DOMPERIDONE IN THE MANAGEMENT OF SYMPTOMS OF DIABETIC GASTROPARESIS -EFFICACY, TOLERABILITY, AND QUALITY-OF-LIFE OUTCOMES IN A MULTICENTERCONTROLLED TRIAL

The purpose of this clinical study was to determine the efficacy, tole rability, and impact on quality of life of domperidone-a specific peri pherally acting dopamine antagonist-in the management of symptoms of g astroparesis, a common and potentially debilitating condition in patie nts with diabetes mellitus. In the first phase of this multicenter, tw o-phase withdrawal study, 257 diabetic patients with symptoms of gastr oparesis of at least 6 months' duration received domperidone 20 mg QID in a single-masked fashion for 4 weeks;. Efficacy was evaluated using a four-point rating scale (0 = none, 1 = mild, 2 = moderate, 3 = seve re) for each of the following symptoms: nausea, abdominal distention/b loating, early satiety vomiting, and abdominal pain. At the end of the first phase, patients with sufficient improvement in their total symp tom score (a score less than or equal to 6 and a decrease in score of greater than or equal to 5 units from the baseline [selection] visit) were eligible for the 4-week, randomized, placebo-controlled, double-m asked withdrawal phase of the study. The impact of domperidone on qual ity of life was del-ermined using the Medical Outcomes Study Short For m-36 (SF-36). Of 269 patients with data from the single-masked phase, 208 (77%) qualified for entry into the double-masked phase based on a statistically significant improvement in total symptom score, from a m ean score of 10.32 at baseline (initial visit) to 3.79 after 4 weeks o f single-masked domperidone therapy. During the double-masked phase, p atients in the placebo group had significantly greater deterioration i n total symptom scores compared with patients in the domperidone group (mean changes of 1.84 and 0.85, respectively). Similar significant di fferences in favor of domperidone were seen in the secondary efficacy variables tie, patients' diary scores and global assessments of sympto ms). The tolerability profile of domperidone was similar to that of pl acebo. Patients who responded to domperidone experienced significant i mprovements in quality of life, as indicated by the SF-36 physical and mental component summary scores. During the double-masked phase, pati ents who were randomized to placebo experienced a significant deterior ation in the physical component summary score compared with patients i n the domperidone group. The results of this study suggest that domper idone 20 mg QID provides significant improvement in the upper gastroin testinal symptoms of diabetic gastroparesis and is well tolerated in p atients with this condition.