Neurocrine (NBIX) Reports Notable Safety Results from NBI-98854 Phase II
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Neurocrine Biosciences, Inc. (Nasdaq: NBIX) announced efficacy and safety results from a Phase II trial of NBI-98854 in 37 tardive dyskinesia patients. For the final analysis, data from one site was removed due to the inconsistent and incorrect application of the efficacy assessment protocol. With this site removed, the results showed a significant reduction in tardive dyskinesia symptoms at end of two weeks of active treatment with 50mg once-daily doses of NBI-98854.
After database lock and unblinding of study data, the pre-specified statistical assessment was conducted and the normal quality control evaluation of the output performed. An inconsistent pattern of Abnormal Involuntary Movement Scale (AIMS) scores emerged at one of the eight sites that was not evident during the blinded data review. Potential errors in randomization and drug exposure as causes for this data inconsistency were ruled out. However, a review of videotaped AIMS assessments at this single site noted discrepancies between the clinical score and the video record which were well outside of the variability associated with the AIMS. Additionally, videotaped AIMS assessments were reviewed at other sites and found to be administered appropriately.
Based on these findings, the AIMS data from this single site was removed and the statistical assessment was repeated. This post-hoc analysis demonstrated a clinically meaningful and statistically significant improvement in tardive dyskinesia symptoms for the subjects while receiving the 50mg once-daily dose. These subjects had a significant reduction in tardive dyskinesia symptoms at the end of two weeks of active treatment vs. the end of two weeks of placebo (difference in LS mean of 4.2 for the 50mg period vs. the placebo period, p-value=0.002). As expected, the 12.5mg dosing group was not statistically better during the active treatment period than during the placebo period (difference in LS mean of 0.4 for the 12.5mg period vs. placebo period, p-value=0.68).
The improvement in symptomology is also evidenced by the significant improvement in AIMS scores over baseline levels relative to placebo, excluding the one site. NBI-98854 reduced the average baseline AIMS score by 9.2 points in the 50mg period (p-value=0.0004) vs. a reduction of 4.9 points in the 12.5mg period and 4.7 for the placebo periods. A responder analysis also showed improvement in both the investigator reported Clinical Global Impression-Tardive Dyskinesia and the patient reported Patient Global Impression of Change.
When including the data from the site in question, this study did not meet the pre-specified primary endpoint of reducing the AIMS scores during active treatment periods. The efficacy results from the entire study population showed a non-significant reduction in tardive dyskinesia at the end of two weeks of active treatment vs. the end of two weeks of placebo (difference in LS mean of 1.1 for the 50mg period vs. the placebo period (n=15), p-value=0.42) (difference in LS mean of 0.7 for the 12.5mg period vs. placebo period (n=17), p-value=0.59).
After database lock and unblinding of study data, the pre-specified statistical assessment was conducted and the normal quality control evaluation of the output performed. An inconsistent pattern of Abnormal Involuntary Movement Scale (AIMS) scores emerged at one of the eight sites that was not evident during the blinded data review. Potential errors in randomization and drug exposure as causes for this data inconsistency were ruled out. However, a review of videotaped AIMS assessments at this single site noted discrepancies between the clinical score and the video record which were well outside of the variability associated with the AIMS. Additionally, videotaped AIMS assessments were reviewed at other sites and found to be administered appropriately.
Based on these findings, the AIMS data from this single site was removed and the statistical assessment was repeated. This post-hoc analysis demonstrated a clinically meaningful and statistically significant improvement in tardive dyskinesia symptoms for the subjects while receiving the 50mg once-daily dose. These subjects had a significant reduction in tardive dyskinesia symptoms at the end of two weeks of active treatment vs. the end of two weeks of placebo (difference in LS mean of 4.2 for the 50mg period vs. the placebo period, p-value=0.002). As expected, the 12.5mg dosing group was not statistically better during the active treatment period than during the placebo period (difference in LS mean of 0.4 for the 12.5mg period vs. placebo period, p-value=0.68).
The improvement in symptomology is also evidenced by the significant improvement in AIMS scores over baseline levels relative to placebo, excluding the one site. NBI-98854 reduced the average baseline AIMS score by 9.2 points in the 50mg period (p-value=0.0004) vs. a reduction of 4.9 points in the 12.5mg period and 4.7 for the placebo periods. A responder analysis also showed improvement in both the investigator reported Clinical Global Impression-Tardive Dyskinesia and the patient reported Patient Global Impression of Change.
When including the data from the site in question, this study did not meet the pre-specified primary endpoint of reducing the AIMS scores during active treatment periods. The efficacy results from the entire study population showed a non-significant reduction in tardive dyskinesia at the end of two weeks of active treatment vs. the end of two weeks of placebo (difference in LS mean of 1.1 for the 50mg period vs. the placebo period (n=15), p-value=0.42) (difference in LS mean of 0.7 for the 12.5mg period vs. placebo period (n=17), p-value=0.59).
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