ENT-01 relieves constipation in patients with Parkinson’s disease

Oral ENT-01 safely and significantly improves constipation in patients with Parkinson’s disease (PD), results of a phase IIb study have shown.

A total of 150 patients with PD and constipation were randomized to receive either ENT-01 or placebo daily for up to 25 days. The investigators escalated daily dosing to the prokinetic dose, the maximum dose (250 mg), or the tolerability limit, followed by a washout period, after baseline assessment of constipation severity.

The weekly rate of complete spontaneous bowel movements (SBMs) improved from 0.7 to 3.2 in the ENT-01 group compared with 0.7 to 1.2 in the placebo group (p<0.001). SBMs (p=0.002), stool consistency (p<0.001), ease of passage (p=0.006), and laxative use (p=0.041) also improved.

In patients with dementia, the Mini-Mental State Examination scores improved by 3.4 points 6 weeks after treatment with ENT-01 compared with 2.0 points with placebo. Among those with psychosis, scores in the Scale for the Assessment of Positive Symptoms adapted for PD improved from 6.5 to 1.7 after 6 weeks of treatment in the ENT-01 group and from 6.3 to 4.4 in the placebo group.

ENT-01 was well tolerated, with no deaths or drug-related serious adverse events (AEs) occurring. Most AEs were gastrointestinal, including nausea (34.4 percent with ENT-01 vs 5.3 percent with placebo; p>0.001) and diarrhoea (19.4 percent with ENT-01 vs 5.3 percent with placebo; p=0.016).

Future studies should investigate longer treatment periods, according to the authors.

“PD is associated with α-synuclein (αS) aggregation within enteric neurons,” the authors said. “ENT-01 inhibits the formation of αS aggregates and improved constipation in an open-label study in patients with PD.”