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Clinical Trial
. 2018 Oct;84(10):2325-2335.
doi: 10.1111/bcp.13688. Epub 2018 Aug 7.

MEDI0382, a GLP-1/glucagon receptor dual agonist, meets safety and tolerability endpoints in a single-dose, healthy-subject, randomized, Phase 1 study

Philip D Ambery  1 , Sebastian Klammt  2 , Maximillian G Posch  2 , Marcella Petrone  1 , Wenji Pu  3 , Cristina Rondinone  3 , Lutz Jermutus  1 , Boaz Hirshberg  3
Affiliations
Clinical Trial

MEDI0382, a GLP-1/glucagon receptor dual agonist, meets safety and tolerability endpoints in a single-dose, healthy-subject, randomized, Phase 1 study

Philip D Ambery et al. Br J Clin Pharmacol. 2018 Oct.

Abstract

Aims: MEDI0382 is a balanced glucagon-like peptide-1/glucagon receptor dual agonist under development for the treatment of type 2 diabetes mellitus and non-alcoholic steatohepatitis. The primary objective was to assess the safety of MEDI0382 in healthy subjects.

Methods: In this placebo-controlled, double-blind, Phase 1 study, healthy subjects (aged 18-45 years) were randomized (3:1) to receive a single subcutaneous dose of MEDI0382 or placebo after ≥8 h of fasting. The study consisted of six cohorts that received study drug at 5 μg, 10 μg, 30 μg, 100 μg, 150 μg or 300 μg. The primary objective was safety and tolerability. Secondary endpoints included assessments of pharmacokinetics and immunogenicity. All subjects were followed for up to 28 days.

Results: A total of 36 subjects received MEDI0382 (n = 6 per cohort) and 12 subjects received placebo (n = 2 per cohort). Treatment-emergent adverse events (TEAEs) occurred more frequently with MEDI0382 vs. placebo, which was mostly due to an increased occurrence at MEDI0382 doses ≥150 μg. All TEAEs were mild or moderate in severity. The most common TEAEs were vomiting, nausea and dizziness. There appeared to be a dose-dependent increase in heart rate with MEDI0382 treatment. MEDI0382 showed linear pharmacokinetic profile (time to maximum plasma concentration: 4.50-9.00 h; elimination half-life: 9.54-12.07 h). No immunogenicity was observed in the study.

Conclusions: In this single-dose, Phase 1 study in healthy subjects, the safety and pharmacokinetic profiles of MEDI0382 support once-daily dosing and further clinical development of MEDI0382.

Keywords: Phase 1; diabetes; drug safety; pharmacokinetics-pharmacodynamics; randomized controlled trial.

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Figures

Figure 1
Figure 1
Planned and actual study doses and cohort population sizes
Figure 2
Figure 2
Subject disposition
Figure 3
Figure 3
Effect of study drug treatment on heart rate (mean ± SEM) BPM, beats per minute; D, Day; h, hour; PD, pre‐dose
Figure 4
Figure 4
Dose proportionality of AUC0–∞ (A) and C max (B) observed with MEDI0382 treatment AUC0–∞, area under the concentration–time curve from time zero to infinity; C max, maximum observed plasma concentration
Figure 5
Figure 5
Effect of study drug treatment and food intake on median glucose levels over time
See this image and copyright information in PMC

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