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New Medical Therapies™

Chronic Pain

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November 4, 2013

AstraZeneca released results of a phase III trial of naloxegol for the treatment of non-cancer pain and opioid-induced constipation (OIC). The study enrolled 844 patients, provided a once-daily 25mg dose of naloxegol and lasted 52 weeks, comparing naloxegol (n=534) to usual care (n=270). Usual care was defined as the investigator’s choice of an existing laxative treatment regimen for OIC. Most naloxegol-emergent gastrointestinal adverse events (AEs) occurred early in treatment and were transient with nine patients (1.6%) discontinuing naloxegol due to abdominal pain. Most common treatment-emergent AEs occurring more often with naloxegol v. usual care were abdominal pain (17.8% v. 3.3%), diarrhoea (12.9% v. 5.9%), nausea (9.4% v. 4.1%), headache (9.0% v. 4.8%) and flatulence (6.9% v. 1.1%). Pain scores and opioid doses were comparable between treatment groups and were stable throughout the study. There were two opioid withdrawal AEs reported in patients taking naloxegol (both were deemed unrelated to treatment with naloxegol).

July 8, 2013

Nektar Therapeutics issued results from a randomized, double-blind, placebo- and active-controlled, five-way crossover trial of NKTR-181 for the treatment of moderate-to-severe chronic pain. The trial compared three doses of NKTR-181 oral solution (100mg, 200mg, and 400mg) to the effects of 40mg of oxycodone oral solution and placebo. Participants were healthy adults (N=42) who were not currently physically opioid-dependent but had used opioids to attain non-medical effects on at least 10 occasions during the past year and at least once in the 12 weeks before the study. All oral doses of NKTR-181 scored similar to placebo in a Drug Effects Questionnaire (DEQ) assessing the treatment’s effect on how “high” the subject felt (on a scale of 0 to 100). Maximum mean DEQ scores were 14, 14 and 23 for 100mg, 200mg tablet and 400mg, respectively, with p-values < 0.0001 as compared to oxycodone. Placebo achieved a maximum mean score of nine. NKTR-181 is currently being evaluated in phase II development as a twice-daily oral tablet.

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 13, 2012

Array BioPharma released results from a phase II trial of ARRY-797 for the treatment of moderate to severe chronic knee pain despite the use of non-steroidal anti-inflammatory drugs (NSAIDs). This randomized, placebo-controlled and active controlled study enrolled 157 patients with osteoarthritis. Subjects were divided (1:1:1) to receive ARRY-797, placebo or oxycodone ER while continuing their use of NSAIDs for four weeks. Data showed a statistically significant reduction in pain compared to placebo, as measured using the Western Ontario and McMaster Universities Arthritis Index (WOMAC) pain subscale. Patients receiving ARRY-797 experienced a mean reduction in the WOMAC pain subscale score at day 28 vs. baseline that was 0.8 greater than those receiving placebo (2.4 vs. 1.6; one-sided p=0.0247). ARRY-797 was well tolerated. The most frequent adverse events were dizziness, diarrhea and nausea. Array will begin seeking a partner to maximize the value of ARRY-797.

April 16, 2012

QRxPharma issued results from two phase I trials of MoxDuo CR, their controlled release formulation of morphine and oxycodone for chronic pain. Data demonstrated MoxDuo CR's superior results, with sustained blood levels for up to 24 hours. The first trial enrolled 10 healthy subjects and compared MoxDuo CR (30mg morphine/20mg oxycodone) to the pharmacokinetic profiles of the same doses of MS Contin and OxyContin, using a three-way crossover design. Pharmacokinetic results from the measurement of opioid blood levels over time revealed a MoxDuo CR profile consistent with expectations for a once to twice-daily formulation. The second trial enrolled 17 healthy subjects who received MoxDuo CR or morphine and oxycodone tablets using a two-way crossover design. The trial evaluated the effects of chronic use on steady-state blood levels and measured the repetitive-dose pharmacokinetic profiles of morphine and its metabolites as well as oxycodone during twice daily administration of MoxDuo CR tablets for five days. Data showed food consumption does not alter the pharmacokinetic profiles of morphine and oxycodone from MoxDuo CR.

