Hospital Pharmacy - September 2017 - 538
538
Intervention: Background antiparkinson drugs were
adjusted to minimize motor fluctuation during a 10-day
screening period. Patients were then observed on the stable dose for a minimum of 4 weeks, at the end of which
they were still required to be experiencing daily "off"
time of greater than 1.5 hours. The randomized portion of
the study began after the screening and observation periods. Patients were randomized (1:1) to receive either
safinamide 50 mg/d or placebo as 1 tablet once daily with
breakfast for 24 weeks. If there were no tolerability
issues by day 14, the starting dosage of safinamide (50
mg/d) was increased to 100 mg/d; at day 14, 90.9% in the
safinamide group and 94.1% in the placebo group were
prescribed the 100-mg target dose. If an upward increase
in dose of any of the other antiparkinson drugs was necessary prior to week 24, the assessment used for the primary efficacy end point was conducted prior to the
dosage adjustment. If patients completed the 24-week
study, they were eligible for enrollment in an open-label
extension study.
Results
Primary End Point(s)
** Change in mean daily "on" time without troublesome
dyskinesia from baseline to week 24, as recorded by
patients or caregivers in a diary recording each
30-minute interval during the 18-hour day (0600 to
2400 hours) as "on" time, "on" time with nontroublesome dyskinesia, "on" time with troublesome dyskinesia, "off" time, or time asleep: Mean increase in
total daily "on" time without troublesome dyskinesia
was 1.42 hours in the safinamide group and 0.57 hours
in the placebo group (LS mean difference, 0.96 hours;
95% CI, 0.56-1.37; P < .001). In the mixed-effects
repeated-measures model, the mean increases were
1.61 and 0.17 hours, respectively (LS mean difference, 0.93 hours; 95% CI, 0.5-1.36; P < .001).
Hospital Pharmacy 52(8)
** Nominal differences were also observed for change in
CGI-C rating, CGI-S rating, Patient Global Impression-
Change rating, PDQ-39 score, and EuroQoL 5 dimensions (EQ-5D) score.
** Change in levodopa daily dosage was −1.11% in the
safinamide group and 0.78% in the placebo group
(nominal P = .02).
** "Off" time after the morning levodopa dose was −0.26
hours in the safinamide group and −0.09 hours in the
placebo group (P < .001 nominal).
Comments: This study was conducted in Europe, the
Asia-Pacific region, and North America using an ITT population for the efficacy analysis. The 24-week study was
completed by 89.4% of the safinamide group and 87.6% of
the placebo group. Discontinuation of study drug and a
change in antiparkinson treatment was necessary in 4.4%
of the safinamide group and in 3.6% of the placebo group.
Any missing data were imputed using the LOCF method.
Background antiparkinson therapy consisted of dopamine
agonist (74.3%), amantadine (30.2%), an anticholinergic
(17.3%), and entacapone (15.1%). Statistical analysis was
conducted using a hierarchical approach; if no statistical
difference was found, further analyses were performed to
obtain nominal P values. A sensitivity analysis was conducted, in which the change in daily "on" time was examined using a mixed-effects repeated-measures model, with
no imputation of missing data. The safety analysis was
performed using the modified ITT population (ie, those
who received the study medication).
Post hoc analysis of the SETTLE trial and of Study 016
found that mean daily "on" time and "off" time improved,
compared with placebo, to similar extents regardless of
whether patients were receiving concomitant dopamine
agonists, COMT inhibitors, or amantadine.23 Another post
hoc analysis of the same 2 studies suggests that safinamide may have a positive effect on the nonmotor symptom pain.24
Limitations: The evaluation phase of the study was only
24 weeks.
Secondary End Point(s)
** Mean decrease in daily "off" time was −1.56 hours in
the safinamide group and −0.54 hours in the placebo
group (LS mean difference, −1.03 hours; 95% CI,
−1.4 to −0.67; P < .001).
** Mean decrease (improvement) in UPDRS part III
(motor examination) score, rated during an "on"
phase, was −3.43 in the safinamide group and −1.83
in the placebo group (LS mean difference, −1.82; 95%
CI, −3.01 to −0.62; P = .003); and mean change in
UPDRS part II (activities of daily living) score was
−1.07 and −0.75, respectively (LS mean difference,
−0.43; 95% CI, −1.02 to 0.16; P = .15).
