A post hoc analysis of subgroup outcomes and creatinine in the phase III clinical trial (EMPOWER) of dexpramipexole in ALS.

Abstract

Our objective was to compare the phase II and phase III (EMPOWER) studies of dexpramipexole in ALS and evaluate potential EMPOWER responder subgroups and biomarkers based on significant inter-study population differences. In a post hoc analysis, we compared the baseline population characteristics of both dexpramipexole studies and analyzed EMPOWER efficacy outcomes and laboratory measures in subgroups defined by significant inter-study differences. Results showed that, compared with phase II, the proportion of El Escorial criteria (EEC) definite participants decreased (p = 0.005), riluzole use increased (p = 0.002), and mean symptom duration increased (p = 0.037) significantly in EMPOWER. Baseline creatinine (p < 0.001) and on-study creatinine change (p < 0.001) correlated significantly with ALSFRS-R in EMPOWER. In the EMPOWER subgroup defined by EEC-definite ALS, riluzole use, and < median symptom duration (15.3 months), dexpramipexole-treated participants had reduced ALSFRS-R slope decline (p = 0.015), decreased mortality (p = 0.011), and reduced creatinine loss (p = 0.003). In conclusion, significant differences existed between the phase II and EMPOWER study populations in ALS clinical trials of dexpramipexole. In a post hoc analysis of EMPOWER subgroups defined by these differences, potential clinical benefits of dexpramipexole were identified in the subgroup of riluzole-treated, short-symptom duration, EEC-definite ALS participants. Creatinine loss correlated with disease progression and was reduced in dexpramipexole-treated participants, suggesting it as a candidate biomarker.

• Authors: Michael E Bozik, Hiroshi Mitsumoto, Benjamin R Brooks, Stacy A Rudnicki, Dan H Moore, Bing Zhang, Albert Ludolph, Merit E Cudkowicz, Leonard H van den Berg, James Mather, Thomas Petzinger Jr, Donald Archibald
• Journal: Amyotrophic lateral sclerosis & frontotemporal degeneration (Amyotroph Lateral Scler Frontotemporal Degener) Vol. 15 Issue 5-6 Pg. 406-13 (Sep 2014) ISSN: 2167-9223 [Electronic] England
• PMID: 25125035 (Publication Type: Clinical Trial, Phase III, Comparative Study, Journal Article)

Chemical References

• Adrenergic beta-Antagonists
• Neuroprotective Agents
• Riluzole
• Propranolol
• Creatinine

Topics

• Adrenergic beta-Antagonists (therapeutic use)
• Amyotrophic Lateral Sclerosis (drug therapy, metabolism)
• Clinical Trials, Phase II as Topic
• Creatinine (metabolism)
• Female
• Follow-Up Studies
• Humans
• Male
• Middle Aged
• Neuroprotective Agents (therapeutic use)
• Propranolol (therapeutic use)
• Riluzole (therapeutic use)
• Severity of Illness Index
• Treatment Outcome