@article{4bf97add4ff04b8eb46cff66f6ce25f7,
title = "Effect of Oral CNSA-001 (sepiapterin, PTC923) on gastric accommodation in women with diabetic gastroparesis: A randomized, placebo-controlled, Phase 2 trial",
abstract = "Aims: Diabetic gastroparesis may be associated with impaired nitric oxide metabolism and reduced tetrahydrobiopterin (BH4) synthesis. Oral treatment with CNSA-001 (sepiapterin, currently known as PTC923) increased BH4 levels in humans in a previous study. This Phase 2 study evaluated CNSA-001 in women with diabetic gastroparesis. Methods: Non-pregnant diabetic women with moderate/severe symptomatic gastroparesis, delayed gastric emptying, and impaired gastric accommodation (nutrient satiety testing) were randomized to 10 mg/kg BID CNSA-001 or matching placebo for 14 days. The primary endpoint was change in gastric accommodation (maximal tolerated liquid meal volume) at 14- and 28-days' follow-up. Results: Gastric accommodation improved in CNSA-001-treated vs. placebo-treated subjects at 28 days (least squares mean [LSM] difference: 98 [95% CI 36 to 161], p = 0.0042). Subjects' ratings of bloating, fullness, nausea, and pain were lower vs. baseline in the CNSA-001 group at 14 and 28 days, though these improvements were not observed consistently in placebo-treated subjects. There were no significant group differences in upper gastrointestinal symptom scores, and in gastric emptying breath test parameters. CNSA-001 was well tolerated, with no withdrawals for adverse events. Conclusions: CNSA-001 improved gastric accommodation in women with diabetic gastroparesis. Further evaluation of CNSA-001 in gastroparesis is warranted; ClinicalTrials.gov number, NCT03712124.",
keywords = "CNSA-001, Gastric accommodation, Gastroparesis, Nitric oxide, PTC923, Sepiapterin",
author = "Abell, {Thomas L.} and Garcia, {Lazaro M.} and Wiener, {Gregory J.} and Wo, {John M.} and Bulat, {Robert S.} and Neil Smith",
note = "Funding Information: Editorial assistance was provided by Dr Mike Gwilt, GT Communications, and funded by PTC Therapeutics Inc. Declaration of competing interest: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Drs. Abell, Garcia, Wiener, Wo, and Bulat are Principal Investigators at study sites, and NS is an employee of the pharmaceutical sponsor of the study. Accordingly, all contributed to the design and conduct of the study. NS led the statistical analysis of the study data, and initial drafting of this article, to which all authors contributed subsequently. Dr. Abell is a consultant for Censa and Nuvaira, and investigator for Alnylam, PTC Therapeutics Inc., Allergan, Vanda and Cin-dome. He is a writer for Med Study and a reviewer for UpToDate. He is the founder of ADEPT-GI that holds IP on bio-electric therapies and on autonomic and enteric profiling. Dr. Garcia is an investigator for PTC Therapeutics Inc. Dr. Wiener is an investigator for PTC Therapeutics Inc. Dr. Wo is an investigator for PTC Therapeutics Inc., Allergan, Vanda and Progenity. Dr. Bulat is an investigator for PTC Therapeutics Inc. NS is an employee of PTC Therapeutics Inc. which acquired Censa Pharmaceuticals Inc., the pharmaceutical sponsor of PTC923 responsible for funding this study. Funding Information: Declaration of competing interest: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Drs. Abell, Garcia, Wiener, Wo, and Bulat are Principal Investigators at study sites, and NS is an employee of the pharmaceutical sponsor of the study. Accordingly, all contributed to the design and conduct of the study. NS led the statistical analysis of the study data, and initial drafting of this article, to which all authors contributed subsequently. Dr. Abell is a consultant for Censa and Nuvaira, and investigator for Alnylam, PTC Therapeutics Inc., Allergan, Vanda and Cin-dome. He is a writer for Med Study and a reviewer for UpToDate. He is the founder of ADEPT-GI that holds IP on bio-electric therapies and on autonomic and enteric profiling. Dr. Garcia is an investigator for PTC Therapeutics Inc. Dr. Wiener is an investigator for PTC Therapeutics Inc. Dr. Wo is an investigator for PTC Therapeutics Inc., Allergan, Vanda and Progenity. Dr. Bulat is an investigator for PTC Therapeutics Inc. NS is an employee of PTC Therapeutics Inc. which acquired Censa Pharmaceuticals Inc., the pharmaceutical sponsor of PTC923 responsible for funding this study. Funding Information: Editorial assistance was provided by Dr Mike Gwilt, GT Communications, and funded by PTC Therapeutics Inc. Publisher Copyright: {\textcopyright} 2021",
year = "2021",
month = sep,
doi = "10.1016/j.jdiacomp.2021.107961",
language = "English (US)",
volume = "35",
journal = "Journal of Diabetes and its Complications",
issn = "1056-8727",
publisher = "Elsevier Inc.",
number = "9",
}