Limited therapeutic options exist for severe gastroparesis, where severe nausea and vomiting can lead to weight loss, dehydration and malnutrition due to inadequate caloric and fluid intake. TZP-101 (ulimorelin) is a ghrelin receptor agonist that accelerates gastric emptying and improves upper gastrointestinal symptoms in diabetic patients with gastroparesis.
To assess effects of TZP-101 in diabetic gastroparesis patients with severe nausea/vomiting and baseline severity scores of >= 3.5 (range: 0-5) on the Gastroparesis Cardinal Symptom Index (GCSI) Nausea/Vomiting subscale.
Patients were hospitalised and received four single daily 30-min infusions of one of six TZP-101 doses (range 20-600 mu g/kg) or placebo. Efficacy was assessed by symptom improvement.
At baseline, 23 patients had a mean severity score for GCSI Nausea/Vomiting of 4.45 +/- 0.44. Statistically significant improvements over placebo occurred in the 80 mu g/kg group for end of treatment changes from baseline in GCSI Nausea/Vomiting subscale (reduction in score of -3.82 +/- 0.76, P = 0.011) and the GCSI Total score (-3.14 +/- 0.78, P = 0.016) and were maintained at the 30-day follow-up assessment (-2.02 +/- 1.63, P = 0.073 and -1.99 +/- 1.33, P = 0.032 respectively). The proportion of days with vomiting was reduced significantly (P = 0.05) in the 80 mu g/kg group (mean of 1.2 days of vomiting for four treatment days) compared with placebo (mean of 3.2 days of vomiting across 4 treatment days).
TZP-101 substantially reduced the frequency and severity of nausea and vomiting as well as overall gastroparesis symptoms. The results are consistent with gastrointestinal motility effects of TZP-101, supporting further investigation of TZP-101 in the management of severe gastroparesis.
2011. Vol. 33, no 6, 679-688 p.