Overall safety of relamorelin in adults with diabetic gastroparesis: Analysis of phase 2a and 2b trial data

Michael Camilleri, Anthony Lembo, Richard McCallum, Stavros Tourkodimitris, Lara Kemps, Matthew B Miller, Kirk Bertelsen, Alexandru Iacob, Michael Camilleri, Anthony Lembo, Richard McCallum, Stavros Tourkodimitris, Lara Kemps, Matthew B Miller, Kirk Bertelsen, Alexandru Iacob

Abstract

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.

© The Authors. Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd.

Figures

FIGURE 1
FIGURE 1
Phase 2a and 2b trial designs. AE, adverse event; b.d., twice daily; q.d. pm, once daily in the evening; RLM, relamorelin
FIGURE 2
FIGURE 2
Proportion of patients in each treatment group with ≥1 TEAE. b.d., twice daily; q.d. pm, once daily in the evening; RLM, relamorelin; TEAE, treatment‐emergent adverse event
FIGURE 3
FIGURE 3
Mean change from baseline in percentage HbA1c values for each treatment group in the phase 2b trial. HbA1c values were measured in %. b.d., twice daily; CFB, change from baseline; HbA1c, glycated haemoglobin; RLM, relamorelin; SD, standard deviation
FIGURE 4
FIGURE 4
Change from baseline of fasting blood glucose values for each treatment group in the phase 2a and phase 2b trials. To convert blood glucose values from units of mmol/L to units of mg/dL, multiply by 18.0. In phase 2a, CFB values were 4.14, 17.48 and 10.99 mg/dL for the placebo, relamorelin 10 µg q.d. pm and 10 µg b.d. groups. In phase 2b, CFB values were 25.04, 32.61, 43.24 and 56.39 mg/dL for the placebo, relamorelin 10, 30 and 100 µg groups, respectively. b.d., twice daily; CFB, change from baseline; q.d. pm, once daily in the evening; RLM, relamorelin; SD, standard deviation

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