Randomised clinical trial: ghrelin agonist TZP-101 relieves gastroparesis associated with severe nausea and vomiting--randomised clinical study subset data.

Abstract

BACKGROUND:

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.

AIM:

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.

METHODS:

Patients were hospitalised and received four single daily 30-min infusions of one of six TZP-101 doses (range 20-600 μg/kg) or placebo. Efficacy was assessed by symptom improvement.

RESULTS:

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 μg/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 μg/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).

CONCLUSIONS:

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.

• Authors: J M Wo, N Ejskjaer, P M Hellström, R A Malik, J C Pezzullo, L Shaughnessy, P Charlton, G Kosutic, R W McCallum
• Journal: Alimentary pharmacology & therapeutics (Aliment Pharmacol Ther) Vol. 33 Issue 6 Pg. 679-88 (Mar 2011) ISSN: 1365-2036 [Electronic] England
• PMID: 21214610 (Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: © 2011 Blackwell Publishing Ltd.

Chemical References

• Gastrointestinal Agents
• Ghrelin
• Macrocyclic Compounds
• ulimorelin

Topics

• Adolescent
• Adult
• Aged
• Aged, 80 and over
• Diabetes Complications (drug therapy)
• Dose-Response Relationship, Drug
• Double-Blind Method
• Female
• Gastrointestinal Agents (administration & dosage, adverse effects, therapeutic use)
• Gastroparesis (complications, drug therapy)
• Ghrelin (agonists)
• Humans
• Macrocyclic Compounds (administration & dosage, adverse effects, therapeutic use)
• Male
• Middle Aged
• Nausea (etiology)
• Severity of Illness Index
• Treatment Outcome
• Vomiting (etiology)
• Young Adult