Safety, Tolerability, and Physiological Effects of AXA1665, a Novel Composition of Amino Acids, in Subjects With Child-Pugh A and B Cirrhosis
| Autor: | Sean M. Carroll, Tony Tramontin, Michael Hamill, Manu V. Chakravarthy, Peng Zhao, Sam Rebello, Noriaki Tatsuta, Scharmen Confer, Joel Neutel, Arun J. Sanyal, William Comb, Raffi Afeyan |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Adult
Liver Cirrhosis Male medicine.medical_specialty Cirrhosis Anabolism Gastroenterology Severity of Illness Index Article law.invention 03 medical and health sciences 0302 clinical medicine Randomized controlled trial law Ammonia Internal medicine Severity of illness medicine Humans Aged chemistry.chemical_classification Cross-Over Studies business.industry Drugs Investigational Middle Aged medicine.disease Crossover study Amino acid Solutions Treatment Outcome chemistry Tolerability Liver 030220 oncology & carcinogenesis 030211 gastroenterology & hepatology Composition (visual arts) Female business Amino Acids Branched-Chain |
| Zdroj: | Clinical and Translational Gastroenterology |
| ISSN: | 2155-384X |
| Popis: | INTRODUCTION: AXA1665 is a novel investigational amino acid (AA) composition specifically designed to impact AA imbalance, ammoniagenesis, and dysregulated anabolic activity associated with cirrhosis. METHODS: This 2-part study examined AXA1665 effects on safety, tolerability, and hepatic/muscle physiology in subjects with Child–Pugh A and B cirrhosis. Part 1 established plasma ammonia and AA concentration baselines with a standardized protein supplement. Part 2 included two 15-day domiciled periods separated by a 14-day washout. In period 1, subjects were randomly distributed to 2 groups: AXA1665 14.7 g t.i.d. (group 1) or control t.i.d. (group 2). In period 2, subjects from group 1 crossed over to control and those in group 2 crossed over to AXA1665 4.9 g t.i.d. All subjects were maintained on standard of care (standardized meals; 30-minute daily, supervised, mandatory physical activity; and daily late-evening snack). RESULTS: In parts 1 and 2, 23 and 17 participants were enrolled, respectively. Dose-dependent increases were observed in plasma concentrations of AXA1665-constituent AAs. Fasted branched-chain AA-to-aromatic AA and valine-to-phenylalanine ratios were both increased (AXA1665 14.7 g t.i.d. control-adjusted change: 44.3% ± 2.7% and 47.2% ± 3.9%, respectively; P < 0.0001). Despite provision of additional nitrogen, mean fasted plasma ammonia concentration at day 15 numerically decreased (−21.1% in AXA1665 14.7 g t.i.d. vs −3.8% in control; P > 0.05). AXA1665 14.7 g t.i.d. produced a leaner body composition and significantly decreased Liver Frailty Index at day 15 vs control (−0.70 ± 0.15 vs −0.14 ± 0.17; P < 0.05). AXA1665 was safe and well tolerated. DISCUSSION: AXA1665 has potential to mitigate core metabolic derangements associated with cirrhosis. |
| Databáze: | OpenAIRE |
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