Chronic Back Pain

September 14, 2015

Collegium Pharmaceutical reported results of a phase III trial of Xtampza ER (oxycodone extended-release capsules) for moderate-to-severe chronic low back pain. The multicenter, randomized, double-blind, enriched enrollment, randomized withdrawal, placebo-controlled study met its primary endpoint, which showed a statistically significant difference in average pain intensity from Randomization Baseline to week 12 between the Xtampza ER and placebo groups (p<0.0001). All sensitivity analyses of the primary endpoint also were statistically significant. Xtampza ER had an adverse event profile consistent with other opioids, was well-tolerated, and no new safety concerns were identified. The company is seeking FDA approval for Xtampza ER.

January 26, 2015

Mesoblast has issued positive results of a phase II program of MPC-06-ID for the treatment of chronic low back pain due to degenerative disc disease. In the randomized, placebo-controlled trial of 100 patients, a single injection of Mesoblast’s allogeneic investigational mesenchymal precursor cell (MPC) product, MPC-06-ID, was welltolerated. A single injection of 6 million MPCs induced substantial and sustained pain relief over 24 months. At 12 and 24 months, 46% and 48% of MPC-06-ID-treated patients achieved minimal or no residual pain (VAS less than or equal to 20) compared with 13% and 13% of saline treated patients, p=0.042 and 0.093, respectively. In patients who received a single injection of six or 18 million MPCs, 44% and 42%, respectively, achieved the target composite endpoint of treatment success at both six and 12 months (50% reduction in pain, 15-point improvement in function and no further treatment intervention), compared with 13% of saline controls (p=0.006 and p=020). In patients who received six million MPCs and achieved the target composite endpoint of treatment success at both six and 12 months, 86% (11 of 13) maintained treatment success at 24 months (32% v. 11% saline controls, p=0.001). The phase III program for this indication has been initiated.

August 18, 2014

Collegium Pharmaceutical issued results of a phase III study of Oxycodone DETERx for the treatment of patients with moderate-to- severe chronic low back pain. The phase III study was a multicenter, double-blind, enriched-enrollment, randomized-withdrawal, placebo-controlled study of Oxycodone DETERx versus placebo in opioid-experienced and opioid-naïve subjects with moderate-to-severe chronic low back pain. Patients who achieved a stable and effective dose of Oxycodone DETERx during the open-label titration phase were randomized (n=389) into the 12-week, double-blind maintenance phase, in which they either were maintained on their current dose regimen of Oxycodone DETERx or were tapered to placebo. The primary efficacy endpoint of the study was the change in average pain intensity from baseline to week 12; pain was measured using an 11-point pain intensity numerical rating scale (PI-NRS). The study met the primary efficacy endpoint, showing patients with chronic low back pain treated with Oxycodone DETERx experienced a statistically significant reduction in pain compared with placebo (p< 0.0001). The company is positioned to file an NDA with the FDA for Oxycodone DETERx by the end of 2014.

August 20, 2012

Eli Lilly released results from a phase III trial of Forteo (teriparatide injection) compared to risedronate for the treatment of back pain. This randomized, double-blind, double-dummy, active-controlled study enrolled 710 postmenopausal women with at least one moderate or severe vertebral fracture thought to be the cause of back pain. Subjects received either Forteo 20mg/day or risedronate 35mg/week for 18 months. From baseline to six months, data showed no difference between Forteo (59.2%) and risedronate (57.4%) on the primary endpoint of at least a 30% reduction in worst back pain, as assessed by a numeric rating scale in each treatment group. However, there were statistically significant differences in favor of Forteo in some exploratory measures, including greater increases in bone mineral density (BMD) and fewer patients with new vertebral fractures. Furthermore, significantly fewer patients treated with Forteo experienced a worsening of average back pain between six and 18 months (23.6% versus 30.6% of risedronate-treated patients; p=0.04). Forteo was well tolerated. The most frequent adverse events were similar between both treatment groups. Eli Lilly did not note its plans for Forteo.

