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Lupus Clinical Trials

New Medical Therapies™

Heart Disease

September 3, 2012

Novartis issued results from a phase II trial of LCZ696 for the treatment of heart failure with preserved ejection fraction (HF-PEF). This randomized, double-blind, multicenter,parallel group, active-controlled study, PARAMOUNT, enrolled 301 patients with HFPEF who also had elevated NT-proBNP (>400pg/ml). After halting any treatment with an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker, subjects received 50mg LCZ696 or 40mg valsartan twice-daily for 36 weeks. Doses of both drugs were doubled after one week and doubled again after another week to a maximum dose of 200mg LCZ696 and 160mg valsartan twice-daily. Results demonstrated that after 12 weeks of treatment, reduction in NT-proBNP was 23% greater with LCZ696 than valsartan (p=0.005). In addition, there was a greater reduction (p=0.003) in left atrial size (cardiac remodeling) in LCZ696-treated patients at the end of the 36-week study. The drug was well tolerated. Novartis is also conducting phase II and III studies of LCZ696 for the reduction of blood pressure and treatment of hypertension, respectively.

Pozen issued results from a phase I trial of PA32540 for the treatment of cardiovascular disease. This randomized, openlabel, two-arm crossover study enrolled 30 patients with cardiovascular disease at risk for aspirin-associated gastric ulcers. Subjects were divided into two arms. The first arm received PA32540 in the morning plus 300mg clopidogrel over 10 hours later on Day One, and PA32540 in the morning plus 75mg clopidogrel 10 hours later on day two through seven. The second arm received 81mg enteric-coated aspirin, 300mg clopidogrel and 40mg EC omeprazole all in the morning on day one, followed by 81mg enteric-coated aspirin, 75mg clopidogrel and 40mg EC omeprazole all in the morning on day two through seven. When subjects completed treatment, they had a 14-day washout period and then crossed over to the alternate treatment. Data showed the PA32540 arm resulted in greater antiplatelet effects than the EC aspirin arm (46.5% versus 39.9%, respectively, at day seven: 95% confidence interval of the difference [2.57, 11.91]; p=0.004). The drug was well tolerated.

August 6, 2012

Bristol-Myers Squibb and AstraZeneca issued results from five phase III trials of Onglyza (saxagliptin) for the treatment of cardiovascular disease. These randomized, placebo-controlled studies enrolled 1,681 patients with type 2 diabetes and varying degrees of cardiovascular risk. Subjects received Onglyza 5mg or placebo for 24 weeks. Data demonstrated improvements across key measures of blood sugar control (glycosylated hemoglobin levels, or HbA1c; fasting plasma glucose, or FPG and postprandial glucose, or PPG) compared to placebo in patients at high risk for cardiovascular disease. Decreases in FPG for Onglyza at week 24 ranged from -14.2 mg/dL to -16.0 mg/dL versus placebo. Similarly, PPG results at week 24 ranged from -36.1 mg/dL to -47.0 mg/dL compared to placebo. Finally, achievement of target HbA1c (less than 7.0%) ranged from 15.7% to 21.8% versus placebo. The drug was well tolerated. The most frequent adverse event was hypoglycemia. BMS and AZ did not note their future plans for Onglyza.

March 3, 2008

Medicure reported negative results from a phase III trial of MC-1 for the treatment of coronary artery disease. This double-blind, randomized, placebo-controlled trial, dubbed MEND-CABG II, enrolled three thousand subjects undergoing coronary artery bypass graft surgery, at several cardiac surgical centers throughout North America and Europe. Subjects were randomized to receive placebo or MC-1 (250mg) prior to surgery and for thirty days post operatively (POD 30). They were then followed for sixty days after treatment (ninety days post operatively) for additional safety and efficacy analysis. The study failed to meet the primary endpoint, the reduction in the composite of cardiovascular death and non-fatal myocardial infarction up to POD 30. Based on the data, Medicure does not plan on filing for FDA approval of MC-1 for this indication.

January 21, 2008

Anthera released positive preliminary results from a phase IIb trial of A-002 for the treatment of cardiovascular disease. This multi-center, randomized, double-blind, placebo- controlled trial enrolled one hundred and forty subjects with stable coronary heart disease in the United States. The subjects received one of two different daily doses of A-002 or placebo, in addition to standard of care therapies, for up to eight weeks. The primary endpoint was reduction in secretory phospholipase A2 (sPLA2) levels. Secondary endpoints included a number of lipid and inflammatory biomarkers. Once-daily A-002 lowered sPLA2 levels and resulted in significant reductions in blood levels of total cholesterol, Non-High Density Lipoprotein Cholesterol (non HDL-C), and Low Density Lipoprotein Cholesterol (LDL-C), oxidized LDL, and apolipoprotein-B100 (Apo-B). Full results are expected later in 2008, with phase III trials to follow.

