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, when no primary underlying disorder is demonstrated, or secondary, when related to systemic diseases. MedDRA version: 20.0 Level: SOC Classification code 10017947 Term:
Conditions
Sponsors
ALFASIGMA S.P.A.
Eligibility
Sex/Gender
All
Inclusion criteria
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 the entire study. 7. All female participants must be: • of non-childbearing potential, i.e.: i) post-menopausal (at least 2 years without spontaneous menses), or ii) surgically sterile (bilateral tubal occlusion, or hysterectomy), or iii) ablation of both ovaries or • 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. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 12 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 4
Exclusion criteria
Exclusion criteria: 1. Subjects with primary CIPO or CIPO secondary to other known endocrine/metabolic, autoimmune diseases and neurologic conditions other than neurodegenerative or demyelinating diseases. 2. Subjects with conditions characterized by mechanical intestinal obstruction. 3. 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 (“total non-oral nutrition”, see 21.3 Appendix 3: Artificial Food Need" (AFN) Scale for CIPO patients). 4. Presence of untreated clinically relevant thyroid dysfunction or known thyroid dysfunction not well controlled by treatment (e.g., subjects with abnormal thyroid stimulating hormone [TSH], and, if available, triiodothyronine [T3] and thyroxin [T4] levels) deemed clinically significant by the Investigator. 5. Subjects with history of diabetes at screening. 6. Clinically significant ECG abnormalities (e.g., ST segment elevation or depression suggestive of ischemia, partial or complete left bundle branch block [LBBB]) at Screening and randomization. 7. Screening ECG with a QTcF >450 msec in males or >470 msec in females or family history of sudden cardiac death. 8. Subjects requiring a low galactose diet. 9. Hypersensitivity or documented intolerance to lactulose, lactose or any excipient of the lactulose preparation to be used for L-BT. 10. History of sensitivity to velusetrag, or any of the velusetrag or placebo excipients. 11. Use of scopolamine or erythromycin within 2 weeks prior to Screening and/or planned throughout the duration of the study. 12. Use of 5-HT4 receptor agonists (e.g., prucalopride, cisapride, clebopride and cinitapride) within 5 days prior to randomization and/or planned throughout the duration of the study 13. Use of opioids within 8 weeks from screening and/or planned throughout the duration of the study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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.).;Secondary Objective: N/A;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.;Timepoint(s) of evaluation of this end point: Every 7 days | — |
Secondary
| Measure | Time frame |
|---|---|
| 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 stag | — |
Countries
Belgium, Italy, Spain
Contacts
Public ContactEarly Stage Clinical Development
Alfasigma .S.p.A.
Outcome results
None listed