Mild to Moderate Alzheimer's Disease MedDRA version: 16.1 Level: LLT Classification code 10001896 Term: Alzheimer's disease System Organ Class: 100000004852
Conditions
Interventions
Trade Name: Nilvadil 8mg Prolonged Release Capsule
Product Name: Nilvadil 8mg Prolonged release capsules
Product Code: not applicable
Pharmaceutical Form: Capsule
INN or Proposed INN: NILVADIPINE
CAS
Sponsors
St James's Hospital
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Age range: Adult subjects, males and females over age 50 years. 2.Subjects with a diagnosis of probable Alzheimer’s disease based on the National Institute of Neurological and Communicative Disorders and Stroke/Alzheimer’s disease and Related Disorders Association, Inc (NINCDS-ADRDA) criteria (McKhann et al, 1984) 3. Subjects with a Standardised Mini-Mental State Examination (SMMSE) (Standish & Molloy, 1991) score of greater than or equal to 12 and less than 27. 4.Subjects on a stable dose (>3 months) of cholinesterase inhibitor or memantine. The dose must be stabilised prior to randomisation. Patients due to begin these medications must not be enrolled until the dose is stabilised. Subjects who are not on cholinesterase inhibitors or memantine due to poor tolerability and/or who will not require treatment with these medications during the course of the study can be included . 5. Subjects who retain capacity will provide written informed consent for participation. The procedure for obtaining informed consent when the subject has reduced decision making capacity will follow national law and will be assessed by the relevant bodies in each of the participating countries. 6.Fluency in relevant language sufficient to reliably complete all study assessments. 7. Subjects with blood pressure values greater than 100/65 mmHg but less than 159/99 mmHg (Grade 1 hypertension, ECS guidelines 2007; escardio.org/guidelines) using an office based BP measurement will be included. Subjects with blood pressure values greater than 105/70mmHg but less than 140/90 mmHg using an Ambulatory BP measurement will be included. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 200 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 300
Exclusion criteria
Exclusion criteria: 1. Subjects with co-morbid dementia due to other neurological disorders such as Parkinson's disease, vascular dementia, Huntington's disease, Pick's disease, Creutzfeldt-Jakob disease, normal pressure hydrocephalus, brain tumour, 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 neurological deficits, known structural brain abnormalities, or any other condition known to interfere with cognitive function. 2. Subjects currently taking any calcium channel blocker or ?-blocker. 3. Subjects who in the opinion of the investigator, have a medical condition that would preclude them from participating in the study (e.g.hemodynamically significant coronary artery disease., chronic heart failure, syncope within the past year, significant valvular heart disease i.e. severe aortic and mitral stenosis symptomatic orthostatic hypotension within the last year, or subjects who in the opinion of the investigator are unlikely to complete per protocol due to care issues etc. 4.Current Axis I diagnosis of schizophrenia, bipolar disorder, major depression. Subjects who are currently or who have within the past year met criteria for drug or alcohol abuse or dependence. 5.Pregnant women or women who may possibly become pregnant. 6.Female subjects who are breastfeeding will be excluded from the study 7.Subjects with a history of hypersensitivity to nilvadipine (Nivadil). 8.Subjects who have taken an investigational or other unapproved drug during the 30 days or five half-lives, whichever is longer, prior to baseline. 9. Subjects who are taking any medication listed in the list of exclusion medication for the study. 10. Subjects with abnormal ECG results which prevent participation in the study. 11. Standardised Mini-Mental State Examination (SMMSE) score of less than 12 or greater than 26. 12. Subjects who are participating in other clinical research studies. 13.Subjects with any clinically significant laboratory blood test abnormality on his/her screening test. 14.Subjects with blood pressure values less than 100/65 mmHg but greater than 159/99 mmHg (Grade 1 hypertension, ECS guidelines 2007; escardio.org/guidelines) using an office based BP measurement will be excluded. Subjects with blood pressure values less than 105/70mmHg but greater than 140/90 mmHg using an Ambulatory BP measurement will be excluded. 15.Subjects with clinically significant abnormalities in their CT/MRI results which would prevent inclusion in the study. 16. Patients with sigificant renal insuffiency (estimated glomerular filtration rate : eGFR <30ml/min) will be excluded . 17.Subjects with severly impaired hepatic function (liver cirrhosis)will be excluded. 18.The medical food stuff SouvenaidR is under exclusion from the study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To investigate the efficacy of Nilvadipine as a disease course modifying treatment for mild to moderate AD in a phase III double-blind placebo-controlled study.;Secondary Objective: Not applicable;Primary end point(s): The Alzheimer's Disease Assessment Scale (Cognitive) (ADAS-Cog) is the primary efficacy end point and includes 12 items of cognitive evaluation, namely immediate word recall, naming objects and fingers, commands, constructional praxis, ideational praxis, orientation, word recognition, remembering test instructions, spoken lanuage ability, word finding difficulty in spontaneous speech, comprehension and delayed recall. A higher ADAS-cog score indicates poorer cognitive function. ;Timepoint(s) of evaluation of this end point: The primary end point (ADAS-Cog) will be evaluated at Week 0, Week 13, Week 52 and Week 78. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The Clinical Dementia rating sum of boxes (CDR-sb) and the Disability Assessment for Dementia (DAD) are the secondary end points for the study. The CDR-sb is a semi-structured interview with the caregiver and the patient. The patient’s performance in the domains of memory, orientation, judgment, problem solving, community affairs, home and hobbies and personal care are assessed. The CDR-sb is scored from 0-18, with the higher score indicated greater impairment. The DAD is a key secondary efficacy outcome measure and evaluates the basic and instrumental activities in daily activities of elderly people with dementia. This 40-item scale addresses a range of functional domains: eating, meal preparation, telephoning, hygienic, dressing, medication, corresponding, finance, leisure, and housework.;Timepoint(s) of evaluation of this end point: The secondary end points (CDR-sb and DAD) will be evaluated at Week 0, Week 13, Week 52 and Week 78. | — |
Countries
Germany, Greece, Hungary, Ireland, Netherlands, Sweden, United Kingdom
Contacts
Public ContactFiona Cregg
St James's Hospital
Outcome results
None listed