velusetrag for the treatment of chronic intestinal pseudo-obstruction (cipo).

Conditions: Chronic Intestinal Pseudo-obstruction

Summary: 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.


Eligibility criteria:
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 safeparticipation 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