Safety, tolerability, pharmacokinetics and pharmacodynamics of multiple ascending doses of the novel long-acting glucagon analogue HM15136 in overweight and obese patients with co-morbidities
- Author(s)
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Shin, Wonjung, Hompesch, Marcus, Byeon, JinHee, Kang, Seohyun, Choi, Jaehyuk, Baek, Seungjae
- Issued Date
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2023-06
- DOI
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10.1111/dom.15162
- URI
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https://scholarworks.unist.ac.kr/handle/201301/64787
- Citation
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DIABETES OBESITY & METABOLISM, v.25, no.9, pp.2723 - 2733
- Abstract
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Aim To evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of multiple ascending doses of the novel long-acting glucagon analogue HM15136 in overweight/obese patients with co-morbidities, with and without type 2 diabetes (T2D).Materials and Methods This was a phase 1, double-blind, randomized, placebo-controlled, two-part trial with a 12-week treatment period of once-weekly subcutaneous HM15136 (0.02/0.04/0.06 mg/kg). Part 1 included patients with dyslipidaemia and/or hypertension and no T2D. Part 2 included patients with dyslipidaemia and/or hypertension plus T2D.Results In part 1, 23/27 (85.2%) patients receiving HM15136 and all patients receiving placebo (9/9 [100%]) experienced a treatment-emergent adverse event (TEAE). Five of 27 (18.5%) patients receiving HM15136 developed anti-HM15136 antibodies. Dose-dependent increases in mean HM15136 serum concentration and fasting plasma glucose (FPG) were observed, as were dose-dependent weight reductions of 0.5%/2.3%/2.6% at doses of 0.02/0.04/0.06 mg/kg, respectively. In part 2, 8/12 (66.7%) patients receiving HM15136 and all patients receiving placebo (4/4 [100.0%]) reported a TEAE. Two (16.7%) patients developed anti-HM15136 antibodies. Dose-dependent increases in mean HM15136 serum concentration were observed. FPG of more than 200 mg/dL was reported in 4/9 (44.4%) and 2/3 (66.7%) patients receiving 0.02 and 0.06 mg/kg, respectively. The 0.06 mg/kg dose was not tolerated in part 2 because of hyperglycaemia. Patients receiving 0.02 mg/kg showed a 0.9% weight reduction. No serious TEAEs leading to discontinuation were reported in either study part.Conclusions This study of HM15136 provides a preliminary safety and tolerability profile with initial insights into its efficacy profile.
- Publisher
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WILEY
- ISSN
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1462-8902
- Keyword (Author)
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glucagon, hypoglycaemia, pharmacodynamics, pharmacokinetics
- Keyword
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RECEPTOR
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