Efficacy and Safety of ASP0819 in Patients with Fibromyalgia: Results of a Proof-of-Concept, Randomized, Double-Blind, Placebo-Controlled Trial

Abstract

Purpose: ASP0819 is a novel, non-opioid KCa3.1 channel opener that reverses abnormal nerve firing of primary sensory afferent nerves. Currently available treatments for fibromyalgia provide only modest relief and are accompanied by a host of adverse side effects.

Patients and methods: In this phase 2a, double-blind trial (NCT03056690), adults meeting fibromyalgia diagnostic criteria were randomized 1:1 to receive either 15 mg/day of oral ASP0819 (n=91) or placebo (n=95). The primary endpoint was the change from baseline to Week 8 in the mean daily average pain score. Changes in the Fibromyalgia Impact Questionnaire Revised (FIQR) symptoms, function, and overall impact subscales, as well as changes in the patients' global impression of change, were secondary endpoints; treatment effects on FIQR total score and impact on sleep were exploratory analyses.

Results: There was no statistically significant difference between ASP0819 and placebo for the primary endpoint (P=0.086); however, ASP0819 versus placebo significantly improved daily average pain at Weeks 2, 6, and 7 (all P<0.05). Numerical improvements were observed on the FIQR total score and several sleep items showed statistically significant improvements with ASP0819 versus placebo. There were no major safety concerns with ASP0819. Headache was the most common treatment-emergent adverse event (TEAE) occurring in both study arms; most TEAEs were mild or moderate in severity and no TEAEs suggestive of potential drug abuse were observed, as assessed by TEAE reporting and/or safety evaluations. Withdrawal effects also were not observed.

Conclusion: ASP0819 demonstrated some signals suggestive of efficacy and had a good tolerability profile in patients with fibromyalgia. Further studies are required to determine if ASP0819 can be a novel non-opioid treatment option in this patient group.

Clinicaltrialsgov registration: NCT03056690.

Keywords: ASP0819; clinical trial; fibromyalgia; non-opioid treatment; pain.

Conflict of interest statement

L. Arnold has consulted for Pfizer, Eli Lilly, Astellas, Teva, Allergan, Daiichi Sankyo, Jazz Pharmaceuticals, Zynerba, Prismic, Cinrx, Innovative Med Concepts, and Lundbeck and has received research support from Pfizer, Eli Lilly, Daiichi Sankyo, Axsome, Tonix, Allergan, Aptinyx, Teva, Astellas, and Cefaly; and reports grants and personal fees from Astellas, during the conduct of the study; personal fees from Pfizer, Eli Lilly, Teva, Allergan, Daiichi Sankyo, Jazz Pharmaceuticals, Zynerba, Prismic, Cinrx, Innovative Med Concepts, and Lundbeck, and grants from Pfizer, Eli Lilly, Daiichi Sankyo, Axsome, Tonix, Allergan, Aptinyx, Teva, and Cefaly, outside the submitted work. Mark Walzer and Paul Blahunka have a patent pending: Methods of treating sleep disorders associated with pain (PCT2020/043047). K. Tracy and P. Blahunka are former employees of Astellas. All other authors are current employees of Astellas Pharma Global Development. The authors report no other potential conflicts of interest for this work.

© 2020 Arnold et al.

Figures

Figure 1

Mechanism of action of ASP0819. ASP0819 enhances late hyperpolarization and subsequently decreases firing of primary sensory afferent nerves, which potentially reduces the fibromyalgia pain.

Figure 2

Patient disposition. Of the 406 patients who provided informed consent, 186 eligible patients were randomized 1:1 to receive oral ASP0819 15 mg or placebo. Patients who discontinued the study during the treatment period could enter the follow-up period.

Figure 3

Change from baseline in mean daily average pain score during double-blind treatment period and follow-up period (full analysis set). The mean daily average pain score assessed by the Numeric Rating Scale, which consists of a single question that asks patients to record their daily average pain on an 11-point scale (ranging from 0=no pain to 10=pain as bad as you can imagine) over the previous 24 hours. Data from the double-blind period are presented as LS mean ± standard error; data from the follow-up period are presented as mean ± standard error. *Indicates P<0.05.

Figure 4

Change from baseline during double-blind treatment period and follow-up period in FIQR subscales (full analysis set). Changes from baseline in the mean FIQR subscale scores: (A) Symptom, (B) Overall Impact, and (C) Function are depicted. All questions in each subscale are rated on an 11-point numeric scale, ranging from 0 to 10 with 10 being the worst. Data from the double-blind period are presented as LS mean ± standard error; data from the follow-up period are presented as mean ± standard error. *Indicates P<0.05.

Figure 5

Change from baseline during double-blind treatment period and follow-up period in FIQR total (full analysis set). The change from baseline in FIQR total score is depicted. The FIQR total score represents the sum of the three subscale scores: symptom, function, and overall impact. The symptom subscale accounts for 50%, the function subscale accounts for 30%, and the overall impact subscale accounts for 20% of the total score. Data from the double-blind period are presented as LS mean ± standard error; data from the follow-up period are presented as mean ± standard error. *Indicates P<0.05.

Figure 6

Change from baseline during double-blind treatment period and follow-up in mean daily average FMSD Item 1: Difficulty with falling asleep (full analysis set) and Item 2: Restlessness of sleep (full analysis set). The change from baseline in Item 1 of the FMSD, difficulty with falling asleep, is shown in (A). The change from baseline in Item 2 of the FMSD, restlessness of sleep, is displayed in (B). Patients rated their difficulty falling asleep or restlessness of sleep over the previous night on an 11-point numeric rating scale ranging from “0–not at all” to “10–extremely” in an e-diary. Data from double-blind period are presented as LS mean ± standard error; data from the follow-up period are presented as mean ± standard error. *Indicates P<0.05.