued for at least 5 half-lives if the subject were to be randomized to the DaTSCAN group (these include amphetamine, benztropine, bupropion, cocaine, mazindol, methylphenidate, phentermine and sertraline). (9) Presence of moderate to severe renal or hepatic impairment. (10) Occupational exposure to radiation equal to or above 15 mSv per year. (11) History of abuse or current abuse of drugs. (12) History of alcohol abuse where period of abstinence is less than 3 years. (13) Hypersensitivity to DaTSCAN or any of its ingredients. (14) Previous inclusion in this study. (15) Female subjects who are pregnant or breast-feeding or planning a pregnancy during the course of this study or within 3 cycles of completing the study. Women of childbearing potential, have to provide a negative beta human chorionic gonadotropin (b-HCG) pregnancy test (by urine dipstick method) at screening and also prior to IMP administration. (16) Participation in a clinical study involving an unlicensed pharmaceutical product within 30 days prior to screening, and/or an unlicensed/licensed radiopharmaceutical within 5 radioactive half-lives prior to screening. (17) The subject has a life threatening disease state with a life expectancy of less than 1 year or history of significant medical disease, trauma, or surgical intervention that in the judgement of the investigators makes the subject unsuitable for the study. (18) The subject has already had DaTSCAN SPECT imaging or any other similar functional imaging test of the pre-synaptic and/or post-synaptic dopaminergic system (e.g., [18F]DOPA PET, [123I]iodobenzamide). | |
E.5 End points |
E.5.1 | Primary end point(s) | The primary endpoint is the proportion of subjects in each group who have had a change in a diagnostic category between the baseline visit (V1) and the 8-week visit (V2). | |
E.5.1.1 | Timepoint(s) of evaluation of this end point | Baseline visit V1 8 week visit V2 | |
E.5.2 | Secondary end point(s) | • Confidence in clinical diagnosis. This will be assessed at baseline (V1), 8 weeks (V2), and 24 weeks (V3) visits, using a visual analogue scale ranging 0 to 100% with predefined qualitative levels of confidence. • Changes in clinical diagnostic category between the baseline (V1) and 24 week (V3) visits. | |
E.5.2.1 | Timepoint(s) of evaluation of this end point | Clinical diagnosis confidence evaluated at: Baseline V1 8 weeks V2 24 weeks V3 Changes in clinical diagnostic category evaluated at: Baseline V1 24 weeks V3 | |
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Yes |
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 | Yes |
E.7.1.3.1 | Other trial type description | Phase IV diagnostic trial | |
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 | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
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 | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description | parallel group without DaTSCAN imaging | |
E.8.2.4 | Number of treatment arms in the trial | 1 |
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 | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 25 |
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 | |
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 | 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 | 9 |
E.8.9.2 | In all countries concerned by the trial days | 0 |