December 12, 2016
Recro Pharma reported results of a phase III trial of intravenous (IV) meloxicam for the treatment of acute postoperative pain. In the multicenter, randomized, double-blind, placebo-controlled clinical trial, 219 patients were enrolled and randomly assigned to receive a postoperative regimen of IV meloxicam (30mg bolus injection) or placebo in a 1:1 ratio, once every 24 hours. The IV meloxicam treatment arm demonstrated a statistically significant reduction in SPID24 (p=0.0145) compared to the placebo arm. The study also achieved statistical significance for 10 of the secondary endpoints, including statistically significant differences in SPID12 (p=0.0434), time to perceptible pain relief (p=0.0050), subjects with =30% improvement at 24 hours (p=0.0178), number of times patients required rescue in the first 24 hours after randomization (p=0.0275), as well as number of times rescued from 24 to 48 hours (p=0.0009), and several other pain relief metrics, compared to placebo. The safety results demonstrated that IV meloxicam was well-tolerated, with no difference in serious adverse events (SAEs) related to bleeding for IV meloxicam treated patients versus placebo (1 each). The company believes this completes the efficacy program for the IV meloxicam New Drug Application (NDA).
November 9, 2015
Elite Pharmaceuticals has reported
results of a phase III trial of opioid abuse-deterrent
candidate ELI-200 for the treatment
of moderate to severe pain. It was a
multicenter, randomized, multiple-dose,
double blind, placebo-controlled and parallel
group study. The trial randomized 163
patients. The pivotal trial met its primary
endpoint (p=0.001), demonstrating statistical
significance that the product provided
pain relief following surgery in the treatment
group using ELI-200 compared to the
placebo group. Secondary endpoint results
were consistent with primary findings and
included safety measures. There were no
serious adverse events or deaths related to
ELI-200 reported during the conduct of the
trial. Elite intends to submit an NDA to the
FDA for abuse-deterrent ELI-200 by year-end.
April 22, 2013
Iroko Pharmaceuticals issued results from a phase III trial of lower dose submicron indomethacin for the treatment of post surgical acute pain. This multi-center, double-blind, placebo- and active- controlled study enrolled 462 patients with moderate to severe pain following bunionectomy surgery. Subjects received 40mg submicron indomethacin three times daily or twice daily, 20mg submicron indomethacin three times daily, 400mg loading dose of celecoxib plus 200mg twice daily, or placebo. Statistically significant overall decreases in pain intensity were demonstrated for 40mg submicron indomethacin three times daily (509.6, p<0.001), 40mg submicron indomethacin twice daily (328.0, p=0.046), 20mg submicron indomethacin three times daily (380.5, p=0.017), compared with placebo (67.8). Although there was some evidence of analgesia for celecoxib (279.4), it did not achieve statistical significance compared with placebo. Some evidence of pain control was observed as early as 30 minutes in the 40mg submicron indomethacin three times daily (2.9) and 40mg submicron indomethacin twice daily (2.6) groups compared with placebo (0.2). The drug was well tolerated. The most frequent adverse events were similar across treatment groups and included nausea, post-procedural edema, dizziness and headache.
March 11, 2013
AcelRx issued results from a phase III trial of sublingual Sufentanil NanoTab PCA (patient-controlled analgesia) for the treatment of acute post-operative pain. This randomized, double-blind, placebo-controlled trial enrolled 178 adults who were treated for post-operative pain immediately following major abdominal surgery. The subjects were treated for a minimum of 48 hours and up to 72 hours with either sufentanil or placebo. Both treatments were delivered by the each subject, as needed, using the NanoTab System with a 20-minute lock-out period. Both groups could receive up to 2mg morphine intravenously per hour as a rescue medication. The primary endpoint evaluated pain intensity over the 48-hour study period compared to baseline, or Summed Pain Intensity Difference (SPID-48). The sufentanil NanoTabs arm reached a significantly greater SPID-48 during the study period than placebo arm (p=0.001). In addition, 24 hours and 72 hours after first dose, SPID was significantly greater in the sufentanil-treated arm than in the placebo-treated arm (p<0.001 and p=0.004, respectively).
