Background: MEDI0382 is an oxyntomodulin-like peptide with targeted GLP-1/glucagon receptor activity that is under development for type 2 diabetes mellitus. This study was conducted in subjects of Japanese and Chinese descent to facilitate expansion of its global clinical development in Japan and China.
Methods: This phase 1, randomized, blinded study evaluated the safety, tolerability, pharmacokinetics, and immunogenicity of single subcutaneous (SC) doses of MEDI0382. In part A, 24 subjects of Japanese descent across 3 cohorts (8 per cohort) received single SC doses of MEDI0382 at a dose of 50 µg (cohort 1), 100 µg (cohort 2), or 150 µg (cohort 3) or placebo in a 3:1 ratio. In part B, 8 subjects of Chinese descent received a single SC dose of MEDI0382 at 100 µg or placebo in a 3:1 ratio (cohort 4).
Results: In part A, the incidence of treatment-emergent adverse events (TEAEs) was highest in the 150-μg group (5 of 6 subjects). In part B, 2 of 6 subjects in the MEDI0382 group reported TEAEs. Nausea, headache, and vomiting were most common. A trend of increased pulse rate post-dose was seen in subjects of Japanese descent in the MEDI0382 100- and 150-µg groups. No clinically meaningful changes from baseline in vital signs were observed in part B. Median tmax values were 6.15-8.16 h at doses of 50-150 μg, both in subjects of Japanese and Chinese descent. In part A subjects receiving MEDI0382 100 and 150 µg, postprandial mean glucose levels remained closer to baseline levels as compared with changes seen with MEDI0382 50 µg or placebo.
Discussion: The safety profile of single doses of MEDI0382 at doses of 50, 100, and 150 µg supports its further development in subjects of Japanese and Chinese descent. The pharmacokinetic data for MEDI0382 in the range of 50-150 µg also support its further clinical development in subjects of Japanese and Chinese descent.
D. Robertson: Employee; Self; AstraZeneca. Employee; Spouse/Partner; GlaxoSmithKline plc. Stock/Shareholder; Self; AstraZeneca. M. Petrone: Employee; Self; MedImmune. L. Tsai: Employee; Self; MedImmune. Other Relationship; Self; AstraZeneca. R.A. Gasser: Employee; Self; AstraZeneca, MedImmune.