E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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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 investigate the safety and efficacy of nilvadipine and its effects on the serum and plasma levels of the protein beta-amyloid. |
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E.2.2 | Secondary objectives of the trial |
To examine the effects of nilvadipine on cerebrovascular and peripheral haemodynamics in patients with Alzheimer’s disease. |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
1. Age range: Adult subjects between the ages of 60 and 90 years-old. 2. Sex distribution: both men and women. 3. Prior diagnosis of mild to moderate AD based on NINCDS-ADRDA criteria and an MMSE score > 14 and < 27 and CDR-SB score between 1 and 2. 4. Health: vision and hearing (corrective lenses and hearing aid permissible) sufficient for compliance with testing procedures. 5. A collateral informant such as a spouse, family member, close friend, etc. The informant must have daily contact with the subject and agree to monitor/manage study drug adherence, observe for possible adverse events, assist with psychometric measures requiring informant information, and accompany the subject to all evaluation visits. The subject’s collateral or designee will record blood pressure measurements each day. 6. Fluency in relevant language sufficient to reliably complete all study assessments. 7. Prior brain imaging (CT or MRI) scan consistent with a diagnosis of Alzheimer’s Disease. 8. Systolic BP 120+ and a diastolic BP of 75+.
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E.4 | Principal exclusion criteria |
• Subjects with co-morbid dementia or other neurologic disorders such as Parkinson's disease, vascular dementia, Huntington's disease, Pick's disease, Creutzfeldt-Jakob disease, normal pressure hydrocephalus, brain tumor, progressive supranuclear palsy, seizure disorder, subdural hematoma, or multiple sclerosis, as well as subjects with HIV disease, neurosyphilis, history of significant head trauma with loss of consciousness followed by persistent neurologic deficits, known structural brain abnormalities, or any other condition with known interference with cognitive function. • History of hemodynamically significant coronary artery disease. • History of chronic heart failure. • Syncope within the past year. • History or finding on examination of significant valvular heart disease i.e severe aortic and mitral stenosis. • History or finding on examination of significant outflow tract obstruction i.e loud murmurs on physical exam. • History or finding on examination of hemodynamically significant tachycardia. • History of symptomatic orthostatic hypotension within the last year • Call PI/Medical Monitor for consultation regarding subjects on Cardiac medications including Antiarrhythmics and Digoxin. • Currently taking any calcium channel blocker or other antihypertensive medications for any reason. • Presence of hepatitis B or C antigen or laboratory values of liver enzymes > 2.0 x normal. • Subjects who have been diagnosed with hepatic function disorder to include elevated AST (GOT), ALT (GPT), or -GT levels at levels 2x normal. • Current diagnosis of clinical psychopathology such as schizophrenia, bipolar disorder, somataform disorder, etc. • Subjects who are currently or who have within the past year met criteria for drug or alcohol abuse or dependence. • Subjects with suspected incomplete hemostasis following intracranial hemorrhage. • Subjects with elevated intracranial pressure during the acute stage of cerebral stroke. • Pregnant women or women who may possibly become pregnant. • Subjects with a history of hypersensitivity to nilvadipine (Nivadil). • Subjects who have suffered a severe infection or a major surgical procedure within six months prior to screening. • Subjects who have taken an investigational or other unapproved drug during the 30 days or five half-lives, which ever is longer, prior to baseline. • Subjects who are taking or have taken within the past 30 days any of the unacceptable concomitant drugs listed in Appendix C. • Compromised kidney function as assessed by laboratory values (less than 75%) or any condition which would make the subject, in the opinion of the investigator, unsuitable for the study. • Subjects who, in the opinion of the investigator, may not be able to comply with the protocol.
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint of the study will be the completion of study patients on 6 weeks of nilvadipine treatment with cognitive assessment and measurement of serum and plasma levels of beta-amyloid throughout the study. |
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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 | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
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) | 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 |
The comparator group will consist of those patients not taking study medication. |
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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 | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
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 trial will conclude after 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 | 2 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |