Indikation: Diabetes - Typ II

January 18, 2016

Mesoblast issued results of a phase II trial of mesenchymal precursor cells (MPCs) for the treatment of type 2 diabetes. The randomized, single-blind, placebo-controlled study was conducted across 18 sites in the U.S. and evaluated the effects of a single intravenous infusion of 0.3, 1 or 2 million MPCs/kilogram (kg) or placebo over 12 weeks in 61 patients with a mean diabetes duration of 10 years. A single MPC infusion ranging from 0.3 to 2 million MPCs/kg was safe and well-tolerated, with no treatment-related adverse events, and no serious adverse events over the 12-week study period. There were no anti-human leukocyte antigen antibody immune responses against MPC donor antigens identified in any subject. Following a single intravenous MPC infusion, there was an improvement in glycemic control as evidenced by a decrease at all timepoints after week one in HbA1c in MPC-treated patients compared with an increase in HbA1c in placebo-controlled patients. The highest dose (2 million MPCs/kg) showed the greatest overall reduction in HbA1c, with a peak decrease of 0.4% at eight weeks compared with placebo (p<0.05). In the less well-controlled subjects, as defined by a baseline HbA1c greater than 8%, a 0.6% decrease in HbA1c was seen at eight weeks in the high dose cohort compared with placebo. The clinical target of good glycemic control, HbA1c less than 7%, was achieved by 5/15 (33%) subjects in the MPC 2 million/ kg group v. 0/15 (0%) in the placebo group, (p<0.05).

December 7, 2015

Eli Lilly released results of a phase III trial of Trulicity (dulaglutide) 1.5 mg plus a sulfonylurea for lowering hemoglobin A1C. The randomized, double-blind, placebo-controlled, 24-week study compared the efficacy and safety of once-weekly Trulicity 1.5mg to placebo in sulfonylurea-treated patients with type 2 diabetes and inadequate glycemic control. The primary objective of the study, in 299 patients with a mean baseline A1C of 8.4%, was to demonstrate superiority of Trulicity 1.5mg to placebo on A1C reduction in patients treated with sulfonylurea monotherapy. At the primary endpoint of 24 weeks, Trulicity 1.5mg plus sulfonylurea provided superior A1C reduction from baseline (-1.38%) compared to sulfonylurea with placebo (-0.11%). Significantly more patients treated with Trulicity 1.5mg plus a sulfonylurea achieved an A1C of less than 7% (55.3%) compared to sulfonylurea with placebo (18.9%); and Trulicity plus sulfonylurea significantly reduced fasting serum glucose levels compared to sulfonylurea with placebo (-30.60mg/dL v. +2.93mg/dL). As a secondary endpoint of the study, Trulicity plus a sulfonylurea showed weight reduction from baseline (-0.91kg), though the difference compared to sulfonylurea with placebo did not reach statistical significance.

November 9, 2015

Alizé Pharma has reported positive results from a phase Ib trial of AZP-531 in type 2 diabetes (T2D). The trial was the last stage in an overall phase I program performed in 112 healthy volunteers, obese subjects and T2D patients. The T2D trial was a double-blind 14- day multiple ascending dose study. The aim of the trial was to assess the effect of three doses of AZP-531 v. placebo in a total of 36 uncontrolled T2D patients treated with metformin as a single agent. The results showed an improvement in the metabolic status of patients in all groups, including placebo, suggesting a study effect in an uncontrolled T2D patient population. Notwithstanding this study effect, there was a better metabolic improvement with AZP-531. In particular, at the highest doses being studied (60mcg/kg QD and 30mcg/kg BID), HbA1c was significantly decreased with a mean decrease of -0.4% in 14 days (p<0.01 v. baseline). Body weight also significantly decreased at the highest dose (60mcg/kg QD) with a mean decrease of -2.1kg in 14 days (p<0.001 v. baseline). Administration of AZP-531 for 14 days was well-tolerated across all doses. The single and multiple-dose PK parameters were comparable to those observed in healthy and obese study populations from previous AZP-531 trials.

November 18, 2013

Elcelyx Therapeutics reported results of a 12-week phase IIb study of NewMet, a delayed-release formulation of metformin for the treatment of patients with type 2 diabetes. The randomized, 240-patient, multicenter, double-blind, dose-finding trial evaluated NewMet once-daily doses of 1000mg, 800mg and 600mg compared to placebo. There also were two unblinded reference arms with Glucophage XR dosed once-daily at 1000mg and 2000mg. All NewMet arms showed efficacy comparable to or greater than 1000mg of Glucophage XR. The NewMet 1000mg dose was approximately 50% more effective than 1000mg of Glucophage XR and approximately 70% as effective as 2000mg of Glucophage XR. A dose response trend was observed across the three NewMet doses, indicating higher doses of NewMet may provide greater efficacy. All doses of NewMet and Glucophage XR prevented the rise in HbA1c seen with placebo due to washout of previous anti-diabetic medications. All doses of NewMet and Glucophage XR were well-tolerated and there were no meaningful weight changes observed.

