Clinical Trials Resource Center


May 29, 2017

Anika Therapeutics reported results of a phase III trial of CINGAL for the treatment of symptoms associated with osteoarthritis (OA) of the knee. The multicenter, double-blind, saline-controlled clinical trial evaluated 368 patients with knee osteoarthritis who were randomized for treatment with a single injection of CINGAL (n=149), MONOVISC (n=150) or saline (n=69). Changes in pain, stiffness and physical function were assessed using a variety of validated measurement tools including the Western Ontario and McMaster Universities Arthritis Index (WOMAC). CINGAL reduced WOMAC Pain by 70% at 12 weeks and 72% at 26 weeks as compared to saline—more improvement than that reported in previous viscosupplement studies. CINGAL demonstrated rapid pain relief following administration (a 59% improvement in WOMAC Pain at one week and 68% at three weeks), unmatched by prior trials of triamcinolone hexacetonide alone. CINGAL was shown to be safe, and was associated with a low incidence of adverse events (n=6) that resolved over time. There were no serious adverse events considered to be related to CINGAL. These phase III study results were part of the comprehensive clinical data package that formed the basis for CINGAL’s CE Mark and Health Canada approval in 2016. CINGAL is commercially available in certain countries of the European Union, and Canada, and is under regulatory review in the U.S. Anika recently completed site initiation in the E.U. to begin enrolling patients in a supplemental phase III study requested by the FDA. Anika anticipates FDA approval of CINGAL after it completes the study in 2018.

November 14, 2016

Flexion Therapeutics has released results of Zilretta (FX006) on blood glucose levels in adults with osteoarthritis (OA) of the knee who also have type 2 diabetes. The objective of the double-blind, randomized, parallel group, single-dose study was to examine if Zilretta had effects on blood glucose levels that differ from IR TCA. Investigators from seven study sites enrolled 33 patients, randomized 1:1 to receive a single intra-articular injection of 40mg Zilretta or 40mg IR TCA. Blood glucose levels were evaluated for a total of three weeks (one week prior to injection and two weeks post injection) using a continuous glucose monitoring device. Patients returned for follow up visits at day eight, day 15 and day 43. Results from the trial demonstrated Zilretta is associated with a statistically significant (p<0.05, two-sided) and clinically relevant reduction in the rise of blood glucose compared to that observed following immediate-release (IR) triamcinolone acetonide (TCA) injection in patients who also have knee OA. Zilretta has previously demonstrated clinically meaningful improvement of pain, stiffness and function in its phase III pivotal trial in patients with knee OA.

August 29, 2016

Antibe Therapeutics issued results of a phase II trial of ATB-346 as a treatment of osteoarthritis (OA). Twelve patients with OA of the knee were treated once daily for 10 days with ATB-346 at a dose of 250mg. This dose of ATB-346 contains one-sixth of the typical daily dose of naproxen for treating OA. This lower dose was very effective at reducing pain, and equal to or better than naproxen or celecoxib in comparable studies. The patients recorded their level of pain one day prior to starting treatment and again on days four and 10 of treatment. The “WOMAC pain scale” was used as the measure of beneficial effect, since it is the gold standard in arthritis clinical trials. In this trial, a once daily dose of ATB-346 produced a reduction of the WOMAC pain score of 4.3 units on day four, increasing to 7.6 units on day 10, with a very high level of statistical significance in comparison to baseline pain (p<0.001). The drug was also safe and well-tolerated. ATB-346 has only one possibly drug-related adverse event, an allergic reaction graded as mild by the study’s supervising physician.