November 28, 2012
AcelRx Pharmaceuticals reported results from a phase III trial of sublingual ARX-01 (Sufentanil NanoTab PCA System) for the treatment of post-operative pain. This randomized, open-label, parallel-group study enrolled 359 patients with acute post-operative pain immediately following major abdominal or orthopedic surgery. Subjects received (15mcg/dose) of the NanoTab System or 1mg/dose of PCA with morphine for a minimum of 48 hours and a maximum of 72 hours. Data demonstrated that the NanoTab System was non-inferior (p<0.001) to IV PCA morphine for the primary endpoint of PGA over the 48-hour study period as determined by the combined percentage of patients with PGA ratings of “good” or “excellent” (78.5% versus 66.1% respectively). In this study, the NanoTab System was found to be statistically superior to IV PCA morphine for the PGA endpoint (p=0.009). This statistically superior PGA was also seen at the 24-hour and 72-hour time points. Additionally, the percentage of patients rating the NanoTab System as “excellent” was higher than those rating IV PCA morphine as excellent (42.9% versus 30.6%, p=0.016). Similar percentages of NanoTab System-treated and IV PCA morphine-treated patients dropped out of the study prematurely due to lack of efficacy (7.3% versus 8.3% respectively) or due to an adverse event (7.9% versus 11.1% respectively). The NanoTab System was well tolerated. AcelRx Pharmaceutical will complete two other phase III trials of the NanoTab System before submitting an NDA to the FDA.
July 2, 2012
Iroko Pharmaceuticals issued results from a phase III trial of diclofenac for the treatment of post-surgery pain. The multi-center, randomized, double-blind, active- and placebo-controlled study enrolled 428 patients. Subjects received diclofenac 18mg or 35mg three times daily, or celecoxib 400mg on day one then 200mg twice a day, or placebo. The trial demonstrated significant improvement in pain relief as measured by the combined differences in pain intensity measured at intervals over 48 hours using a visual analog scale (VASSPID 48) in patients with acute pain. Pain relief scores were 524 for submicron particle diclofenac 35mg, 393 for 18mg, 390 for celecoxib and 0 for placebo. Subjects receiving submicron particle diclofenac capsules 35mg achieved pain relief (P=0.009) during the first four hours after initiating oral treatment (TOTPAR-4). The most frequent adverse events, comparable across treatment groups, were post-procedural swelling, nausea and headache. Based on these data, Iroko will pursue diclogenac as a low-dose alternative to NSAIDs.
January 16, 2012
DURECT issued results from a phase III trial of Posidur, their sustained release formulation of bupivacaine for the treatment of post-surgical pain. This international, multi-center, randomized, double-blind, controlled trial, BESST, enrolled 305 subjects undergoing general abdominal surgical procedures. The subjects were placed in one of three cohorts: Cohort 1: subjects were randomized to either Posidur 5.0 mL or Bupivacaine HCl solution after laparotomy, in cohort 2 subjects were randomized to either Posidur 5.0 mL or Bupivacaine HCl solution after laparoscopic cholecystectomy and in cohort 3 subjects were randomized to either Posidur 5.0 mL or placebo after laparoscopically-assisted colectomy. The co-primary endpoints were pain intensity and the use of opioid analgesics over the first three days (72 hours) following surgery. Although the results trended positive for both endpoints, they did not reach statistical significance. Pooled data from cohorts 1 and 2 showed a mean reduction in pain of approximately 20% (p≡0.0111) for the Posidur group compared to the bupivacaine HCl group and approximately 18% less opioids were consumed for supplemental analgesia compared to the bupivacaine HCl arm (p≡0.5455). In cohort 3 the group treated with Posidur reported a mean reduction in pain of approximately 7% (p≡0.1466) and approximately 16% less opioids were consumed for supplemental analgesia compared to the bupivacaine HCl arm (p≡0.5897).
October 10, 2011
InSite Vision reported results from a phase II trial of BromSite, their low dose formulation of bromfenac for the reduction of pain and inflammation associated with ocular surgery. This randomized, double-masked, two-arm study was designed to compare the tissue penetration profile of BromSite versus Bromday, a high dose of bromfenac and the current standard of care. The trial enrolled 58 subjects who were dosed two days before and the morning of the day of cataract surgery. Study results showed that the mean concentration of bromfenac in the aqueous humor of subjects in the BromSite group was more than twice greater compared to subjects in the Bromday group (p≡0.0032).
September 19, 2011
Innocoll issued results from two phase II trials of Xaracoll, their collagen/bupivacaine sponge implant, for the treatment of post-operative pain. Study INN-CB-010 was a randomized, single dose, double-blind, placebo controlled study in 50 men undergoing open laparotomy inguinal herniorrhaphy. Two sponges were implanted during surgery, either placebo or Xaracoll sponges. Study INN-CB-011was a single-dose, open-label study in ten men undergoing laparoscopic inguinal or umbilical herniorrhaphy. The subjects receiving XaraColl demonstrated a statistically significant reduction in the total use of opioid medication through 24 and 48 hours post-surgery as well as a statistically significant increase in the time before rescue opioid medication.
March 28, 2011
InSite Vision released results from a phase I/II trial of ISV-303 for the reduction of pain and inflammation associated with ocular surgery. The randomized, placebo-controlled study enrolled 160 subjects who were placed in one of four study arms: ISV-303 administered once-daily or twice-daily, Xibrom (standard of care) administered twice-daily, or placebo. The drug therapy was administered for two weeks following an ocular surgery procedure. The primary endpoint was the absence of cells in the anterior chamber of the eye at day 15 post surgery. Once-daily ISV-303 achieved statistically significant superiority compared to placebo (53.3% versus 19%; p≡0.0016) for the primary endpoint. Secondary endpoints, including reduction of flare, pain and discomfort, also achieved statistical significance compared with placebo. While once-daily ISV-303 achieved a numerically superior difference in the primary endpoint versus twice-daily Xibrom (53.3% versus 42.2%), the results did not reach statistical significance. ISV-303 was well tolerated.
August 16, 2010
QRxPharma released positive results from a phase II trial of MoxDuo IV for the treatment of moderate to severe postoperative pain following hip replacement surgery. This double blind, active controlled study enrolled 40 subjects at two sites in Germany. Following hip replacement surgery, the subjects were randomized to intravenous MoxDuo (morphine and oxycodone) or morphine alone over a two-part, 48-hour treatment period. The first part consisted of a 65 minute dose-titration in which fixed doses were given once every five minutes until a strong analgesic effect occurred. This was followed by a 47 hour patient controlled analgesia (PCA) period in which patients could self administer a fixed amount of study drug as frequently as once every six minutes. During the initial 65 minute dose-titration period, sum of pain intensity (SPID) scores from baseline were 50% higher among patients in the MoxDuo arm compared to the morphine alone arm. In addition, 67% of subjects receiving MoxDuo reported good to excellent global improvement compared to 53% of those receiving morphine alone. During the entire 48 hour study period, SPID scores were 10% higher among MoxDuo arm compared to the morphine alone arm. PCA data also indicated that subjects in the MoxDuo study arm were able to achieve better pain relief faster and with fewer doses (13 doses versus 17 doses).