August 26, 2013

Boehringer Ingelheim Pharmaceuticals and Eli Lilly released results of a phase III study of dipeptidyl peptidase-4 (DPP-4) inhibitor linagliptin (TRADJENTA) for the treatment of type 2 diabetes (T2D). The 24-week, double-blind, parallel-group, multinational study was conducted in 33 centers in five countries (Australia, Canada, Denmark, The Netherlands and Sweden). A total of 241 elderly people (=70 years; mean age, 74.9 years) with T2D were randomized to receive linagliptin 5mg (n=162) or placebo (n=79), in addition to existing glucose-lowering drugs (i.e. metformin and/or sulfonylurea and/or basal insulin). Key results from the study showed that the mean change from baseline in HbA1c with linagliptin was -0.64% (p<0.0001) after 24 weeks, which showed superiority v. placebo, adjusted for a mean 0.04% HbA1C increase for placebo. In addition, analysis of a secondary endpoint showed that the placebo-adjusted mean reduction in fasting plasma glucose from baseline with linagliptin was -20.7mg/dL (-1.15 mmol/L; p<0.0001). The percentage of people with any adverse event was the same in both treatment groups (75.9%).

MannKind reported results of a phase III study of AFREZZA Inhalation Powder in patients with type 2 diabetes. The study was a double-blind, placebo-controlled study involving 353 patients with type 2 diabetes whose disease was inadequately controlled on metformin with or without a second or third oral medication. Patients were studied at sites in the U.S., Russia, Ukraine and Brazil. After a six-week run-in period, patients entered a 24-week treatment period in which they were randomized to one of two groups where, in addition to their oral medication, they received either AFREZZA Inhalation Powder (177 patients) or Technosphere Inhalation Powder (placebo, 176 patients). Mean A1c levels decreased by 0.82% in the AFREZZA group compared to a decrease of 0.42% in the comparator oral-therapy group, a statistically significant (p<0.0001) change. The incidence of serious adverse events was lower in the AFREZZA group (2.8%) compared to the comparator oraltherapy group (5.1%).

July 1, 2013

Boehringer Ingelheim Pharmaceuticals and Eli Lilly released results from a phase III trial of empagliflozin for the treatment of drug-naive adults with type 2 diabetes (T2D). The 24-week, randomized, double-blind, placebo-controlled trial enrolled 14,500 multinational patients. Patients were randomized to receive empagliflozin 10mg (n=224) or 25mg per day (n=224), sitagliptin 100mg per day (n=223) or placebo (n=228) for 24 weeks. Patients with average blood glucose (HbA1c) more than 10% (n=87) received open-label empagliflozin 25mg per day for 24 weeks. Results of the primary endpoint showed placebo-adjusted reductions in HbA1c from baseline to week 24 of 0.74% and 0.85% (p<0.001) for the 10mg and 25mg doses, respectively. After 24 weeks, body weight decreased by 4.25 lbs and 4.74 lbs (p<0.001) in patients treated with empagliflozin 10mg and 25mg, respectively, versus placebo. Changes in diastolic blood pressure were statistically significant for the empagliflozin 25mg treatment group only (1.9 mmHg reduction v. 0.5 mmHg reduction for placebo, p=0.030).

April 22, 2013

Eli Lilly released results from a phase III trial of dulaglutide for the treatment of type 2 diabetes. This randomized, 52-week, open-label study, AWARD-4, enrolled 884 patients with type 2 diabetes. Subjects received 1.5mg dulaglutide once-weekly plus insulin lispro, or insulin glargine plus insulin lispro. Primary efficacy endpoints of non-inferiority to insulin glargine, as measured by the reduction of hemoglobin A1c (HbA1c) levels at the 1.5 mg dose, were met. Furthermore, results showed that the dulaglutide and insulin lispro arm demonstrated statistically superior reduction in HbA1c from baseline compared to insulin glargine in combination with insulin lispro at 26 weeks. Dulaglutide was well tolerated. The most frequent adverse events were gastrointestinal-related. Based on these results, Eli Lilly expects to submit dulaglutide to regulatory authorities in 2013.

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