This is a phase II, multicenter, double-blind, placebo-controlled trial to evaluate the efficacy and safety of velusetrag once a day, compared to placebo, in subjects with CIPO.

Inclusion Criteria:

• Subjects with history of chronic idiopathic intestinal pseudo-obstruction or CIPO secondary to neurodegenerative or demyelinating disease.
• Subjects with estimated oral caloric intake of at least 30% of the daily age- and sex-recommended caloric intake.
• Subjects with at least 2 out of 4 CIPO gastrointestinal symptoms each of the 2 with a score ≥3 (on a 0 to 4 scale) at Day -1
• Subjects accepting to provide and legally capable of providing free and informed consent to all procedures included in the protocol.
• All sexually active male participants who are partner of women of childbearing potential must use condom during intercourse until the 90th day after the end of the entire study.
• Female participants are eligible if they are: i) of non-childbearing potential or ii) of childbearing potential with a negative pregnancy test result at screening and randomization AND agreeing to use a highly effective method of contraception (i.e., with failure rate of less than 1% per year) until the end of the entire study.

Exclusion Criteria:

• Subjects with primary CIPO or CIPO secondary to other known endocrine/metabolic, autoimmune diseases and neurologic conditions other than neurodegenerative or demyelinating diseases.
• Subjects with conditions characterized by mechanical intestinal obstruction.
• Nasogastric tube, gastrostomy tube, or jejunostomy feeding tube in place at randomization or planned throughout the duration of the study, or artificial food need scale stage 3.
• Presence of untreated clinically relevant thyroid dysfunction or known thyroid dysfunction not well controlled by treatment deemed clinically significant by the Investigator.
• Subjects with history of diabetes at screening.
• Clinically significant ECG abnormalities at screening and randomization.
• Screening ECG with a QTcF >450 msec in males or >470 msec in females or family history of sudden cardiac death.
• Subjects requiring a low galactose diet.
• Hypersensitivity or documented intolerance to lactulose, lactose or any excipient of the lactulose preparation to be used for L-BT.
• History of sensitivity to velusetrag, or any of the velusetrag or placebo excipients.
• Use of scopolamine or erythromycin within 2 weeks prior to screening and/or planned throughout the duration of the study.
• Use of 5-HT4 receptor agonists within 5 days prior to randomization and/or planned throughout the duration of the study
• Use of opioids within 8 weeks from screening and/or planned throughout the duration of the study.
• Received strong cytochrome P450-isozyme 3A4 (CYP3A4) inhibitors within 2 weeks prior to screening and/or planned throughout the duration of the study.
• Received strong P-glycoprotein (P-gp) transporter inhibitors within 2 weeks prior to Screening and/or planned throughout the duration of the study.
• Received strong breast cancer resistance protein transporter inhibitors within 2 weeks prior to screening and/or planned throughout the duration of the study.
• Current swab-positive or suspected (under investigation) COVID-19 infection.
• Cancer (excluding non-melanoma skin cancer) and/or need of any anti-cancer treatment (also including radiotherapy) within the last 5 years.
• Severe kidney impairment.
• Aspartate aminotransferase (AST) or alanine transaminase (ALT) levels >2.5 times the upper limit of normal (ULN); bilirubin (unless deemed to be due to Gilbert's Syndrome) or alkaline phosphatase (ALP) >1.5 times ULN.
• Severe hepatic impairment defined as Child-Pugh C.
• History of any of the following cardiac disorders: i) torsade de pointes, ventricular tachycardia, ventricular fibrillation; ii) previous myocardial infarction, unstable angina pectoris, acute coronary syndrome, coronary artery or cerebral revascularization procedure or stroke within the previous 18 months; iii) angina pectoris class 2-4 during the last 12 months prior to screening; iv) congestive heart failure NYHA class III-IV during the last 18 months prior to screening.
• History of any alcohol or drug abuse or dependence within the last year (Investigator's judgement).
• Any current significant health condition that in the Investigator's judgement may: i) jeopardize the patient's safe participation in the trial or ii) make unlikely the patient's completion of the study or iii) make unlikely the patient's compliance with the study procedures.
• Pregnant or breastfeeding woman.
• Use of any experimental drug within 12 weeks prior to screening

6 months