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June 10, 2013
Boehringer Ingelheim issued results from a phase III trial of LUME-Lung 1 for the treatment of advanced non-small cell lung cancer (NSCLC). This randomized, openlabel, double-blind study enrolled 1,314 patients with locally advanced or metastatic (stage IIIb/IV or recurring) NSCLC after first-line therapy. The subjects received nintedanib 200mg BID plus docetaxel 75mg/m(2) once a day for three weeks (n=655), or docetaxel plus placebo (n=659). LUME-Lung 1 improved progression-free survival (PFS)—the primary endpoint—as a second-line treatment in patients with NSCLC compared to docetaxel alone. Secondary endpoints included overall survival. Results showed patients treated with nintedanib plus docetaxel lived for a median of 3.4 months before their tumor started to grow again, versus 2.7 months with docetaxel alone (HR 0.79; p=0.0019). The most common adverse events (AEs) of any grade in the nintedanib combination and docetaxel alone groups were diarrhea (42.3% v. 21.8%, respectively) and ALT elevations (28.5% v. 8.4%, respectively). Incidence of > grade 3 AEs was 71.3% in patients treated with nintedanib plus docetaxel compared to 64.3% with docetaxel alone. A higher incidence of > grade 3 diarrhea and elevated ALT were observed in patients treated with nintedanib plus docetaxel compared to docetaxel alone (> grade 3 diarrhea: 6.6% v. 2.6%; elevated ALT: 7.8% v. 0.9%). Incidence of > grade 3 hypertension, bleeding and thrombosis were similar in both treatment arms. There was a 1% difference in discontinuation between the treatment arms, with 22.7% of patients stopping treatment with nintedanib plus docetaxel versus 21.7% with docetaxel alone.
April 5, 2010
GW Pharmaceuticals and Otsuka reported positive preliminary results from a phase IIb trial of Sativex for the treatment of pain related to cancer. This international, randomized double-blind placebo-controlled parallel-group study enrolled 360 subjects with advanced cancer who experienced inadequate analgesia during optimized chronic opioid therapy. The subjects received three dose ranges of Sativex a low dose (1-4 sprays per day), mid dose (6-10 sprays per day), and high dose (11-16 sprays per day) over a 5 week treatment period. Sativex or placebo was administered as add-on treatment to strong opioid therapy and the subjects remained on stable doses of their background optimized opioid therapy during the study. The primary efficacy measure of the study was a patient assessment of pain using a 0-10 Numeric Rating Scale (NRS), which was analyzed using three , the 30% responder analysis, continuous response analysis and change from baseline analysis in NRS average pain. The 30% responder analysis was numerically in favor of Sativex but did not show a statistical difference compared to placebo. The continuous response analysis did show statistically significant results in favor of Sativex for both the low and mid dose groups versus placebo (p≡0.008 and p≡0.038, respectively). The change from baseline in NRS average pain score also showed a statistically significant difference between the Sativex low dose group and placebo (p≡0.006). The Sativex low dose group also showed a statistically significant difference versus placebo in reducing sleep disruption, a key secondary endpoint (p≡.003).
September 1, 2008
Xenome reported positive results from a phase II trial of Xen2174 for the treatment of chronic cancer pain. This study enrolled 37 subjects who received a single increasing dose of Xen2174 (from 0.025 to 40 mg) injected into the fluid surrounding the spine for four days. Xen2174 was found to be well tolerated. Evidence of pain relief was seen at most dose levels over the four day observation period and was characterized by rapid onset of action and long-lasting effect. The majority of adverse events attributable to Xen2174 were either mild or moderate. Analysis of Xen2174 levels demonstrated that standard pharmacokinetic parameters varied in a predictable manner with increasing doses. Peak drug levels and rates of clearance were within acceptable clinical parameters. Based on the results, Xenome plans to commence a phase II trial of Xen2174 for acute, post-surgical pain by the end of 2008.