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 2, 2011

Pain Therapeutics reported results from a study of Remoxy, an oral abuse resistant formulation of oxycodone. The double blind, placebo and active-controlled, six-way crossover study enrolled 45 healthy subjects with histories of non-dependent recreational opioid use. The study assessed the abuse potential of Remoxy 40 mg whole and chewed, oxycodone ER 40 mg whole and crushed, oxycodone IR 40 mg crushed and placebo. Treatments were administered in-clinic under various fed/fast conditions that produced the highest bioavailability for each drug. Data are from 32 subjects. The primary endpoint was Drug Liking, as assessed by various pharmacodynamic parameters. Drug Liking was significantly lower for Remoxy 40mg (whole) compared with oxycodone ER 40mg (whole) or oxycodone IR 40 mg (p<0.05). Drug Liking was significantly lower for Remoxy 40mg (chewed) compared with oxycodone ER 40mg (crushed) or oxycodone IR 40 mg (p<0.05). Time to Peak Drug Liking was significantly delayed for Remoxy 40mg (chewed) compared with oxycodone ER 40mg (crushed) or oxycodone IR (p<0.05). Secondary endpoints, including Drug High and Good Effects, chewing duration, taste/texture assessments and safety assessments, were generally the same consistency of effects observed in the primary endpoints. In addition, no subject could chew Remoxy for more than 1.5 minutes despite an allotted time of ten minutes, due to the unpleasant taste/texture.

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).

March 30, 2009

NeuroMed issued positive results from a phase III trial of Exalgo for the treatment of chronic pain. This US-based, randomized withdrawal, placebo-controlled, double-blind trial enrolled 268 opioid-tolerant subjects with chronic moderate to severe low back pain. The subjects received placebo or Exalgo at doses between 12 mg and 64 mg. The primary endpoint was the mean change from baseline to week 12 in pain intensity, assessed by an 11 point Likert Numerical Rating Scale (NRS). The study showed statistically significant results in the specified primary efficacy endpoint (p<0.0001). Results from multiple secondary efficacy endpoints were consistent with the primary efficacy endpoint. The overall safety profile and reported adverse events in the study were consistent with that of other opioids.

March 23, 2009

Durect reported positive results from a phase IIb trial of Transdur-sufentanil, a transdermal patch formulation of the opioid sufentanil. This open label, two-stage study enrolled 74 opioid-experienced subjects with non-malignant moderate to severe chronic pain. The study was designed to explore the conversion schedule for transitioning this population from current oral and transdermal opioid therapies to Transdur-Sufentanil. Following a baseline screening, the subjects were randomized into multiple titration regimens. After achieving an endpoint of adequate, stable pain control and an acceptable safety profile on Transdur-Sufentanil, they entered a 28-day continuous treatment maintenance period. This was followed by a seven day follow-up period to ensure that an adequate pain control regimen was re-established. Of the 74 initially enrolled subjects, 36 successfully entered the maintenance period. Two acceptable dose titration intervals achieved the desired analgesic effect and side-effect profile. The mean pain score during the maintenance period was 3.88 (on a ratings scale for pain intensity, with 0 being no pain) representing a reduction of approximately 19% from the mean baseline pain score of 4.78. Treatment was safe and well tolerated.

October 20, 2008

Acura and King Pharmaceuticals issued positive results from a phase II trial of Acurox tablets, under investigation for the treatment of pain. This randomized, double-blind study was designed to assess the abuse liability potential of Acurox in 30 subjects with a history of opioid abuse. The subjects were fasted and received a single dose of Acrux (oxycodone HCl 40mg + niacin 240mg) or oxycodone HCl 40mg alone every 48 hours for nine days. On each dosing day, vital sign measures and subjective and behavioral effects were assessed at baseline and at several time points up to 12 hours post-dosing. Acurox showed the potential to be aversive when compared to oxycodone HCl 40mg alone, as shown by statistically significant and clinically meaningful results in the subjective dislike/like scores (p = .033), the Treatment Enjoyment Assessment scores (p = .005) and the LSD/dysphoria scores (p<.001). Treatment was well tolerated and no adverse events were reported. The companies plan to submit an NDA to the FDA by the end of 2008.

August 25, 2008

Pain Therapeutics and King Pharmaceuticals released positive top-line results from a phase III trial of Remoxy for the treatment of chronic pain. This randomized, double-blinded, placebo-controlled, multi-center study enrolled 412 subjects with osteoarthritis of the knee or hip and moderate-to-severe pain. Following a wash-out and dose titration period, the subjects received twice-daily Remoxy (10-80 mg) or matching placebo for a twelve week treatment period. The primary endpoint, the mean decrease in pain intensity scores between the Remoxy and placebo groups, was reached with statistical significance (p = 0.007). Secondary endpoints were also reached with significance, including Quality of Analgesia (p = 0.004), Global Assessment (p = 0.007), the pain subscale of the WOMAC Osteoarthritis Index (p=0.023) and the physical component of the SF-12 Health Survey (p=0.003). No drug-related safety issues were reported. An NDA is currently under review by the FDA.

