Long-term tolerability and maintenance of therapeutic response to sodium oxybate in an open-label extension study in patients with fibromyalgia

Abstract

Introduction: The long-term safety and therapeutic response of sodium oxybate (SXB) in fibromyalgia syndrome (FM) patients were assessed for a combined period of up to 1 year in a prospective, multicenter, open-label, extension study in patients completing 1 of 2 phase 3 randomized, double-blind, controlled, 14-week trials that examined the efficacy and safety of SXB 4.5 g, SXB 6 g, and placebo for treatment of FM.

Methods: This extension study comprised an additional 38 weeks of treatment and was carried out at 130 clinical sites in 7 countries. Initial entry criteria for the previous 2 double-blind clinical trials required that patients aged ≥ 18 years met the American College of Rheumatology 1990 criteria for FM, had a body mass index (BMI) < 40 kg/m2, and had a score ≥ 50 on a 100-mm pain visual analog scale (VAS) at baseline. All patients began treatment in the extension study with SXB 4.5 g/night (administered in 2 equally divided doses) for at least 1 week, followed by possible serial 1.5 g/night dose increases to 9 g/night (maximum) or reductions to 4.5 g/night (minimum).

Results: Of the 560 FM patients enrolled in this extension study, 319 (57.0%) completed the study. The main reason for early discontinuation was adverse events (AEs; 23.0% of patients). Patients were primarily middle-aged (mean 46.9 ± 10.8 years), female (91.1%), white (91.4%), with a mean duration of FM symptoms of 9.9 ± 8.7 years. Serious AEs were experienced by 3.6% of patients. The most frequently reported AEs (incidence ≥ 5% at any dose or overall) were nausea, headache, dizziness, nasopharyngitis, vomiting, sinusitis, diarrhea, anxiety, insomnia, influenza, somnolence, upper respiratory tract infection, muscle spasms, urinary tract infection, and gastroenteritis viral. Maintenance of SXB therapeutic response was demonstrated with continued improvement from controlled-study baseline in pain VAS, Fibromyalgia Impact Questionnaire (FIQ) total scores, and other measures. Responder analyses showed that 68.8% of patients achieved ≥ 30% reduction in pain VAS and 69.7% achieved ≥ 30% reduction in FIQ total score at study endpoint.

Conclusions: The long-term safety profile of SXB in FM patients was similar to that in the previously reported controlled clinical trials. Improvement in pain and other FM clinical domains was maintained during long-term use.

Trial registration: ClinicalTrials.gov NCT00423605.

Figure 1

Disposition of patients. Studies 06–008 and 06–009 were concurrent phase 3, double-blind, placebo-controlled, clinical trials; 06–010 is the open-label extension of the phase 3 trials. The denominator for studies 06–008 and 06–009 is the number of randomized patients, and the denominator for 06–010 is the number of treated patients. *Denominator is the number of completed patients from 06–008/06–009. PBO, placebo; SXB, sodium oxybate.

Figure 2

Kaplan-Meier survival curve of subjects in studies 06–008 and 06–009 pooled, stratified, and summarized by double-blind treatment group and sequentially linked with data from subjects continuing into the open-label extension.

Figure 3

Mean weight change from baseline for patients who entered the OLE study, by prior double-blind phase 3 study treatment. 06–010 is the OLE of the DB phase 3 trials (placebo patients in the DB phase were initiated on active treatment at the start of the OLE phase). DB, double-blind; OLE, open-label extension; SEM, standard error of the mean; SXB, sodium oxybate.

Figure 4

Maintenance of sodium oxybate therapeutic response in open-label extension study for patients with at least 12 months of sodium oxybate exposure (n = 210). *SF-36 PCS is reported for weeks 14, 18, 38 and 42. FIQ, Fibromyalgia Impact Questionnaire; SEM, standard error of the mean; SF-36 PCS, 36-item short-form health survey physical component summary; VAS, visual analog scale.