April 19, 2010
QRxPharma reported positive results from a phase III trial of MoxDuoIR, an immediate-release Dual-Opioid therapy, for the treatment of post-surgical pain. This U.S.-based, double-blind, randomized and repeat fixed-dose study enrolled 522 subjects experiencing moderate to severe pain following bunionectomy surgery. The subjects received MoxDuoIR 12 mg/8 mg versus its milligram components of morphine 12 mg and oxycodone 8 mg, both administered every six hours. The primary endpoint was the difference in pain intensity scores for each group over a 48-hour treatment period (SPID48). MoxDuoIR demonstrated statistically superior analgesic effect compared to its individual components of morphine (p≡0.01) and oxycodone (p≡0.01). MoxDuoIR also demonstrated significantly greater analgesic effect compared to its components during the first day of dosing using SPID24, the difference in pain intensity scores from over the first 24-hour treatment period.
February 15, 2010
Cara Therapeutics released positive results from a phase II trial of CR845 for the treatment of post-operative pain. This U.S.-based, double-blind, placebo-controlled trial enrolled 46 female subjects who had undergone laparoscopic-assisted hysterectomy. The subjects received a single intravenous infusion of 0.040 mg/kg CR845 or placebo following surgery and upon reporting a moderate-to-severe pain intensity level of 5 to 8 on a 0-10 pain scale. Significant pain relief was observed in CR845-treated arm over placebo from 4-8 hrs post-drug administration, as demonstrated by a significant change in pain intensity difference scores (p<0.05). In addition, CR845-treated subjects required 32% less morphine than placebo-treated patients over the 16 hour post-drug administration (p<0.05). This morphine-sparing effect was accompanied by a substantial decrease in the incidence of side effects often associated with morphine use, including an absence of vomiting and a 72% reduction in nausea (p<0.05). CR845 was safe and well-tolerated.
January 11, 2010
Durect reported positive phase results from a phase IIb trial of Posidur for the prevention of post-operative pain. This double blind, multi-center, placebo controlled, parallel group trial enrolled 60 subjects undergoing arthroscopic shoulder surgery. The subjects were randomized to receive Posidur or placebo prior to surgery. Supplemental rescue analgesia for both treatment groups was provided if needed. Top line results showed a consistent reduction of pain scores (as measured by mean pain intensity on movement during the period 0 to 72 hours post-surgery) in parallel with a reduction of opioid use (as measured by the amount of opioids taken in the three days post-surgery) in favor of Posidur versus placebo. There was a comparable safety profile between the two groups and Posidur was well tolerated.
January 5, 2009
Anesiva reported positive results from a phase III trial of Adlea for the reduction of post-surgical pain following total knee replacement surgery. This multi-center, randomized, double-blind, placebo-controlled phase II study, dubbed ACTIVE-2, enrolled 217 subjects undergoing total knee replacement. The subjects were randomized to receive either a single 60 mL dose of Adlea (0.25 mg/mL drug concentration) or placebo instilled into the surgical site immediately prior to wound closure. The primary endpoint was a time-weighted pain score (using a standard 0 - 10 numerical rating scale of pain intensity) from four to 48 hours following knee replacement surgery. The study achieved its primary efficacy endpoint of reducing post-surgical pain versus placebo (p≡0.03). Adlea also demonstrated a highly significant reduction in opioid medication consumption compared to placebo (p≡0.005), a key secondary endpoint. Phase III trials are currently underway.
November 17, 2008
Anesiva reported positive results from a phase III trial of Adlea for the treatment of pain following bunionectomy surgery. This multi-center, double-blind, placebo-controlled study, dubbed ACTIVE-1, enrolled 301 subjects in the US. The subjects were randomized to receive either a single 4 mL dose of Adlea (0.25 mg/mL) or placebo into the surgical site prior to closure. The primary endpoint, time-weighted reduction of post-surgical pain versus placebo at four to 32 hours post-surgery, narrowly missed statistical significance (p=0.07). However this measure was highly significant from four to 48 hours post-surgery (p=0.004). The trial also achieved a key secondary endpoint of reducing opioid use for Adlea versus placebo over the four to 32 hour period (p=0.012). Adverse events were similar for both active treatment and placebo groups.