May 19, 2008

Johnson and Johnson reported positive results from a phase III trial of tapentadol IR for the treatment of osteoarthritic pain. This double-blind, randomized, placebo-controlled, multi-center study enrolled 659 subjects who were candidates for primary joint replacement surgery for end-stage joint disease. The subjects received an oral dose of placebo, tapentadol IR 50 or 75 mg, or oxycodone IR 10 mg every four to six hours. The primary endpoint was the sum of pain intensity over five days; this was also measured at the two- and ten-day time points. The subjects treated with the 50 mg or 75 mg dose of tapentadol experienced significant relief in end-stage joint disease pain compared to placebo when assessed over five days of treatment (P<0.001). The subjects in the tapentadol arms also experienced significantly better digestive tract tolerability compared to subjects treated with 10 mg of oxycodone IR. Both doses of tapentadol IR showed a significant reduction in the incidence of gastrointestinal side effects such as nausea, vomiting and constipation when compared to oxycodone IR. An NDA is currently under review by the FDA.

May 12, 2008

Nektar reported positive results from a phase I trial of NKTR-118 for the treatment of opiod-induced bowel dysfunction. This multi-dose, double-blind, randomized, placebo-controlled study enrolled 32 healthy subjects not receiving opioid therapy. The subjects received NKTR-118 (in escalating doses up to 250 mg) or placebo twice daily for seven days, with a single dose on the eighth day. NKTR-118 was shown to be safe and generally well-tolerated at doses up to 250 mg twice daily, with no serious or severe adverse events. The pharmacokinetics of NKTR-118 were dose-proportional and the observed terminal half-life of the drug was approximately eleven hours, independent of dose. At all dose levels, NKTR-118 was rapidly absorbed after oral administration, as evidenced by a steep increase of plasma NKTR-118 concentration. Phase II trials of NKTR-118 are currently underway.

February 11, 2008

BioLine RX reported positive results from a phase IIa trial of BL-1020 for the treatment of schizophrenia. This open label, 6-week study enrolled 36 treatment refractory and hospitalized subjects. The subjects were started on 32mg (20mg free base) of BL-1020 and received increasing dosages over the first 7 days in order to reach the maximum dose of 64 mg (40mg free base). The primary endpoints were reached in the BL-1020 arm, with significant improvements from baseline in the Positive and Negative Syndrome Scale (PANSS) and Clinical Global Impression of Severity and Improvement (CGI-S, CGI-I). There was a statistically significant improvement on the PANSS total (baseline=84.9; day 42=63.8), and the positive (baseline=22.3; day 42=15.1) negative (baseline=20.9; day 42=16.6) and general psychopathology subscales (baseline=42.4; day 42=32.1) (p less than 0.001). In addition, more than 80% of the subjects treated with BL-1020 showed a clinically significant improvement as reflected by the CGI-S and CGI-I. Treatment was well tolerated, with no unexpected adverse events. Based on the results, BioLine RX is planning to commence a phase IIb trial during the second quarter of 2008.

Neuro-Hitech released mixed results from the double blind portion of a phase II trial of Huperzine A for the treatment of Alzheimers disease. This multi-center, randomized, double-blind, placebo-controlled trial enrolled two hundred subjects with mid-to-moderate Alzheimers disease. The subjects were administered either 200 or 400 micrograms of Huperzine A or placebo, orally twice a day for sixteen weeks. Approximately half the subjects received concomitant treatment with Namenda, an approved treatment for Alzheimers. The primary endpoint was the mean change on AD Assessment Scale- Cognitive (ADAS-Cog) scores after sixteen weeks. Results showed that there was no statistical difference in the mean ADAS-Cog scores for the Huperzine A 200 micrograms arm compared to placebo (p=0.81). However, the higher dose tested, 400 micrograms, showed cognitive enhancement on the ADAS-Cog versus placebo; the maximum cognitive improvement was observed at week eleven of treatment (p=0.001). Over sixteen weeks the Huperzine A 400 micrograms arm improved cognition compared to placebo (p=0.03) and there was a trend to cognitive improvement over placebo at week 16 (p=0.069). There was no statistical difference between placebo and either 200 or 400 micrograms of Huperzine A in any of the secondary endpoints, including clinical global impression of change (ADCS-CGIC) and the Neuropsychiatric Inventory (NPI). Treatment was safe and well tolerated, with an adverse event profile similar to placebo. Neuro-Hitech plans to move forward with the development of Huperzine A.

