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Overall safety of relamorelin in adults with diabetic gastroparesis: Analysis of phase 2a and 2b trial data
Author(s) -
Camilleri Michael,
Lembo Anthony,
McCallum Richard,
Tourkodimitris Stavros,
Kemps Lara,
Miller Matthew B.,
Bertelsen Kirk,
Iacob Alexandru
Publication year - 2020
Publication title -
alimentary pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.308
H-Index - 177
eISSN - 1365-2036
pISSN - 0269-2813
DOI - 10.1111/apt.15711
Subject(s) - tolerability , medicine , placebo , adverse effect , type 2 diabetes , diabetes mellitus , glycated haemoglobin , gastroenterology , endocrinology , pathology , alternative medicine
Summary Background Relamorelin, a pentapeptide ghrelin receptor agonist, accelerated gastric emptying significantly and improved symptoms in adults with diabetic gastroparesis in phase 2 trials. Aim To assess the safety and tolerability of relamorelin across phase 2 trials. Methods Safety assessments in patients aged 18‐75 years (weight, adverse events [AEs] and laboratory tests) from two randomised, double‐blind phase 2 trials (NCT01571297, NCT02357420; results published previously) were reviewed descriptively. Analysis of covariance assessed treatment effect on glycated haemoglobin (HbA1c) and blood glucose post hoc . Phase 2a and 2b trial durations were, respectively, 4 weeks (relamorelin 10 µg once or twice daily [b.d.] or placebo b.d.) and 12 weeks (relamorelin 10, 30 or 100 µg or placebo b.d.) with 1‐ and 2‐week, single‐blind placebo run‐ins. Results Among 204 phase 2a and 393 phase 2b patients, respectively, 67% and 62% were female, and 88% and 89% had type 2 diabetes. Proportions of patients reporting serious AEs were similar across treatment groups, as were those with ≥1 treatment‐emergent AE (TEAE). TEAE‐related discontinuations were proportionally higher in relamorelin groups than placebo. Of 12 serious TEAEs in phase 2a, none occurred in >1 patient. In phase 2b, five serious TEAEs were reported in >1 patient, and one (100 µg) died (urosepsis), all unrelated to relamorelin. In phase 2b, increased HbA1c and fasting blood glucose levels were dose‐related ( P < 0.0001 and P = 0.0043, respectively). Conclusions Relamorelin showed acceptable safety and tolerability in phase 2 trials. Relamorelin may elevate blood glucose: this should be managed proactively in relamorelin‐treated patients.