Contraindications, Warnings, and
Precautions
Contraindications
Safinamide is contraindicated with concomitant use of other
drugs in the MAOI class or other drugs that are potent inhibitors of monoamine oxidase (eg, linezolid); opioid drugs (eg,
meperidine and its derivatives, methadone, propoxyphene,
tramadol); SNRIs; tricyclic, tetracyclic, or triazolopyridine
antidepressants; cyclobenzaprine; methylphenidate, amphetamine, and their derivatives; St. John's wort; and dextromethorphan.2 Use with MAOIs or related drugs may result in
Table of Contents for the Digital Edition of Hospital Pharmacy - September 2017
Pharmacy Transitions of Care and Culture
Bivalirudin Medication Use Evaluation and Cost Savings Initiative
Navigating the New Antimicrobial Stewardship Regulations
Safinamide
Biosimilar Substitution Laws
Evaluation of Corticosteroid Dose in Acute Exacerbation of Chronic Obstructive Pulmonary Disease
Hazardous Drug Contamination of Drug Preparation Devices and Staff: A Contamination Study Simulating the Use of Chemotherapy Drugs in a Clinical Setting
A Case of Metronidazole Injection Infiltration Without Sequelae
Doubling Pharmacist Coverage in the Intensive Care Unit: Impact on the Pharmacists’ Clinical Activities and Team Members’ Satisfaction
Extended Stability of Epinephrine Hydrochloride Injection in Polyvinyl Chloride Bags Stored in Amber Ultraviolet Light–Blocking Bags
Formation of a Citywide Pharmacy Residents’ Collaborative Committee
Hospital Pharmacy - September 2017 - 513
Hospital Pharmacy - September 2017 - 514
Hospital Pharmacy - September 2017 - 515
Hospital Pharmacy - September 2017 - 516
Hospital Pharmacy - September 2017 - 517
Hospital Pharmacy - September 2017 - 518
Hospital Pharmacy - September 2017 - 519
Hospital Pharmacy - September 2017 - Pharmacy Transitions of Care and Culture
Hospital Pharmacy - September 2017 - 521
Hospital Pharmacy - September 2017 - Bivalirudin Medication Use Evaluation and Cost Savings Initiative
Hospital Pharmacy - September 2017 - 523
Hospital Pharmacy - September 2017 - 524
Hospital Pharmacy - September 2017 - 525
Hospital Pharmacy - September 2017 - 526
Hospital Pharmacy - September 2017 - Navigating the New Antimicrobial Stewardship Regulations
Hospital Pharmacy - September 2017 - 528
Hospital Pharmacy - September 2017 - 529
Hospital Pharmacy - September 2017 - 530
Hospital Pharmacy - September 2017 - 531
Hospital Pharmacy - September 2017 - Safinamide
Hospital Pharmacy - September 2017 - 533
Hospital Pharmacy - September 2017 - 534
Hospital Pharmacy - September 2017 - 535
Hospital Pharmacy - September 2017 - 536
Hospital Pharmacy - September 2017 - 537
Hospital Pharmacy - September 2017 - 538
Hospital Pharmacy - September 2017 - 539
Hospital Pharmacy - September 2017 - 540
Hospital Pharmacy - September 2017 - 541
Hospital Pharmacy - September 2017 - 542
Hospital Pharmacy - September 2017 - 543
Hospital Pharmacy - September 2017 - Biosimilar Substitution Laws
Hospital Pharmacy - September 2017 - 545
Hospital Pharmacy - September 2017 - Evaluation of Corticosteroid Dose in Acute Exacerbation of Chronic Obstructive Pulmonary Disease
Hospital Pharmacy - September 2017 - 547
Hospital Pharmacy - September 2017 - 548
Hospital Pharmacy - September 2017 - 549
Hospital Pharmacy - September 2017 - 550
Hospital Pharmacy - September 2017 - Hazardous Drug Contamination of Drug Preparation Devices and Staff: A Contamination Study Simulating the Use of Chemotherapy Drugs in a Clinical Setting
Hospital Pharmacy - September 2017 - 552
Hospital Pharmacy - September 2017 - 553
Hospital Pharmacy - September 2017 - 554
Hospital Pharmacy - September 2017 - 555
Hospital Pharmacy - September 2017 - 556