August 25, 2008
Javelin reported positive results from a phase III trial of Dyloject for the treatment of postoperative pain following abdominal and pelvic surgery. This randomized, multi-center, double-blind, placebo- and comparator-controlled study enrolled 360 subjects in the U.S. The subjects received either one of two doses of Dyloject (18.75 or 37.5 mg) intravenously every six hours, ketorolac 30 mg intravenously every six hours, or placebo. Patient global evaluation scores and related measures of efficacy at 24 and 48 hours were statistically significantly higher than placebo for all three arms of the study. In addition, when compared to the ketorolac group, the Dyloject groups had a lower incidence of thrombophlebitis, and numerically fewer adverse events associated with postoperative bleeding. Treatment was safe and well tolerated. Based on the results, Javelin plans to pursue the approval of Dyloject in several European countries.
June 23, 2008
Acura and King Pharmaceuticals reported positive results from a phase III trial of Acurox for the treatment of pain. This randomized, double-blind, placebo-controlled study, dubbed AP-ADF-105, was conducted under a US SPA. It enrolled 405 subjects with moderate to severe pain following bunionectomy surgery. The subjects were randomized to one of three treatment arms: two Acurox Tablets 5/30mg, two Acurox Tablets 7.5/30mg or two placebo tablets, all administered every 6 hours. The primary endpoint was the sum of the difference in pain intensity, measured on a 100mm visual analog scale, compared to baseline over a 48 hour period (SPID48). Both Acurox 5mg/30mg and 7.5mg/30mg tablet strengths met the primary endpoint (p=.0001 and p<.0001, respectively). Treatment was generally well tolerated, with all adverse events mild to moderate in nature. No serious adverse events were reported. Based on the results, Acura and King plan to file an NDA with the FDA by the end of 2008.
May 12, 2008
QRxPharma issued positive results from a phase III trial of Q8003IR for the treatment of moderate to severe pain. This double-blind, placebo-controlled study enrolled 256 subjects with moderate to severe pain following bunionectomy, in the United States. The subjects received one of four different dosage regimens of Q8003IR or placebo over a 48 hour dosing period. Per treatment group, median doses received every four hours ranged from 3mg/2 mg to 9mg/6 mg of Q80031R. The primary endpoint was the change in pain intensity scores over the 48 hour dosing period (SPID48) in subjects receiving Q8003IR versus placebo. A strong dose-response effect in reducing pain intensity scores (SPID48) and other measures of analgesic effect were observed (p<0.001). In addition, among all Q8003IR treatment arms approximately 50% of the subjects reported good to excellent global improvement compared to 13% for placebo. Q8003IR was generally well tolerated. Based on positive phase III results QRxPharma plans to submit an NDA to the FDA in 2009.
December 10, 2007
Targacept issued negative results from a phase II trial of TC-2696 for the treatment of acute post-operative pain. This US based, randomized, double-blind, single-dose trial enrolled one hundred and eighty one subjects. The subjects received 10, 25 or 50 mg TC-2696, ibuprofen (400 mg) or placebo following third molar extraction surgery. Treatment was well tolerated with an adverse event profile similar between all arms. However, TC-2696 did not meet the primary endpoints, superior pain relief four or six hours after dosing as compared to placebo. Targacept plans to fully evaluate the data in order to determine a future course of action for TC-2696.
December 3, 2007
Osiris released positive results from a phase I/II trial of Chondrogen for the regeneration of meniscus in the knee following knee surgery. This double blind trial enrolled fifty-five subjects. One week following surgery subjects received a single injection of either placebo, a low dose (50 million cells) of Chondrogen or high dose (150 million cells) of Chondrogen. Results after one year showed a statistically significant 20 mm reduction in pain, as measured by the visual analog scale (VAS), in subjects Chondrogen over those receiving placebo (Chondrogen 48 mm versus placebo 28 mm, p=0.05). The reduction in pain increased to 37 mm with more severe osteoarthritic changes in the patient's joint (Chondrogen 56 mm versus placebo 19 mm, p=0.004). There was also a positive dose-response effect. At one year, the improvement in pain relative to baseline (prior to surgery) was 56 mm for high dose Chondrogen, 26 mm for low dose Chondrogen, and 19 mm for placebo. In addition, bony changes associated with osteoarthritis, including subchrondral sclerosis and osteophyte formation, were reported in 21% of the placebo arm compared to 6% of the Chondrogen-treated arms. Based on the results, Osiris plans to move forward with the development of Chondrogen.