September 17, 2007

Atherogenics reported positive results from a phase III trial of AGI-1067 for the treatment of diabetes and coronary heart disease. This trial, dubbed ARISE (Aggressive Reduction of Inflammation Stops Events), enrolled over 6,000 subjects internationally. Subjects received AGI-1067 or placebo both in conjunction with standard of care. After 12 months of treatment, AGI-1067 significantly lowered levels of glycated hemoglobin A1c, a measure of glycemic control, in subjects with and without diabetes. In addition, the data showed a 59% reduction in the development of new onset diabetes in subjects with impaired fasting glucose (p < 0.0001). In the subjects with diabetes, AGI-1067 showed a 22% reduction in hard cardiovascular events of cardiovascular death, cardiac arrest, myocardial infarction and stroke (p=0.062). Additional phase III trials are currently underway.

March 19, 2007

Liponex released negative results from a phase I/II trial of CRD5 for thetreatment of dyslipidemia and heart disease. This single-blinded trial enrolled56 subjects with elevated LDL and HDL. Following a dietary lead-in periodsubjects were given daily doses of CRD5 capsules (1, 3 or 5 grams) or placebofor 12 weeks. Treatment was well tolerated for the lower doses. However,enrollment was suspended in the 5 gram dose group due to a high number ofwithdrawals as a result of gastrointestinal related adverse events. The primaryendpoint, increase in serum HDL was not met. The mean increase in HDL levels atboth the 1 and 5 gram doses was less than 5% and thus not statisticallysignificant. Based on the results Liponex plans to further assess the data andpossibly commence phase I/II trials with new formulations later in 2007.

December 11, 2006

Astellas and CV Therapeutics released positive results from a phase III trial of regadenoson for the potential use as a pharmacologic stress agent in myocardial perfusion imaging (MPI) studies. This randomized, double-blind trial enrolled 1,231 subjects, all of who received a clinically indicated baseline MPI study using Adenoscan (adenosine injection). Subjects then received either regadenoson or Adenoscan in a second MPI study. The trial was designed to evaluate the comparability of MPI studies conducted with regadenoson and Adenoscan. Treatment was well tolerated with the most common adverse events including shortness of breath, headache, chest pain, flushing and gastrointestinal discomfort. The trial met the primary endpoint by showing with 95% confidence that MPI studies conducted with regadenoson were comparable to MPI studies conducted with Adenoscan. Based on the results of the phase III trials CV plans to file a NDA with the FDA in 2007.

Cytokinetics issued positive results from a phase I trial of CK-1827452 for the treatment of acute and chronic heart failure. This randomized, open-label, four way crossover trial enrolled 10 healthy subjects who received CK-1827452 at 0.125 mg/kg administered as a reference intravenous infusion at a constant rate over one hour, as a liquid solution taken orally in a fasted state, as an immediate-release solid formulation taken orally in a fasted state and as an immediate-release solid formulation taken orally following consumption of a standard, high-fat breakfast. The trial was designed to evaluate the absolute bioavailability and the effects of food on the bioavailability of CK-1827452 when administered orally. All four treatment administrations were well tolerated, with no reported serious adverse events. Pharmacokinetic data from this study demonstrated oral bioavailability of approximately 100% for each of the three conditions of oral administration. Oral absorption while fasting was rapid for the liquid solution and immediate-release solid formulation. The median time to maximum plasma concentration after dosing (Tmax) was 0.5 hours for the liquid solution and 1 hour for the immediate-release formulation. Food delayed the rate of absorption, with a median Tmax of 3 hours, but did not diminish the extent of absorption. Based on these results, Cytokinetics plans to initiate an international phase II trial of CK-1827452 in late 2006 or early 2007.

September 11, 2006

AstraZeneca announced results from a clinical trial, dubbed EXPLORER, of Crester (40 mg) and < for the treatment of elevated levels of C-reactive protein (CRP), a marker of inflammation and a risk factor for cardiovascular disease. Results demonstrated that 58% of the subjects on the combination therapy achieved dual LDL-C/CRP goals of LDL-C <100 mg/dL or <70 mg/dL and CRP <2 mg/L at six weeks, versus 24% on Crestor monotherapy. In addtion, the Cestor combination therapy: reduced CRP levels by 46% versus 29% with the monotherapy, reduced mean LDL-C by 70%, and allowed 94% of the subjects to achieve the NCEP ATP III LDL-C goal of <100 mg/dL versus 79% on monotherapy (p<0.001). Based on these results AstraZeneca plans to move this combination forward in clinical trials.