September 17, 2007
Akela released positive results from a phase IIb trial of Fentanyl TAIFUN for the treatment of pain. This double-blind, randomized extension study enrolled 50 subjects with break-through cancer pain who received titrated doses of Fentanyl-TAIFUN or placebo. Statistical significance was reached in the trials primary endpoints when compared to placebo. The median time to significant pain relief in the Fentanyl TAIFUN group, as measured by a decrease of at least 2 points on the numerical pain scale (NPS), was 5.2 minutes (P=0.007). The mean difference in sum of pain intensity difference (SPID) was also in favor of Fentanyl TAIFUN for the whole 60 min pain episode (P=0.050). This was already seen in numerical pain scale scores up to 15 minutes (P=0.008) when compared to placebo. Based on the results Akela is preparing for phase III trials.
May 28, 2007
Sosei reported positive results from a phase I trial of AD 923 for the treatment of breakthrough pain in cancer. This open-label, single dose, cross-over, randomized study enrolled 24 subjects in the US. It was designed to evaluate the pharmacokinetics of AD 923 (sublingual fentanyl spray) compared to Actiq (oral fentanyl) and fentanyl citrate injection. Statistical significance was reached in median time to maximum plasma concentration (Tmax) for AD 923 compared to Actiq (40 minutes versus 120 minutes, respectively). The higher absolute bioavailability of AD 923 compared with Actiq also reached statistical significance. Treatment was well tolerated, with no significant adverse events. Sosei has reached agreement with EU regulatory authorities to move AD 923 directly into phase III trials. They are in discussions with the FDA to determine the requirements for a phase III program in the United States.
January 24, 2005
GW Pharmaceuticals has announced preliminary results of a phase III trial of Sativex (tetrahydrocannabinol/cannabidiol), their fixed-dose direct cannabinoid-receptor agonist, for the treatment of severe cancer pain. GW is also pursing development of the drug for multiple sclerosis and neuropathy/neuropathic pain in Canada and the UK; the drug is not currently in development in US markets. Study results indicated that the drug met its primary endpoint, with a significant improvement in patient-reported experience of pain (p=0.014), vs. placebo. This included a significantly greater portion of subjects receiving Sativex reporting a 30% or greater reduction in pain, vs. placebo (40% of subjects receiving Sativex; p=0.024). Furthermore, the study indicated that subjects who received only tetrahydrocannabinol did not show a significant improvement in ratings of pain vs. placebo (p=0.24), confirming Sativex’s fixed-dose combination. This multi centre double-blind, placebo-controlled parallel group study randomized 117 patients experiencing severe cancer pain unresponsive to opioid therapy to receive Sativex, tetrahydrocannabinol alone, or placebo at a 1:1:1 ratio. The company announced that it would review any additional steps needed for regulatory submission, including the design of an additional confirmatory phase III trial.
Phytopharm issued positive interim data from a ongoing phase II proof-of-principle study of their drug Cogane (PYM50028), for the treatment of Alzheimer’s disease. The interim safety review yielded no serious safety concerns, based on data from the first 60 subjects. Furthermore, independent review estimated a total necessary enrollment of between 200 and 238 subjects (the secondary purpose of the interim review). This randomized, double-blind, placebo-controlled study was designed to evaluate the safety, efficacy and pharmacokinetic profile of PYM50028 after once daily oral administration for 12 weeks to patients with Alzheimer's disease. Phytopharm announced plans to submit the necessary applications to expand the trial size, based on these results.
August 26, 2002
In a long-term clinical study of Ligand's morphine product, Avinza, 137 subjects with chronic, moderate-to-severe pain of malignant and non-malignant origin were evaluated for safety and efficacy over a one-year treatment period. These subjects had each completed one of four previous clinical trials with Avinza. The median daily dose of Avinza was 120 mg at baseline, 180 mg at six months and remained stable from six to 12 months. Subjects did not experience any statistically significant changes in pain or intensity, indicating that Avinza may provide effective long-term analgesia. In a second study with Avinza, 300 subjects with osteoarthritis took Avinza for up to 30 weeks. In one portion of the study, the safety and efficacy was compared to placebo and to MS Contin. Compared to placebo, Avinza taken once-daily in the morning showed statistically significant improvement in physical functioning compared to placebo at all four weekly visits. Similar significant improvement was found at the first three visits in subjects who took Avinza once-daily in the evening. In subjects receiving MS Contin, significant improvements in physical functioning were observed only at the first weekly visit.