Christine Strohmaier

Randomized, Double-Blind, Parallel-Group, 48-Week Study for Efficacy and Safety of a Higher-Dose Rivastigmine Patch (15 vs. 10 cm2) in Alzheimer’s Disease

Aim: Determine whether patients with Alzheimer’s disease demonstrating functional and cognitive decline, following 24–48 weeks of open-label treatment with 9.5 mg/24 h (10 cm2) rivastigmine patch, benefit from a dose increase in a double-blind (DB) comparative trial of two patch doses. Methods: Patients meeting prespecified decline criteria were randomized to receive 9.5 or 13.3 mg/24 h (15 cm2) patch during a 48-week, DB phase. Coprimary outcomes were change from baseline to week 48 on the Instrumental Activities of Daily Living domain of the Alzheimer’s Disease Cooperative Study–Activities of Daily Living (ADCS-IADL) scale and the Alzheimer’s Disease Assessment Scale–cognitive subscale (ADAS-cog). Safety and tolerability were assessed. Results: Of 1,584 patients enrolled, 567 met decline criteria and were randomized. At all timepoints, ADCS-IADL and ADAS-cog scores favoured the 13.3 mg/24 h patch. The 13.3 mg/24 h patch was statistically superior to the 9.5 mg/24 h patch on the ADCS-IADL scale from week 16 (p = 0.025) onwards including week 48 (p = 0.002), and ADAS-cog at week 24 (p = 0.027), but not at week 48 (p = 0.227). No unexpected safety concerns were observed. Conclusions: The 13.3 mg/24 h rivastigmine patch significantly reduced deterioration in IADL, compared with the 9.5 mg/24 h patch, and was well tolerated.

Long-term safety of rivastigmine in parkinson disease dementia: an open-label, randomized study.

ObjectiveThis study investigated the long-term safety of rivastigmine (12 mg/d capsules, 9.5 mg/24 h patch) and effects on motor symptoms in patients with mild-to-moderately severe Parkinson disease dementia. MethodsThis was a 76-week, prospective, open-label, randomized study in patients aged 50 to 85 years. Primary outcomes included incidence of, and discontinuation due to, predefined adverse events (AEs) potentially arising from worsening of Parkinson disease motor symptoms with capsules. Secondary outcomes included frequency of AEs/serious AEs. Efficacy outcomes included Alzheimer’s Disease Cooperative Study-Activities of Daily Living (ADCS-ADL), Neuropsychiatric Inventory (NPI-10), and Mattis Dementia Rating Scale (MDRS). ResultsFive hundred eighty-three patients were randomized to rivastigmine capsules (n = 295) or patch (n = 288). Incidence of predefined AEs was 36.1% for capsules, 31.9% for patch; discontinuation due to worsening of motor symptoms was 4.4% and 2.4%, respectively. Most common AEs were nausea (capsules, 40.5%; patch, 8.3%), tremor (24.5%; 9.7%), fall (17.0%; 20.1%), vomiting (15.3%; 2.8%), and application site erythema (0%; 13.9%). Significant efficacy in favor of capsules was observed at weeks 24 to 76 on MDRS; 24 and 76 on NPI-10; weeks 52 and 76 on ADCS-ADL. In patients with Mini-Mental State Examination (MMSE) greater than 21, no differences in efficacy on MDRS and ADCS-ADL were observed at any time point; significant differences in favor of capsules were maintained in patients with MMSE less than or equal to 21. ConclusionsThis study supports the long-term safety of rivastigmine in Parkinson disease dementia. The rate of worsening of motor symptoms was in the range expected due to the natural progression of Parkinson disease, no new or unexpected safety issues emerged in the long-term.