August 29, 2011

Zogenix released results from a phase III trial of Zohydro (extended release hydrocodone bitartrate) for the treatment of chronic pain. This US-based, randomized, double blind, placebo controlled trial enrolled approximately 600 subjects with chronic low back pain and inadequate pain relief from their existing therapy. The subjects received Zohydro capsules (20-100 mg) or placebo every 12 hours. The primary endpoint was the mean change from baseline to the end of 12 weeks of treatment in the average 24-hour pain intensity ratings based on the 0-10 Numerical Rating Scale. Zohydro resulted in significantly (p≡0.008) improved chronic pain relief compared to placebo. The two key secondary endpoints were also met: the proportion of subjects with at least 30% improvement in pain intensity and the improvement of overall satisfaction of medication.

May 1, 2006

Dov Pharmaceutical reported negative results of a phase III trial of bicifadine, for the treatment of chronic lower back pain. Results from the study failed to meet their primary efficacy endpoint, with none of the three trial doses yielding significant improvements on the patient-reported Visual Analog Scale, relative to placebo. Preliminary evidence of a high placebo response was noted. This multi-center, double-blind, placebo-controlled study enrolled 600 subjects in the US, who received one of 3 oral doses of the drug (200 mg, 300 mg or 400 mg) or placebo twice daily for 12 weeks. Additional analyses of study data were ongoing.

March 28, 2005

Pain Therapeutics issued positive results of a phase III trial of their investigational opiod analgesic Oxytrex. Results from the study demonstrated a superior tolerability and cessation profile, with subjects receiving Oxytrex experiencing over 50% less symptoms of physical dependence and withdrawal effects after cessation of high-dose therapy, vs. approved therapy with oxycodone (p<0.01). Incidence of certain opioid-related side effects during treatment were also significantly lower, including somnolence (p<0.05), pruritus (p<0.05) and moderate-to-severe constipation (p<0.05), vs. oxycodone. Analgesic efficacy was found to be non-inferior to the approved drug. This randomized, double-blind, placebo and active-controlled trial enrolled 719 patients with persistent moderate-to-severe low-back pain at sites in the US. Following a 4-10 day washout, subjects were enrolled into one of four dosing cohorts: Oxytrex twice daily (n=206), Oxytrex four times daily (n=206), oxycodone four times daily (n=206), or placebo (n=101) for 6 weeks of dose-escalation (maximum dose: 80 mg), followed by 3 months of fixed dose treatment and follow-up observation of withdrawal symptoms.

March 24, 2003

Endo Pharmaceuticals reported positive results from a series of phase IV trials investigating Lidoderm (lidocaine patch 5%) for the treatment of pain. The first study a randomized, open-label, multicenter, two-week pilot study designed to assess the impact of Lidoderm in subjects with postherpetic neuralgia (PHN), diabetic neuropathy (DN), or low back pain. Results showed that addition of Lidoderm reduced most pain interference in the PHN group and all interference in the DN and back pain groups. In the second study, an open-label, two-week pilot study of low back pain, subjects were treated with the patch for two weeks. Results showed that Lidoderm produced significant improvements in pain intensity in all groups and the treatment was well tolerated. Positive results were also reported in trials for the treatment of osteoarthritis knee pain and diabetic neuropathy.

January 21, 2002

Phase III trial results indicate that Biovail's extended release tramadol formulation (Tramadol ER) produces statistically significant dose-related reductions in chronic low back pain. The trial included an open label run-in phase to identify subjects for continuation in a double-blind phase. At the beginning of the double-blind treatment phase, approximately 380 eligible subjects were randomly assigned to receive Tramadol ER 300 mg, Tramadol ER 200 mg or placebo. At the first time point evaluated (Week 1), Tramadol ER was statistically superior to placebo in reducing pain, with the Tramadol ER 300 mg dose demonstrating more effectiveness than the 200 mg dose. The effects of Tramadol ER were sustained over the 12-week duration of the double-blind phase.