Effects of Rivastigmine Patch on Activities of Daily Living and Cognition in Patients With Severe Dementia of the Alzheimer's Type (ACTION) (Study Protocol CENA713DUS44, NCT00948766) and a 24 Week Open-label Extension to Study CENA713DUS44
Condition: Alzheimer's Disease
MeSH terms: Alzheimer Disease; Dementia
Intervention: Rivastigmine 4.6 mg/24 h (5 cm^2); Rivastigmine 9.5 mg/24 h (10 cm^2); Rivastigmine 13.3 mg/24 h (15 cm^2); Placebo
Intervention description: Rivastigmine was supplied in a 5 cm^2 patch which released 4.6 mg/24 h. Patches were changed daily.; Rivastigmine was supplied in a 10 cm^2 patch which released 9.5 mg/24 h. Patches were changed daily.; Rivastigmine was supplied in a 15 cm^2 patch which released 13.3 mg/24 h. Patches were changed daily.; Placebo patches were identical in size and composition to the corresponding rivastigmine patches, except that they did not contain rivastigmine. Patches were changed daily.
Intervention MeSH terms: Rivastigmine
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 716.0
Sex: All
Minimum age: 50 Years
Healthy volunteers: No
Keywords: Alzheimer's disease; dementia; Alzheimer's type

Summary:

      The core study assessed the efficacy of a higher dose of rivastigmine 13.3 mg/24 h
      transdermally (15 cm^2 patch) compared to a lower dose of the rivastigmine 4.6 mg/24 h
      transdermally (5 cm^2 patch) in patients with Severe Dementia of the Alzheimer's Type in a
      24-week study. The extension study obtained additional safety and efficacy data, as well as
      provided the higher dose rivastigmine patch to all patients who completed the core study for
      an additional 24 weeks.
    

Eligibility criteria:

        Core study

        Inclusion Criteria:

          -  Diagnosis of probable Alzheimer's disease (AD) according to National Institute of
             Neurological Disorders and Stroke and the Alzheimer's Disease and Related Disorders
             Association (NINCDS/ADRDA) criteria.

          -  A Mini-Mental State Examination (MMSE) score of ≥ 3 and ≤ 12.

          -  Be able to complete at least 1 item on the Severe Impairment Battery (SIB).

          -  Residing with someone in the community or in regular contact with the primary
             caregiver.

          -  Be ambulatory or ambulatory with aid.

        Exclusion Criteria:

          -  An advanced, severe, progressive, or unstable disease of any type that may interfere
             with efficacy and safety assessments or put the patient at special risk.

          -  Patients currently residing in a nursing home.

          -  Any current medical or neurological condition other than AD that could explain the
             patient's dementia.

          -  A current diagnosis of probable or possible vascular dementia.

          -  A current diagnosis of severe or unstable cardiovascular disease.

          -  A current diagnosis of bradycardia (< 50 beats per minute [bpm]), sick-sinus syndrome,
             or conduction defects.

          -  Clinically significant urinary obstruction.

          -  History of malignancy of any organ system within the past 5 years unless patient is
             verified to be in stable condition with no active metastasis.

          -  Current diagnosis of an active skin lesion/disorder that would prevent the patient
             from using a transdermal patch every day.

          -  A known exaggerated pharmacological sensitivity or hypersensitivity to drugs similar
             to rivastigmine, or to other cholinergic compounds.

          -  Taken any of the following substances (at the time of the Baseline Visit [Visit 2]).

          -  Succinylcholine-type muscle relaxants during the previous 2 weeks.

          -  Lithium during the previous 2 weeks.

          -  An investigational drug during the previous 4 weeks.

          -  A drug or treatment known to cause major organ system toxicity during the previous 4
             weeks.

          -  Rivastigmine (oral or transdermal patch), donepezil, galantamine, other cholinesterase
             inhibitors (eg, tacrine, physostigmine, or pyridostigmine), or other approved
             treatments for Alzheimer's disease during the previous 2 weeks, with exception of
             stable treatment with memantine for at least 3 months before study entry (Visit 1).

          -  Centrally acting anticholinergic drugs including tricyclic and tetracyclic
             antidepressants during the previous 4 weeks.

          -  Selegiline unless taken at a stable dose during the previous 4 weeks.

          -  Peripheral anticholinergics not taken at a stable dose during the previous 4 weeks.

        Extension study

        Inclusion Criteria:

          -  Complete the double-blind phase (Week 24) of the core study.

          -  Provide, if mentally competent, a separate written informed consent prior to
             participation in the extension study. In addition, the patient's caregiver, will
             provide written informed consent prior to the patient's participation in the
             open-label extension study. If the patient is not able to provide written informed
             consent, written informed consent must be obtained from the legally authorized
             representative on the patient's behalf.

          -  Continue to reside with someone in the community or in regular contact with the
             primary caregiver; patients who reside in an assisted living facility are eligible to
             participate.

          -  Continue to have a primary caregiver willing to accept responsibility for supervising
             treatment (eg, application and removal of the patch daily at approximately the same
             time of day), assessing the condition of the patient throughout the extension study.

          -  Must be medically stable and tolerating the current dose of rivastigmine patch as
             determined by the investigator.

        Exclusion Criteria:

        Refer to the core study protocol for full details of the exclusion criteria.

          -  Patients who discontinued the core study due to any reason are excluded.

          -  No additional exclusions may be applied by the investigator, in order to ensure that
             the study population will be representative of all eligible patients.

        Other protocol-defined inclusion/exclusion criteria applied to the study.