February 29, 2016

Flexion Therapeutics released results of a phase III study of Zilretta (FX006) for moderate to severe osteoarthritis (OA) knee pain. The randomized, double-blind, placebo-controlled, active-comparator trial enrolled 486 patients at approximately 40 centers worldwide. Patients were randomized to one of three treatment groups (1:1:1) and received either a single IA injection of 40mg of Zilretta, normal saline or 40mg of immediate-release triamcinolone acetonide (TCA). Each patient was evaluated for efficacy and safety during seven outpatient visits over 24 weeks after receiving an injection. Zilretta met its primary endpoint at week 12, demonstrating highly significant (p<0.0001), durable and clinically meaningful pain relief against placebo in patients with moderate to severe OA knee pain. In addition, Zilretta achieved statistically significant analgesia against placebo at weeks one through 16 and patients treated with Zilretta experienced, on average, a 50% reduction in pain from baseline over weeks one through 12. In pre-specified analyses, Zilretta achieved statistical significance against placebo in validated OA and quality-of-life secondary measures through week 12. The frequency of treatment-related side effects was comparable across all treatment arms in the trial. No drug-related serious adverse events were observed and no patients treated with Zilretta were discontinued from the study due to a treatment-related side effect. An NDA to the FDA is being prepared by Flexion.

August 11, 2014

Ampio Pharmaceuticals released results on an open-label study of injectable Ampion for osteoarthritis (OA) of the knee in seven subjects. Patients receive a series of 4ml injections of Ampion intra-articularly (at baseline, two weeks and four weeks following the initial visit). The WOMAC A pain score improved by 65% from baseline with the multiple injections at one month post injection (WOMAC A mean improved from 2.2 (0.55) to 0.8(0.62), mean difference 1.43 (0.406), p=0.01) compared to 33% in a previous study of Ampio at the same time point. In addition, the function score WOMAC C compared to baseline improved by 74 % at four weeks (WOMAC C mean improved from 2.3(0.55) to 0.6 (0.58), mean difference 1.70(0.374), p=0.004). No serious drug-related adverse events were reported. Ampio is proceeding with the randomized portion of this study and the first 10 randomized patients already have been treated. A BLA filing is expected in the first quarter of 2015.

May 12, 2014

Iroko Pharmaceuticals released results of a phase III study of ZORVOLEX (diclofenac) for osteoarthritis (OA) of the hip and knee. The overall differences in Patient Global Impression of Change (PGIC) compared with placebo were significant in the ZORVOLEX 35mg three times daily (P < 0.0001) and twice daily (P = 0.0008) treatment groups. Two-thirds of patients receiving ZORVOLEX 35mg three times daily (P < 0.0006) and half of the patients receiving ZORVOLEX 35mg twice daily (P = 0.0071) reported PGIC as “very much” or “much” improved relative to placebo. Patients treated with ZORVOLEX 35mg three times daily reported statistically significant improvements in five SF-36 domains, four of which were clinically meaningful (=Minimally Clinical Important Difference). These included physical functioning, role physical, bodily pain and social functioning. The most common adverse events (>2%) in studies of ZORVOLEX include: edema, nausea, headache, dizziness, vomiting, constipation, pruritus, flatulence, pain in extremity and dyspepsia. ZORVOLEX was recently approved by the FDA for the treatment of mild to moderate acute pain in adults. A sNDA for ZORVOLEX for the treatment of OA pain also was accepted for review by the FDA in January.

September 2, 2013

Ampio Pharmaceuticals issued results of a phase III trial of Ampion for the treatment of osteoarthritis of the knee. The randomized (1:1:1:1), double-blind, vehicle controlled trial enrolled 329 patients treated with a single intra-articular injection of Ampion. Patients received one of two doses (4mL or 10mL) of Ampion or corresponding saline control via intra-articular injection. Patients receiving Ampion achieved significantly greater reduction in pain from baseline to 12 weeks compared to saline (p = 0.0038). Patients receiving Ampion experienced, on average, a greater than 40% reduction in pain from baseline and achieved significantly greater improvement in function from baseline to 12 weeks compared to saline (p = 0.044). Patients receiving Ampion also demonstrated significantly greater improvement in overall quality of life measures from baseline to 12 weeks compared to saline (p = 0.012). There were no significant differences between the efficacy of the two Ampion doses. Selection of the optimal dose for the second phase III trial will be decided with the FDA.