Penwest issued mixed results from a phase IIa trial of nalbuphine ER for the treatment of moderate chronic pain. This randomized, double-blind, placebo controlled study enrolled one hundred and thirty eight subjects with chronic pain secondary to osteoarthritis of the knee or hip. The subjects received the lowest dose of nalbuphine ER for week one, increased to a mid-dose level for week two, and increased to the highest dose studied for week three. The primary endpoint was the Sum of Pain Intensity Differences between baseline and day twenty one. Nalbuphine ER did not meet this endpoint, which was possibly due to patient dropouts in the first week of dosing. The drug did, however, achieve a number of the secondary endpoints compared to placebo, including statistical significance in the Global Assessment of Pain Control (p=0.006) and the Integrated Assessment of Pain Intensity and Rescue Medication Use (p=0.009). Nalbuphine ER was well tolerated, with no reports of drug related serious adverse events. Based on the results, a phase IIb trial is planned for later in 2008.

December 10, 2007

Pain Therapeutics and King Pharmaceuticals reported positive results from a phase III trial of Remoxy for the treatment of pain associated with osteoarthritis. This randomized, double-blinded, placebo-controlled, multi-center study enrolled four hundred and twelve subjects with osteoarthritis of the knee or hip and moderate-to-severe pain. Following a wash-out and dose titration period, the subjects received twice-daily Remoxy (10-80 mg) or matching placebo for a twelve week treatment period. The primary endpoint was defined as mean decrease in pain intensity scores between the Remoxy and placebo groups. Top-line data revealed this endpoint was reached with statistical significance (p<0.01). Secondary endpoints, including Quality of Analgesia and Global Assessment, also reached statistical significance (p<0.01). Based on the results, Pain Therapeutics and King Pharmaceuticals plan to file an NDA with the FDA in the second quarter of 2008.

September 24, 2007

Nektar issued positive results from a phase I trial of NKTR-118 for the treatment of opioid bowel dysfunction (OBD). This single-dose, double-blind, placebo-controlled study enrolled healthy male subjects who received placebo or escalating, single oral doses of NKTR-118 up to 1,000 mg. The trial measured the morphine-induced delay in gastrointestinal transit time using the lactulose hydrogen gastrointestinal motility test. NKTR-118 antagonized morphine-induced delay in gastrointestinal transit time, demonstrating the potential of the drug to relieve constipation. Further, no dimunition of morphine-induced miosis, a CNS effect, was observed at single oral doses of NKTR-118 of 125 mg or less. NKTR-118 was rapidly absorbed with dose-proportional pharmacokinetics and it was well tolerated at single doses up to 1,000 mg. Based on the results, Nektar plans to initiate a phase I multi-dose trial later in 2007.

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.

August 20, 2007

Cephalon issued positive results from a phase III trial of Fentora for the treatment of break-through pain associated with chronic non-cancer pain conditions. This double-blind, placebo-controlled, variable dose trial enrolled 148 opioid-tolerant subjects who received treatment for 12 weeks. The primary endpoint was the Sum of Pain Intensity Differences from five to 60 minutes (SPID) after 12 weeks of treatment. Subjects treated with Fentora showed a statistically significant improvement in the primary endpoint compared to placebo (p<0.0001). Treatment was well tolerated, with no reported unexpected adverse events. Based on the results, Cephalon plans to file a sNDA with the FDA in Q4 of 2007.

NeurAxon released positive results from a phase I trial of NXN-188 for the treatment of migraine headaches. This randomized, double-blind, placebo-controlled dose escalation study was designed to evaluate the safety and pharmacokinetics of the drug. Subjects received nine single oral dose levels of either NXN-188 or placebo. Treatment was determined to be well tolerated at all dose levels, with no reported adverse events. Based on the results, NeurAxon plans to initiate phase IIa trials in Q3 of 2007.

July 23, 2007

Newron announced positive results from a phase II trial of ralfinamide for the treatment of neuropathic pain. This double-blind, randomized, placebo controlled trial enrolled 272 subjects internationally. Subjects received ralfinamide at doses ranging from 80 to 320 mg/day or placebo for eight weeks. The primary endpoint was efficacy measured via a patient rated visual analogue scale (VAS) of the severity of pain compared to baseline. Treatment was generally safe and well tolerated at the highest dose tested. Ralfinamide reached statistical significance in reduction in pain severity when compared to placebo on the VAS scale, with a score of -18.1 compared to a placebo score of -12.5 (p=0.075). In addition, ralfinamide showed significant improvement in the mean ratings of the patient rated Daily Pain Diary: (p=0.003), significant improvement in the quality of sleep (p=0.002) and significant improvement in daily activities (p=0.033). Several phase II trials are currently underway and an IND was recently approved for the commencement of US based trials.

