A Phase II, multicenter, randomized, double-blind, placebo-controlled crossover study of CJC-1008--a long-acting, parenteral opioid analgesic--in the treatment of postherpetic neuralgia.

CJC-1008 is a chemical modification of the opioid peptide dynorphin A (1-13) (Dyn A) that promotes dynorphin's covalent attachment to human serum albumin in vivo after administration, thus prolonging its duration of action. The primary objective of this study was to evaluate the preliminary efficacy and safety of CJC-1008 as compared with placebo in patients with postherpetic neuralgia (PHN). Patients with PHN were assigned 1:1 to receive active study medication or placebo. After dosing, measurements were made every 15 minutes for the first hour; at two, three, four, six, and eight hours postdose; and during return visits to the study site after two, seven, and 28 days (as necessary), as well as during precrossover and exit visits. These measurements examined: 1) overall pain intensity, 2) pain intensity for each individual PHN type, 3) categorical overall pain intensity, 4) categorical pain relief and 5) adverse events (AEs). When PHN pain intensity returned to baseline and/or at patients' first request for rescue analgesia other than acetaminophen (typically around 28 days after dosing but sometimes as soon as two days postdose), patients were to cross over to the alternative treatment and be monitored on the same schedule. A substantial placebo response was observed, but the analgesic effect observed in the active group was greater than that in the placebo group for the first eight hours. By 24 hours, the difference was not significant. A total of 29 out of 30 patients (96 percent) experienced at least one treatment-emergent AE during active drug treatment, while 14 of 27 patients (52 percent) reported such AEs during placebo treatment. Of the AEs occurring within the first eight hours after dosing, 97 percent were reported during treatment with active drug and 3 percent were reported during treatment with placebo. The majority of these AEs were mild in intensity. This study provides evidence of a greater analgesic effect when using CJC-1008 compared to placebo in patients with PHN. However, the effect only lasted through eight hours postdose and diminished by 24 hours. This study provides evidence of a peripheral action of dynorphin, since CJC-1008 does not cross the blood-brain barrier.