Relamorelin effective, safe for diabetic patients with gastroparesis
Relamorelin appears to be effective in reducing core symptoms of gastroparesis, as well as improving overall composite symptom severity score and accelerated gastric emptying (GE), in diabetic patients with moderate to severe gastroparesis, according to the results of a phase IIB trial.
Researchers randomly assigned 393 patients with gastroparesis to groups given placebo (n=104) or relamorelin at a dose of 10 μg (n=98), 30 μg (n=109) or 100 μg (n=82) twice daily for 12 weeks, following a 2-week, single-blind, placebo run-in period. The median age of the cohort was 58.2 years, majority were female (62.3 percent), and 9.9 percent had type 1 diabetes. Median body mass index and HbA1c level were 31.4 kg/m2 and 7.6 percent, respectively.
All patients presented with 13C-spirulina GE breath test T1/2 values of ≥79 min (with 89.8 percent delayed relative to 90th percentile of normal, 85.75 minutes), recent vomiting and gastroparesis cardinal symptom index-daily diary scores of ≥2.6.
Patients kept daily e-diaries to record vomiting frequency and gastroparesis symptom (nausea, abdominal pain, postprandial fullness and bloating) scores on a scale of 0 to 10. Endpoints investigated included change from baseline in vomiting frequency, composite gastroparesis symptom severity score, GE and safety. Analysis was performed using longitudinal, mixed-effects model with repeated measures, including baseline and baseline-by-week interaction values as covariates.
Results showed that patients on relamorelin had a 75-percent reduction from baseline in vomiting frequency, but this difference was not significant when compared with the placebo group. A significant reduction was seen in all four symptoms of gastroparesis (composite or individual symptoms) over the 12-week study period in all three relamorelin dose groups vs placebo (p<0.05 for all).
Compared with placebo, relamorelin also significantly accelerated GE from baseline (p<0.05 for the 10 and 30 μg groups; p=0.051 for the 100 μg group). Dose-related worsening of glycaemic control was observed in 14.5 percent of patients who received relamorelin, with some requiring insulin or other diabetes drug dosage adjustments.