July 23, 2007
Durect and Nycomed released positive results from a phase IIb trial of Posidur for the treatment of post-operative pain in patients undergoing inguinal hernia repair. This randomized, double blind, placebo-controlled trial enrolled 122 subjects in Australia and New Zealand. Subjects received Posidur 2.5 mL, Posidur 5 mL and placebo. The co-primary endpoints were Mean Pain Intensity on Movement area under the curve (AUC) 1-72 hours post-surgery and the proportion of subjects requiring supplemental opioid analgesic medication during the study. The subjects receiving Posidur 5 mL reported 31% less pain versus placebo (p=0.0033) and 53% of those in the Posidur 5 mL arm took supplemental opioid analgesic medications versus 72% of those in the placebo arm (p=0.0909). Posidur administered at 5 mL reached statistical significance on all secondary endpoints. Posidur 2.5 mL showed a positive trend when compared to placebo but failed to reach statistical significance on any of the endpoints. Based on the results, phase III trials were under development.
June 11, 2007
Roxro announced positive results from a phase III trial of ROX-888 for the treatment of acute pain following major abdominal surgery. This multi-center, double-blind, placebo-controlled trial enrolled 321 subjects who were randomized to receive either intranasal ROX-888 (30 mg) or placebo when their pain reached a moderate level following surgery. All subjects had access to patient-controlled morphine. Results demonstrated that the subjects who received ROX-888 reported greater improvement in pain relief and required 22% less morphine in the first 24 hours following surgery compared to subjects who had access to morphine alone. Based on the results, Roxro plans to file a NDA with the FDA in the first half of 2008.
February 26, 2007
CeNeS announced positive preliminary results from a phase III trial of M6G for the treatment of post-operative pain. This randomized, double-blind trial enrolled 517 subjects in Europe undergoing abdominal surgery. Subjects received an initial loading dose of intravenous M6G or morphine prior to administration on the ward. Once on the ward, subjects self-administered treatment as required to control their pain. The primary endpoint was for non-inferiority in pain level management with M6G when compared to morphine and that treatment with M6G would result in lower levels of nausea and vomiting when compared to morphine. Preliminary results revealed that M6G was as good as morphine in terms of analgesia up to 48 hours post-operatively. In addition, treatment with M6G led to a 28% reduction post-operative nausea and vomiting 6 to 24 hours after treatment when compared to morphine (p=0.018). Dry retching/vomiting was reduced by 32% in the M6G arm when compared to placebo 24 hours post treatment (p= 0.044) and post-operative nausea was reduced by 26% when compared to placebo 6-24 hours after treatment (p=0.052). Based on the results, CeNeS plans to file an IND with the FDA in Q1 of 2007.
February 12, 2007
ISTA reported positive preliminary results from a phase III trial of Xibrom once daily for the treatment of pain and inflammation following cataract surgery. This randomized, double-blind, placebo-controlled trial enrolled 500 subjects who received Xybrom or placebo following cataract surgery. Treatment was well tolerated with a safety profile consistent with the currently marketed twice daily formulation of Xibrom. In addition, preliminary analysis has revealed statistical significance in the efficacy of Xibrom for treating these conditions. Pending positive final results, ISTA plans to file a sNDA in the second half of 2007.