Nuvelo released positive results from the ANTHEM phase IIa/II trial of rNAPc2 for the treatment of acute coronary syndromes. This multi-center, randomized, double-blind, placebo-controlled, ascending dose-ranging study enrolled 175 subjects in the US and Canada. Subjects received seven ascending doses of rNAPc2 (1.5, 2.0, 3.0, 4.0, 5.0, 7.5 and 10 micrograms/kg) intravenously every 48 hours, along with low molecular weight heparin or unfractionated heparin and aspirin. Results demonstrated that treatment at 7.5 and 10 mcg/kg reduced incidence and duration of ischemia by more than 50%. In the heparin de-escalation portion of the trial rNAPc2 (10 mcg/kg) was shown to reduce ischemia even in the absence of heparin and enoxaparin. Additionally, treatment at 7.5 and 10 mcg/kg suppressed prothrombin fragment F1+2 levels compared to placebo (p<0.01). Hemorrhage rates were 2.5% for placebo, 2.9% for low dose rNAPc2 and 4.5% for higher-dose rNAPc2 (p = 0.77). Based on these results Nuvelo plans to advance rNAPc2 into future trials.

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.

September 19, 2005

Novogen has reported positive results of a phase Ib trial of their investigational drug trans NV-04, for the treatment of cardiovascular diseases related to obesity. The drug was shown to significantly improve symptoms of arterial stiffness, and to significantly lower both systolic and diastolic blood pressure. Pharmacokinetic data yielded good bioavailability, and safety data yielded no serious adverse events. This double-blind placebo-controlled cross-over study enrolled 25 overweight patients, who received the drug and placebo over two consecutive 5 week periods.

September 5, 2005

Cardiome has announced positive results of a phase I trial of oral RSD1235, for the treatment of atrial arrhythmia. Trial data indicated that the drug was generally safe and well tolerated across all dosing regimens, with no serious adverse events reported and no clinically relevant changes in laboratory values, vital signs or ECG measurements. Pharmacokinetic data indicated that the highest dosing group experienced peak serum drug concentrations comparable to those seen with IV administration of the drug and an extended serum half-life suitable for chronic dosing. This open-label study enrolled 55 healthy volunteers, who received escalating oral dose regimens (up to 900 mg) twice daily for 7 days. Based on these results the company announced plans to move the drug into phase II trials, with the first to be initiated in Q4 2005.

November 15, 2004

AVI BioPharma reported positive phase II results for Resten-NG (AVI-4126), their third-generation antisense oligonucleotide for the treatment of cardiovascular restenosis. Results indicated that the drug met its primary endpoint, demonstrating significant efficacy in preventing restenosis following balloon angioplasty compared with subjects receiving standard therapy or sub-therapeutic doses of Resten-NG, as confirmed by quantitative angiography and ultrasound imaging. Secondary efficacy was seen in significantly reducing neointimal growth. This multi-center, double-blind, study randomized coronary artery disease patients at risk for restenosis to receive either a therapeutic or sub-therapeutic dose regimen of Resten-NG or standard therapy following balloon angioplasty. AVI announced plans to initiate a phase III clinical trial of the drug in Europe based upon these results.

NitroMed has issued results from a phase III study of BiDil (isosorbide dinitrate/hydralazine), for the treatment of heart failure in African American patients. Trial results demonstrate that the drug met its primary efficacy endpoints, with a 43% improvement in patient survival (p=0.01), a lower sudden death rate (6.2% vs. 10.2%; p=0.02), a 33% reduction in first hospitalization for heart failure (p=0.001), and a significant improvement in quality of life (p=0.02), vs. placebo. This double-blind, placebo-controlled trial enrolled 1,050 African American patients with heart failure across 170 investigative sites, who were randomized to receive either BiDil or placebo in addition to standard therapy for 18 months. NitroMed announced that it had submitted the data from the trial to the FDA, as required to amend their NDA for the treatment of heart failure in African American patients.

October 18, 2004

Critical Therapeutics has issued positive results of a phase I trial of their investigational anti-inflammatory cytokine-synthesis inhibitor CTI-01 (ethyl pyruvate), for the treatment of critical inflammatory conditions. The trial met its primary safety endpoint, with multiple escalating dose regimens of the drug producing no serious adverse events, including doses higher than the anticipated therapeutic range. This double-blind, placebo-controlled study randomized a total of 60 healthy subjects to receive one of eight escalating multi-dose regimens of the drug. The trial followed the successful completion of a single escalating-dose study of the drug, initiated in June 2003. Critical Therapeutics announced plans to initiate a phase II trial of the drug in the prevention of organ damage following cardiopulmonary bypass by the end of Q4 2004, based upon these results.

