Phase II multicenter clinical trial, with treatment randomly assigned, in which patient nor physician are aware of the assigned treatment, active or placebo, to evaluate efficacy and safety of Velusetrag 15 mg (3 x 5 mg capsule) in patients with Chronic Intestinal Pseudo-Obstruction (CIPO)

INTERVENTION: Product Name: Velusetrag Product Code: [TD‐5108 hydrochloride] Pharmaceutical Form: Capsule, hard INN or Proposed INN: Velusetrag CAS Number: 866933‐51‐9 Current Sponsor code: TD‐5108 Other descriptive name: THRX‐199687 hydrochloride Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 5‐ Pharmaceutical form of the placebo: Capsule, hard Route of administration of the placebo: Oral use CONDITION: Chronic intestinal pseudo‐obstruction (CIPO) is a rare, severe condition characterized by an impairment of coordinated propulsive activity in the intestinal tract resulting in a clinical picture similar to that of mechanical intestinal obstruction, although in the absence of any lesion occluding the gut. CIPO can be idiopathic or secondary. ; MedDRA version: 20.0 Level: SOC Classification code 10017947 Term: Gastrointestinal disorders System Organ Class: 10017947 ‐ Gastrointestinal disorders Therapeutic area: Diseases [C] ‐ Digestive System Diseases [C06] PRIMARY OUTCOME: Main Objective: The objective of this study is to investigate the safety, tolerability and efficacy of velusetrag in improving the symptoms severity associated with CIPO, in subjects with idiopathic CIPO and CIPO secondary to neurodegenerative or demyelinating conditions (e.g., Parkinsonian Syndromes, multiple sclerosis, etc.). Primary end point(s): Change in weekly global gastrointestinal symptoms average index score from start to the end of each treatment period.; The weekly global gastrointestinal symptoms average index score is obtained by averaging the scores for each of the 4 symptoms assessed weekly: abdominal pain, bloating, nausea and vomiting. Secondary Objective: N/A Timepoint(s) of evaluation of this end point: Every 7 days INCLUSION CRITERIA: 1. Men or women aged 18‐80 years. 2. Subjects with history of chronic idiopathic intestinal pseudo‐obstruction or CIPO secondary to neurodegenerative or demyelinating disease. 3. Subjects with estimated oral caloric intake of at least 30% of the daily age‐ and sex‐recommended caloric intake (stage 0, 1 or 2 of the “artificial food need” scale, see 21.3 Appendix 3: Artificial Food Need" (AFN) Scale for CIPO patients). 4. Subjects with at least 2 out of 4 CIPO gastrointestinal symptoms (i.e., abdominal pain, bloating, nausea and vomiting), each of the 2 with a score =3 (on a 0 to 4 scale) collected on the gastrointestinal symptom questionnaire at Day ‐1 5. Subjects accepting to provide and legally capable of providing free and informed consent to all procedures included in the protocol. 6. 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 SECONDARY OUTCOME: Secondary end point(s): 1. Change in waist circumference from start to the end of each treatment period.; 2. Proportion of subjects with 1‐point improvement in weekly global gastrointestinal symptoms average index score from start to the end of each treatment period.; 3. Change in individual symptoms score from start to the end of each treatment period for:; o Abdominal Pain; o Bloating; o Nausea; o Vomiting; 4. Change in number of weekly bowel movements from start to the end of each treatment period (only in subjects with Bristol stool scale type 1 or 2 at the start of the treatment period).; 5. Change in number of weekly complete evacuations from start to the end of each treatment period (only in subjects with Bristol stool scale type 1 or 2 at the start of the treatment period). ; 6. Change in stool type at the Bristol stool scale from start to the end of each treatment period.; 7. Change in weekly bowel habit satisfaction score from start to the end of each treatment period measured using a scale from 0 to 10.; 8. Change from start in orocecal transit time measured using lactulose breath test (only at the end of the first treatment period).; 9. Change in serum albumin, pre‐albumin, vitamin B12 and folic acid levels from start of each treatment period to the end of each 2 week wash out period (or follow up period).; 10. Proportion of days with change in permitted medications used to relieve main CIPO gastrointestinal symptoms during each treatment period and wash out period (or follow up period):; o Proportion of days with dose increased compared to the start of the period.; o Proportion of days with dose decreased compared to the start of the period.; o Proportion of days with drug added compared to the start of the period.; o Proportion of days with drug removed compared to the start of the period.; 11. Change in quality of life (SF‐12) from the start to the end of each treatment period.; 12. Number of CIPO‐related hospitalizations during the treatment periods.; 13. Change in stage of the “artificial food need” scale from start to the end of each period.; 14. Number of pseudo‐obstruction episodes based on investigator’s judgement from start to the end of each period. ; 15. Change from the end of each treatment period to the ends of the first and the second week of wash out (or follow up period) in: ; o weekly abdominal pain score.; o weekly bloating score.; o weekly nausea score.; o weekly vomiting score.; o weekly global gastrointestinal symptoms average index score.; o number of weekly bowel movements (only in subjects with Bristol stool scale type 1 or 2 at the start of the treatment period).; o number of weekly complete evacuations (only in subjects with Bristol stool scale type 1 or 2 at the start of the treatment period). ; o stool type at the Bristol stool scale.; o weekly bowel habit satisfaction score measured using a scale from 0 to 10. Timepoint(s) of evaluation of this end point: Day 1‐28‐43‐70‐85‐112‐127‐154‐169