Clinical Trials Resource Center

New Medical Therapies™

Clostridium Difficile-Associated Diarrhea

February 15, 2010

Optimer issued positive results from a phase III trial of fidaxomicin for the treatment of Clostridium difficile Infection (CDI). This double-blind, randomized, parallel group trial enrolled 535 adult subjects with confirmed CDI across North America and Europe. The subjects received either fidaxomicin (200 mg every 12 hours) or oral vancomycin (125 mg every 6 hours) for a 10-day course of therapy. The trial met the primary endpoint of non-inferiority with 91.7% of subjects treated with fidaxomicin achieving clinical cure versus 90.6% for Vancocin. Fidaxomicin also resulted in significantly lower recurrence rates: 12.8% versus 25.3% for the Vancocin arm (p≡0.002) and higher global cure rates, defined as cure with no recurrence within four weeks of completing therapy: 79.6% versus 65.5%, respectively (p<0.001). Fidaxomicin was well-tolerated in the study.

November 17, 2008

Optimer released positive results from a phase III trial of OPT-80 for the treatment of Clostridium difficile Infection (CDI). This multi-center, randomized, double-blind study enrolled 629 adult subjects with confirmed CDI, in North America. The subjects received either 200 mg OPT-80 dosed orally twice daily or 125 mg Vancocin (standard of care) dosed orally four times daily. The objective of the study was to show that a 10-day course of OPT-80 is non-inferior and as safe as a 10-day course of Vancocin. The primary endpoint was clinical cure, defined as no further CDI therapy required by two days after completion of study medication. Both the objective and the primary endpoint were reached. Clinical cure was achieved by 92.1% of subjects treated with OPT-80 versus 89.8% for Vancocin. In addition, 13.3% of subjects treated with OPT-80 experienced a recurrence versus 24.0% for Vancocin (p = 0.004). Global cure (cure with no recurrence within four weeks) was reached by 77.7% of subjects treated with OPT-80 compared to 67.1% of those treated with Vancocin at 67.1% (p = 0.006). OPT-80 was well-tolerated.

November 10, 2008

Medarex released positive preliminary results from a phase II trial of MDX-066 for the treatment of C. difficile Associated Diarrhea (CDAD). This multi-center, randomized, double-blind, placebo-controlled study enrolled 200 subjects symptomatic with CDAD receiving standard of care antibiotics (metronidazole or vancomycin). The subjects received either intravenous placebo or intravenous administration of a combination of MDX-066 (CDA-1) and MDX-1388 (CDB-1). They were then monitored for 84 days, with the first 20 subjects also receiving a visit at day 168. In comparison with placebo, MDX- 066/MDX-1388 treatment reduced recurrence rates by approximately 70% (p≡0.0004). The antibody combination treatment was generally safe and well-tolerated. Full results are expected later in 2008 or early 2009.

Medarex released positive preliminary results from a phase II trial of MDX-066 for the treatment of C. difficile Associated Diarrhea (CDAD). This multi-center, randomized, double-blind, placebo-controlled study enrolled 200 subjects symptomatic with CDAD receiving standard of care antibiotics (metronidazole or vancomycin). The subjects received either intravenous placebo or intravenous administration of a combination of MDX-066 (CDA-1) and MDX-1388 (CDB-1). They were then monitored for 84 days, with the first 20 subjects also receiving a visit at day 168. In comparison with placebo, MDX- 066/MDX-1388 treatment reduced recurrence rates by approximately 70% (p=0.0004). The antibody combination treatment was generally safe and well-tolerated. Full results are expected later in 2008 or early 2009.

April 21, 2008

Napo and Glenmark released positive results from a phase II trial of crofelemer for the treatment of acute infectious diarrhea. This randomized, parallel group, double-blind, placebo-controlled study enrolled ninety-eight adult subjects in India. All subjects had experienced acute diarrhea, defined as the occurrence of three or more unformed stools (soft or watery consistency) within the twenty four hour period preceding entry into the study. The subjects received 250 mg of crofelemer four times per day until recovery or for a maximum of three days. The primary endpoint was improvement in gastrointestinal symptoms, including stool weight, stool frequency, stool consistency and duration of diarrhea. These were recorded by the investigators at baseline, and days one, two and three of treatment. Statistically significant improvements were reached in all the primary endpoints. Overall clinical success was achieved in 79.1% of the evaluable subjects receiving crofelemer compared to 28.2% of the evaluable subjects receiving placebo. Crofelemer was well tolerated and most adverse events were mild to moderate in severity and not different from the placebo group. Based on the results the companies plan to begin another dose-ranging trial in 2008, investigating lower doses and lower dosing frequency.

July 16, 2007

Genzyme reported negative results from a phase III trial of tolevamer liquid for the treatment of Clostridium difficile associated diarrhea (CDAD). This randomized double-blind trial, dubbed PACT (Polymer Alternative for CDAD Treatment), enrolled 1,100 subjects internationally. Half of the subjects received liquid tolevamer and half received metronidazole and vancomycin. The primary endpoint was non-inferiority against the standard oral dose of vancomycin, as measured by the percent of subjects with resolution of CDAD. This endpoint was not met. A second phase III trial is currently underway. Genzyme plans to fully analyze the combined data in order to determine a future course of action.

