Trial Outcomes & Findings for A Phase IV Study to Evaluate Safety, Tolerability and Effectiveness of Rivastigmine Patch 15cm2 in Patients With Severe Dementia of the Alzheimer's Type. (NCT NCT02989402)

Results Overview

Number of participants with treatment emergent AEs (any AE regardless of seriousness), AEs related to study treatment, AEs led to study treatment discontinuation, and SAEs.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

100 participants

Primary outcome timeframe

Adverse events were reported from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to a maximum duration of approximately 142 days.

Results posted on

2024-05-31

Participant Flow

Participants took part in 9 investigative sites in India.

Participants who were treated according to local routine clinical practice were enrolled in the study upon signing informed consent.

Participant milestones

Participant milestones
Measure	Rivastigmine Patch 15 cm\^2 patch sizes loaded with 27 mg of rivastigmine - one patch per day
Overall Study STARTED	100
Overall Study COMPLETED	72
Overall Study NOT COMPLETED	28

Reasons for withdrawal

Reasons for withdrawal
Measure	Rivastigmine Patch 15 cm\^2 patch sizes loaded with 27 mg of rivastigmine - one patch per day
Overall Study Adverse event, or serious adverse event	4
Overall Study Death	2
Overall Study Discontinuation of study treatment and premature patient withdrawal	3
Overall Study Lost to Follow-up	8
Overall Study Patient no longer on monotherapy	1
Overall Study Patient stopped Exelon® patch treatment	1
Overall Study Withdrawal by Subject	7
Overall Study Other	2

Baseline Characteristics

Race and Ethnicity were not collected from any participant.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Rivastigmine Patch n=100 Participants 15 cm\^2 patch sizes loaded with 27 mg of rivastigmine - one patch per day
Age, Continuous	72.3 years STANDARD_DEVIATION 9.05 • n=100 Participants
Sex: Female, Male Female	51 Participants n=100 Participants
Sex: Female, Male Male	49 Participants n=100 Participants

PRIMARY outcome

Timeframe: Adverse events were reported from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to a maximum duration of approximately 142 days.

Population: The safety set included all patients who provided informed consent to collect information and who were treated with at least one patch of Rivastigmine 27 mg -15 cm2 transdermal patch during this study.

Number of participants with treatment emergent AEs (any AE regardless of seriousness), AEs related to study treatment, AEs led to study treatment discontinuation, and SAEs.

Outcome measures

Outcome measures
Measure	Rivastigmine Patch n=100 Participants 15 cm\^2 patch sizes loaded with 27 mg of rivastigmine - one patch per day
Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) At least one AE	32 Participants
Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) AEs related to study treatment	13 Participants
Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) AEs leading to treatment discontinuation	4 Participants
Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) At least one SAE	4 Participants

SECONDARY outcome

Timeframe: Baseline, 16 weeks

Population: Patients in the intend to treat (ITT) set who had a valid assessment of the outcome measure at week 16. The intend to treat (ITT) set included all patients who signed the informed consent and who had at least one post-baseline assessment.

The MMSE is a brief, practical screening test for cognitive dysfunction. The test consists of five sections (orientation, registration, attention-calculation, recall, and language); and results in a total score can range from 0 to 30, with higher scores indicating better function.

Outcome measures

Outcome measures
Measure	Rivastigmine Patch n=63 Participants 15 cm\^2 patch sizes loaded with 27 mg of rivastigmine - one patch per day
Change From Baseline in Mini-Mental State Examination (MMSE)	3.1 Score on a scale Standard Deviation 4.79

SECONDARY outcome

Timeframe: Baseline, 16 weeks

Population: Patients in the intend to treat (ITT) set who had a valid assessment of the outcome measure at week 16. The intend to treat (ITT) set included all patients who signed the informed consent and who had at least one post-baseline assessment.

Alzheimer's Disease Cooperative Study - Activities of Daily Living Inventory - Severe Impairment Version (ADCS-ADL SIV) score is a tool to assess the ability of patients with moderate to severe dementia to perform activities of daily living. The ADCS-ADL SIV assessment is done at start and end of visit. The assessment includes 19 questions. The total score ranges from 0 - 54. Higher scores indicate less functional impairment and greater competence.

Outcome measures

Outcome measures
Measure	Rivastigmine Patch n=69 Participants 15 cm\^2 patch sizes loaded with 27 mg of rivastigmine - one patch per day
Change From Baseline in Alzheimer's Disease Cooperative Study - Activities of Daily Living Inventory - Severe Impairment Version (ADCS-ADL SIV) Score	-1.6 Score on a scale Standard Deviation 10.47

SECONDARY outcome

Timeframe: Week 16

Population: Patients in the intend to treat (ITT) set who had a valid assessment of the outcome measure at week 16. The intend to treat (ITT) set included all patients who signed the informed consent and who had at least one post-baseline assessment.

Caregiver evaluation of the medications used for Alzheimer Disease was assessed using the Caregiver Medication Questionnaire (CMQ). Compliance was rated on a scale from 0 = "never took the medication as prescribed" to 10 = "always took the medication as prescribed."