September 27, 2004

Avant Immunotherapeutics has published the results from a phase II trial of their cardioprotective investigational drug TP10 in the journal Circulation. The trial did not meet its primary endpoint, a significant decrease in mortality or acute myocardial infarction following cardiopulmonary bypass (CPB) during cardiac surgery. However, when data were analyzed for male patients only, the drug was successful in both outcomes, reducing mortality by 36% in all men and by 43% in CABG men. The drug did demonstrate significant pharmacodynamic activity on its target in both men and women. This multi-center, double-blind, placebo-controlled study enrolled a total of 564 high risk men and women undergoing cardiac surgery including CPB. Avant announced that it plans to initiate a second, all-female phase II trial, in addition to phase III testing.

Medicure has announced positive results from a phase I trial of a new IV formulation of their lead compound MC-1, for the treatment of cardiovascular emergencies, including stroke and acute coronary syndrome. The drug was found to be safe and well tolerated in healthy volunteers, and, similar to the effect observed with the drug’s oral formulation, did not produce any significant adverse cardiovascular effects, a common concern with other similar products. This trial and the IV formulation of the drug were designed to expand the clinical potential of MC-1, and permit use of the drug both pre-operatively, as a cardioprotective, and as an intervention therapy in acute cardiovascular events.

September 20, 2004

Vasogen announced preliminary results of their phase II study of Celacade, for the immunomodulatory treatment of advanced chronic heart failure. The study found that the drug significantly improved disease severity scores, including significant improvements in risk of death (p=0.022), all-cause hospitalization (p=0.008) and composite clinical score (p=0.006), and key electrocardiogram measurements (p=0.035), compared with placebo. Furthermore, the condition of subjects receiving Celacade improved significantly more often, and worsened significantly less often, than subjects receiving placebo. No significant difference from placebo was found in 6-minute walk endurance test or left-ventricular ejection fraction. This randomized, double-blind, controlled study enrolled a total of 75 chronic heart failure patients, who received either Celacade or placebo adjuvant to standard pharmacological therapy for six months. Vasogen announced that these results, which were published in the September 15th edition of the Journal of the American College of Cardiology, would be used as the basis for advancing Celacade into phase III trials.

September 13, 2004

CEL-SCI announced positive results from a clinical trial investigating Multikine, an immunotherapeutic agent for the treatment of elevated cholesterol. Multikine is a mixture of naturally occurring cytokines including interleukins, interferons, chemokines and colony-stimulating factors. Results showed that treatment with Multikine showed no liver toxicity while achieving reduction in total cholesterol levels. A meta-analysis showed the reduction of total cholesterol following treatment with Multikine to be highly statistically significant (p<0.0001). The drug did not affect the levels of AST/ALT (liver enzymes) nor did it produce any severe adverse effects. Subjects were treated with Multikine for 2 to 24 weeks. The study enrolled 120 subjects and was designed to evaluate multiple doses and different treatment regimens in head and neck cancer. Multikine is also under investigation for the treatment of several types of cancer, including head & neck; this is these are the first data reported for the drug for a cardiological indication. The company is now planning to initiate phase III trials for head and neck cancer.

Lilly and Sankyo have reported positive results of a phase II comparative safety study of CS-747, their investigational anti-platelet agent. Trial data met the study’s primary safety endpoint, and demonstrated CS-747 has a comparable safety profile to the current approved therapy clopidogrel: CS-747 produced significant differences in 30-day-post-treatment bleeding in patients who had undergone coronary artery stent implantation. In addition, the trial found non-significant reductions in the incidence of 30-day-post-treatment major coronary events (including death, re-ischemia, target vessel thrombosis, heart attack or stroke; this was the secondary endpoint). The trial enrolled a total of 904 subjects in the US and Canada, who were randomized to receive one of three regimens of CS-747 or a standard regimen of clopidogrel, all of whom had undergone implantation of a coronary stent to open a blocked artery; following the initial dose, all subjects were followed for 30 days for safety and efficacy observations. Based on these results, the companies announced plans to move forward into phase III testing.

