Clinical Trials Resource Center

New Medical Therapies™

Surgery

November 11, 2013

Cara Therapeutics issued results of a phase II trial of I.V. CR845 for the treatment of acute pain. The randomized, doubleblind, placebo-controlled trial of I.V. CR845 (0.005mg/kg/dose) enrolled 51 women and men undergoing a primary unilateral first-metatarsal bunionectomy surgery in the U.S. Repeat dosing of I.V. CR845 over 48 hours post-surgery provided statistically greater pain reduction than placebo at both the 24- and 48-hour time points following initiation of treatment, as assessed using the FDA recommended endpoint, the Summed Pain Intensity Difference (SPID). The I.V. CR845 treatment arm met the trial’s primary endpoint of a statistically significant reduction in pain intensity, as measured by the SPID score, over the initial 24-hour time period (SPID0-24; p<0.05) compared to placebo. The I.V. CR845 treatment arm also met the secondary endpoint of a statistical reduction in pain intensity over the entire 48-hour dosing period (SPID0-48; p<0.025). In addition, I.V. CR845 treatment resulted in a statistically significant reduction in the incidence of opioid-related adverse events of nausea and vomiting (by 60% and 80%, respectively; p<0.05) compared to placebo during the 48-hour treatment period.

October 13, 2008

OMRIX reported positive interim results from a phase II trial of Evicel, a Patch for the treatment of mild to moderate bleeding during surgery. This randomized, controlled study planned to enroll up to 210 subjects in the United States who were treated with Evicel or Surgicel, the current standard of care. To date 90 subjects have been enrolled and treated. Evicel was superior to Surgicel in the primary efficacy endpoint, which measured the proportion of subjects achieving hemostatic success at 4 minutes after randomization with no re-bleeding requiring treatment during a subsequent 6-minute observation period. In accordance with the study protocol, since superiority was established, randomization has been stopped and additional non-randomized subjects are undergoing enrollment and treatment with Evicel.

August 18, 2008

Nuvelo issued positive results from a phase Ib trial of NU172 as a potential short-acting anticoagulant during medical procedures. This single center study enrolled 24 healthy male subjects who were placed into four dosing cohorts. Each cohort received a 2 mg/kg bolus dose followed by escalating infusion doses of NU172 for four hours. In all four cohorts, NU172 produced dose-dependent increases in anticoagulation, measured by activated clotting time (ACT), prothrombin time (PT) and activated partial thromboplastin time (aPTT). The highest infusion dose rate tested, 6.0 mg/kg/hr, resulted in an average ACT per subject ranging from 373 to 414 seconds and an increase of approximately three times baseline. Average PT values per subject ranged from 56 to 92 seconds and had an increase of approximately five times baseline. Average aPTT values per subject ranged from 130 to 178 seconds and had an increase of approximately five times baseline. These measurements remained stable throughout the four-hour infusion. Once the infusion ended, the coagulation parameters showed a rapid return toward baseline. NU172 was well-tolerated with no serious adverse events. Based on the results, Nuvelo plans to commence phase II studies in the fourth quarter of 2008 or the first quarter of 2009.

September 11, 2006

Zymogenetics issued positive results from a phase III trial of rhThrombin for the treatment of blood loss during surgery. This multiple site, randomized, double-blind, controlled trial enrolled 400 subjects undergoing surgery. Subjects were randomized in a 1:1 ratio to receive rhThrombin (1000 U/mL) or bovine thrombin (1000 U/mL). During the surgical procedure subjects were treated with one of the two study drugs, in combination with an absorbable gelatin sponge, at appropriate bleeding evaluation sites. The primary outcome was time to hemostasis when compared to currently approved bovine-derived thrombin, measured by incidence of hemostasis within 10 minutes. The trial met the primary endpoints, with hemostasis occurring within 10 minutes in both treatment groups. Secondary endpoints were met as well with adverse effects comparable between the two groups and the rate of antibody formation at 1.5% in the rhThrombin group, versus 22% for those treated with the bovine thrombin product (p < 0.0001). ZymoGenetics plans to submit a Biologics Licensing Application for rhThrombin to the FDA in late 2006.

