title: 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.
  
  
  OBJECTIVE
  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.affiliation: Division of Gastroenterology, Hepatology and Nutrition, University of Louisville School of Medicine, Louisville, KY, USA.
authors.forename: J M
authors.initials: JM
authors.lastname: Wo
authors.forename: N
authors.initials: N
authors.lastname: Ejskjaer
authors.forename: P M
authors.initials: PM
authors.lastname: Hellström
authors.forename: R A
authors.initials: RA
authors.lastname: Malik
authors.forename: J C
authors.initials: JC
authors.lastname: Pezzullo
authors.forename: L
authors.initials: L
authors.lastname: Shaughnessy
authors.forename: P
authors.initials: P
authors.lastname: Charlton
authors.forename: G
authors.initials: G
authors.lastname: Kosutic
authors.forename: R W
authors.initials: RW
authors.lastname: McCallum
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D048909:Diabetes Complications / Q000188:drug therapy; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D005765:Gastrointestinal Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D018589:Gastroparesis / Q000150:complications / Q000188:drug therapy*; D054439:Ghrelin / Q000819:agonists; D006801:Humans; D047028:Macrocyclic Compounds / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009325:Nausea / Q000209:etiology*; D012720:Severity of Illness Index; D016896:Treatment Outcome; D014839:Vomiting / Q000209:etiology*; D055815:Young Adult
chemical_list: D005765:Gastrointestinal Agents; D054439:Ghrelin; D047028:Macrocyclic Compounds; C528884:ulimorelin