Outcome measures

Outcome measures
Measure	Rivastigmine Patch n=69 Participants 15 cm\^2 patch sizes loaded with 27 mg of rivastigmine - one patch per day
Compliance by Caregiver Medication Questionnaire (CMQ) Score	8.1 Score on a scale Standard Deviation 2.78

SECONDARY outcome

Timeframe: Week 16

Population: Patients in the safety set who had a dermal response score at week 16. The safety set included all patients who provided informed consent to collect information and who were treated with at least one patch of Rivastigmine 27 mg -15 cm2 transdermal patch during this study.

The following score system were used to assess skin irritation: I. Dermal response: Score 0 = No erythema (normal skin) Score 1 = Erythema barely visible Score 2 = Mild erythema Score 3 = Moderate erythema Score 4 = Severe erythema Score 5 = Severe erythema with vesicles or blisters

Outcome measures

Outcome measures
Measure	Rivastigmine Patch n=70 Participants 15 cm\^2 patch sizes loaded with 27 mg of rivastigmine - one patch per day
Number of Participants With a Skin Irritation Score 0	65 participants
Number of Participants With a Skin Irritation Score 1	3 participants
Number of Participants With a Skin Irritation Score 2	2 participants
Number of Participants With a Skin Irritation Score 3 to 5	0 participants

SECONDARY outcome

Timeframe: 16 weeks

Population: The safety set included all patients who provided informed consent to collect information and who were treated with at least one patch of Rivastigmine 27 mg -15 cm2 transdermal patch during this study.

Urine samples were collected to assess the number of patients with UTI.

Outcome measures

Outcome measures
Measure	Rivastigmine Patch n=100 Participants 15 cm\^2 patch sizes loaded with 27 mg of rivastigmine - one patch per day
Number of Participants With a Urinary Tract Infection (UTI)	10 Participants

SECONDARY outcome

Timeframe: Week 16

Population: Patients in the safety set who had a dermal response score at week 16. The safety set included all patients who provided informed consent to collect information and who were treated with at least one patch of Rivastigmine 27 mg -15 cm2 transdermal patch during this study.

Patch adhesion to the skin was evaluated by the caregiver. An estimate of the patch adherence was provided and graded according to the patch adhesiveness score. Following scores were used to capture comments relating to patch adhesion: 0 = 90 % adhered (essentially no lift off of the skin) 1. = 75% to \< 90% adhered (some edges only lifting off of the skin) 2. = 50% to \< 75% adhered (less than half of the patch lifting off the skin) 3. = \< 50% adhered but not detached (more than half the system lifting off of the skin without falling off) 4. = the patch was completely detached. The score ranges from 1 to 4 where a higher score indicates less adhesion.

Outcome measures

Outcome measures
Measure	Rivastigmine Patch n=70 Participants 15 cm\^2 patch sizes loaded with 27 mg of rivastigmine - one patch per day
Patch Adhesion to the Skin Score 0	60 participants
Patch Adhesion to the Skin Score 1	4 participants
Patch Adhesion to the Skin Score 2	0 participants
Patch Adhesion to the Skin Score 3	4 participants
Patch Adhesion to the Skin Score 4	2 participants

Adverse Events

Rivastigmine Patch

Serious events: 4 serious events

Other events: 16 other events

Deaths: 2 deaths

Serious adverse events

Serious adverse events
Measure	Rivastigmine Patch n=100 participants at risk 15 cm\^2 patch sizes loaded with 27 mg of rivastigmine - one patch per day
Cardiac disorders ARRHYTHMIA	1.0% 1/100 • Adverse events were reported from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to a maximum duration of approximately 142 days.
Infections and infestations RESPIRATORY TRACT INFECTION	1.0% 1/100 • Adverse events were reported from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to a maximum duration of approximately 142 days.
Nervous system disorders CEREBRAL HAEMORRHAGE	1.0% 1/100 • Adverse events were reported from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to a maximum duration of approximately 142 days.
Nervous system disorders CEREBROSPINAL FLUID LEAKAGE	1.0% 1/100 • Adverse events were reported from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to a maximum duration of approximately 142 days.
Nervous system disorders DEMENTIA	1.0% 1/100 • Adverse events were reported from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to a maximum duration of approximately 142 days.
Nervous system disorders HYPONATRAEMIC SEIZURE	1.0% 1/100 • Adverse events were reported from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to a maximum duration of approximately 142 days.
Respiratory, thoracic and mediastinal disorders PNEUMONIA ASPIRATION	1.0% 1/100 • Adverse events were reported from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to a maximum duration of approximately 142 days.

Other adverse events

Other adverse events
Measure	Rivastigmine Patch n=100 participants at risk 15 cm\^2 patch sizes loaded with 27 mg of rivastigmine - one patch per day
Gastrointestinal disorders VOMITING	3.0% 3/100 • Adverse events were reported from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to a maximum duration of approximately 142 days.
Infections and infestations URINARY TRACT INFECTION	10.0% 10/100 • Adverse events were reported from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to a maximum duration of approximately 142 days.
Metabolism and nutrition disorders DECREASED APPETITE	3.0% 3/100 • Adverse events were reported from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to a maximum duration of approximately 142 days.
Skin and subcutaneous tissue disorders SKIN IRRITATION	3.0% 3/100 • Adverse events were reported from first dose of study treatment until end of study treatment, plus 30 days post treatment, up to a maximum duration of approximately 142 days.

Additional Information

Study Director

Novartis Pharmaceuticals

Phone: + 1 862 778 8300

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial.
Publication restrictions are in place

Restriction type: OTHER