May 15, 2006

Cardiome issued additional results of a phase I trial of an oral formulation of RSD1235, for the treatment of atrial arrhythmia; preliminary results were announced in August 2005. The additional data concerned the drug's effects on QT interval: subjects receiving a 300 mg twice daily dose of the drug had a baseline QT interval of 396 +/- 25 msec, and a value at maximum plasma concentration (Cmax) of 394 +/- 13 msec; the 600 mg twice daily group had a baseline QT of 402 +/- 19 msec, and a Cmax value of 405 +/- 18 msec; and the 900 mg twice daily dose had a baseline QT of 413 +/- 19 msec and a Cmax value of 408 +/- 25 msec. Prolongation of QT interval is a frequent complication of antiarrhythmic therapy, and Cardiome was encouraged by the lack of this complication. The company announced plans to initiate a phase IIb trial of oral RSD1235 in the second half of 2006.

Scios issued positive results of a phase II trial, dubbed NAPA (Nesiritide Administered Peri-Anesthesia in Patients Undergoing Cardiac Surgery) of nesiritide for the maintenance of post-operative renal function following coronary artery bypass graft (CABG). These results were announced at the 7th Scientific Forum on Quality of Care and Outcomes Research in Cardiovascular Disease and Stroke meeting in Washington, DC. Trial data yielded significant improvements in both maximum mean increase in serum creatinine from baseline (0.15+/-0.29 mg/dl for nesiritide, vs. 0.34+/-0.48 mg/dl for placebo; p<0.001), and in maximum decrease in glomerular filtration rate from baseline (-10.8 mL/min/1.73 m2 vs. -17.2 mL/min/1.73 m2; p=0.001). This prospective, multi-center, randomized, double-blind pilot study enrolled 279 heart failure patients scheduled for CABG surgery across 54 sites, who received an infusion of the drug or placebo after induction of anesthesia, with subsequent 14 day follow-up.

December 12, 2005

Medicure has announced positive results of a phase II trial, dubbed MEND-CABG, of MC-1, for the treatment of acute cardiovascular events following coronary artery bypass graft (CABG) surgery. The drug produced significant efficacy in the primary composite efficacy endpoint, significantly reducing incidence of death, non-fatal myocardial infarction (peak CK-MB >/= 100ng/ml) and non-fatal stroke, at a dose of 250 mg, vs. placebo (-37.2%; p=0.028). Additional efficacy was noted in reduction of myocardial infarction (peak CK-MB >/= 100ng/ml) alone, vs. placebo (-46.9%; p=0.008); and in the rate of physician diagnosed myocardial infarction (-78.7%; p=0.0065). The 250 mg dose produced superior efficacy to the 750 mg dose, and neither dose group yielded significant efficacy in the composite endpoint when it included myocardial infarctions with peak CK-MB >/= 50ng/ml. This double blind, parallel group, randomized, placebo-controlled study enrolled 901 CABG patients across 42 sites in Canada and the US, who received one of two daily doses of MC-1 (250 mg or 750 mg) or placebo for 30 days. Based on these results, the company announced plans to move forward with phase III studies of the drug.

December 5, 2005

Alexion and Procter & Gamble announced negative preliminary results of a phase III study, dubbed PRIMO-CABG2, of pexelizumab, for the prevention of myocardial infarction following coronary artery bypass graft (CABG) surgery. Trial data demonstrated a positive trend, but failed to reach statistical significance, in the primary endpoint of reducing the combined incidence of nonfatal myocardial infarction or death through 30 days in moderate-to-high risk patients, compared to placebo. This randomized, double-blind, placebo controlled, parallel assignment study enrolled 4,250 subjects across 250 sites worldwide. The company announced that they were assessing the impact of these results on their other ongoing phase III studies, and full results of PRIMO-CABG2 were to be released in the near future at a major medical conference.