Efficacy of Higher Dose 13.3 mg/24 h Rivastigmine Patch on Instrumental Activities of Daily Living in Patients with Mild-to-Moderate Alzheimer's Disease

Background: Stabilizing/reducing decline in the ability to perform activities of daily living (ADLs) is important in management of Alzheimer’s disease (AD). Methods: Post hoc analysis of OPtimizing Transdermal Exelon In Mild-to-moderate Alzheimer’s disease (OPTIMA), a double-blind trial comparing 13.3 and 9.5 mg/24 h rivastigmine patch in patients with AD demonstrating functional and cognitive decline with 9.5 mg/24 h patch. Efficacy on Alzheimer’s disease Cooperative Study-instrumental ADL (ADCS-IADL) items, higher level function (HLF), and autonomy factors was assessed. Results: The ADCS-IADL, HLF, and autonomy factors favored 13.3 mg/24 h patch at all time points, reaching significance from weeks 16 to 48, 24 to 48, and 32 to 48, respectively. Higher dose patch demonstrated significantly greater efficacy on 10 of 17 ADCS-IADL items at 1 or more time points (P < .05 vs 9.5 mg/24 h patch). More adverse events were observed with higher dose patch; study discontinuations were similar between the doses. Conclusions: Greater efficacy of 13.3 versus 9.5 mg/24 h patch on ADL, including autonomy and HLF factors, supports this additional dosing option to prolong patients’ independence.

Rivastigmine Patch in Chinese Patients with Probable Alzheimer's disease: A 24-week, Randomized, Double-Blind Parallel-Group Study Comparing Rivastigmine Patch (9.5 mg/24 h) with Capsule (6 mg Twice Daily).

To compare the once‐daily rivastigmine patch 9.5 mg/24 h (10 cm2) versus twice‐daily capsule (12 mg/day) in Chinese patients with probable Alzheimers disease (AD) (mini‐mental state examination [MMSE] scores of 10–20).

A 24-Week, Randomized, Controlled Study to Evaluate the Tolerability, Safety and Efficacy of 2 Different Titration Schemes of the Rivastigmine Patch in Japanese Patients with Mild to Moderate Alzheimer's Disease

Aim: To investigate whether 1-step titration of the rivastigmine patch (initiated at 5 cm2 and titrated to 10 cm2 after 4 weeks) is well tolerated in Japanese patients with Alzheimers disease (AD) as compared to 3-step titration (initiated at 2.5 cm2 and titrated by 2.5 cm2 every 4 weeks to 10 cm2). Methods: A 24-week, multicenter, randomized, double-blind study was conducted in Japan between July 2012 and May 2014. Patients with mild to moderate AD aged 50-85 years were randomized 1:1 to 1-step or 3-step titration of the rivastigmine once-daily patch. The primary endpoint was the proportion of patients with adverse events leading to discontinuation. Results: Of 216 patients randomized, 215 (1-step, n = 107; 3-step, n = 108) were included in the safety analysis. The primary endpoint outcome was 15.0% in the 1-step group and 18.5% in the 3-step group. The observed treatment difference was −3.6% (95% confidence interval: −17.0, 9.6), falling within the prespecified acceptance range. Conclusion: The tolerability of two different titration schemes was similar in Japanese patients with AD.

BGG492 as an adjunctive treatment in patients with partial-onset seizures: A 12-week, randomized, double-blind, placebo-controlled, phase II dose-titration study with an open-label extension

To evaluate dose–response relationship of BGG492 as add‐on therapy to 1–3 antiepileptic drugs in patients with partial‐onset seizures and to investigate safety and tolerability of BGG492.

High-dose 13.3 mg/24 h rivastigmine transdermal patch demonstrates efficacy on instrumental activities of daily living: Individual item analysis

