| Eligibility |
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
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