Once‐weekly administration of a long‐acting fibroblast growth factor 21 analogue modulates lipids, bone turnover markers, blood pressure and body weight differently in obese people with hypertriglyceridaemia and in non‐human primates

• DOI: 10.1111/dom.13023
• Publication Date: 2017-06-02T03:22:43Z
• Authors: Albert M. Kim; Veena R. Somayaji; Jennifer Q. Dong; Timothy P. Rolph; Yan Weng; Jeffrey R. Chabot; Kathryn E. Gropp; Saswata Talukdar; Roberto A. Calle
• Keywords: Tolerability; Pharmacodynamics; N-terminal telopeptide; Bone remodeling

Aims To assess the safety, tolerability, pharmacokinetics and pharmacodynamics of PF ‐05231023, a long‐acting fibroblast growth factor 21 ( FGF 21) analogue, in obese people with hypertriglyceridaemia on atorvastatin, or without type 2 diabetes. Methods Participants received ‐05231023 placebo intravenously once weekly for 4 weeks. Safety (12‐lead ECG s, vital signs, adverse events [ AEs ], laboratory tests) longitudinal weight assessments were performed. Blood samples collected pharmacokinetic pharmacodynamic analyses. Cardiovascular safety studies also conducted telemetered rats monkeys. pressure BP ; mean, systolic diastolic) ECGs monitored. Results A total 107 randomized. significantly decreased mean placebo‐adjusted fasting triglycerides (day 25, 33%‐43%) increased HDL cholesterol 15.7%‐28.6%) adiponectin 1574 to 3272 ng/mL) across all doses, significant changes body −0.45% −1.21%). Modest decreases from baseline observed N‐terminal propeptides 1 collagen (P1NP) day although C‐telopeptide cross‐linking (CTX‐1) minimally. Systolic, diastolic , pulse rate dose‐ time‐related manner. There 5 serious AE s (one treatment‐related) no deaths. Three participants discontinued because s. The majority gastrointestinal. heart rats, but not Conclusions Once‐weekly lowered markedly absence loss, modest markers bone homeostasis. This is first report showing increases humans after pharmacological administration molecule.