PMID- 32301137
OWN - NLM
STAT- MEDLINE
DCOM- 20201119
LR  - 20201119
IS  - 1365-2036 (Electronic)
IS  - 0269-2813 (Print)
IS  - 0269-2813 (Linking)
VI  - 51
IP  - 11
DP  - 2020 Jun
TI  - Overall safety of relamorelin in adults with diabetic gastroparesis: Analysis of 
      phase 2a and 2b trial data.
PG  - 1139-1148
LID - 10.1111/apt.15711 [doi]
AB  - 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 microg once or twice daily [b.d.] or placebo b.d.) and 12 weeks (relamorelin 10, 
      30 or 100 microg 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 microg) 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.
CI  - (c) The Authors. Alimentary Pharmacology & Therapeutics published by John Wiley & 
      Sons Ltd.
FAU - Camilleri, Michael
AU  - Camilleri M
AUID- ORCID: 0000-0001-6472-7514
AD  - Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA.
FAU - Lembo, Anthony
AU  - Lembo A
AUID- ORCID: 0000-0002-4479-1188
AD  - Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard 
      Medical School, Boston, MA, USA.
FAU - McCallum, Richard
AU  - McCallum R
AD  - Division of Gastroenterology, Texas Tech University Health Sciences Center, El 
      Paso, TX, USA.
FAU - Tourkodimitris, Stavros
AU  - Tourkodimitris S
AD  - Biostatistics, Allergan plc, Madison, NJ, USA.
FAU - Kemps, Lara
AU  - Kemps L
AD  - Clinical Development, Allergan plc, Madison, NJ, USA.
FAU - Miller, Matthew B
AU  - Miller MB
AD  - Chemistry, Manufacturing and Controls, Allergan plc, Madison, NJ, USA.
FAU - Bertelsen, Kirk
AU  - Bertelsen K
AD  - Clinical Pharmacology, Allergan plc, Madison, NJ, USA.
FAU - Iacob, Alexandru
AU  - Iacob A
AD  - Medical Safety, Allergan plc, Madison, NJ, USA.
LA  - eng
SI  - ClinicalTrials.gov/NCT01571297
SI  - ClinicalTrials.gov/NCT02357420
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20200417
PL  - England
TA  - Aliment Pharmacol Ther
JT  - Alimentary pharmacology & therapeutics
JID - 8707234
RN  - 0 (Blood Glucose)
RN  - 0 (Oligopeptides)
RN  - BIW199E18V (relamorelin)
SB  - IM
CIN - Aliment Pharmacol Ther. 2020 Aug;52(3):546-547. PMID: 32656828
CIN - Aliment Pharmacol Ther. 2020 Aug;52(3):545-546. PMID: 32656829
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Blood Glucose/metabolism
MH  - Body Weight/drug effects
MH  - Diabetes Mellitus, Type 2/*complications/drug therapy/epidemiology
MH  - Diabetic Neuropathies/*drug therapy/epidemiology/etiology
MH  - Double-Blind Method
MH  - Female
MH  - Gastric Emptying/drug effects
MH  - Gastroparesis/*drug therapy/epidemiology
MH  - Humans
MH  - Injections, Subcutaneous
MH  - Male
MH  - Middle Aged
MH  - Oligopeptides/*administration & dosage/*adverse effects
MH  - Retrospective Studies
MH  - Young Adult
PMC - PMC7318559
EDAT- 2020/04/18 06:00
MHDA- 2020/11/20 06:00
PMCR- 2020/06/26
CRDT- 2020/04/18 06:00
PHST- 2019/08/28 00:00 [received]
PHST- 2019/09/17 00:00 [revised]
PHST- 2020/03/16 00:00 [accepted]
PHST- 2020/04/18 06:00 [pubmed]
PHST- 2020/11/20 06:00 [medline]
PHST- 2020/04/18 06:00 [entrez]
PHST- 2020/06/26 00:00 [pmc-release]
AID - APT15711 [pii]
AID - 10.1111/apt.15711 [doi]
PST - ppublish
SO  - Aliment Pharmacol Ther. 2020 Jun;51(11):1139-1148. doi: 10.1111/apt.15711. Epub 
      2020 Apr 17.