November 28, 2005

AstraZeneca reported positive results of their phase IIb DISPERSE2 trial of AZD6140, their investigational platelet-aggregation inhibitor for the treatment of acute coronary syndromes (ACS). Primary safety data indicated comparable rates of bleeding events for low- and high-dose treatment groups and a control group receiving the approved drug clopidogrel at the end of the treatment period: 10.2% of subjects in each of the two treatment groups experienced bleeds of any severity, vs. 9.2% for the approved drug. Incidence of major bleed events were 7.8% and 6.2% for low- and high-dose AZD6140 groups respectively, vs. 8.0% for the approved drug. Finally, data from an interim 4-week analysis indicated all-severity bleed rates of 9.6%, 7.7% and 8.0%, respectively. This double-blind, parallel group, randomized, dose-ranging study enrolled 990 ACS patients, who received one of two doses of AZD6140 (90 or 180 mg, twice daily) or a standard dose of clopidogrel (75 mg once daily) for 12 weeks.

Corgentech announced negative results of a phase III trial, dubbed PREVENT IV, of edifoligide for the prevention of graft failure in coronary artery bypass graft (CABG) surgery. Trial data failed to significantly reduce the number of patients with one or more grafts at least 75% blocked at 1 year, the trial’s primary endpoint: 45.2% of patients who received the drug had 75% blockage, compared to 46.3% for the control group. Further, no difference was noted in the total number of 75%-occluded graft veins between edifoligide (28.5% of grafts) and control. (29.7% of grafts) groups. This randomized, double-blind, placebo-controlled trial enrolled 3,014 CABG patients across 107 US sites, each of whom had received at least two venous grafts. Further development of edifoligide for this indication was not planned.

October 10, 2005

Lumen Therapeutics issued positive interim results from the phase I portion of their phase I/II trial of LT-1951, for the prevention of graft failure following saphenous vein coronary artery bypass graft (CABG) surgery. Data from the ongoing study indicated that the drug was safe and generally well tolerated, with no serious adverse events reported and an expected incidence and profile of overall adverse events. These results were sufficiently positive to warrant expansion of the trial into its phase II portion. This placebo-controlled, two stage study enrolled 20 CABG patients in the first stage, with each subject receiving both drug- and placebo-treated venous grafts. The company announced that it planned to expand the enrollment to an additional 30 subjects in the phase II portion of the trial, which was designed to investigate the preliminary efficacy of the drug in preventing graft lumen loss.

August 29, 2005

ZymoGenetics reported aggregate results of four-phase II trials of their recombinant human Thrombin (rhThrombin) being investigated to control bleeding during surgery. Combined results showed product appeared to be safe and well tolerated, with a favorable immunogenicity profile. The trial enrolled 130 subjects undergoing various procedures including spinal surgery, liver section, peripheral artery bypass, or arteriovenous graft construction. The results were presented at The International Society on Thrombosis and Haemostasis annual meeting in Sydney, Australia. The company also announced it is finalizing its plans for a phase III pivotal trial for late 2005.

June 27, 2005

ZymoGenetics reported positive results of a pair of phase II trials of rhThrombin (recombinant human thrombin) for use as a surgical homeostat. The drug was shown to be efficacious in promoting homeostasis, with 90% of bleeding sites treated with rhThrombin achieving homeostasis within 10 minutes, vs. 74% for placebo. Average time to homeostasis was 27% lower for rhThrombin treated subjects. Furthermore, only 2.7% of treated subjects (n=1) demonstrated antibody response against the drug, vs. over 40% for bovine thrombin. These randomized, double-blinded trials enrolled a total of 60 patients undergoing either arteriovenous grafting surgery or peripheral artery bypass surgery, who were treated with either rhThrombin- or placebo-soaked sponges at bleeding sites during the surgery. ZymoGenetics announced plans initiate pivotal trials of rhThrombin during the second half of 2005.

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