A DOUBLE-MASKED PLACEBO-CONTROLLED TRIAL ASSESSING EFFECTS OF VARIOUSDOSES OF BTS-67-582, A NOVEL INSULINOTROPIC AGENT, ON FASTING HYPERGLYCEMIA IN NIDDM PATIENTS

OBJECTIVE - To determine the effect over a 4-week period of varying do ses of BTS 67 582, a novel nonsulfonylurea insulinotropic agent, on Ea sting plasma glucose (FPG) levels in sulfonylurea-responsive NIDDM pat ients. RESEARCH DESIGN AND METHODS - This was a 12-week multicenter, d ouble-masked, placebo-controlled trial. Patients entered a 4-week stab ilization period during which they received their previously prescribe d sulfonylurea. Qualified patients (FPG less than or equal to 10 mmol/ l) then entered a di-week sulfonylurea withdrawal single-masked placeb o run-in period. Qualified patients (FPG 8.9-16.7 mmol/l) were randomi zed to either placebo (n = 14), 50 mg b.i.d. BTS 67 582 (n = 18), 250 mg b.i.d. BTS 67 582 (n = 18), 500 mg b.i.d. BTS 67 582 (n = 15), 100 mg q.d. BTS 67 582 (n = 17), or 500 mg q.d. BTS 67 582 (n = 16). The p rimary efficacy variables were mean changes from baseline in FPG and f ructosamine (FRUC). Additional variables included mean changes from ba seline in HbA(1c), fasting serum insulin (FSI), and fasting serum C-pe ptide. RESULTS - After 4 weeks of treatment, all BTS 67 582 dose group s showed a decrease from baseline in FPG and FRUC compared with the pl acebo group. The treatment groups of 250 mg b.i.d. (-3.1 +/- 0.7 mmol/ l), 500 mg b.i.d. (-2.3 +/- 0.6 mmol/l), and 500 mg q.d. (-1.2 +/- 0.7 mmol/l) had statistically significant (P < 0.05) decreases in FPG com pared with placebo (0.7 +/- 0.6 mmol/l). Similarly, there were statist ically significant (P < 0.05) decreases from baseline in FRUC for the 250 mg b.i.d (-55 +/- 10 mu mol/l), 500 mg b.i.d. (-40 +/- 12 mu mol/l ), and 500 mg q.d. (-13 +/- 9 mu mol/l) treatment groups compared with placebo (15 +/- 11 mu mol/l). Although the treatment period was only 4 weeks in duration, there were also significant differences (P < 0.05 ) in the HbA(1c) changes from baseline for the 250 mg b.i.d (0.0 +/- 0 .1%) and 500 mg b.i.d. (-0.2 +/- 0.1%) treatment groups compared with placebo (0.6 +/- 0.2%). There were no significant differences among th e treatment groups in the changes from baseline for FSI or C-peptide l evels. The most frequently reported side effects were headache, asthen ia, infection, and thirst, and the incidence of these events as well a s the incidence of study drug discontinuation was comparable in all tr eatment groups including placebo. CONCLUSIONS - Four weeks of treatmen t with BTS 67 582 at doses of 250 mg b.i.d. and 500 mg b.i.d. in NIDDM patients was effective in reducing FPG and FRUC, with significant res ults also seen for HbA(1c). The drug was well tolerated with an incide nce of discontinuations and laboratory side-effect safety profiles com parable to placebo. BTS 67 582 is a safe and effective oral treatment for NIDDM patients.