Tolerability of Rivastigmine Before and After Switching From Oral Formulation to Transdermal Patch in Alzheimer's Dementia

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2014 by Novartis
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01585272
First received: April 23, 2012
Last updated: October 16, 2014
Last verified: October 2014
  Purpose

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 cm2) for the first 24 weeks and the dose will be escalated to Exelon Patch 9.5 mg/24 hours (Exelon Patch 10 cm2) 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.


Condition Intervention Phase
Alzheimer's Dementia
Drug: ENA713
Phase 4

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A 52-week, Prospective, Multi-center, Open-label Study to Assess the Tolerability of Rivastigmine Before and After Switching From Oral Formulation to Transdermal Patch in Patients With Alzheimer's Dementia in a Controlled Titration Schedule

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Tolerability of rivastigmine switching from an oral capsule (3 mg b.i.d.) to a transdermal patch 5 cm2 [ Time Frame: Baseline ] [ Designated as safety issue: Yes ]
    The tolerability of rivastigmine in terms of adverse event of special interest (including confusion, dizziness, vomit, diarrhea, anorexia, weight loss and application site irritation) switching from an oral capsule (3 mg b.i.d.) to a transdermal patch 5 cm2 during the first 28-week treatment period

  • Tolerability of rivastigmine switching from an oral capsule (3 mg b.i.d.) to a transdermal patch 5 cm2 [ Time Frame: 3 days after treatment ] [ Designated as safety issue: Yes ]
    The tolerability of rivastigmine in terms of adverse event of special interest (including confusion, dizziness, vomit, diarrhea, anorexia, weight loss and application site irritation) switching from an oral capsule (3 mg b.i.d.) to a transdermal patch 5 cm2 during the first 28-week treatment period

  • Tolerability of rivastigmine switching from an oral capsule (3 mg b.i.d.) to a transdermal patch 5 cm2 [ Time Frame: 1 week after treatment ] [ Designated as safety issue: Yes ]
    The tolerability of rivastigmine in terms of adverse event of special interest (including confusion, dizziness, vomit, diarrhea, anorexia, weight loss and application site irritation) switching from an oral capsule (3 mg b.i.d.) to a transdermal patch 5 cm2 during the first 28-week treatment period

  • Tolerability of rivastigmine switching from an oral capsule (3 mg b.i.d.) to a transdermal patch 5 cm2 [ Time Frame: 2 weeks after treatment ] [ Designated as safety issue: Yes ]
    the tolerability of rivastigmine in terms of adverse event of special interest (including confusion, dizziness, vomit, diarrhea, anorexia, weight loss and application site irritation) switching from an oral capsule (3 mg b.i.d.) to a transdermal patch 5 cm2 during the first 28-week treatment period

  • Tolerability of rivastigmine switching from an oral capsule (3 mg b.i.d.) to a transdermal patch 5 cm2 [ Time Frame: 4 weeks after treatment ] [ Designated as safety issue: Yes ]
    the tolerability of rivastigmine in terms of adverse event of special interest (including confusion, dizziness, vomit, diarrhea, anorexia, weight loss and application site irritation) switching from an oral capsule (3 mg b.i.d.) to a transdermal patch 5 cm2 during the first 28-week treatment period

  • Tolerability of rivastigmine switching from an oral capsule (3 mg b.i.d.) to a transdermal patch 5 cm2 [ Time Frame: 8 weeks after treatment ] [ Designated as safety issue: Yes ]
    the tolerability of rivastigmine in terms of adverse event of special interest (including confusion, dizziness, vomit, diarrhea, anorexia, weight loss and application site irritation) switching from an oral capsule (3 mg b.i.d.) to a transdermal patch 5 cm2 during the first 28-week treatment period

  • Tolerability of rivastigmine switching from an oral capsule (3 mg b.i.d.) to a transdermal patch 5 cm2 [ Time Frame: 12 weeks after treatment ] [ Designated as safety issue: Yes ]
    the tolerability of rivastigmine in terms of adverse event of special interest (including confusion, dizziness, vomit, diarrhea, anorexia, weight loss and application site irritation) switching from an oral capsule (3 mg b.i.d.) to a transdermal patch 5 cm2 during the first 28-week treatment period

  • Tolerability of rivastigmine switching from an oral capsule (3 mg b.i.d.) to a transdermal patch 5 cm2 [ Time Frame: 16 weeks after treatment ] [ Designated as safety issue: Yes ]
    the tolerability of rivastigmine in terms of adverse event of special interest (including confusion, dizziness, vomit, diarrhea, anorexia, weight loss and application site irritation) switching from an oral capsule (3 mg b.i.d.) to a transdermal patch 5 cm2 during the first 28-week treatment period

  • Tolerability of rivastigmine switching from an oral capsule (3 mg b.i.d.) to a transdermal patch 5 cm2 [ Time Frame: 20 weeks after treatment ] [ Designated as safety issue: Yes ]
    the tolerability of rivastigmine in terms of adverse event of special interest (including confusion, dizziness, vomit, diarrhea, anorexia, weight loss and application site irritation) switching from an oral capsule (3 mg b.i.d.) to a transdermal patch 5 cm2 during the first 28-week treatment period

