Eluxadoline benefits patients with irritable bowel syndrome with diarrhea in a phase 2 study.

BACKGROUND & AIMS: Simultaneous agonism of the µ-opioid receptor and antagonism of the δ-opioid receptor can reduce abdominal pain and diarrhea in patients with irritable bowel syndrome with diarrhea (IBS-D) without constipating side effects. We evaluated the efficacy and safety of a minimally absorbed, µ-opioid receptor agonist and δ-opioid receptor antagonist (eluxadoline) in a phase 2 study in patients with IBS-D. METHODS: We randomly assigned 807 patients to groups that received oral placebo twice daily or 5, 25, 100, or 200 mg oral eluxadoline for 12 weeks. The primary end point was clinical response at week 4, defined by a mean reduction in daily pain score from baseline of ≥ 30%, and of at least 2 points on 0-10 scale, as well as a stool consistency score of 3 or 4 on the Bristol Stool Scale (1-7) for at least 66% of daily diary entries during that week. RESULTS: Significantly more patients receiving 25 mg (12.0%) or 200 mg (13.8%) eluxadoline met the primary end point of clinical response than patients given placebo (5.7%; P < .05). Patients receiving eluxadoline at 100 mg and 200 mg also had greater improvements in bowel movement frequency and urgency, global symptoms, quality of life, and adequate relief assessments (P < .05). Additionally, patients receiving 100 mg (28.0%) or 200 mg (28.5%) eluxadoline were significantly more likely than those receiving placebo (13.8%; P < .005) to meet the US Food and Drug Administration response end point during the full 12 weeks of the study. Eluxadoline was well tolerated with a low incidence of constipation. CONCLUSIONS: In a phase 2 study of the mixed µ-opioid receptor agonist/δ-opioid receptor antagonist eluxadoline vs placebo in patients with IBS-D, patients given eluxadoline were significantly more likely to be clinical responders, based on a composite of improvement in abdominal pain and stool consistency. Further study of eluxadoline is warranted to assess its potential as a treatment for IBS-D.

Memory-Assisted Global Impression of Change (MAGIC).

BACKGROUND: The United States Food and Drug Administration is developing a series of patient-focused drug development guidance documents regarding the collection of patient experience data, including methods for understanding treatment benefit from the patient perspective. The goal of this research was to investigate the concern that the global impression of change scale is subject to recall error and thus not optimal for use as an anchor for estimating meaningful within-person change thresholds. We explored whether memory assistance for recalling baseline status would make a difference in how study participants diagnosed with Parkinson's disease (PD) responded to a patient global impression of change (PGIC) and patient global impression static (PGIS) item. METHODS: The research was completed as a secondary objective of a non-interventional 28-day (± 4 days) study among persons with Parkinson's disease and associated motor fluctuations. At baseline, participants completed the PGIS and then recorded a voice message to their future self in which they spoke about how their PD had affected their "day-to-day" activities over the preceding few days. At the final visit, the PGIC and PGIS were completed, after which participants listened to their memory assistance voice recording, and then completed both items for a second time to calculate a memory-assisted global impression static and change scores (MAGIS and MAGIC, respectively). Spearman correlations (ρ) were examined for the pre- and post- memory assistance evaluations. The degree of agreement pre- and post-memory assistance was quantified using the Shrout & Fleiss intraclass correlation coefficient (ICC [2,1]). An ICC(2,1) ≥ 0.7 served as the pre-specified criterion of acceptability for both the ρ and ICC(2,1) values. RESULTS: Participants in the analytic sample were mean age 68.7 and mostly white (91.7%) and male (69.4%). The average length of time since PD diagnosis was 6.5 years. Correlations between the PGIS and MAGIS were ρ = 0.88; correlations between PGIC and MAGIC were ρ = 0.86. The estimated ICC(2,1) for both the PGIS/MAGIS and PGIC/MAGIC exceeded target success criterion of ICC(2,1) ≥ 0.70. CONCLUSION: Our results show that the MAGIS/MAGIC methodology is feasible and that memory assistance did not substantially alter the PGIS/PGIC scores at the final visit.