Convenience, Tolerability, and Safety of Change in the Administration of Rivastigmine From Capsules to a Transdermal Patch in Patients With Mild to Moderate Alzheimer's Disease (KAPA)

• ClinicalTrials.gov Identifier: NCT00549601
• Recruitment Status: Completed
• First Posted: October 26, 2007
• Results First Posted: March 24, 2011
• Last Update Posted: March 24, 2011
• Sponsor: Novartis
• Information provided by: Novartis

Study Description

Brief Summary:

This study used two doses of rivastigmine transdermal patch (5 cm^2, 10 cm^2) to establish the feasibility of 2 switch schedules (with transdermal patch one-step dose titration or without dose titration) from rivastigmine capsules (3 mg bid (bis in die, twice a day), 4,5 mg bid, 6 mg bid) to rivastigmine transdermal patch and to assess safety, tolerability, convenience, and caregivers preferences of rivastigmine transdermal patch versus capsules.

Condition or disease	Intervention/treatment	Phase
Alzheimer's Disease	Drug: Rivastigmine patch (4.6 mg/day switch to 9.5 mg/day); Drug: Rivastigmine patch (9.5 mg/day); Drug: Rivastigmine capsules (6 mg to 12 mg/day)	Phase 4

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 142 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Multi-center, Randomised, Open-label Study to Evaluate Convenience and Safety of Change in the Mode of Administration of Rivastigmine (From Capsules to a Transdermal Patch) in Patients With Alzheimer's Disease
• Study Start Date: September 2007
• Actual Primary Completion Date: April 2009
• Actual Study Completion Date: April 2009

Arms and Interventions

Arm	Intervention/treatment
Experimental: Rivastigmine patch (4.6 mg/day switch to 9.5 mg/day)	Drug: Rivastigmine patch (4.6 mg/day switch to 9.5 mg/day); Rivastigmine administered transdermally via patches at increasing doses (1 patch/day of 4.6 mg for the first month, changing to 1 patch/day of 9.5 mg for the remaining two months).
Experimental: Rivastigmine patch (9.5 mg/day)	Drug: Rivastigmine patch (9.5 mg/day); Rivastigmine administered transdermally via patches at a constant dose (9.5 mg/day for the 3 months of treatment).
Active Comparator: Rivastigmine capsules (6 mg to 12 mg/day)	Drug: Rivastigmine capsules (6 mg to 12 mg/day); Rivastigmine administered orally, following the same regime as prior to randomization (doses between 6 mg and 12 mg/day), which remained unchanged throughout the 3 months of treatment.

Outcome Measures

Primary Outcome Measures :

1. Percentage of Patients Who Had a Gastrointestinal Adverse Event (AE) at Any Time During the Study [ Time Frame: Baseline to end of study (Month 3) ]
   Gastrointestinal adverse events (including nausea, vomiting, and diarrhea) were coded using the medical dictionary MedDRA v11.0 and the number of patients who suffered an AE were described by system organ class (SOC) and preferred term (PT).

Secondary Outcome Measures :

1. Percentage of Patients With an AE Involving the Skin (Local Tolerance) Recorded Over the Course of the Study Period (Patch Groups Only) [ Time Frame: Baseline to end of study (Month 3) ]
   Adverse events involving the skin included urticaria, pruritus, erythema, and pigmentation disorder. Only the groups administered rivastigmine transdermally via patch were analyzed. The adverse events were coded using the medical dictionary MedDRA v11.0 and the number of patients who suffered an AE were described by system organ class (SOC) and preferred term (PT).
2. Percentage of Patients With at Least 1 AE of Any Kind Recorded During the Period of the Study. [ Time Frame: Baseline to end of study (Month 3) ]
   Adverse events were coded using the medical dictionary MedDRA v11.0 and the number of patients who suffered an AE were described by system organ class (SOC) and preferred term (PT). They were also tabulated by severity, relationship with study treatment, and action taken.
3. Overall Caregiver Satisfaction With Treatment [ Time Frame: At end of study (Month 3) ]
   Caregivers were asked to rate their overall degree of satisfaction with the Alzheimer's disease treatment on a scale of 1 to 5 (1 "Very good" - 5 "Very poor") at the end of the study (Month 3). A higher score indicates less satisfaction.
4. Overall Patient Satisfaction With Treatment [ Time Frame: At end of study (Month 3) ]
   Patients were asked to rate their overall degree of satisfaction with the Alzheimer's disease treatment on a scale of 1 to 5 (1 "Very good" - 5 "Very poor") at the end of the study (Month 3). A higher score indicates less satisfaction.
5. Change in the Total Mini-Mental State Examination (MMSE) Score From Baseline to Month 1 and Month 3 [ Time Frame: Baseline to Month 1 and Month 3 ]
   The Mini Mental State Examination (MMSE) was used to evaluate the patient's cognitive status and how it progressed over time. The 35-point version used in this study was made up of five sections: orientation, fixation, attention and calculation, memory and language, and constructional praxis. The total score for each patient was obtained by adding the score from each of the above sections. The individual receives 1 point for each correct answer. The total score can range from 0 to 30, with a higher score indicating better function. A positive change score indicates improvement.

Eligibility Criteria

• Ages Eligible for Study: 60 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Meet DSM-IV (Diagnostic & Statistical Manual of Mental Disorders, Version IV) criteria for dementia of Alzheimer type and NINCDS-ADRDA (National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association) criteria for probable Alzheimer's disease (AD), have a MMSE (Mini Mental State Examination) score > 10 and < 26
• Have received continuous treatment with rivastigmine capsules at least with 3 mg bid (6 mg of total daily dose) for at least 3 months before entering in the study
• Cooperative, willing to complete all aspects of the study, and capable of doing so, either alone or with the aid of a responsible caregiver
• Have a primary caregiver willing to accept responsibility for supervising the treatment, (eg, application and removal of the patch daily at approximately the same time of day) and assessing the condition of the patient throughout the study.

Exclusion Criteria:

• A medical or neurological condition other that AD that could explain the patients dementia (eg, Huntington's disease, Parkinson's Disease, abnormal thyroid function test, B12 or folate deficiency, post-traumatic conditions, syphilis)
• Current diagnosis of an active skin lesion/disorder that would prevent accurate assessment of the adhesion and potential skin irritation of the patch (e.g., atopic dermatitis, wounded or scratched skin in the area of the patch application)
• History of allergy to topical products containing vitamin E

• Taken any of the following substances prior to randomization:

  • succinylcholine-type muscle relaxants during the previous 2 weeks
  • an investigational drug during the previous 4 weeks

Other protocol-defined inclusion/exclusion criteria applied to the study.

Contacts and Locations

Locations

Spain

Novartis Investigative Site

Barcelona, Spain

Sponsors and Collaborators

Novartis

Investigators

• Study Director: Novartis Pharmaceuticals, MD; Novartis Pharmaceuticals

More Information

• Responsible Party: External Affairs, Novartis
• ClinicalTrials.gov Identifier: NCT00549601
• Other Study ID Numbers: CENA713DES07
• First Posted: October 26, 2007
• Results First Posted: March 24, 2011
• Last Update Posted: March 24, 2011
• Last Verified: February 2011

Keywords provided by Novartis:

Alzheimer's; rivastigmine; transdermal; safety; randomized; switch; patch

Additional relevant MeSH terms:

Alzheimer Disease; Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders; Rivastigmine; Cholinesterase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Cholinergic Agents; Neurotransmitter Agents; Physiological Effects of Drugs; Neuroprotective Agents; Protective Agents