  • Tolerability of rivastigmine switching from an oral capsule (3 mg b.i.d.) to a transdermal patch 5 cm2 [ Time Frame: 24 weeks after treatment ] [ Designated as safety issue: Yes ]
    the tolerability of rivastigmine in terms of adverse event of special interest (including confusion, dizziness, vomit, diarrhea, anorexia, weight loss and application site irritation) switching from an oral capsule (3 mg b.i.d.) to a transdermal patch 5 cm2 during the first 28-week treatment period

  • Tolerability of rivastigmine switching from an oral capsule (3 mg b.i.d.) to a transdermal patch 5 cm2 [ Time Frame: 28 weeks after treatment ] [ Designated as safety issue: Yes ]
    the tolerability of rivastigmine in terms of adverse event of special interest (including confusion, dizziness, vomit, diarrhea, anorexia, weight loss and application site irritation) switching from an oral capsule (3 mg b.i.d.) to a transdermal patch 5 cm2 during the first 28-week treatment period


Secondary Outcome Measures:
  • The changes in Mini-Mental Status Examination (MMSE) of patients with Alzheimer's disease treated with Exelon 5 cm2 Patch at Week 28 and Exelon 10 cm2 Patch at Week 52 [ Time Frame: Baselin, week 16, 28 and 52 ] [ Designated as safety issue: No ]
    The changes in Mini-Mental Status Examination (MMSE) of patients with Alzheimer's disease treated with Exelon 5 cm2 Patch at Week 28 and Exelon 10 cm2 Patch at Week 52 versus baseline, the treatment-switching day at Week 4. MMSE is a multi-item instrument that examines orientation, registration, attention, calculation, recall, visuospatial ability and language. The maximum score is 30 with higher scores indicating better cognitive function. The assessments will be conducted at Visit 1, 2, 8, 11 and 17 (screening, Week 4 (baseline), 16, 28 and 52).

  • The changes in Alzheimer Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) of patients with Alzheimer's disease treated with Exelon 5 cm2 Patch at Week 28 and Exelon 10 cm2 Patch at Week 52 [ Time Frame: Baseline, week 16, 28 and 52 ] [ Designated as safety issue: No ]
    The changes in Alzheimer Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) of patients with Alzheimer's disease treated with Exelon 5 cm2 Patch at Week 28 and Exelon 10 cm2 Patch at Week 52 versus baseline, the treatment-switching day at Week 4. ADAS-Cog has been used as the major cognitive measure of anti-dementia drugs. The total score range is 0 to 70 points, with higher scores indicating greater cognitive impairment. The assessments will be conducted at Visit, 2, 8, 11 and 17 (Week 4 (baseline), 16, 28 and 52).

  • The discontinuation rate due to the treatment switching from oral capsule to rivastigmine patch treatment [ Time Frame: Baseline through week 52 ] [ Designated as safety issue: No ]
    The discontinuation rate due to the treatment switching from oral capsule to patch treatment. For patients who discontinue earlier due to intolerance of patch treatment, the proportion will be analyzed. Both the discontinuation rate of 5 cm2 and 10 cm2 patch therapy will be presented.

  • Percentage of patients successfully titrated to rivastigmine patch 10 cm2 [ Time Frame: Baseline through week 52 ] [ Designated as safety issue: No ]
    The percentage of patients successfully titrated to rivastigmine patch 10 cm2


Estimated Enrollment: 127
Study Start Date: July 2012
Estimated Study Completion Date: May 2015
Estimated Primary Completion Date: May 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Optimize AD treatment with rivastigmine
Eligible patients, who are under rivastigmine capsule 3 mg b.i.d. treatment for 4 weeks before Visit 2, will be recruited, followed by treatment switch from oral capsule to transdermal patch for 48 weeks maintenance treatment.
Drug: ENA713
Other Name: Rivastigmine

  Eligibility

Ages Eligible for Study:   50 Years to 85 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01585272

Contacts
Contact: Novartis Pharmaceuticals +41613241111
Contact: Novartis Pharmaceuticals

Locations
Taiwan
Novartis Investigative Site Active, not recruiting
Taichung, Taiwan ROC, Taiwan
Novartis Investigative Site Recruiting
Taipei, Taiwan, ROC, Taiwan, 112
Novartis Investigative Site Active, not recruiting
Taichung, Taiwan, 40447
Novartis Investigative Site Active, not recruiting
Taipei, Taiwan, 10002
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

No publications provided

Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01585272     History of Changes
Other Study ID Numbers: CENA713DTW04
Study First Received: April 23, 2012
Last Updated: October 16, 2014
Health Authority: United States: Food and Drug Administration
Taiwan: Department of Health

Keywords provided by Novartis:
Alzheimer's dementia, AD

Additional relevant MeSH terms:
Alzheimer Disease
Dementia
Brain Diseases
Central Nervous System Diseases
Delirium, Dementia, Amnestic, Cognitive Disorders
Mental Disorders
Nervous System Diseases
Neurodegenerative Diseases
Tauopathies
Rivastigmine
Central Nervous System Agents
Cholinergic Agents
Cholinesterase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Neuroprotective Agents
Neurotransmitter Agents
Pharmacologic Actions
Physiological Effects of Drugs
Protective Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on October 30, 2014