AcelRx Pharmaceuticals, Inc., a specialty pharma company focused on the development and commercialization of innovative therapies for the treatment of acute and breakthrough pain, has reported top-line results demonstrating that a placebo-controlled, dose-finding, phase II study of its investigational single-dose sublingual sufentanil NanoTab for acute pain, ARX-04, successfully met its primary endpoint.

Results demonstrated that patients receiving 30 mcg sufentanil NanoTab doses, administered by a healthcare professional, no more frequently than once per hour, had significantly greater pain reduction as measured by Summed Pain Intensity Difference to baseline during the 12-hour study period (SPID-12) than placebo-treated patients (p=0.003).

Adverse events reported in the study were generally mild-to-moderate in nature, with two serious adverse events of post-surgical infection reported, both of which were determined by the investigator to be unrelated to study drug. Two patients dropped out of the study due to adverse events, one patient's discontinuation considered unrelated to study drug, and the other considered probably related to study drug, both in the 30 mcg-treated group.

"The goal of this programme, to find an effective sublingual sufentanil dose that could be administered less frequently by a healthcare professional than our patient-administered ARX-01 product candidate, has been met," said Dr Pamela Palmer, chief medical officer, AcelRx Pharmaceuticals. "There is a need for a non-invasive, rapid-onset strong analgesic to provide short-term treatment of pain for the wounded soldier on the battlefield, the trauma victim at the site of a road-traffic accident, the migraine patient in the emergency room, or in general for patients in moderate-to-severe acute pain where intravenous access is not readily available."

This study randomized 101 patients following bunionectomy surgery in a 2:2:1 ratio to 30 mcg sufentanil, 20 mcg sufentanil or placebo treatment arms. The intent-to-treat (ITT) population in this study averaged 42.5 years of age with an average Body Mass Index of 28.2, and was evenly balanced for males and females (51 per cent:49 per cent) and ethnicity (54 per cent Caucasian:46 per cent non-Caucasian). Ninety-one percent of patients entering the study completed the full 12-hour study period. SPID-12 scores were +6.53 for 30 mcg sufentanil-treated patients and -7.12 for placebo-treated patients, the difference between the two groups being highly statistically significant (p=0.003).  The 20 mcg sufentanil-treated patients did not achieve SPID-12 scores that differentiated from placebo.

"The results from this study, funded by the US Army Medical Research and Materiel Command, provide further validation of our sufentanil NanoTab product platform as an effective treatment for moderate-to-severe acute pain," said Richard King, president and CEO of AcelRx. "AcelRx will present these positive top-line data to USAMRMC, and intends to hold an End of phase II meeting with the FDA to define the phase III clinical programme for ARX-04."

ARX-04 is a product candidate in development for the treatment of moderate-to-severe acute pain, consisting of sufentanil, a high therapeutic index opioid, in AcelRx's proprietary NanoTab technology that enables rapid sublingual absorption when the NanoTab is placed under the tongue.  As a result, sufentanil NanoTabs are designed to provide rapid onset of analgesia in a non-invasive method of administration and display a consistent pharmacokinetic profile due to a high percentage of drug being absorbed sublingually instead of through the gastrointestinal tract.  We believe ARX-04 may ultimately be proven beneficial in a variety of medically supervised settings, including use in battlefield casualty treatment, by paramedics during patient transport, in the emergency room, for non-surgical patients experiencing pain in the hospital, or for post-operative patients, following either short-stay or ambulatory surgery, who do not require more long-term patient-controlled analgesia (PCA).

In situations of trauma or injury, it is advantageous to have a rapid-acting, non-invasive method of treating acute pain. In the battlefield, in the emergency room and in ambulatory care environments, patients often do not have immediate intravenous, or IV, access available. Intramuscular injections are the current standard of care on the battlefield, but they are invasive, painful, and present an increased risk of infection to both patient and healthcare professional. In addition, in cases of severe trauma where the patient is often in hypovolemic shock and muscles are not well perfused, pain medication given by intramuscular injection may not readily reach the blood stream to provide pain relief, rendering this route of delivery suboptimal. Oral pills and liquids generally have slow and erratic onset of analgesia. Even patients with IV access may have undesirable side effects with the commonly used IV opioids morphine and hydromorphone, such as sedation or oxygen desaturation. Moreover, IV dosing results in high peak plasma levels, thereby limiting the opioid dose and requiring frequent redosing intervals to titrate to satisfactory analgesia. Additional treatment options are needed which can safely and rapidly treat acute pain, in both civilian and military settings.