Speaker: Edda Gomez-Panzani, MD, Director of Clinical Research and Development, and Head of Medical Affairs, Altea Therapeutics, Tucker, Georgia
An investigational transdermal hydromorphone patch (Altea Therapeutics) seems to be effective for patients with moderate-to-severe acute pain after knee or hip replacement surgery.
The delivery of hydromorphone through the skin was achieved by Altea’s patented PassPort System, an advanced technique that enhances the permeability of the skin by creating aqueous channels (micropores) through the stratum corneum using thermal ablation via an array of metallic filaments. A short pulse of electrical current is generated from a reusable, hand-held applicator.
A randomized, multicenter, parallel-design, three-day study was conducted to evaluate the analgesic effect and safety of two dosages of transdermal hydromorphone in 14 patients. Seven patients were assigned to receive one patch, and seven patients were to receive two patches.
Primary efficacy endpoints were pain relief, defined as a composite of a decrease in VAS pain severity scores of 20 mm or more from baseline, a VAS score of 50 mm or lower at the follow-up visit, and the lack of need for a rescue medication before the follow-up visit. Secondary efficacy endpoints included the time to meaningful pain relief, the amount of rescue medication needed and the time elapsed until its first use, and patients’ assessments of the study drug.
At the end of the first day, the average number of doses of rescue medication needed was significantly higher with one patch (9.5 doses) than with two patches (1.5 doses). This result correlated with the analgesic effect of a serum hydro-morphone level of 3 mg/ml, delivered by two patches. Patients rated the patch as “good” in terms of effectiveness (77%); they reported experiencing no sensation from the micropores (69%); they considered the patch comfortable to wear (85%); and they reported a good-to-excellent skin appearance (85%).
Fentanyl Effervescent Buccal Tablets for Cancer-Related Breakthrough Pain
Speaker: Donald R. Taylor, MD, Medical Director, Comprehensive Pain Care PC, Marietta, Georgia
An effervescent buccal tablet formation of fentanyl (Actiq, Ceph-alon) appears to be a superior treatment option for breakthrough pain in cancer patients who can tolerate opioids. Buccal tablets dissolve in the buccal pouch (between the cheek and the gum).
After an open-label titration study established an effective dose for the tablets, 123 patients were randomly assigned to receive one of 18 predefined dose sequences of 10 tablets (seven fentanyl tablets and three placebo tablets). All 10 doses were to be taken within a two-day period. A maximum of four episodes of breakthrough pain were treated each day.
Pain intensity, as measured on an 11-point scale, and pain relief, as measured on a 5-point scale, were recorded at 15, 30, 45, and 60 minutes after the dose was given. The summed pain intensity difference (SPID30) and total pain relief were recorded at 30 minutes after the dose was given. ADEs and supplemental medication were also assessed.
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Eighty of the initial patients (65%) identified an effective tablet dose during titration, ranging from 100 to 800 mcg. Of these patients, 77 continued in the double-blind phase of the study; 72 patients were evaluable for efficacy. Overall, significantly greater analgesic effects were recorded at all time points for the tablets, compared with placebo, for the mean difference in pain intensity, pain relief, SPID30, and total pain relief from zero to 60 minutes.
The primary efficacy endpoint, SPID30, was 3.0 ±0.12 SD for breakthrough pain episodes treated with the tablets and 1.8 ± 0.18 SD for episodes treated with placebo. This highly statistically significant difference favored the tablets (P < .0001). Patients who took placebo were twice as likely as patients using the tablets to need supplemental medications for episodes of breakthrough pain.
ADEs were similar to those of opioids. The most common ADEs were nausea, dizziness, and headache. Only two patients stopped therapy because of problems with oral tolerability.
Lower Doses of Epidural Steroids Recommended for Lumbar Radiculopathy and Spinal Stenosis
Speaker: Damon Robinson, MD, Clinical Fellow, Anesthesia, Critical Care, and Pain Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts
In a study designed to determine the optimal steroid dose needed for lumbar epidural steroid injections, it was found that lower doses of triamcinolone (Fujisawa) injections for back pain were more effective than higher doses. Injectable triamcinolone 80 mg was the lower optimal dose for lumbo-sacral radiculopathy and spinal stenosis.
Although steroid injections have been used to treat lumbo-sacral radical pain and spinal stenosis since the 1960s, the optimal steroid dose has yet to be determined. A prospective, randomized, double-blind clinical trial was performed to evaluate the effects of five different doses of epidural in 160 patients with lumbosacral radiculopathy (60%) or spinal stenosis (40%), as confirmed by magnetic resonance imaging or electromyography.
The patients were randomly assigned to receive 40, 80, 120, 160, or 200 mg of epidural triamcinolone. The same dose was administered for each subsequent injection. Up to three injections were administered over a six-month period.
At the baseline examination, before injection therapy, the average VAS score was 7 mm, defined as no pain relief. After one week of injections, the average VAS score was below 2 mm, with 77% (123 patients) reporting substantial pain relief. The 80- and 120-mg doses of triamcinolone were optimal for pain relief. Higher doses provided no additional reduction in VAS scores, and the 200-mg dose was associated with an increased number of ADEs.
Duloxetine Safe for Long-Term Management of Diabetic Peripheral Neuropathic Pain
Speaker: Yili L. Pritchett, PhD, Research Scientist, Eli Lilly, Indianapolis, Indiana
Duloxetine HCl (Eli Lilly), a dual reuptake inhibitor of both serotonin and norepinephrine, was recently approved for the management of diabetic peripheral neuropathic pain (DPNP). Researchers have now found it to be safe and well tolerated, compared with routine care, in the long-term management of patients with DPNP
Initially, three independent 12-week studies of acute therapy confirmed the safety and efficacy of duloxetine 60 mg once daily and 60 mg twice daily for patients with DPNP. The objectives were to evaluate the safety of duloxetine 60 mg twice daily over a 52-week, open-label extension period; to assess this treatment and progression of diabetic complications for up to 65 weeks; and to compare the effect of duloxetine 60 mg twice daily with routine care in patient-reported health outcomes.
A total of 237 patients who completed a double-blind 13-week period and placebo therapy were randomly reassigned, in a 2:1 ratio, to receive duloxetine 60 mg twice daily (161 patients) or routine care (76 patients) for an additional 52 weeks. Routine care consisted primarily of gabapentin (Neurontin, Pfizer), venlafaxine (Effexor, Wyeth), and ami-triptyline (various manufacturers).
The study enrolled men and women 18 years of age or older with a diagnosis of DPNP caused by either type-1 or type-2 diabetes. Overall, a higher percentage of the patients receiving routine care experienced one or more serious ADEs than those taking duloxetine. For the duloxetine patients, changes in laboratory and vital sign values were not considered clinically relevant because of the small magnitude of the changes.
Duloxetine did not appear to have an adverse effect on nerve function, to change the progression of retinopathy, or to have a negative effect on the course of DPNP. Neither therapy group showed any statistically significant differences in the 36-item Short-Form Health Survey (SF-36) subscales or in the EuroQd 5-Dimension Questionnaire (EQ-5D).
The lack of significant cardiovascular changes with dulox-etine suggests that patients with diabetes mellitus do not need more intensive assessment of their cardiovascular status with canadian duloxetine than they require for their underlying diabetes.