Tolerability of Rivastigmine Before and After Switching From Oral Formulation to Transdermal Patch in Alzheimer's Dementia
Condition: Alzheimer's Dementia
MeSH terms: Dementia; Alzheimer Disease
Intervention: ENA713
Intervention MeSH terms: Rivastigmine
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 121.0
Sex: All
Minimum age: 50 Years
Maximum age: 85 Years
Healthy volunteers: No
Keywords: Alzheimer's dementia, AD

Summary:

      This phase IIIb study is intended to implement a consistent treatment way for switching to
      Exelon transdermal patch from oral formulation of rivastigmine to stress the importance of
      (1) advantages of transdermal patch over conventional oral therapies: smooth drug delivery
      with reduced side effects;(2) encourage treatment compliance in the Alzheimer's dementia
      setting.

      This study is a single-arm, treatment-switched design. Eligible patients, who are under
      Exelon capsule 3 mg b.i.d. treatment for 4 weeks before Visit 2, will be recruited, followed
      by treatment switch from oral capsule to patch for 48 weeks maintenance treatment. During the
      maintenance period, the treatment will be initiated with Exelon Patch 4.6 mg/24 hours (Exelon
      Patch 5 cm^2) for the first 24 weeks and the dose will be escalated to Exelon Patch 9.5 mg/24
      hours (Exelon Patch 10 cm^2) for another 24 weeks if well tolerated. Visits to assess safety
      are scheduled at baseline, 3 days, 1 week and 2 weeks after the first treatment switch, every
      4 weeks until Week 40, and at the end of study (Week 52). The assessment to address the
      primary objective will focus on the safety of treatment switching (Week 0~28); however the
      safety assessment will be performed during the whole study period.
    

Eligibility criteria:

        Inclusion Criteria:

          -  With diagnosis of mild to moderate Alzheimer's disease.

          -  Mini-Mental Status Examination score of 10-26 within 3 months before starting oral
             rivastigmine treatment.

          -  A clinical diagnosis of probable AD according to NINCDS/ADRDA criteria. The brain scan
             (magnetic resonance imaging (MRI) or computed tomography (CT) used for establishing
             that these criteria are met must have been available on the source document within one
             year prior to study participation.

          -  Patients who are currently taking or planned to receive Exelon 3 mg capsule
             twice-daily treatment.

          -  Written informed consent must be obtained before any assessment is performed.

          -  If female, must be surgically sterile or at least one year post-menopausal.

          -  Sufficient education to read, write, and communicate effectively.

          -  Capable of complying with the requirements of the study

        Exclusion Criteria:

          -  Any advanced, severe or unstable disease that could interfere with study evaluation or
             completion or put patient at special risk.

          -  Any medical or neurological condition other than AD that could explain the patient's
             dementia (e.g., abnormal thyroid function tests, Vitamin B12 or folate deficiency,
             posttraumatic conditions, Huntington's disease, Parkinson's disease, syphilis).

          -  Active uncontrolled peptic ulceration, or gastrointestinal bleeding, within the
             previous 3 months prior to visit 1.

          -  A current diagnosis of active, uncontrolled seizure disorder.

          -  A history within the past year or current diagnosis of cerebrovascular disease (e.g.,
             stroke, transient ischemic attacks, aneurysms).

          -  Bradycardia (< 50 beats per minute), sick sinus syndrome, conduction deficits (S-A
             block, second or third degree A-V block)

          -  Severe or unstable cardiovascular disease.

          -  Use of other investigational drugs at the time of enrollment, or within 30 days or 5
             half-lives of enrollment, whichever is longer.

          -  History of hypersensitivity to any of the study drugs or to drugs of similar chemical
             classes, or other components of the formulation.

          -  Current diagnosis of a systemic active skin disorder or lesion that would prevent
             accurate assessment of the adhesion and skin irritation potential of the patch.

          -  Previous lack of efficacy with cholinesterase inhibitors.

          -  History of malignancy of any organ system (other than localized basal cell carcinoma
             of the skin), treated or untreated, within the past 5 years, regardless of whether
             there is evidence of local recurrence or metastases. Patients with history of
             malignancy yet have been treated and defined as complete remission for more than 5
             years are not excluded from study participation.

          -  Pregnant or nursing (lactating) women.

          -  Concurrently treated with succinylcholine, similar neuromuscular blocking agents or
             cholinergic agonists such as bethanechol 2 weeks before the start of study drug and
             during the treatment period.