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Safety, Tolerability, and Physiological Effects of AXA1665, a Novel Composition of Amino Acids, in Subjects With Child-Pugh A and B Cirrhosis.

ABSTRACT:

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.

SUBMITTER: Chakravarthy MV 

PROVIDER: S-EPMC7423914 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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Safety, Tolerability, and Physiological Effects of AXA1665, a Novel Composition of Amino Acids, in Subjects With Child-Pugh A and B Cirrhosis.

Chakravarthy Manu V MV   Neutel Joel J   Confer Scharmen S   Zhao Peng P   Tatsuta Noriaki N   Rebello Sam S   Comb William C WC   Hamill Michael M   Tramontin Tony T   Carroll Sean S   Afeyan Raffi R   Sanyal Arun J AJ  

Clinical and translational gastroenterology 20200801 8

<h4>Introduction</h4>AXA1665 is a novel investigational amino acid (AA) composition specifically designed to impact AA imbalance, ammoniagenesis, and dysregulated anabolic activity associated with cirrhosis.<h4>Methods</h4>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  ...[more]