Hospital Pharmacy - September 2017 - 557
Hospital Pharmacy - September 2017 - 558
Hospital Pharmacy - September 2017 - A Case of Metronidazole Injection Infiltration Without Sequelae
Hospital Pharmacy - September 2017 - 560
Hospital Pharmacy - September 2017 - 561
Hospital Pharmacy - September 2017 - 562
Hospital Pharmacy - September 2017 - 563
Hospital Pharmacy - September 2017 - Doubling Pharmacist Coverage in the Intensive Care Unit: Impact on the Pharmacists’ Clinical Activities and Team Members’ Satisfaction
Hospital Pharmacy - September 2017 - 565
Hospital Pharmacy - September 2017 - 566
Hospital Pharmacy - September 2017 - 567
Hospital Pharmacy - September 2017 - 568
Hospital Pharmacy - September 2017 - 569
Hospital Pharmacy - September 2017 - Extended Stability of Epinephrine Hydrochloride Injection in Polyvinyl Chloride Bags Stored in Amber Ultraviolet Light–Blocking Bags
Hospital Pharmacy - September 2017 - 571
Hospital Pharmacy - September 2017 - 572
Hospital Pharmacy - September 2017 - 573
Hospital Pharmacy - September 2017 - Formation of a Citywide Pharmacy Residents’ Collaborative Committee
Hospital Pharmacy - September 2017 - 575
Hospital Pharmacy - September 2017 - 576
Hospital Pharmacy - September 2017 - 577
Hospital Pharmacy - September 2017 - 578
Hospital Pharmacy - September 2017 - 579
Hospital Pharmacy - September 2017 - 580
https://www.nxtbook.com/nxtbooks/sage/hospitalpharmacy_december2020
https://www.nxtbook.com/nxtbooks/sage/psychologicalscience_demo
https://www.nxtbook.com/nxtbooks/sage/hospitalpharmacy_october2020
https://www.nxtbook.com/nxtbooks/sage/fai_202009
https://www.nxtbook.com/nxtbooks/sage/hospitalpharmacy_august2020
https://www.nxtbook.com/nxtbooks/sage/hospitalpharmacy_june2020
https://www.nxtbook.com/nxtbooks/sage/hospitalpharmacy_april2020
https://www.nxtbook.com/nxtbooks/sage/hospitalpharmacy_february2020
https://www.nxtbook.com/nxtbooks/sage/hospitalpharmacy_december2019
https://www.nxtbook.com/nxtbooks/sage/hospitalpharmacy_october2019
https://www.nxtbook.com/nxtbooks/sage/fai_201909
https://www.nxtbook.com/nxtbooks/sage/hospitalpharmacy_july2019
https://www.nxtbook.com/nxtbooks/sage/hospitalpharmacy_june2019
https://www.nxtbook.com/nxtbooks/sage/canadianpharmacistsjournal_05062019
https://www.nxtbook.com/nxtbooks/sage/hospitalpharmacy_april2019
https://www.nxtbook.com/nxtbooks/sage/sri_supplement_201903
https://www.nxtbook.com/nxtbooks/sage/hospitalpharmacy_february2019
https://www.nxtbook.com/nxtbooks/sage/hospitalpharmacy_december2018
https://www.nxtbook.com/nxtbooks/sage/tec_20180810
https://www.nxtbook.com/nxtbooks/sage/hospitalpharmacy_october2018
https://www.nxtbook.com/nxtbooks/sage/hospitalpharmacy_julyaugust2018
https://www.nxtbook.com/nxtbooks/sage/fai_201807
https://www.nxtbook.com/nxtbooks/sage/hospitalpharmacy_june2018
https://www.nxtbook.com/nxtbooks/sage/hospitalpharmacy_april2018
https://www.nxtbook.com/nxtbooks/sage/sri_supplement_201803
https://www.nxtbook.com/nxtbooks/sage/slas_discovery_201712
https://www.nxtbook.com/nxtbooks/sage/hospitalpharmacy_february2018
https://www.nxtbook.com/nxtbooks/sage/hospitalpharmacy_december2017
https://www.nxtbook.com/nxtbooks/sage/hospitalpharmacy_november2017
https://www.nxtbook.com/nxtbooks/sage/hospitalpharmacy_october2017
https://www.nxtbook.com/nxtbooks/sage/hospitalpharmacy_september2017
https://www.nxtbook.com/nxtbooks/sage/hospitalpharmacy_julyaugust2017
https://www.nxtbook.com/nxtbooks/sage/fai_supplement_201709
https://www.nxtbook.com/nxtbooks/sage/hospitalpharmacy_june2017
https://www.nxtbook.com/nxtbooks/sage/hospitalpharmacy_may2017
https://www.nxtbook.com/nxtbooks/sage/fai_201706
https://www.nxtbook.com/nxtbooks/sage/fai_201607
https://www.nxtbookmedia.com