Zenvia™ bij diabetische neuropathie
Zenvia ™ is in ontwikkeling als middel bij diabetische neuropathie. Zenvia™ is de handelsnaam van een combinatie tussen dextromethorphan hydrobromide, en quinidine sulfaat door Avanir Pharmaceuticals.
Enkele jaren geleden kwamen de eerste resultaten van een fase III studie beschikbaar, en we citeren uit de press release:
Avanir Pharmaceuticals (NASDAQ: AVNR) today announced positive top-line results from the company’s Phase III clinical trial evaluating the investigational drug Zenvia(TM) (dextromethorphan hydrobromide/quinidine sulfate (“DMQ”)), an NMDA antagonist and sigma-1 agonist, in diabetic neuropathic pain. The primary endpoint of the trial was based on the daily diary entries for the Pain Rating Scale as defined in the Special Protocol Assessment (SPA) with the U.S. Food and Drug Administration (FDA).
In the trial, two doses of Zenvia, 45/30 mg DMQ dosed twice daily (“DMQ 45”) and 30/30 mg DMQ dosed twice daily (“DMQ 30”), were compared to placebo based on daily patiënt diary entries for the Pain Rating Scale. Both Zenvia treatment groups had lower pain ratings than placebo patients (p less than 0.0001 in both cases).
In the DMQ 45 patiënt group, average reductions were significantly greater than placebo patients at Days 30, 60, and 90 (p less than 0.0001 at each time point). In the DMQ 30 patiënt group, average reductions were also significantly greater than placebo patients at Days 30 and 60 (p less than 0.0001) and Day 90 (p=0.007).
Pain Relief Ratings Scale
Zenvia also demonstrated statistically duidelijk improvements in a number of key secondary endpoints. Including the Pain Relief Ratings Scale and the Pain Intensity Ratings Scale. The secondary endpoints compared the baseline value to the average rating values at each study visit after randomization. The average pain relief reductions as measured on the Pain Relief Rating Scale were greater for the DMQ 45 patiënt group (p=0.0002). And for the DMQ 30 patiënt group (p=0.0083), compared with placebo.
In addition, the DMQ 45, but not the DMQ 30, patiënt group demonstrated statistically duidelijk improvements in the Pain Intensity Rating Scale compared with placebo (p=0.029). Although not powered to detect differences in the secondary endpoint of Peripheral Neuropathy Quality of Life Scale Composite score, the DMQ 45 patients showed a greater improvement than placebo patients (p=0.05) and the DMQ 30 patients showed a greater improvement than placebo patients (p=0.08).
Analyses are on-going
Overall, the safety data from this study are consistent with data from previous studies. The most commonly reported adverse events were dizziness, nausea, diarrhea, fatigue and somnolence. These were generally mild to moderate in nature. A higher number of patients in the DMQ 45 and DMQ 30 treatment groups (25.2% and 21.0%, respectively) discontinued due to an adverse event than compared to placebo (11.4%). There were no significant differences in serious adverse events with 7.6%, 4.8% and 4.1% reported in the DMQ 45, DMQ 30 and placebo groups, respectively.
In addition, no deaths occurred throughout the study. Further safety and efficacy analyses are on-going and are expected to be presented at an upcoming public medical forum. “We are extremely encouraged by the results of this trial. This is consistent with Avanir’s prior Phase II study in patients with diabetic neuropathic pain”. Said Randall Kaye, MD, Senior Vice President and Chief Medical Officer of Avanir Pharmaceuticals. “We look forward to meeting with the FDA to discuss the next study for Zenvia for the treatment of diabetic neuropathic pain given the robustness of the clinical results.”
Resultaten binnen neuropathische pijn zijn nog niet gepubliceerd.
Maart 2010, prof. dr. Jan M. Keppel Hesselink
Bekijk hier video’s van onze patienten over diabetes.
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