May 27, 2013

Medivir reported results from a phase Ia trial of MIV-711 for osteoarthritis and osteoporosis. This double-blind, placebo-controlled, randomized study enrolled nine patients with osteoarthritis and osteoporosis. Subjects received daily doses of MIV-711 20mg to 600mg, or placebo. Data demonstrated MIV-711 decreased serum levels of the bone resorption biomarker, CTX-I, in a dose-dependent manner. Maximal reduction occurred with 600mg dose (79 ± 4% reduction at 24 h post dose) and at the 100mg dose CTX-I levels were reduced by 51 ± 4% at 24 h post-dose compared to baseline levels. Anticipating a target reduction of circulating CTX-I levels of approximately 50%, the results indicate low doses will be sufficient for the desired pharmacological effects. MIV-711 was well tolerated. No apparent effects were seen on vital signs and no significant changes in hematology or clinical chemistry were observed. Based on this data, Medivir has initiated a phase Ib study of MIV-711 lasting four weeks. Data is expected to be available around mid-year.

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.

October 31, 2011

Ampio Pharmaceuticals released interim results from a phase Ib trial of Ampion for osteoarthritis of the knee. The three arm, placebo controlled trial enrolled 60 subjects who were placed in one of three arms: A) steroid, lidocaine, and saline; B) steroid, lidocaine, and Ampion and C) steroid, saline, and Ampion. The average baseline pain score, based on a numeric rating scale, was comparable for all groups. At each study time point (six hours, 24 hours, 72 hours) measurements of the difference in pain relief from baseline was greater in the group that included Ampion, steroids and lidocaine than the group that included only steroids and lidocaine, reaching a 37% better improvement at 72 hours for the Ampion group. Based on these results, the trial was expanded to include two additional arms, Ampion alone versus saline alone.

July 4, 2011

Nuvo Research reported results from a phase II trial of Pennsaid Viscous Solution 2% for the treatment of osteoarthritis pain. The four-week, two-arm, double-blind, vehicle-controlled, parallel, randomized trial enrolled 259 subjects who received either Pennsaid Viscous Solution 2% twice daily or a matching placebo. The primary endpoint was the reduction of pain from baseline to week four, measured on the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). The primary endpoint was reached with Pennsaid showing a greater reduction in osteoarthritis pain versus placebo (p≡0.042). The most common adverse event in both groups was application site dryness.

January 5, 2009

CrystalGenomics reported positive results from a phase IIa trial of CG100649 for the treatment of osteoarthritis. This randomized, double-blind study, dubbed CG100649-2-01, enrolled 248 subjects in Germany, Hungary, and Ukraine. The subjects received placebo or CG100649 in three loading (2, 4 or 8 mg) and maintenance dose levels (0.3, 0.6, and 1.2 mg/day) administered orally, once a day in the morning, for 21 days. The primary endpoint was the change in the WOMAC OA score from baseline to Day 21. This endpoint was reached with statistical significance over placebo (p≡0.010); the greatest effect seen with the high dose of CG100649 (median values were 37% versus 17%, respectively). The study also met all key secondary endpoints, with the high dose demonstrating statistically significant superiority in the WOMAC OA score over the entire 21-day active treatment period (p≡0.009) and in the WOMAC subscales of pain, stiffness and physical function (p≡0.016, p≡0.023, p≡0.010, respectively) over the entire 35-day treatment and follow-up evaluation periods. Weekly pain relief scores showed statistically significant improvements at Days 7, 14, 21, and 28 (p<0.05 at all time periods), demonstrating an early onset of activity and sustained treatment benefits. There were no safety concerns or drug-related serious adverse events. Based on the data, CrystalGenomics plans to move into phase II trials.

December 1, 2008

NicOx released positive results from a phase III trial of naproxcinod for the treatment of osteoarthritis of the hip. This 13-week, double-blind, placebo and naproxen controlled trial, dubbed Study 303, enrolled 810 subjects in North America and Europe. The subjects were randomized to three arms: naproxcinod 750 mg, naproxen 500 mg or placebo, all administered twice daily. The primary endpoints were based on a comparison of the efficacy of naproxcinod to placebo, based on the mean change between baseline and week 13 in the following scores: the WOMAC pain subscale, the WOMAC function subscale and the subjects overall rating of disease status. The results demonstrated that naproxcinod was superior to placebo with high statistical significance on all three of these co-primary endpoints (p<0.001). Naproxcinod behaved in a similar fashion to naproxen on these efficacy scores. Naproxcinod had a positive overall safety and tolerability profile.