June 25, 2007

Javelin announced positive results from a phase III trial of Rylomine for the treatment of moderate to severe pain following elective orthopedic surgery. This double-blind trial, dubbed MOR-003, enrolled 278 subjects in the US. Subjects were randomized to receive either 7.5 mg Rylomine every hour as needed, 15 mg Rylomine every three hours as needed, 7.5 mg IV morphine, or matching placebos. The trial met its primary endpoint, the Sum of the Pain Intensity Difference (SPID) scores over 0-24 hours postoperatively. Subjects in each of the three Rylomine treatment groups had significantly better SPID scores over 24 hours than the corresponding placebo groups (p less than .01 or less). Treatment was well tolerated, with no serious adverse events reported. An additional phase III trial of Rylomine is underway at this time.

December 4, 2006

Pain Therapeutics reported positive results from a phase I trial of PTI-202, an abuse- resistant opioid painkiller. The trial was designed to assess the safety, tolerability, pharmacokinetic and pharmacodynamic profiles of a single, oral dose of PTI-202 in healthy subjects. Results revealed treatment to be safe and well tolerated, with no adverse events reported. Its release profile appears to be well-suited to use with a chronic pain population. Based on these results, Pain Therapeutics plans to move development of PTI-202 into phase II trials.

January 2, 2006

Durect Corporation has reported positive results of a phase II trial of their TRANSDUR sufentanil patch, for the treatment of chronic pain. Preliminary data met all primary endpoints, including pharmacokinetic measures of dose-proportional absorption rates and steady state plasma levels, and a positive overall safety and tolerability profile. Efficacy data yielded comparable levels of pain for the drug and treatment with Duragesic, an approved sufentanil patch. This open-label study enrolled 13 patients across 2 sites (1 in the US, 1 in Europe), who were transitioned from approved treatment with Duragesic to TRANSDUR sufentanil for 4 weeks.

Saegis Pharmaceuticals issued positive results of a phase IIa trial of SGS518, for the treatment of cognitive impairment associated with schizophrenia (CIAS), at the American College of Neuropsychopharmacology Annual Meeting. Trial data indicated a dose-proportional pharmacokinetic profile, with steady-state plasma concentrations reached within 3 days. No dose-limiting toxicities or serious toxicities were observed. Preliminary evidence of efficacy was also noted, with statistically significant improvements vs. baseline in Brief Assessment of Cognition in Schizophrenia score, compared to no improvement for placebo. This placebo-controlled, blinded study enrolled 20 schizophrenic patients at the Claghorn-Lesem Clinic in Houston. Subjects were randomized to one of two dose-escalating cohorts (60 mg/180mg or 120 mg/240 mg; 8 active:2 placebo) for 14 days.

November 28, 2005

Pain Therapeutics has reported mixed results of a phase III trial of Oxytrex (oxycodone/naltrexone), their mixed opioid agonist/antagonist for the treatment of chronic pain. Trial data exceeded their pretrial efficacy goals, producing a 28% lower rate of physical dependency than a comparable dose of oxycodone alone, based on Short Opioid Withdrawal Scale diagnostic score (pretrial reduction goal: 25%); however, this reduction failed to meet statistical significance, due in part to dropout rates in treatment arms of 48%-60%, which exceeded pretrial estimates of 40%. Secondary efficacy endpoints were met: subpopulation analysis indicated a 75% lower dependence rate vs. oxycodone in patients 50 or older (p=0.04), the drug demonstrated statistical non-inferiority and a non- significant trend towards superiority in analgesia compared to oxycodone, and significant superiority to placebo (p<0.05; oxycodone did not achieve significant superiority to placebo in this measure). This randomized, double- blind, multi-center study enrolled 775 patients with osteoarthritic pain in the US, who received one of two doses of Oxytrex (20 or 40 mg) or placebo for 12 weeks, followed by a drug-free washout and re-randomization into one of 6 treatment arms (10 mg or 20 mg twice daily, or 10 mg four times daily Oxytrex; 10 mg four times daily oxycodone, ultra-low-dose naltrexone, or placebo).

October 31, 2005

LAB International announced positive results of a phase I trial of fentanyl TAIFUN, their inhaled opioid analgesic under investigation for the treatment of acute pain. Pharmacokinetic data indicated a rapid absorption profile, with a mean peak plasma concentration of 935 pg/ml reached in one minute, compared to 371 pg/ml one hour after administration for an identical dose of fentanyl (200 mcg) delivered via approved oral lozenge (Actiq). Peak concentrations for this dose of the TAIFUN formulation fell within 15 minutes of administration to a plateau level comparable to peak Actiq concentration; this plateau was maintained for at least one hour. This profile represented an 8-fold increase in bioavailability at 20 minutes and a 4- fold increase at 3-minutes for the TAIFUN formulation, relative to the oral lozenge. No unexpected local pulmonary adverse events were reported. This open-label randomized study enrolled 32 healthy subjects, who received single doses of 100-800 mcg fentanyl TAIFUN or an approved dose of 200 mcg fentanyl via Actiq lozenge.