July 9, 2007

Cosmo reported positive preliminary results from a phase II/III trial of Rifamycin for the treatment of infectious diarrhea. This placebo controlled, randomized, double blind trial enrolled 120 subjects in South Africa. Subjects were treated with Rifamycin or Normix (rifaximin), the standard of care, administered as a 200 mg tablet, 4 times per day for 3 days. The primary endpoint was to establish non-inferiority between the two treatments and the time from first ingestion of tablet to the last unformed stool. Initial data suggest that this was achieved. Cosmo plans to further analyze the results and move forward with the development of Rifamycin.

August 16, 2004

ID Biomedical reported preliminary results from an expanded phase II trial investigating StreptAvax, their streptococcal vaccine. No subject in the clinical trial has developed antibodies that cross-reacted with human tissues, one of the primary safety endpoints. There have been no vaccine-related serious adverse events. Results showed that the vaccine induced high titers of antibodies to all targeted (26) serotypes of group A streptococcus. All subjects have completed at least 194 days of observation since vaccine exposure. ID Biomedical plans to begin their next phase of trials in Q1 2005.

Oscient Pharmaceuticals reported positive results from a phase II trial investigating Ramoplanin, a glycolipodepsipeptide antibiotics for the treatment of Clostridium difficile-associated diarrhea (CDAD). The study compared Ramoplanin (200 mg) twice daily, Ramoplanin (400 mg) twice daily and vancomycin (125 mg) four times daily. The primary endpoint of the trial, response rates at 7-14 days post therapy, showed a 71% response rate with Ramoplanin (400mg) compared to 78% with vancomycin. Results showed that non-inferiority was observed, but not statistically demonstrated because the response rates of all arms were lower than the previously published vancomycin response rates. Ramoplanin (400 mg) and vancomycin had response rates at end of therapy of 85.2% and 85.7%, respectively. The open-label, non-inferiority study enrolled 87 subjects with CDAD at 24 sites in the U.S. Adverse events profiles were similar for both drugs. Oscient hopes to move forward with phase III trials by the end of 2004.

May 17, 2004

Genzyme reported positive results from a phase II trial investigating tolevamer sodium, an investigational polymer therapy for the treatment of Clostridium difficile associated diarrhea. The primary endpoint was non-inferiority to vancomycin with respect to time to resolution of diarrhea. Data demonstrated that tolevamer met the non- inferiority endpoint at the six gram dose level. In addition, tolevamer was found to be similar to vancomycin in median days to resolution of diarrhea. The randomized, double-blind, active-controlled study enrolled 300 subjects at 58 sites in the U.S., Canada and the UK. It was designed to determine the safety and effectiveness of tolevamer at two dose levels (6-3 g per day), versus an oral dose of vancomycin. Results were reported at the European Congress of Clinical Microbiology and Infectious Diseases meeting in Prague. Based on these results, Genzyme is now planning phase III trials to begin in early 2005.

Hemispherx Biopharma reported positive results from a phase III trial investigating Ampligen, an immunomodulator and antiviral drug for the treatment of Chronic Fatigue Syndrome (CFS). Results demonstrated a statistically significant increase in physical performance as measured by Treadmill Exercise Tolerance Testing compared with placebo, the study’s primary endpoint. Data showed that subjects on Ampligen had an improved exercise treadmill performance of 19.4% compared with 5.1% for subjects given placebo. The multi-center, double-blind, randomized, placebo-controlled pivotal study enrolled 234 subjects with CFS at 12 sites in the U.S. The study was designed to test the efficacy and safety of Ampligen at 400 mg twice weekly for 40 weeks. Results were reported at the 17th International Conference on Antiviral Research in Tucson, Arizona.

Vicuron Pharmaceuticals reported positive results from a phase II trial investigating dalbavancin, an injectable glycopeptide antibiotic for the treatment of catheter-related bloodstream infections (CR-BSI). The primary endpoint showed an overall response rate of 87% in dalbavancin treated subjects compared with 50% in those treated twice daily with vancomycin. The randomized, comparative, open-label study enrolled 67 subjects with CR-BSI in North America. Subjects received two doses of dalbavancin one week apart or vancomycin twice daily for 14 days. The primary endpoint was based on a composite of clinical and microbiological responses measured at 21 days after treatment. Results were reported at the 14th annual European Congress of Clinical Microbiology and Infectious Diseases meeting in Prague.

November 3, 2003

Genzyme reported positive preliminary results from a phase II trial investigating tolevamer sodium, a polymer therapy for the treatment of Clostridium difficile associated diarrhea (CDAD). Results showed that 22% of subjects taking vancomycin experienced recurrence of CDAD, while 19% taking tolevamer (6g) recurred. Data showed the study reached the primary endpoint of non-inferiority to vancomycin with respect to time to resolution of diarrhea. Tolevamer was found to be similar to vancomycin in median days to resolution of diarrhea and demonstrated a risk ratio relative to vancomycin of 0.98. The randomized, double blind, active-controlled study trial enrolled 289 subjects at 58 sites in the U.S. Canada and the United Kingdom. The study was designed to determine the safety and effectiveness of tolevamer capsules at two dose levels (6g & 3g), versus vancomycin.

Idenix Pharmaceuticals and the University of Hong Kong reported positive results from a phase IIb trial investigating telbivudine (L-deoxythymidine or LdT), a selective nucleoside for the treatment of hepatitis B virus (HBV). Results showed that telbivudine achieved significantly better suppression of HBV compared to lamivudine monotherapy, the current standard of care. Subjects receiving telbivudine achieved an average reduction in viral load of one million fold. The randomized, double-blind, international study enrolled 104 treatment-naive subjects with HBV. Results were reported at the 54th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD) in Boston.

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.