September 22, 2008

NicOx released positive results from a phase III trial of naproxcinod for the treatment of osteoarthritis of the knee. This randomized, double-blind trial, dubbed 302, enrolled 1,020 subjects in the US. Subjects placed into one of the following treatment groups: naproxcinod 375 mg twice daily (bid) for 52 weeks, naproxcinod 750 mg bid for 52 weeks, naproxen 500 mg bid for 52 weeks or placebo bid during the first 13 weeks. After 13 weeks the subjects on placebo were randomized to either naproxcinod 375 mg bid or naproxcinod 750 mg bid for the remainder of the trial. The primary endpoints were based on the mean change between baseline and week-13 in the two naproxcinod groups versus placebo in the following scores: WOMAC pain subscale, WOMAC function subscale and the subject's overall rating of disease status. Both doses of naproxcinod (750 mg and 375 mg bid) met the three co-primary efficacy endpoints at week-13 (p<0.001). The main secondary endpoint of the trial was the non-inferiority of naproxcinod 750 bid when compared to naproxen 500 mg on the WOMAC pain and function subscales at week 13 and 26. Naproxcinod 750 mg bid was established as being statistically non-inferior to naproxen 500 mg bid, thus meeting this secondary endpoint. Treatment was generally well tolerated. Based on the results NicOx plans to move forward towards regulatory approval.

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.

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

Orthogen released positive results from a clinical trial of Orthokine for the treatment of osteoarthritis (OA). This randomized, prospective, placebo-controlled study, dubbed GOAT (German OsteoArthritis Trial) enrolled 376 subjects with OA of the knee joint. The subjects received Orthokine, hyaluronic acid, or placebo for six total treatment periods. Analysis of the subjects was conducted at six weeks, three months and six months using various measurements including the visual analogue scale (VAS) and the WOMAC questionnaire. At baseline the average VAS score was 70 (intense pain). After six months, 57% of the Orthokine group reported a 50-percent reduction compared to 29% and 28% for the hyaluronic acid and placebo groups, respectively. The Orthokine arm also showed improvements of over 50% on the WOMAC survey compared to 20% in the two other treatment arms. Based on the results, the development of Orthokine will continue.

Zelos issued positive results from a phase II extension trial of Ostabolin-C for the treatment of postmenopausal osteoporosis. This double-blind eight month trial enrolled 198 postmenopausal women who received one of four subcutaneous doses of Ostabolin-C (7.5, 15, 30 or 45 microgram/day) or placebo. The primary endpoint, a significant change in lumbar spine bone mineral density (LS-BMD) at one year, was achieved. A maximum mean LS-BMD increase of 11% was observed in all treatment groups. In the 45 microgram dose group, a clinically relevant LS-BMD increase of 3% or more was observed in 79% of the subjects after 4 months and 97% after 12 months. Significant increases in BMD of the hip were also observed. Based on the results, Zelos plans to move ahead with the development of Ostabolin-C.

August 6, 2007

Bone Medical released positive results from a phase II trial of Capsitonin for the treatment of osteoporosis. This trial enrolled 36 subjects in Australia who received four formulations over five days. The trial was designed to compare Capsitonin, an oral formulation of calcitonin, to a nasal formulation of calcitonin, with a primary endpoint of bioequivalence. The nasal calcitonin positive control gave a 60% fall in C-telopeptide collagen type I cross-linker (CTX-I) after 5 hours. In all four oral formulations of Capsitonin, the CTX-I concentration fell to exactly the same level, with no more than 10% variation either way (p < 0.05). Based on the data, Bone Medical plans to meet with the FDA to determine a future course of action.

