5. N3-378 Template 12/31/2018 7:52 PM

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10. In the 14-week fixed-dose trial, pregabalin demonstrated significant pain reduction as early as week 1 in some patients. In addition, pregabalin maintained relief of FM pain in patients with moderate to severe FM for 14 weeks with the exception of week 11 at the 300 mg/day dose1-2
In the trial, patients in the pregabalin treatment groups showed a statistically significant (P≤0.0125) improvement in the end point mean pain score compared to placebo-treated patients3
The end point mean pain score is based on the modified BOCF analysis which censors patients who discontinue for adverse events (baseline score is carried forward), but carries the last observation forward (LOCF) for patients who discontinue for other reasons
Significant differences in mean pain reduction from baseline were noted for some patients as early as week 1 for all doses
All treatment groups showed significant improvement in mean pain scores from baseline at each time point with the exception of week-11 at the 300 mg/day dose
Pregabalin maintained relief of pain at each week with the exception of the 300 mg/day dose at week 11
The 600 mg/day pregabalin dose is not approved for use in FM. It did not show additional benefit over the 450 mg/d dose and there was evidence of dose-related adverse events4
End point mean pain score based on modified baseline observation carried forward approach (BOCF).
P value–based LS means using MMRM ANCOVA. Scored 0-10, lower score represents improvement.
References:
Arnold et al. A 14-week, randomized, double-blinded, placebo-controlled monotherapy trial of pregabalin in patients with fibromyalgia. J Pain 2008;9(9):
Data on file. Pfizer Inc, New York, NY.

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13. Key Points
The changes in the Brief Pain Inventory average pain severity score are shown in this slide
Compared with patients on placebo who completed the study, those who completed the study on duloxetine 60 mg QD had a significant (p=0.001) improvement in the Brief Pain Inventory average pain severity score. Patients who completed the study on duloxetine 60 mg BID also had a significant (p=0.001) improvement in the Brief Pain Inventory average pain severity score
There were no significant differences in pair wise comparisons between duloxetine 60 mg QD and duloxetine 60 mg BID in patients who completed the study
Background
This was a 12-week, randomized, double-blind, placebo-controlled trial to assess the efficacy and safety of duloxetine, a selective serotonin and norepinephrine reuptake inhibitor, in 354 female patients with primary fibromyalgia, with or without current major depressive disorder
The Brief Pain Inventory (BPI) (severity and interference scores) is a self-reported scale that measures the severity of pain and the interference of pain on function2
The severity scores range from 0 (no pain) to 10 (pain as bad as you can imagine)
There are four questions assessing the severity for worst pain, least pain, and average pain in the past 24 hours, and the pain right now
The interference scores range from 0 (does not interfere) to 10 (completely interferes)
There are seven questions assessing the interference of pain in the past 24 hours for general activity, mood, walking ability, normal work, relations with other people, sleep, and enjoyment of life
References
Arnold LM, Rosen A, Pritichett YL, et al. A randomized, Double-Blind, Placebo-Controlled Trial of Duloxetine in the Treatment of Women with Fibromyalgia with or without Major Depressive Disorder. Pain 2005; 119:5-15.
Cleeland CS, Ryan KM. Pain Assessment: Global use of the Brief Pain Inventory. Ann Acad Med 1994; 23(2):

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18. Both 4.5 and 6 gm sodium oxybate improved POV (composite score for>30% change from baseline in pain VAS, FIQ and P-GIC. AEs led to drop-out in 5% placebo, 9% 4.5 gm dose and 17% in 6 gm dose.2nd dose of drug or placebo needed. Sleep improved.

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