October 25, 2004

Merck reported mixed results of a one-year pivotal study of Arcoxia (etoricoxib), their investigational COX-2 inhibitor for the treatment of pain in osteoarthritis (OA). Trial data met their primary endpoint, a significant reduction in study discontinuation due to gastrointestinal (GI) adverse event compared with subjects receiving diclofenac, an approved NSAID OA treatment (9.4% vs. 19.2%, p<0.001). Furthermore, there was no significant difference in the incidence of thrombotic cardiovascular events, myocardial infarctions, or strokes between the two drugs (all secondary endpoints). However, three times the portion of subjects receiving Arcoxia discontinued the study due to hypertension related adverse events that with those receiving diclofenac (2.3% vs. 0.7%, p<0.001). This double-blind, multi-center trial randomized a total of 7111 subjects to receive either 90 mg. Arcoxia once daily (roughly 1.5 times the anticipated clinical dose), or 50 mg. thrice daily diclofenac for one year. An NDA for Arcoxia is currently under review by the FDA, with an expected action date of October 30th, 2004; the drug has already been approved in 48 international markets across Europe, Asia, and Latin America.

February 2, 2004

Labopharm reported mixed results from two phase III trials investigating tramadol, a once-daily formulation analgesic for the treatment of osteoarthritis pain. In trial MDT3-003, tramadol achieved statistical significance for the three co-primary endpoints, which were reduction in pain, improvement in physical function, and patient's global assessment of the product's effectiveness. In trial MDT3-002, statistical significance was not demonstrated for all of the three co-primary endpoints. Data showed that tramadol gave full 24-hour pain relief and exhibited an adverse events profile clinically superior to that of the immediate release formulation. The double-blind, multi-site, placebo controlled studies, called MDT3-003 and MDT3-002, enrolled 1,100 subjects with moderate to severe pain associated with osteoarthritis of the knee.

October 13, 2003

Indevus Pharmaceuticals reported positive results from a phase II trial investigating IP 751 (CT-3), an analgesic cannabinoid for the treatment of neuropathic pain. Results showed that IP 751 significantly reduced the degree of neuropathic pain without causing psychoactive adverse events. Data demonstrated that the degree of pain experienced by subjects decreased significantly during periods of treatment with IP 751. In addition, no significant differences were observed between treatments of measurements of cognitive function and prototypic subjective experiences. The two-week, randomized, crossover study enrolled 21 subjects with chronic neuropathic pain from spinal nerve injuries. Subjects received IP 751, (20 mg-40mg given 2x a day) or placebo. The study was conducted at the Hannover Medical School in Germany. Results were reported in the Journal of the American Medical Association.

June 16, 2003

AVANIR Pharmaceuticals reported positive results from a phase II trial investigating Neurodex, a neuroprotective for the treatment of neuropathic pain. Results showed the drug was well tolerated and subjects reported a significantly decreased pain from baseline. Data revealed that by day eight, 91% of the subjects reported pain relief compared to baseline, and 97% reported pain relief by Day 15. The Pain Relief Rating Scale, a 6-point Likert, administered on Days 8, 15, 22 and 29 showed a statistically significant difference at all time points. In addition, a Peripheral Neuropathy Quality of Life Scale showed statistically significant improvement at Day 29 compared to Day one. The study enrolled 36 subjects with diabetic neuropathy who experience pain on a daily basis in the lower extremities and was designed to evaluate the safety and tolerability of escalating doses. The trial was conducted at six sites in the U.S. Commonly reported adverse events included nausea, constipation, diarrhea, dry mouth, fatigue, dizziness, insomnia, headache, upper respiratory tract infection, and somnolence.

MetaPhore Pharmaceuticals reported positive results from a phase IIa trial investigating M40403, a superoxide dismutase mimic for the treatment of dental pain. Results showed that after administration of M40403 (20 mg), statistically significant pain relief was achieved compared with placebo treatment. Data also confirmed that M40403 had positive safety profile with no serious adverse events reported. The randomized, double blind, placebo-controlled, parallel group study enrolled 250 subjects with moderate to severe pain following dental extractions. An intravenous bolus dose of 30 mg ketorolac was used as a positive control. The trial compared three doses of M40403 (5, 10, and 20 mg) by intravenous infusion. Earlier data showed evidence of synergistic pain relief, the apparent ability to reverse or prevent tolerance to the analgesic effects of opioids, and lack of sedating side effects.

