Diet and Nutrition

February 8, 2016

Zafgen issued results of a pivotal, double-blind, placebo-controlled, phase III trial evaluating the safety and efficacy of beloranib for Prader-Willi syndrome (PWS). The bestPWS ZAF-311 study randomized 107 patients to receive twice-weekly subcutaneous injections of either 2.4mg or 1.8mg of beloranib or placebo. Seventy-four patients completed the full 26 weeks of treatment per the trial protocol, and 27 patients completed at least 75% of the randomized treatment period prior to the suspension of dosing in the trial in October 2015. There were six patients who discontinued early. The co-primary efficacy endpoints for this trial were improvement in hyperphagia-related behaviors and reduction in body weight. Patients in the trial were on average 20 years old, had an average BMI of 40kg/m2 and an average hyperphagia total score of 16.9, consistent with moderate to severe hyperphagia, at the beginning of randomized treatment. Treatment with the 2.4mg and the 1.8mg doses of beloranib resulted in reductions of hyperphagia-related behaviors of 7 units (p=0.0001) and 6.3 units (p=0.0003) relative to placebo, respectively, as measured by the Hyperphagia Questionnaire for Clinical Trials (HQ-CT). Patients randomized to receive placebo displayed substantial (4.15%) gain in body weight over the course of the six months of randomized treatment. Patients treated with beloranib, in contrast to placebo, lost weight, with the 2.4mg dose arm displaying a 5.3% reduction from baseline, with a placebo-adjusted weight loss of 9.45%. In December 2015, the FDA placed the beloranib IND application on complete clinical hold due to an imbalance in severe venous thromboembolic events, including two patient deaths. Zafgen plans to present to the FDA the efficacy and safety data from the bestPWS ZAF-311 study, data from the phase IIb trial of beloranib in severe obesity complicated by type 2 diabetes and a proposal for a risk mitigation strategy for beloranib in PWS.

February 7, 2011

NPS Pharmaceuticals issued results from a phase III trial of Gattex for the treatment of short bowel syndrome (SBS). This international, double-blind, placebo-controlled study, dubbed STEPS (Study of TEduglutide in PN-dependent Short-bowel syndrome), enrolled 86 adults with SBS and dependent on parenteral nutrition (PN). The subjects received once daily subcutaneous dosing of 0.05 mg/kg of Gattex or placebo over a 24-week treatment period. The primary efficacy endpoint was the percentage of subjects who achieved a 20 percent or greater reduction in weekly PN volume at week 20 and maintained that response at week 24, when compared to baseline. In an intent-to-treat analysis, 63% of the Gattex arm responded versus 30% of the placebo arm (p≡0.002). The subjects treated with Gattex also achieved significantly greater reductions in weekly PN volume versus placebo. On average, the subjects in the Gattex arm experienced a 4.4 liter reduction in weekly PN volume from a pre-treatment baseline of 12.9 liters; those in the placebo arm experienced a 2.3 liter reduction from a pre-treatment baseline of 13.2 liters (p less than or equal to 0.001). Gattex was well tolerated.

March 31, 2008

NPS issued positive results from a phase III extension study of Gattex for the treatment of short bowel syndrome in subjects who are dependent upon parenteral nutrition (PN). This extension study enrolled sixty five of the seventy one subjects who had completed a twenty-four week randomized phase III study that evaluated low-dose Gattex (0.05 mg/kg/day) and high-dose Gattex (0.10 mg/kg/day) versus placebo. The primary objective of the study was to assess the long-term safety and tolerability of daily Gattex dosing for up to fifty two weeks. Sixty-eight percent of the subjects who had received low-dose Gattex therapy and continued on low-dose Gattex, and 52% of the subjects who had received high-dose Gattex therapy and continued on high-dose Gattex achieved a 20% or greater reduction in PN after a total of fifty two weeks of therapy. Subjects treated with low-dose Gattex showed a mean 51% reduction in PN volume from pretreatment baseline to the end of fifty two weeks (p< 0.001) and those treated with high-dose Gattex experienced a mean 24% reduction (p< 0.001). All of the subjects (100%) who had previously received placebo in the phase III study and were randomized to low-dose Gattex therapy, and two out of seven subjects who had previously received placebo in the phase III study and were randomized to high-dose Gattex therapy, achieved a 20% or greater reduction in PN after a total of twenty eight weeks of therapy in the extension study. Two low-dose subjects and one high-dose subject who were able to discontinue PN in the phase III study remained off PN after fifty two weeks of Gattex therapy. Treatment was well tolerated in both dose groups, with no statistical differences in the rate of adverse events compared to the placebo group, with the exception of injection site reactions. Based on positive phase III results, NPS is meeting with the FDA to discuss the path towards regulatory approval.

October 22, 2007

NPS Pharmaceuticals reported positive results from a phase III trial of Gattex for the treatment of short bowel syndrome. This randomized, double blind trial enrolled 83 subjects, 71 of whom completed the study. Following an evaluation period and a period of stabilization, the subjects received daily subcutaneous injections of Gattex (0.05 mg or 0.10 mg/kg of body weight) or a placebo for six months. The primary endpoint was a reduction in parenteral nutrition of at least 20% from baseline to weeks 16 and 24. This endpoint was reached with statistical significance in the low dose Gattex arm, with 45.7% of the subjects achieving this goal (p-value 0.007). In the high dose Gattex arm 25% of the subjects attained this endpoint (p-value 0.161) versus 6% in the placebo arm. Treatment was well tolerated, with no statistically significant differences in adverse events between the two Gattex arms and placebo. Based on the results, NPS plans to meet with the FDA to discuss the next steps towards US regulatory approval.

December 1, 2006

Prostrakan reported positive results from a phase III trial of Sancuso for the treatment of emesis caused by chemotherapy, radiotherapy or anesthetics. This randomized, parallel group, double-blind, double-dummy study enrolled 641 subjects receiving moderately (ME) or highly emetogenic (HE) multi-day chemotherapy, across international sites. The patch was applied 24 to 48 hours before the first dose of chemotherapy, and kept in place for 7 days. Oral granisetron (2 mg) was administered daily for the duration of the chemotherapy regimen, one hour before each dose of chemotherapy. The primary endpoint was the proportion of subjetcs achieving no vomiting/retching, only mild nausea and no rescue medication from the first administration until 24 hours after the start of the last days administration of multi-day chemotherapy. Efficacy was established in 60.2% of subjects in the Sancuso arm and 64.8% of subjects receiving oral granisetron (difference -4.89%; 95% confidence interval -12.91% to +3.13%).

February 19, 2002

Study results indicate that taking Novo Nordisk's Prandin (repaglinide) tablets with three main daily meals produced greater improvements in certain measures of glycemic control than twice-daily dosing. In the double-blind trial, 19 type 2 diabetic subjects received either a 0.25mg dose of repaglinide before each of the three meals, or a 0.5mg dose before breakfast and a 0.25mg dose before the evening meal. Mealtime dosing was doubled after two weeks to a total daily dose of 1.5mg in both groups. Repaglinide tablets are known as Prandin in the United States, NovoNorm in Europe and Gluconorm in Canada.