In a phase 2b study, the oral agent ENT-01 was safe and significantly improved constipation and possibly neurologic symptoms in 150 participants with Parkinson disease (PD). The agent inhibits α-synuclein (αS) aggregation within enteric neurons, which is associated with constipation in patients with PD and may play a role in dementia, psychosis, and other neurologic symptoms associated with PD.
The randomized, open-label, placebo-controlled trial escalated daily doses of ENT-101 to either their prokinetic dose, the maximum dose of 250 mg, or the tolerability limit. The study used a primary efficacy endpoint of the number of complete spontaneous bowel movements (CSBMs) per week and neurologic endpoints of dementia (assessed using the Mini-Mental State Examination, or MMSE) and psychosis (assessed using the Scale for the Assessment of Positive Symptoms adapted for PD, or SAPS-PD).
The study produced these results: “The weekly CSBM rate increased from 0.7 to 3.2 in the ENT-01 group versus 0.7 to 1.2 in the placebo group (P < 0.001). Improvement in secondary endpoints included SBMs (P = 0.002), stool consistency (P < 0.001), ease of passage (P = 0.006), and laxative use (P = 0.041). In patients with dementia, MMSE scores improved by 3.4 points 6 weeks after treatment in the ENT-01 group (n = 14) versus 2.0 points in the placebo group (n = 14). Among patients with psychosis, SAPS-PD scores improved from 6.5 to 1.7 six weeks after treatment in the ENT-01 group (n = 5) and from 6.3 to 4.4 in the placebo group (n = 6). ENT-01 was well tolerated, with no deaths or drug-related serious adverse events. Adverse events were predominantly gastrointestinal, including nausea (34.4% [ENT-01] vs. 5.3% [placebo]; P < 0.001) and diarrhea (19.4% [ENT-01] vs. 5.3% [placebo]; P = 0.016).”