The pivotal inTandem1 phase 3 clinical trial of Sotagliflozin met its primary endpoint, showing a statistically significant reduction in A1C at 24 weeks in patients with type 1 diabetes on a background of optimized Insulin.
Top-line results from the phase 3 study showed that patients treated with Sotagliflozin had a mean A1C reduction from baseline of 0.43% on 200 mg once daily Sotagliflozin dose ( p less than 0.001 ) and a reduction of 0.49% on 400 mg once daily Sotagliflozin dose ( p less than 0.001 ) as compared to a reduction of 0.08% on placebo after 24 weeks of treatment, meeting the study’s primary endpoint.
This statistically significant and clinically meaningful improvement in A1C for both doses of Sotagliflozin was achieved without an increase in severe hypoglycemia, one of the most prevalent serious health challenges in type 1 diabetes, which was seen less frequently in both treatment arms than placebo.
The double-blind, placebo controlled, phase 3 study known as inTandem1 enrolled 793 patients in the United States and Canada with type 1 diabetes on Insulin pump or multiple daily injection therapy who had an A1C level entering the study between 7.0% and 11.0%, which corresponds to an estimated average blood sugar of 154 mg/dl to 269 mg/dl ( 8.6 mmol/l to 15.0 mmol/l ).
The three-arm study evaluated two doses of Sotagliflozin, 200mg and 400mg, each taken once daily before the first meal of the day, against placebo.
Prior to randomization, Insulin was optimized for all patients over a six-week period, with the objective of improving glycemic control using insulin alone.
After completion of this optimization period, patients were maintained on optimized Insulin and randomized to one of two doses of Sotagliflozin or placebo, and their baseline, post-optimization A1C was measured.
The mean baseline A1C level at the time of randomization after the six-week optimization period was 7.6% for all three dose arms.
The primary endpoint of the study was change in A1C from baseline after a 24-week period of treatment.
The trial has a double-blind long term extension of 28-weeks, with a total treatment duration of 52-weeks.
There were 268 patients in the placebo arm, 263 patients in the 200mg dose arm and 262 patients in the 400mg dose arm.
The overall mean placebo adjusted A1C reduction was 0.35% in the 200mg dose arm ( p less than 0.001 ) and 0.41% in the 400mg dose arm ( p less than 0.001 ).
Sotagliflozin was generally well tolerated. Across all three dose arms ( placebo, 200mg, 400mg ), the incidence of treatment-emergent adverse events ( AEs ) were 67.5%, 67.3% and 71.0%, respectively; the incidence of serious AEs ( SAEs ) were 3.4%, 3.8% and 6.9%, respectively; and discontinuation due to AEs were 1.5%, 1.1% and 3.8%, respectively.
There were no reported deaths in the study.
Two primary safety concerns for patients with type 1 diabetes are severe hypoglycemia and diabetic ketoacidosis ( DKA ).
The number of patients with severe hypoglycemic events during the 24-week treatment period was 18 ( 6.7% ), 11 ( 4.2% ), and 12 ( 4.6% ) in the placebo, 200mg and 400mg dose arms, respectively. The number of patients with DKA events during the 24-week treatment period was 0 ( 0.0% ), 3 ( 1.1% ), and 8 ( 3.1% ) in the placebo, 200mg and 400mg dose arms, respectively.
Sotagliflozin is a first-in-class, oral dual inhibitor of two proteins responsible for glucose regulation known as sodium-glucose co-transporter types 1 and 2 ( SGLT1 and SGLT2 ).
SGLT1 is responsible for glucose absorption in the gastrointestinal tract, and SGLT2 is responsible for glucose reabsorption by the kidney.
Sotagliflozin has been shown in a phase 2 study to improve glycemic control in people with type 1 diabetes while reducing their need for mealtime Insulin. ( Xagena )
Source: Lexicon, 2016