October 23, 2006
YM Biosciences issued positive interim results from a phase IIb trial of AeroLEF, an inhaled therapy for the treatment of acute post-surgical pain. This randomized, double-blind, placebo-controlled trial enrolled 21 subjects who self-titrated AeroLEF in an effort to match dosage to individual pain intensity. Treatment was shown to be well tolerated with all adverse events mild in severity. Efficacy results demonstrated that patient self-titrated dosing with AeroLEF provided clinically meaningful analgesia in 81%, 100% and 87.5% of treated pain episodes during doses 1, 2 and 3 respectively. Reduction in pain intensity was reported within the first 10 minutes of initiation of treatment in 38%, 73% and 63% of the subjects during doses 1, 2 and 3 respectively. Part II of this trial is currently underway. It is designed to compare the safety and efficacy of AeroLEF versus placebo for management of pain following elective orthopedic surgery.
September 11, 2006
Epicept reported negative results from a phase III trial of LidoPain for the treatment of post-surgical pain. This randomized, double-blind, placebo-controlled trial enrolled 400 subjects who underwent hernia repair surgery. Subjects received a LidoPAIN or placebo patch for 48 hours following surgery. The trial failed to meet the primary endpoint of self-assessed pain intensity at 4 and 24 hours, measured by the area under the curve (p= 0.4). In addition the secondary endpoint, patient use of "rescue" medications 4 to 24 hours post-surgery, was not met (p= 0.09). EpiCept plans to further analyze data to determine a future course of action for LidoPAIN.
April 3, 2006
Corgentech announced negative results of a phase II trial of ALGRX 4975 for the treatment of hernia repair pain. This randomized, double-blind, placebo-controlled parallel-group pilot study enrolled 41 patients in Denmark, who received single doses of the drug or placebo into the surgical wound site 1 minute prior to closure; following surgery, all subjects received palliative therapy with acetaminophen and ibuprofen for 1 week. Efficacy follow-up occurred one and four weeks after surgery. Trial data yielded no significant differences in pain scores on the visual analog scale for surgical wounds treated with ALGRX 4975 (VAS score = 14.4), compared to placebo (VAS score = 17.5; p>0.05). The drug was well tolerated at all time points. Additional phase II trials of the drug, for the treatment of tendonitis of the elbow, post- bunionectomy pain, Morton's neuroma, total knee replacement and cholecystectomy, were ongoing.
February 6, 2006
Pharmos has reported positive results of a phase I trial of cannabinor, for the treatment of post-operative pain. Trial data yielded a positive safety profile, with no serious adverse events reported. The drug demonstrated a linear and dose-proportional pharmacokinetic profile, consistent with preclinical findings. This randomized, double blind, placebo controlled, escalating-single-dose study enrolled 48 healthy male volunteers at the Harrison Clinical Research Unit in Munich, Germany; subjects received single intravenous doses of the drug or placebo. Based on these results, the company announced plans to initiate a phase IIa trial of the drug in Q2 2006, and phase IIb trials in 2007.
October 17, 2005
Javelin Pharmaceuticals issued positive results of a phase IIb trial, dubbed MOR-002, of Rylomine, their intranasal morphine drug for the treatment of pain following orthopedic surgery. Trial data established linear dose-response in the primary efficacy measure, change in pain severity on the Visual Analog scale at 4 hours post dosing. Efficacy was comparable to intravenous morphine. This multi-center, double- blind, two-stage, randomized, placebo- and active- controlled study enrolled 187 bunionectomy patients, who received single doses one of four doses of Rylomine (3.75 mg to 30 mg), a bolus injection of morphine (7.5 mg), or placebo, followed by a multiple dose stage where subjects received one of two doses of the drug (7.5 mg or 15 mg) over 24 hours.