September 7, 2004

The Medicines Company has published positive long-term efficacy results for their drug Angiomax, their approved anticoagulant. Study data indicated that AngioMax was more effective than an alternative therapy of heparin and platelet blockers, with a significantly greater portion of high-risk AngioMax-treated subjects reaching a one-year survival milestone following angioplasty. This result was a companied by a non-significant improvement in all risk-quantified trial sub-populations. The trial enrolled over 6,000 subjects, who received either AngioMax or heparin/platelet blockers. These results accompany previously announced short-term efficacy data for this trial, which found that AngioMax reduced bleeding, thrombocytopenia, infusion times and costs, compared with heparin/platelet blockers.

January 5, 2004

AstraZeneca reported results of its phase III, EXULT B trial comparing the anticoagulant, Exanta (ximelagatran), to warfarin for the prevention of venous thormboembolism (VTE) in subjects undergoing total knee replacement (TKR) surgery. Of evaluable subjects, 22.5% of subjects receiving Exanta experienced VTE or death, compared to 31.9% of subjects treated with dose-adjusted warfarin. There was no statistically significant difference between the two treatment groups in the incidence of bleeding events, pulmonary embolism or death. This phase III, randomized, double-blind, double-dummy, international trial involved 2,303 subjects who, for 7 – 12 days, were treated with either Exanta 36 mg twice daily or warfarin. Incidence of VTE was measured by mandatory bilateral venography or by objective means, if VTE was symptomatic. The EXULT B study followed a first phase III study, EXULT A, which compared Exanta to warfarin in reducing blood clots following TKR surgery.

Esperion Therapeutics reported positive results from a second phase I study investigating ETC-642 (RLT Peptide), a complex of a 22-amino acid peptide and phospholipids for the treatment of cardiovascular disease. Results demonstrated the drug was safe and well tolerated. Data showed evidence of asymptomatic elevations of liver function tests in a one subject at the highest dose level (30 mg/kg). The randomized, double-blind, placebo-controlled study enrolled 20 subjects with cardiovascular disease. The study was designed to determine the maximum tolerated dose for single intravenous infusions of ETC-642. Subjects received one of three dose levels (10, 20 or 30 mg/kg) of ETC-642 or placebo.

September 8, 2003

Cordis reported positive final results from a medical device trial investigating the CYPHER Sirolimus-eluting coronary stent for the treatment of arterial blockage. Results demonstrated sustained improvement in vessel re-narrowing at 12-month follow-up compared to a conventional bare metal stent. Data also showed a trend towards lower re-blockage rates in subjects treated with the CYPHER Stent without pre-dilation. Earlier results showed that 43.6% of subjects who received the standard metal stent exhibited reblockage compared with 5.8% of subjects treated with the CYPHER. The study, called E-SIRIUS enrolled 352 subjects at 35 sites in Europe. Results were presented at the 2003 European Society of Cardiology Congress in Vienna.

King Pharmaceuticals and Wyeth reported positive results from a post-marketing trial investigating Altace (ramipril), an ACE inhibitor for the prevention of cardiovascular disease. Results showed a sustained effect of ramipril on the prevention of cardiovascular disease and no preventive effects of vitamin E. The study was conducted by the Population Health Research Institute at McMaster University and Hamilton Health Sciences in Hamilton, Ontario, Canada. Results were presented at the European Society of Cardiology Meeting in Vienna, Austria. The HOPE-TOO (HOPE-The Ongoing Outcomes) study began in November 1999 and examined the benefits seen with 4.5 years of treatment with ramipril were sustained and whether longer-term treatment with vitamin E protected against the development of cancer and cardiovascular disease.

Novartis reported positive results from a clinical trial investigating everolimus, an immunosuppressant drug for the treatment of complications from heart transplants. Results showed that everolimus was significantly more effective in reducing the severity and incidence of serious transplant complications than current therapy. Data also showed that everolimus significantly reduced the incidence of cytomegalovirus infection. The two-year international study was conducted at 52 medical centers in four countries and enrolled 634 subjects with heart transplants who were given the standard regimen of cyclosporine and steroids in addition to treatment medication. The study was designed to target acute rejection and cardiac allograft vasculopathy. Results were presented in the Aug. 28th issue of The New England Journal of Medicine.

January 21, 2003

Medicure reported positive results from a phase II trial investigating MC-1, for the treatment of heart disease. Data showed that both the primary and secondary endpoints were achieved. The primary endpoint, infarct size, was determined by the amount of marker cardiac enzyme released over 24 hours following percutaneous coronary intervention (PCI). Certain secondary endpoints showed improvement such as myocardial ischemia, as measured by continuous ST-segment electrocardiographic monitoring, peak periprocedural CK-MB through 24 hours, clinical tolerability and safety. The randomized, placebo-controlled, blinded study evaluated heart muscle damage following elective PCI. The study enrolled 60 subjects at an increased risk of cardiac damage.

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.