July 9, 2007

Anesiva released positive results from a phase II trial of Adlea for the treatment of pain associated with osteoarthritis of the knee. This trial enrolled 55 subjects who were randomized to receive either (I) a single injection of 1 mg of Adlea or (II) three stepped ascending weekly doses totaling 1 mg of Adlea. Results showed a 61% reduction in mean pain intensity from baseline to week one; this effect was sustained at all subsequent weeks to week eight, at which time a 64% reduction from baseline was reported. A cohort of 50 subjects showed a 65% reduction from baseline pain scores. All pain reductions were sustained at week 12. Based on the results, Anesiva plans to advance Adlea into phase II/III trials later in 2007.

Genzyme reported negative results from a pivotal trial of hylastan for the treatment of pain associated with osteoarthritis of the knee. This double-blind, active-control study enrolled 400 subjects in North America and Europe. Subjects were randomized to receive two intra-articular injections of hylastan delivered two weeks apart, a single injection of hylastan, or an injection of a corticosteroid. They were then evaluated for 26 weeks. Each of the three treatment arms showed a statistically significant reduction in knee pain from baseline. However, significance was not reached between the hylastan arm and the corticosteroid arm. Thus, the primary endpoint of demonstrating that hylastan provides superior pain relief to steroids was not achieved. Based on the results Genzyme plans to fully analyze the data in order to determine a future course of action.

May 21, 2007

AlphaRx and Proprius reported mixed results from a phase II trial of Indaflex for the treatment of osteoarthritis (OA) of the knee. This randomized, double-blind, placebo and vehicle controlled trial enrolled 233 subjects in Canada who received topical treatment for six weeks. The primary endpoint was the change from baseline at week 6 in the global Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score and the subject's global assessment of efficacy. The trial failed to meet the primary endpoint. However, subgroup analyses of subjects with moderate to severe pain and more impaired physical function at baseline showed positive trends in the Indaflex group when compared to either placebo or vehicle. Treatment was safe and well tolerated. Based on the results the company plans to advance Indaflex into further trials.

November 6, 2006

NicOx announced positive results from a phase III trial of naproxcinod for the treatment of osteoarthritis of the knee. This 13-week, double-blind, placebo and naproxen-controlled trial randomized subjects into one of four treatment groups: naproxcinod 375 mg bid, naproxcinod 750 mg bid, naproxen 500 mg bid or placebo bid. Treatment showed good safety and tolerability profiles with the number of serious adverse events was low and similar across all treatment groups. Results were positive for all the primary endpoints, statistical significance in the mean change from baseline at week-13 in the WOMAC pain subscale, the WOMAC function subscale and patients' overall rating of disease status scores (p<0.001). Additional phase III trials are planned for 2007.

Regeneron issued positive results from a phase III trial of IL-1 Trap for the treatment of CIAS1-related autoinflammatory periodic syndromes (CAPS). This trial was conducted in two parts: Part A was a double-blind placebo-controlled trial in which subjects were randomized to receive a self-injected 160 mg dose of the IL-1 Trap or placebo once a week, for six weeks. Following a 9-week interval during which all subjects received a 160 mg dose of the IL-1 Trap, part B was initiated. This "randomized withdrawal" study re-randomized the same subjects to switch either to placebo or continue treatment with IL-1 Trap in a double-blind manner. The primary endpoint of both studies was the change in disease activity. The subjects in part A had an approximately 85% reduction in their mean symptom score compared to an approximately 13% reduction in those treated with placebo (p less than 0.0001). During the 9-week randomized withdrawal period, those who were switched to placebo had a five-fold increase in their mean symptom score, compared with those remaining on IL-1 Trap who had no significant change (p less than 0.001). Regeneron plans to file a BLA with the FDA for IL-1 Trap in the second quarter of 2007.

August 7, 2006

Celtic Pharma and IDEA AG have announced positive results of a phase III trial of IDEA-033, for the treatment of osteoarthritis (OA) of the knee. This randomized, double-blind, parallel-group, placebo-controlled study enrolled 833 subjects across 32 sites in Germany, Poland, Croatia and Serbia. Subjects received one of three doses (25 mg, 50 mg, or 100 mg) of the drug or placebo per knee twice daily. Trial data met their primary efficacy endpoint for the two higher trial doses, significantly reducing symptom severity score on the WOMAC visual analog scale at 12 weeks (p<0.05 and p<0.01 for the middle and high dose groups, respectively). Further, statistically significant treatment effects were observed after the first 24 hours of treatment, as measured on the categorical WOMAC scale (p<0.01), and significantly more patients responded to the drug than placebo for all three dosing groups, measured on the OMERACT-OARSI responder criteria. An open-label extension study, gathering long-term safety and efficacy data, was ongoing.