September 19, 2005
DOV Pharmaceutical announced positive results of a phase III trial of bicifadine, for the treatment of post-surgical pain. Trial data met their primary efficacy endpoint, with high-dose bicifadine demonstrating non-inferiority to active-controlled therapy with tramadol, and both demonstrated statistical and clinical superiority to placebo in the sum of the pain relief and intensity differences at 8 hours (SPRID-8; p=0.01). Results also met their secondary endpoints including superiority to placebo for both high-dose bicifadine and tramadol in total of the pain relief scores (TOTPAR-8; p=0.01), the sum of the pain intensity differences (SPID-8; p<0.01). This active- and placebo-controlled, randomized study enrolled 325 patients undergoing bunionectomy across 5 US sites; subjects received one of two doses of the drug (200 mg or 400 mg), an approved dose of tramadol (100 mg), or placebo, three times daily.
August 1, 2005
Cara Therapeutics has reported positive results of a phase Ia trial of their investigational peripheral kappa opioid agonist CR665, for the treatment of post- operative pain. Trial data met their primary safety endpoints, with no serious adverse events reported and a positive overall tolerability profile. Pharmacokinetic data indicated that the drug achieved linear, dose-related drug plasma concentrations; these concentrations reached levels associated with clinical response at multiple doses. The drug also produced endocrine biomarkers associated with kappa receptor activation. This double-blind, randomized, placebo- controlled, single-escalating-dose study enrolled 60 healthy volunteers at a single site, who received single intravenous doses of the drug or placebo. Based on these results, the company announced plans to initiate phase Ib and phase II trials in the near future.
July 18, 2005
Intrac, through its subsidiary Innovative Drug Delivery Systems, announced positive results of a phase II/III trial of their injectable non-opioid analgesic Dyloject (diclofenac sodium), for the treatment of moderate-to-severe post-operative pain. Trial data indicated that the drug produced significant superiority compared to placebo in the speed of onset, duration, and magnitude of pain relief. Analgesic efficacy was non-inferior to Voltarol, an approved formulation of diclofenac delivered via infusion. Safety data were positive, with no unexpected results; the most common adverse events were phlebitis (6.5%), headache (4.5%), fatigue (2.6%) and hematuria (2.6%). The phlebitis rate was half that observed with Voltarol, and incidence of other adverse events was non-inferior to the approved drug. This randomized, double blind, placebo- and comparator-controlled study enrolled 155 subjects at a single site in Europe, who received a single dose of either 75 mg Dyloject via bolus injection, a 30 minute infusion of 75 mg Voltarol, or placebo following surgery. The company announced that these data would support filing of an MAA later in 2005.
September 27, 2004
Cenes Pharmaceuticals has issued positive preliminary results from a phase III study of M6G, their investigational opiate for the treatment of post-operative pain. The trial met its primary endpoint, producing a significant reduction in the need for morphine consumption following dosing with a single administration of M6G versus placebo. The trial also had success in its secondary endpoints, demonstrating equivalent pain control among all study groups, reconfirming the optimal dose, and establishing the efficacy of a single-dose-regimen over 24 hours. Positive, non-significant trends were also observed in reducing nausea and vomiting compared with morphine alone. The randomized, dose-ranging, double-blind, placebo-controlled study enrolled a total of 167 subjects suffering from post-operative pain; subjects received a single dose of M6G or placebo, and then were monitored for the need for additional morphine to manage pain for 24 hours. Cenes announced plans for an additional phase III trial in Europe, which would compare the safety, tolerability and efficacy of the drug with standard morphine therapy.
May 3, 2004
Metaphore Pharmaceuticals reported positive results from a phase II trial investigating M40403, a free-radical fighting enzyme mimetic for the treatment of pain. Results demonstrated M40403 improved the efficacy of morphine by providing a faster onset, longer duration, greater peak effect and greater overall effect. The randomized, double-blind, controlled, parallel group study enrolled 350 subjects with pain following dental surgery and was conducted at two sites in the U.S. Subjects received one of three single intravenous doses of morphine (0.04, 0.08, 0.12 mg/kg) alone or in combination with M40403 (.25 mg/kg). A phase II trial with M40403 is planned for the second quarter of 2004 for the treatment of bunionectomy pain.