Background: OPTIMA, a 48-week randomized, double-blind (DB) study, compared the efficacy and safety of 13.3 and 9.5 mg/24 h rivastigmine patches in patients with AD meeting functional and cognitive decline criteria during an initial open-label (IOL) phasewith 9.5 mg/24 h patch. The current analysis investigated the efficacy of 13.3 mg/24 h patch on the autonomy in instrumental activities of daily living (IADL) in patients by disease severity and time-to-meet decline criteria.Methods: Patients receiving rivastigmine patch 9.5 mg/24 h, were assessed at Weeks 24, 36 and 48 of the IOL phase for functional (investigators’ judgement) and cognitive decline ( 2-point decrease in Mini-Mental State Examination [MMSE] score from previous visit OR 3-point decrease from baseline). Decliners entered the randomized DB phase (9.5 or 13.3 mg/24 h). Co-primary outcomes included change from DB-baseline at Week 48 on the AD Cooperative Study (ADCS)-IADL scale. Prospective subgroup analyses were efficacy on ADCS-IADL by: disease severity at DB-baseline (moderate [MMSE 10 18] versus moderate-to-severe [MMSE 3 18]); and time-to-meet decline criteria ( 36 versus >36 weeks). Results: The mean DB-baseline ADCS-IADL score was higher with 13.3 mg/24 h, compared with 9.5 mg/ 24 h patch, for patients with moderate (26.7 and 24.5, respectively) or moderate-to-severe disease (25.3 and 22.8, respectively). At all time points, regardless of disease severity, slower decline in ADCS-IADL score was observed with 13.3 versus 9.5 mg/24 h patch. The mean DB-baseline ADCS-IADL score was higher with 13.3 mg/24 h, compared with 9.5 mg/ 24 h patch, for patients meeting decline criteria 36 weeks (27.1 and 24.5, respectively), but comparable for patients meeting decline criteria >36 weeks. Regardless of time-to-meet decline criteria, decline in ADCS-IADL score was less with 13.3 mg/24 h patch during Weeks 16 to 48.The superiority of the 13.3 mg/24 h patch compared with the 9.5 mg/ 24 h patch was confirmed by statistical comparisons adjusted for the corresponding baseline value for the different subgroup analyses. Conclusions: High-dose (13.3 mg/24 h) rivastigmine patch demonstrates superior efficacy on functional outcomes and provides additional benefits to patients with AD, compared with 9.5 mg/24 h patch, regardless of their disease severity or time-to-meet decline criteria.

Tolerability, safety, and efficacy of the 1-step titration scheme of rivastigmine patch 10 cm2 in japanese patients with mild-to-moderate Alzheimer’s disease: A 24-week randomized controlled study

Primary outcomes NPI total score Baseline 24 37.4 (13.7) 26 35.6 (13.0) Day14 19 31.0 (11.3) 23 26.1 (16.9) Day 21 23 27.8 (13.1) 24 23.9 (16.8) +3.2 (-3.6 to 10.0) NPI agitation/ aggression subscale Baseline 24 5.7 (3.5) 26 6.2 (4.3) Day 14 19 4.1 (4.7) 23 5.0 (3.9) Day 21 23 4.5 (4.1) 24 4.4 (4.3) -0.1 (-2.0 to 1.9) NPI abemant motor behavior behavior subscale Baseline 24 4.5 (4.6) 26 5.2 (4.1) Day14 19 4.9 (4.0) 23 4.3 (4.2) Day 21 23 3.6 (3.9) 24 3.7 (4.3) -0.3 (-1.0 to 1.7) Secondary outcomes CMAI Baseline 24 58.8 (15.5) 26 61.6 (16.4) Day 21 23 56.5 (17.5) 24 53.7 (18.3) -4.6 (-3.0 to 12.2) Barthel Index Baseline 24 13.8 (5.1) 25 13.3 (5.3) Day 21 22 13.3 (5.0) 24 12.0 (5.5) -0.6 (-0.8 to 1.9) QoL-AD Baseline 24 28.3 (4.9) 24 29.6 (5.2) Day 21 21 27.5 (4.6) 22 29.1 (5.0) -0.5 (-2.6 to 1.6) CCGIC* Day 14 20 3.7 (1.0) 25 3.4 (1.2) Day 21 22 3.5 (1.3) 24 3.2 (1.4) -0.2 (-0.5 to 0.9) Safety assessments Heart rate, bpm. Baseline 23 69.8 (11.4) 24 4.5 (12.5) Day 21 22 66.3 (8.6) 24 71.6 (8.0) -3.3 (-7.5 to 0.9) Systolic blood pressure, mmHg Baseline 23 138.6 (21.2) 24 143.1 (15.9) Day 21 22 143.7 (16.8) 24 141.3 (20.9) -3.4 (-6.5 to 12.2) Diastolic blood pressure, mmHg Baseline 23 77.5 (8.0) 24 82.0 (10.4) Day 21 22 76.9 (7-1) 24 8.2 (9.3) -1.8 (-6.6 to 3.1) Weight, kg Baseline 22 71.0 (14.3) 22 70.9 (13.8) Day 21 20 70.4 (13.8) 22 71.1 (12.9) -0.1 (-0.8 to 0.7)