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

Novartis

Status and phase: Completed; Phase 4

Conditions: Alzheimer's Disease

Treatments: Drug: Rivastigmine 9.5 mg/24 h (10 cm^2); Drug: Rivastigmine 13.3 mg/24 h (15 cm^2); Drug: Placebo; Drug: Rivastigmine 4.6 mg/24 h (5 cm^2)

Study type: Interventional

Funder types: Industry

Identifiers

NCT00948766

CENA713DUS44

Details and patient eligibility

About

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.

Enrollment: 716 patients

Sex: All

Ages: 50+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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716 participants in 2 patient groups

Rivastigmine 13.3 mg/24 h transdermal patch

Experimental group

Description:

In the core study, patients were titrated to the rivastigmine 13.3 mg/24 h dose in 2 steps. For Weeks 1-4, patients received rivastigmine 4.6 mg/24 h. For Weeks 5-8, patients received rivastigmine 9.5 mg/24 h and placebo. For Weeks 9-24, patients received rivastigmine 13.3 mg/24 h and placebo. In the extension study, all patients were switched to rivastigmine 9.5 mg/24 h for a 4-week titration period and were then titrated up to 13.3 mg/24 h for a further 20 weeks of treatment.

Treatment:

Drug: Rivastigmine 9.5 mg/24 h (10 cm^2)

Drug: Placebo

Drug: Rivastigmine 13.3 mg/24 h (15 cm^2)

Drug: Rivastigmine 4.6 mg/24 h (5 cm^2)

Rivastigmine 4.6 mg/24 h transdermal patch

Active Comparator group

Description:

In the core study, patients received rivastigmine 4.6 mg/24 h daily. For Weeks 1-4, patients received rivastigmine 4.6 mg/24 h. For Weeks 5-24, patients received rivastigmine 4.6 mg/24 h and placebo. No patients received this treatment in the extension study.

Treatment:

Drug: Placebo

Drug: Rivastigmine 4.6 mg/24 h (5 cm^2)