Effectiveness and Safety of Intrathecal Ziconotide: Interim Analysis of the Patient Registry of Intrathecal Ziconotide Management (PRIZM).

BACKGROUND: The Patient Registry of Intrathecal Ziconotide Management (PRIZM) evaluated long-term effectiveness, safety, and tolerability of intrathecal ziconotide treatment in clinical practice. METHODS: Patient Registry of Intrathecal Ziconotide Management was an open-label, long-term, multicenter, observational study of adult patients with severe chronic pain. This interim analysis (data through July 10, 2015) of ziconotide as the first vs. not first intrathecal agent in pump included change from baseline in the Numeric Pain Rating Scale (NPRS; primary efficacy measure) and Patient Global Impression of Change (PGIC) scores. RESULTS: Enrollment closed at 93 patients; data collection was ongoing at the time of this interim analysis. Fifty-one patients (54.8%) received ziconotide as the first agent in pump (FIP+), whereas 42 (45.2%) did not (FIP-). Mean (SD) baseline NPRS scores were 7.4 (1.9) and 7.9 (1.6) in FIP+ and FIP- patients, respectively. Mean (SEM) percentage changes in NPRS scores were -29.4% (5.5%) in FIP+ patients (n = 26) and +6.4% (7.7%) in FIP- patients (n = 17) at month 6 and -34.4% (9.1%) in FIP+ patients (n = 14) and -3.4% (10.2%) in FIP- patients (n = 9) at month 12. Improvement from baseline, measured by PGIC score, was reported in 69.2% of FIP+ (n = 26) and 35.7% of FIP- (n = 14) patients at month 6 and 85.7% of FIP+ (n = 7) and 71.4% of FIP- (n = 7) patients at month 12. The most common adverse events (≥ 10% of patients overall as of the data cut) were nausea (19.6% vs. 7.1% of FIP+ vs. FIP- patients, respectively), confusional state (9.8% vs. 11.9%), and dizziness (13.7% vs. 7.1%). CONCLUSIONS: Greater improvements in efficacy outcomes were observed when ziconotide was initiated as first-line intrathecal therapy vs. not first intrathecal agent in pump. The adverse event profile was consistent with the ziconotide prescribing information.

Correlation between the Epworth Sleepiness Scale and the Maintenance of Wakefulness Test in patients with narcolepsy participating in two clinical trials of sodium oxybate.

BACKGROUND: In evaluating pathologic sleepiness, the Epworth Sleepiness Scale (ESS) assesses subjective sleep propensity; the Maintenance of Wakefulness Test (MWT) is an objective measure of the ability to stay awake. This analysis evaluated the strength of the correlation between ESS and MWT with regard to absolute values in scores. METHODS: Data were analyzed separately from the intent-to-treat populations of two eight-week clinical trials of sodium oxybate for the treatment of narcolepsy, SXB-15 and SXB-22. For all treatment groups, correlations between ESS and MWT were evaluated at baseline, week four, and week eight using the Pearson product-moment correlation coefficient. RESULTS: Overall, correlations across all treatment groups in each study described an inverse relationship, reflecting the scoring of each measure (ie, whereas higher ESS scores indicate greater sleepiness, higher MWT scores indicate a greater ability to remain awake). Significant correlations of low-to-moderate strength were observed at all time points in both studies. In SXB-15, correlation coefficients were -0.272, -0.365, and -0.343 at baseline (n = 221), week four (n = 212), and week eight (n = 205), respectively, with all P < 0.0001. Similarly, in SXB-22, correlation coefficients were -0.302 (n = 216), -0.418 (n = 211), and -0.432 (n = 196) at the three time points, respectively, also with all P < 0.0001. CONCLUSION: Although all correlations showed statistical significance, they were of low-to-moderate strength. These results indicate that ESS and MWT measure features of pathologic sleepiness that may be distinct, but partially overlapping. These data corroborate those of other studies, suggesting that physiologic mechanisms that regulate alertness and sleep propensity may function somewhat independently.

Correlation of Changes in Patient-Reported Quality of Life With Physician-Rated Global Impression of Change in Patients With Narcolepsy Participating in a Clinical Trial of Sodium Oxybate: A Post Hoc Analysis.

INTRODUCTION: Narcolepsy patients report lower health-related quality of life (HRQoL) than the general population, as measured by the Short Form-36 Health Survey (SF-36). This analysis evaluated whether changes in SF-36 correlated with physician-rated Clinical Global Impression of Change (CGI-C). METHODS: Data were from 209 of 228 narcolepsy patients participating in an 8-week clinical trial of sodium oxybate. Changes from baseline for SF-36 subscales (Physical Functioning, Role Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role Emotional, and Mental Health) and the summary scores were evaluated for correlation with CGI-C overall and by treatment group. Correlations were calculated using the Pearson product-moment correlation coefficient (r). RESULTS: Correlations described an inverse relationship in scores, but a direct relationship in improvement; lower CGI-C scores (i.e., better) were associated with higher SF-36 subscale scores (i.e., improved HRQoL). Moderate and significant correlations were observed for Vitality (r = -0.464; P < 0.0001) and Role Physical (r = -0.310; P < 0.0001) subscales, but weak correlations were observed with other subscales including summary scores. Correlations were stronger at higher sodium oxybate doses for most SF-36 subscales. CONCLUSION: Some aspects of HRQoL, measured by the SF-36, may be associated with narcolepsy. In particular, Vitality (indicative of energy and tiredness) and Role Physical (impact of physical function on daily roles) moderately correlated with overall change in status observed by clinicians. However, lack of strong correlations between SF-36 and CGI-C indicates differences in patient and clinician perspectives of disease, and suggest a need for broader assessment of the impact of narcolepsy and its treatment on patients. FUNDING: Jazz Pharmaceuticals.