April 7, 2003

NeurogesX reported positive results from a phase II trial investigating NGX-4010, a capsaicin-containing dermal patch for the treatment of postherpetic neuralgia (post-shingles pain). Results showed that 42% of subjects in the active group experienced more than a 33 % pain decrease compared to 8 % in the control group. Treatment consisted of a topical non-prescription anesthetic for one hour, followed by a one-hour patch application. Overall drug tolerability was good with no safety concerns identified. The control group received a low-concentration capsaicin patch. Subjects recorded pain intensity twice daily on an 11-point numerical scale. The double blind, randomized controlled, multi-center study evaluated the tolerability, safety and efficacy of NGX-401 in the treatment of postherpetic neuralgia. The study enrolled 44 subjects for four weeks at nine sites in the U.S.

March 31, 2003

Celgene reported positive results from three late phase trials investigating Thalomid (thalidomide) for the treatment of complex regional pain syndrome (CRPS). Data showed that subjects who experienced a reduction in their CRPS symptoms usually experienced the reduction within four to six weeks of starting treatment. In addition, no subjects developed peripheral neuropathy although it is a known side effect of Thalomid. The most common side effects were constipation, somnolence, rash and edema. The three pilot, open-label trials enrolled over 30 subjects and were conducted at the California Pain Medicine Center, the Mayo Clinic and Drexel University College of Medicine.

NicOx reported further analysis from a phase II trial investigating AZD3582, a COX-inhibiting nitric oxide donator for the treatment of pain. NicOX convened a panel of international experts to review the study after AstraZeneca recently announced negative results. Initial results showed no statistically significant change in the primary endpoint, defined as incidence of gastro-intestinal ulcer. The panel concluded that a number of protocol failures and deficiencies affected the outcome of the study. The review stated the about 30% of the subjects enrolled (310/970) where found to have major protocol violations. A number of subjects were exposed to non-permitted drugs such as proton pump inhibitors and NSAIDs. The report stated that due to these deficiencies, and the fact that all secondary end points were reached, the trial results could not be concluded as negative.

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.

March 17, 2003

NicOx reported mixed preliminary results from a phase II trial investigating AZD3582, a COX-inhibiting nitric oxide donators for the treatment of pain. Results showed no statistically significant change in the primary endpoint, defined as incidence of at least one gastro-intestinal ulcer of 3mm or greater. However, the study did show efficacy of AZD3582 in relieving pain associated with osteoarthritis. NicOx stated that due to a lower than predicted rate of ulcers in the group treated with the reference compound (14% vs. 20-25%) the study was under-powered to detect a significant change. The majority of the secondary objectives were achieved including a statistically significant reduction in the number of stomach ulcers, gastro-duodenal ulcers, and gastro-duodenal erosions. AZD3582 was well tolerated overall and did not produce significant changes in blood pressure.

February 10, 2003

EpiCept reported positive results from a phase II trial investigating EpiCept NP-1, an amitriptyline plus ketamine containing cream for the treatment of neuropathic pain. Data indicated strong pain relief effects in all treatment groups with study results being comparable to those reported with alternative drugs such as gabapentin. Treatment effect was shown in subjects regardless of the cause of the neuropathy. The multi-center, randomized, placebo controlled trial enrolled 80 subjects with chronic neuropathic pain in a double blind fashion. Subjects were randomized into four groups: amitriptyline alone, ketamine alone, amitriptyline plus ketamine, or placebo. EpiCept NP-1 is expected to be a C III controlled substance.

December 9, 2002

Indevus Pharmaceuticals reported positive results from a phase II trial investigating IP 751 (formerly CT-3), an anti-inflammatory and synthetic cannabinoid analgesic for the treatment of neuropathic pain. Results demonstrated that subjects experienced significantly less pain when treated with IP 751 compared to placebo. The degree of pain, as shown by visual analog scores, decreased significantly during treatment periods. The two-week, crossover designed trial enrolled 21 subjects who had all experienced pain for at least six months related to previous spinal cord or peripheral nerve injuries. Subjects were randomized to two 7-day treatment periods and received one to two doses of IP 751 (20 mg or 40 mg) or placebo twice a day during the first week, then were switched to the other regimen during the second week.

November 4, 2002

Endo Pharmaceuticals Holdings reported that results from a phase III trial showed MorphiDex did not reach its primary or secondary end points. The double-blind trial compared MorphiDex (morphine and dextromethorphan) to morphine sulfate among 327 chronic pain subjects at 30 centers in the U.S. The primary end point, that MorphiDex provided superior analgesia (pain relief) compared to morphine, showed no statistically significant difference. The secondary endpoint, a reduction in analgesic tolerance also showed no significance. In June 2002, the company reported similar results from its first phase III trial of MorphiDex versus standard morphine.