January 23, 2006

Nuvo Research reported positive results of a phase III trial, designated Study 112, of Pennsaid, their topical non-steroidal anti-inflammatory (NSAID) for the treatment of osteoarthritis (OA). This double-blind, placebo-controlled study enrolled 775 patients at sites in the US and Canada, who were randomized into one of 5 treatment arms (arm 1: Pennsaid/oral placebo; arm 2: topical placebo/oral placebo; arm 3: topical vehicle control/oral placebo; arm 4: topical placebo/oral diclofenac; or arm 5: Pennsaid/oral diclofenac). Trial data indicated that arm 1 was superior in three clinical measures to both arm 2 (pain: p=0.019; physical function: p=0.046; overall health assessment: p<0.0001) and to arm 3 (p=0.009; p=0.026; p=0.016, respectively). In addition, results for arm 1 were non-inferior to approved treatment (arm 4), and arms 2 and 3 produced similar results (confirming that vehicle gel did not have independent efficacy). Finally, combination of Pennsaid with an approved oral NSAID (arm 5) produced no increase in incidence of adverse events.

January 31, 2005

MedPointe Pharmaceuticals has reported results from a long-term phase III safety and tolerability study of the approved drug Zomig nasal spray, for the treatment of migraine. Data from study patients, accounting for 20,717 migraine attacks, found that the drug was safe and largely well tolerated, with serious adverse events occurring in only 0.1% of attacks, and only three such events were considered drug-related (nausea, vertigo and angina pectoris). Minor adverse events included unusual taste (19.0%) and paresthesia (6.8%), but these were generally tolerated, leading to trial withdrawals in only 0.4% and 0.6% of patients, respectively. Furthermore, adverse event incidence declined over time, from 43.4% of attacks from 0-90 days to 30.7% at 361 days or later. Secondary efficacy endpoints were also met, with 53.8% of attacks resolving within 2 hours. This open-label, noncomparative, multicenter trial enrolled 538 subjects with a history of recurrent migraines; subjects received treatment with Zomig during migraine attacks of any severity for 1 year.

Winston Laboratories has issued positive results of a phase III study of their topical civamide cream 0.075%, for the treatment of pain in osteoarthritis. Data from the trial met their primary efficacy endpoints, with significant improvements noted in symptom severity scores on the Pain and Physical Function subscales of the Western Ontario McMaster Osteoarthritis Index, and Subject Global Evaluation (a measure of patient satisfaction with treatment) after 12 weeks (p<0.05). The data also met secondary pharmacokinetic and safety/tolerability endpoints, with no detectable systemic absorption, no serious adverse events, and a transient, mostly mild-to-moderate burning sensation at the application site which decreased in frequency as treatment progressed (<9% by week 3). This double-blind, vehicle-controlled, parallel arm study enrolled 695 patients with moderate-to- severe osteoarthritis pain that was being treated with, but not sufficiently controlled by, oral NSAID or COX-2 therapy. Subjects were randomized to receive either the experimental 0.075% cream or a vehicle cream containing only a small amount (0.01%) of civamide via topical application for 12 weeks.

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.

August 30, 2004

Novartis has announced positive results from a pivotal phase III study of Prexige (lumiracoxib), their COX-2 inhibitor under investigation for the treatment of osteoarthritis (OA). The trial, which was designed to compare the safety, tolerability and efficacy of Prexige with established NSAID treatments (ibuprofen and naproxen), found that Prexige was as efficacious as existing treatments in managing the symptoms of OA, but showed a 79% reduction in upper gastrointestinal ulcers and significantly fewer changes from baseline in blood pressure compared with the NSAIDs. Furthermore, Prexige did not produce additional cardiotoxicity (a common concern in the generally-elderly OA patient population). The study enrolled a total of 18,325 subjects across more than 800 trial sites worldwide. Novartis has submitted regulatory approval filings for Prexige to numerous regulatory authorities worldwide, and has been approved in England, Australia, and several countries in Latin America; Novartis is currently collecting additional data for the FDA, with submission expected in early 2006.

