A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Multiple Dose Study to Evaluate Safety, Tolerability and Efficacy of Orally Administered ENT-01 for the Treatment of Parkinson's Disease-Related Constipation (KARMET)
This study will be conducted as a multi-center, randomized, double-blind, placebo-controlled study. Approximately 72 patients will be randomized 3:1 to treatment or placebo, with approximately 54 patients allocated to receive the active investigational product and approximately 18 patients allocated to receive placebo. - Study Update- Amendment 3 - In this amendment, an additional 80 patients (approximately) will be randomized 1:1 to treatment or placebo (double-blind) with approximately 40 subjects allocated to each group.
• Subjects aged 30-90 years, both genders
• Subjects must provide written informed consent and be willing and able to comply with study procedures.
• Subjects must be diagnosed with Parkinson's Disease defined as the presence of at least three of the following cardinal features, in the absence of alternative explanations or atypical features: rest tremor, rigidity, bradykinesia and/or akinesia, postural and gait abnormalities.
• There are insufficient criteria for Irritable Bowel Syndrome (IBS)
• Constipation which has been present for over 6 months and is unresponsive to first line, typically over the counter treatments such as Milk of Magnesia (1g), Miralax (17g in 8 ounces of water) or the equivalent at least once weekly with an inconsistent response over a 6-week period or the subject is dissatisfied with first line treatments.
• Body mass index (BMI) of 18-40 kg/m2
• Subjects must fulfill Rome IV criteria for functional constipation which includes 2 or more of the following:
∙ Straining during at least 25% of defecations
‣ Lumpy or hard stools in at least 25% of defecations
‣ Sensation of incomplete evacuation for at least 25% of defecations
‣ Sensation of anorectal obstruction/blockage for at least 25% of defecations
‣ Manual maneuvers to facilitate at least 25% of defecations (e.g., digital evacuation, support of the pelvic floor)
• Self-report of fewer than 3 complete spontaneous bowel movements per week
• Loose stools are rarely present without the use of laxatives
⁃ Subjects must be able to read, understand, and accurately record data into the diary to guarantee full participation in the study.
⁃ Female subjects must have negative serum or urine pregnancy tests and must not be lactating. For females able to bear children, a hormonal (i.e., oral, implantable, or injectable) and single-barrier method, or a double-barrier method of birth control must be used throughout the study. A vasectomized partner will be allowed as one in conjunction with another single-barrier method.
⁃ Female subjects unable to bear children must have this documented in the CRF (i.e., tubal ligation, hysterectomy, or postmenopausal \[defined as a minimum of one year since the last menstrual period\]). Post-menopausal status will be confirmed by follicle stimulating hormone (FSH) in women less than 60 years of age.