title: A phase 2a, randomized, double-blind 28-day study of TZP-102 a ghrelin receptor agonist for diabetic gastroparesis.
abstract: BACKGROUND
  Gastroparesis causes significant morbidity and treatment options are limited. TZP-102 a novel, macrocyclic, selective, oral ghrelin receptor agonist, was evaluated in a randomized, double-blind, placebo-controlled trial in patients with diabetic gastroparesis.
  
  
  METHODS
  A total of 92 outpatients were randomized to once-daily administrations of 10-mg (n = 22), 20-mg (n = 21), 40-mg (n = 23) TZP-102 or placebo (n = 26). The primary endpoint was the change from baseline in gastric half-emptying time (T(½)) utilizing (13)C-breath test methodology and secondary endpoints included symptom improvement using patient-reported gastroparesis symptom scores (PAGI-SYM questionnaire) and patient and physician overall treatment evaluations (OTE).
  
  
  RESULTS
  Gastric T½ changes were not statistically significant between TZP-102 and placebo after 28 days of treatment at any dose. Clinical improvements (-1.0 to -1.4 point mean decrease in symptom severity) occurred in the Gastroparesis Cardinal Symptom Index (GCSI) component of the PAGI-SYM, which was significant vs placebo for all TZP-102 doses combined. Improvements became evident after 1 week of treatment. Significantly, more patients given TZP-102 (any dose) had a 50% reduction in baseline GCSI score (28.8%vs 7.7% placebo). Safety profiles were similar across groups. All TZP-102 doses were well-tolerated with no adverse cardiac, weight, or glucose control outcomes.
  
  
  CONCLUSIONS
  TZP-102 for 28 days, at doses of 10-40 mg once daily, was well-tolerated and resulted in a reduction in symptoms of gastroparesis. The lack of correlation between symptom improvement and gastric emptying change is consistent with previous studies in diabetic gastroparesis, and emphasizes the value of patient-defined outcomes in determining therapeutic benefit.
authors.affiliation: Aarhus University Hospital, Aarhus, Denmark.
authors.forename: N
authors.initials: N
authors.lastname: Ejskjaer
authors.forename: J M
authors.initials: JM
authors.lastname: Wo
authors.forename: T
authors.initials: T
authors.lastname: Esfandyari
authors.forename: M
authors.initials: M
authors.lastname: Mazen Jamal
authors.forename: G
authors.initials: G
authors.lastname: Dimcevski
authors.forename: L
authors.initials: L
authors.lastname: Tarnow
authors.forename: R A
authors.initials: RA
authors.lastname: Malik
authors.forename: P M
authors.initials: PM
authors.lastname: Hellström
authors.forename: E
authors.initials: E
authors.lastname: Mondou
authors.forename: J
authors.initials: J
authors.lastname: Quinn
authors.forename: F
authors.initials: F
authors.lastname: Rousseau
authors.forename: R W
authors.initials: RW
authors.lastname: McCallum
mesh_terms: D000328:Adult; D000368:Aged; D048909:Diabetes Complications / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D005746:Gastric Emptying / Q000187:drug effects; D018589:Gastroparesis / Q000188:drug therapy* / Q000209:etiology; D006801:Humans; D047028:Macrocyclic Compounds / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D054440:Receptors, Ghrelin / Q000819:agonists*; D055815:Young Adult
chemical_list: D047028:Macrocyclic Compounds; D054440:Receptors, Ghrelin