March 15, 2004

The University of Hong Kong reported positive results from a trial investigating Lyprinol, a marine lipid extract for the treatment of osteoarthritis. Results showed a greater improvement in the perception of pain as measured by a 100-mm visual analog scale (VAS). In addition, subjects who took Lyprinol had improved scores in the physical function and psychological status domains from week four. The randomized, placebo-controlled study enrolled 80 subjects with knee OA. Subjects received either Lyprinol or placebo for six months and were allowed paracetamol/acetaminophen rescue treatment during the study. The trial was conducted from 2001-2003 at the Queen Mary Hospital of the University of Hong Kong.

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.

January 26, 2004

The University of Hong Kong reported positive results from a clinical trial investigating Lyprinol, an inflammation pathway inhibitor for the treatment of osteoarthritis (OA). Results showed a greater improvement in the perception of pain as measured by the visual analog scale (VAS) compared with controls. Lyprinol was safe and well tolerated with no serious side effects reported. Data showed no significant differences in adverse reactions or study withdrawals when compared to placebo. Subjects on Lyprinol had improved scores in the Arthritis Impact Measurement Scale 2-short form (CAIMS2-SF) physical function and psychological status domains from week four. The double-blind, placebo-controlled clinical trial enrolled 80 subjects with knee OA. Subjects were randomized to receive either Lyprinol or placebo for six months. The study was conducted at the Queen Mary Hospital of the University of Hong Kong.

October 20, 2003

Pain Therapeutics reported positive results from a phase II trial investigating Oxytrex, a narcotic painkiller for the treatment of osteoarthritis pain. Results demonstrated that Oxytrex achieved a statistically significant result in reducing pain intensity during the 21-day treatment period against oxycodone, the studies primary endpoint. In addition, data showed that Oxytrex achieved a statistically significant result in both the qualities of analgesia and global assessment compared to the placebo group. Oxytrex was well tolerated with no reports of serious adverse events. The randomized, double-blinded, placebo-controlled study enrolled 350 subjects at 30 sites across the U.S. The study was designed to evaluate the safety and efficacy of Oxytrex relative to oxycodone and placebo over a three-week treatment period.

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.

May 6, 2002

Phase III trial results demonstrate that Ligand Pharmaceuticals' Avinza (morphine sulfate extended-release capsules), a once-daily pain medication, reduces pain and improves quality of sleep in osteoarthritis (OA) subjects. The randomized, four-week trial included 295 subjects with chronic, moderate-to-severe OA pain and evaluated Avinza and MS Contin (morphine sulfate controlled-release) versus placebo. Subjects received Avinza 30 mg once daily in the morning (QAM) or evening (QPM), MS Contin 15 mg twice daily, or a placebo. According to the WOMAC OA Index Pain Visual Analogue Scale, statistically significant reductions in pain were obtained with Avinza QAM (17% scale improvement), Avinza QPM (20%) and MS Contin (18%) compared to placebo (4%) over the four-week study duration. Avinza and MS Contin also produced improvements in all sleep measures compared to placebo. Avinza was approved in March by the FDA for the relief of moderate-to-severe pain in patients requiring continuous, around-the-clock opioid therapy for an extended period of time.

March 5, 2002

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.

February 25, 2002

An analysis of placebo-controlled data indicates that European studies of ML-3000 did not meet all of the efficacy endpoints required by the FDA. The European trials, which were conducted by Merckle GmbH, were part of a global development program consisting of both United States and European Union clinical trials. A United States safety and efficacy study is under way and expected to be completed during the next twelve months. If the ongoing trial meets the required efficacy endpoints, additional efficacy studies will be initiated in order to support a potential NDA submission. ML-3000 is being co-developed by Forest Laboratories and Merckle GmbH for the treatment of osteoarthritis.

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.