Abstract # 2163: A Multi-Center Placebo-Controlled “In-Life” Study of MQX-503 in Patients with Raynaud Phenomenon
Authors:
Lorinda Chung1, Murray Baron2, David Collier3, Mary Ellen Csuka4, David Fiorentino1, Barry Gruber5, Vivien Hsu6, Bashar Kahaleh7, Richard Martin8, Maureen Mayes9, Janet Pope10, Naomi Rothfield11, Joseph Shanahan12, Lee Shapiro13, Robert Simms14, Edwin Smith15, Virginia Steen16, Sangeeta Sule17, Nadera Sweiss18, Elena Matthews19, Adam Gilbert19, Frederick J. Dechow20, Fredrick M. Wigley17
Background:
This study is the first of 2 randomized controlled trials to examine the efficacy of a novel nitroglycerin preparation, MQX-503, in the treatment of Raynaud’s phenomenon.
Methods:
This study enrolled 219 subjects who were randomly assigned to either treatment with 1.0% MQX-503 or placebo (111 MQX, 108 placebo). Subjects had to discontinue vasodilators for 2 weeks prior to entry and completed a 2 week observation period to ensure a minimum number of Raynaud’s events (5 attacks/7 days) and underwent 4 weeks of study medication treatment. Subjects were given active/placebo study medication and instructed to treat with a “packet” as needed up to 4 times daily with at least 2 hours between treatments. The primary outcome was change in mean RCS from baseline and a daily RCS was calculated daily. A target week was chosen for each subject to match the baseline period based on ambient temperature and 2 groups were analyzed based on enrollment period (before or after March 1, 2006) to adjust for ambient temperature variability. Subjects were stratified based on enrollment period and by Raynaud’s subtype (primary vs. secondary).
Results:
In the whole ITT population there was a significant difference in the change in RCS in active treatment vs. placebo (-0.49 vs. -0.03, p=0.02). The MQX group had a 14.8% improvement in RCS compared to 0.8% improvement in the placebo group. This significance did not remain when each group (early vs. late) was analyzed separately, although those with secondary RP did also show this difference (-0.05 vs. +0.12, p=0.02). There were no significant differences in adverse events between the two groups.
Editorial Comment:
This is the first of 2 phase III RCT to demonstrate benefit of this novel preparation of nitroglycerin. This suggests a benefit of this medication in patients with Raynaud’s including those with secondary Raynaud’s phenomenon. This preparation seems to be well tolerated. The RCS was used as the primary outcome measure and this is a validated outcome measure, although the minimal clinically important difference in this measure is unknown. The overall effect size seems to be somewhat small. This study did attempt to control for the effect of ambient temperature by choosing comparison week of treatment that was most comparable to the baseline week. There was no data provided on the number of RP events that were noted or the number of treatment applications that were used between the two groups or between the baseline and target week, which would be other measures that would ensure comparability.
