ROME, September 8 /PRNewswire/ --
-- For European Medical Media Only
ROME, September 8 /PRNewswire/ --
-- For Presentation Times and Detailed Study Information Please Refer to Notes to Editors
Results from two 24-week Phase III studies presented at the 44th European Association for the Study of Diabetes Annual Meeting demonstrate that saxagliptin, an investigational selective inhibitor with extended binding to the dipeptidyl peptidase-4 (DPP-4) enzyme, in development by Bristol-Myers Squibb Company (NYSE: BMY) and AstraZeneca, produced significant reductions across all key measures of glucose control studied (glycosylated hemoglobin level (A1C), fasting plasma glucose (FPG) and postprandial glucose (PPG)) when added to a sulphonylurea (SU) or a thiazolidinedione (TZD) in people with inadequately controlled type 2 diabetes, compared with placebo added to either an increased dose of SU or a stable dose of a TZD. The addition of saxagliptin to SU and TZD was well tolerated during the course of the trials, and more people were able to achieve target A1C of less than 7 percent versus the comparators.
"A large number of people with type 2 diabetes have difficulty managing their disease and remain uncontrolled on present therapies," said Professor Anthony Barnett, University of Birmingham and Heart of England NHS Foundation Trust. "Given the growing number of people with diabetes around the world, it is important to investigate new therapeutic options as we fight this chronic disease."
The companies submitted a New Drug Application to the U.S. Food & Drug Administration (FDA) on 30th June, which was officially filed by the FDA, and a Marketing Authorization Application to the European Medicines Agency (EMEA) on 1st July, which has been accepted for review by the Agency. The submissions are based on data from a comprehensive clinical trial programme conducted in addition to standard therapies, as well as in treatment-naïve patients as a monotherapy. The clinical trial programme included studies that evaluated the drug at up to 80 times the proposed usual clinical dose of 5 mg, once daily. The six core Phase III trials assessing the efficacy and safety profile of saxagliptin involved more than 4,000 patients, including 3,000 who were treated with saxagliptin.
Notes to editors
Study results in detail:
1. Phase III - Poster Presentation: Saxagliptin added to sulphonylurea
Presentation: 8 September 2008, 13h30 - 14h30 Central European Time (CET)
This study was designed to assess the addition of saxagliptin to a submaximal dose of sulphonylurea versus increasing the dose of sulphonylurea. The data represent findings from a 24-week, randomized, double-blind, placebo-controlled, three-arm, parallel-group, multi-center international study of 768 people with type 2 diabetes (ages 18-77) whose A1C level was greater than or equal to 7.5 percent and less than or equal to 10 percent after at least two months on a submaximal dose of a sulphonylurea at enrolment. After a four-week, open-label, lead-in phase, where all individuals received glyburide (GLY) 7.5 mg, individuals were randomized to one of three separate treatment arms: saxagliptin 2.5 mg + GLY 7.5 mg (n=248), saxagliptin 5 mg + GLY 7.5 mg (n=253), or placebo + GLY 10 mg (n=267), given daily. In the placebo + GLY 10 mg group, blinded up-titration of GLY was allowed to a maximum total daily dose of 15 mg (UP-GLY). Approximately 92 percent of individuals in the UP-GLY group reached the maximum total daily dose during the study.
The primary endpoint of the study was the change from baseline to week 24 in A1C. The secondary endpoints of the study included changes from baseline to week 24 in FPG, PPG response, as indicated by PPG area under the curve (AUC) from 0 - 180 minutes during an oral glucose tolerance test (OGTT) and the proportion of individuals achieving the American Diabetes Association recommended A1C target of less than 7 percent.
Study results
After 24 weeks, individuals in the saxagliptin + GLY treatment arms demonstrated a significant adjusted mean change in A1C from baseline of -0.5 percent for saxagliptin 2.5 mg + GLY and -0.6 percent for saxagliptin 5 mg + GLY, compared with +0.1 percent for UP-GLY (p-value less than 0.0001 for both treatment arms). Reductions were observed at four weeks, the earliest assessment point in the study. More than twice as many individuals receiving saxagliptin + GLY achieved A1C of less than 7 percent compared to UP-GLY: 22.4 percent for saxagliptin 2.5 mg + GLY and 22.8 percent for saxagliptin 5 mg + GLY, compared with 9.1 percent for UP-GLY (p-value less than 0.0001 for both treatment arms).
Individuals treated with saxagliptin + GLY demonstrated an adjusted mean change in FPG from baseline to week 24: -7.1 mg/dL for saxagliptin 2.5 mg + GLY and
--9.7 mg/dL for saxagliptin 5 mg + GLY, compared with +0.7 mg/dL for UP-GLY (p-value less than or equal to 0.0218 for both treatment arms). Reductions were observed at two weeks, the earliest assessment point in the study. The two saxagliptin + GLY treatment arms also demonstrated adjusted mean decreases in PPG from baseline to week 24, compared with UP-GLY (p-value less than 0.0001 for both treatment arms).
Over 24 weeks, the reported hypoglycemic events were: 13.3 percent for saxagliptin 2.5 mg + GLY, 14.6 percent for saxagliptin 5 mg + GLY and 10.1 percent for UP-GLY (p-value equals NS). The occurrence of confirmed hypoglycemia (symptoms of hypoglycemia with a fingerstick glucose less than or equal to 50 mg/dL) was: 2.4 percent for saxagliptin 2.5 mg + GLY, 0.8 percent for saxagliptin 5 mg + GLY and 0.7 percent for UP-GLY.
Incidence of adverse events was: 75.0 percent for saxagliptin 2.5 mg + GLY, 72.3 percent for saxagliptin 5 mg + GLY and 76.8 percent for UP-GLY. The percentages of the most commonly reported (greater than or equal to 5 percent) adverse events for the saxagliptin 2.5 mg + GLY, saxagliptin 5 mg + GLY and UP-GLY treatment arms, respectively, were: urinary tract infection (5.2, 10.7, 8.2); nasopharyngitis (5.6, 5.9, 6.7); upper respiratory tract infection (4.4, 6.3, 6.7); influenza (5.2, 4.0, 6.0); diarrhoea (5.6, 4.0, 5.2); back pain (4.8, 5.9, 4.5); pain in extremity (4.4, 3.6, 5.6); headache (7.7, 7.5, 5.6); cough (5.2, 4.0, 4.9); and hypertension (3.6, 6.3, 2.2).
2. Phase III - Poster Presentation: Saxagliptin added to thiazolidinedione
Presentation: 8 September 2008, 13h30 - 14h30 Central European Time (CET)
This study was designed to assess the addition of saxagliptin to thiazolidinedione versus the addition of placebo to TZD. The data represent findings from a 24-week, multinational, randomized, placebo-controlled, three-arm, parallel group, double-blind study of 565 people with type 2 diabetes (ages 18-77), whose A1C level was greater than or equal to 7 percent and less than or equal to 10.5 percent and who were receiving stable TZD monotherapy (pioglitazone 30 mg or 45 mg, or rosiglitazone 4 mg or 8 mg, total daily dose) for at least 12 weeks prior to screening. After a two-week lead- in period during which all individuals continued on their previous pioglitazone or rosiglitazone dose, individuals were randomized to one of three treatment arms: saxagliptin 2.5 mg (n=195), saxagliptin 5 mg (n=186) or placebo (n=184), given once daily, in addition to continuing on their previously prescribed TZD dose.
(CONTINUA)