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.

In a phase III double-blind, parallel group study of EN3202, an extended-release (ER) oral formulation of the opioid oxymorphone, subjects with moderate-to-severe pain associated with osteoarthritis of the hip and/or knee experienced significantly greater improvement in pain intensity than subjects treated with placebo. Subjects in the study were randomized to four treatment groups, including a 20 mg dose group of EN3202, a 40 mg dose group of EN3202, a group receiving 10 mg oxycodone ER (Oxycontin), and a placebo group. The significant change in arthritis pain intensity (VAS) from baseline in the EN3202-treated subjects occurred at Week 3. At that point in the treatment period, there was no significant difference between the oxycodone-treated group and the placebo-treated group. EN3202 is being co-developed by Penwest Pharmaceuticals and Endo Pharmaceuticals.

July 1, 2002

The first of three phase III trials of Endo Pharmaceuticals' MorphiDex (morphine/dextromethorphan) did not meet its primary endpoint. One hundred ninety-three chronic pain subjects were randomized to receive either MorphiDex or immediate-release morphine sulfate for a three-month double-blind period. Subjects began the double-blind period with 50% of their morphine-equivalent daily dose, which had been established during a run-in period, and were permitted to self-titrate their dose to achieve the predefined level of pain control. The primary endpoint was to demonstrate that a lower average daily dose of MorphiDex would maintain the same degree of pain control as a higher average daily dose of morphine sulfate. Results showed no statistically significant difference in average daily morphine dose between the MorphiDex and morphine sulfate groups.

June 24, 2002

Purdue Pharma L.P. reported that additional studies would be required to more fully assess the safety and effectiveness of the company's oxycodone/naloxone product, which was developed to reduce abuse of OxyContin (oxycodone HCl). Recent phase I trials showed that the absorption or metabolism of naloxone was more variable than expected, which could potentially compromise pain relief in some patients. While the oxycodone/naloxone formulation could deter intravenous and possibly intranasal OxyContin abuse, it does not address oral abuse of the drug. NDA submission was originally planned for the end of 2002.

March 25, 2002

Results of a pilot phase III trial indicate that patients with chronic pain can be safely transitioned from Janssen's Duragesic (fentanyl) product to Durect's Chronogesic (sufentanil) pain therapy system. The single-center six-week trial included 18 subjects. Those enrolled had moderate-to-severe chronic pain, and their primary opioid medication was the Duragesic product. During the six-week implant period, subjects were evaluated for overdose and overall opioid consumption. Results did not show any evidence of overdose, and the median reduction in opioid consumption other than from the Chronogesic product was 72%.

March 5, 2002

Phase II trial results indicate that OMS-103HP, developed for use with arthroscopy, significantly reduces postoperative pain and improves joint motion and recovery of function. The double-blind, placebo-controlled trial evaluated subjects who underwent arthroscopic anterior cruciate ligament reconstruction of the knee. In the first week following surgery, over three times as many OMS-103HP-treated subjects (compared to the control) met criteria for successful pain relief while requiring a lower total daily dose of pain medication. In terms of joint motion, 31% more OMS-103HP-treated subjects obtained at least 90 degrees of flexion without pain at repeated clinic visits. OMS-103HP is being developed by Omeros Medical Systems.

Phase II trial results suggest that Novartis' intravenous zoledronic acid is as effective in increasing bone mineral density as oral daily or weekly bisphosphonates. The placebo-controlled trial, which was conducted at 25 centers, included 351 women with postmenopausal osteoporosis. In the zoledronic acid groups, subjects received 0.25 mg, 0.5 mg or 1.0 mg every three months, 2.0 mg at study onset and six months, or 4 mg only at study onset. At 12 months, bone mineral density was significantly increased from baseline in all dosing groups.

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.

January 7, 2002

Phase I/II results suggest that PTI-801, a novel narcotic painkiller, is well tolerated in volunteer subjects and those with chronic, moderate-to-severe pain. The studies enrolled 22 subjects and were designed to analyze the safety and pharmacokinetic properties of orally administered PTI-801. Results showed no treatment-related or unexpected adverse events. PTI-801 is being developed by Pain Therapeutics.

This information does not represent a Lupus Research Institute endorsement of any listed study. It is merely a notice that the study is available. If you are presently under the care of a physician for lupus or other conditions, you should not disrupt your current program without discussing it with your doctor(s). Do not contact the Lupus Research Institute for information on these studies. Only contact the listed numbers. The Lupus Research Institute does not have any jurisdiction over or further involvement with these studies, other than to make people aware that they are being conducted.