Hospital Pharmacy - September 2017 - 535

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Baker and Kim
** Average change in UPDRS part II score from baseline
to week 24 was −2.2 with safinamide 100 mg (P =
.0248 vs placebo), −1.4 with safinamide 200 mg (no
difference vs placebo), and −1.2 with placebo.
** No significant differences were observed in change
from baseline to 24 weeks for HAMD, UPDRS part I,
UPDRS part IV, and MMSE scores.
Comments: The study targeted a patient population with
early-stage Parkinson disease. The majority (more than
90%) of the patients received their target dose of 100 or
200 mg/d. Secondary end points were analyzed via ITT
analysis (using the last observation carried forward
[LOCF] method) and via observed case analysis. Blood
samples taken at weeks 8 and 12 revealed safinamide contamination in the placebo group: 2 bulk bottles of unknown
quantity that were supposed to be placebo capsules contained both placebo and safinamide capsules. The investigators determined that this unintended exposure did not
greatly affect the results because the safinamide plasma
concentrations obtained from the patients in the placebo
group were consistently less than 20% of the measured
safinamide concentrations obtained from patients in the
safinamide 100 mg group. Reasons for discontinuing
study drug included withdrawal of consent (approximately 6.3%) and nonserious adverse events (approximately 3%). Patients who completed this study were
invited to enroll in a 12-month blind extension study.5
Limitations: It is unknown to what degree the low level
of exposure to safinamide in the placebo group impacted
outcomes. This study was not conducted in the United
States; subjects were recruited from Italy, Spain, the
United Kingdom, India, Argentina, Chile, and Colombia.
Reference: Schapira A, et al, 2013 (Study 017)5
Study Design: Randomized, double-blind, placebo-controlled, parallel-group, multicenter extension study
(extension of the 24-week Study 015)
Study Funding: Newron Pharmaceuticals, Merck Serono
Patients: 227 of the 269 patients with idiopathic Parkinson
disease (Hoehn and Yahr stage I to III) for less than 5
years from 24-week Study 015 (Stocchi et al, 2012)
entered this 12-month extension study. Patients were
included if they had completed the 24-week study and
demonstrated adherence to treatment, or if they had not
completed the study but completed all evaluations.
Patients were required to be on a stable dose of a single
dopamine agonist for at least 4 weeks before screening. At
baseline, median patient age was 57.7 years; 63.4% were
male; and average duration of Parkinson disease was 2.5
years. Mean UPDRS part II (activities of daily living)
score was approximately 8.1, UPDRS part III (motor
examination) was approximately 21.3, MMSE score was
approximately 28.5, and HAMD score was approximately
4.2, with no meaningful differences among treatment

groups. The majority of dopamine agonist use included
ropinirole (44.9%-48.8%), pramipexole (16.3%-24.6%),
and cabergoline (1.4%-10%).
Intervention: Patients continued receiving the medication they were randomized to in the primary study (safinamide 100 mg [n = 80], safinamide 200 mg [n = 69], or
placebo (n = 78]) once daily with breakfast for 12 months.
All patients were maintained on their preenrollment dose
of dopamine agonist throughout the study; however, for
patients whose Parkinson disease symptoms worsened,
the dopamine agonist dose could be increased or other
Parkinson disease medications added.

Results
Primary End Point(s)
** In the ITT population, the median number of days
from the first day of the 24-week study to intervention (eg, increasing the dopamine agonist dose or
adding another Parkinson disease medication) was
greater for the safinamide 100 and 200 mg groups
combined (559 days) compared with the placebo
group (466 days), but this difference was not statistically significant (P = .33).

Secondary End Point(s)
** Percentage of patients requiring intervention was
39.7% of the pooled safinamide groups and 47.8% of
the placebo group (not statistically significant).
** Mean changes from baseline in UPDRS, CGI-C, CGIS, or Hoehn and Yahr scores were not significantly
different between the pooled safinamide groups and
placebo.

End Point(s)
** Mean changes from baseline for MMSE or HAMD
scores were not significantly different.
Comments: In this 12-month extension of a 24-week
study, safinamide at the doses evaluated was not superior
to established dopamine agonist treatments already available for Parkinson disease. The extension study was completed by 82% of patients. Because the primary end point
was a time-to-event outcome (results shown on KaplanMeier curves), no imputation method was necessary for
missing data. However, secondary and tertiary end points
were analyzed via ITT analysis, using the LOCF method
for any missing data. Reasons for discontinuing study
drug included withdrawal of consent (approximately 7%)
and lack of efficacy (approximately 4.8%).
Limitations: This study was not conducted in the United
States; subjects were recruited from Italy, Spain, the
United Kingdom, India, Argentina, Chile, and Colombia.

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