Effect of Oral CNSA-001 (sepiapterin, PTC923) on gastric accommodation in women with diabetic gastroparesis: A randomized, placebo-controlled, Phase 2 trial.
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 10mg/kg BID CNSA-001 or matching placebo for 14days. 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 28days (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 28days, 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.
['Abell|Thomas L|TL|', 'Garcia|Lazaro M|LM|', 'Wiener|Gregory J|GJ|', 'Wo|John M|JM|', 'Bulat|Robert S|RS|', 'Smith|Neil|N|']
CNSA-001 Sepiapterin PTC923 Gastric accommodation Gastroparesis Nitric oxide