Chronic Constipation
Conditions
Interventions
Trade Name: Resolor 2 mg film-coated tablets
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Resolor
Current Sponsor code: SPD555
Other descriptive name: PRUCALOPRIDE SUCCINATE
Concentrat
Sponsors
Shire-Movetis NV
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Subjects meeting all of the criteria listed below will be included in the study: 1. Male or female age 18-75 years inclusive at the time of consent. The date of signing informed consent is defined as the beginning of screening. This inclusion criterion will only be assessed at the first Screening Visit. 2. Willingness to comply with any applicable contraceptive requirements of the protocol and is: – Non-pregnant, non-lactating female – Females must be at least 90 days postpartum or nulliparous. – Females of childbearing potential should have a negative serum pregnancy test at the Screening Visit and should use a medically-acceptable method of birth control for the entire duration of the study and until the first menses after a 30-day period after the last dose of investigational product. They must be on a stable regimen, for at least 1 month, of oral contraceptives, contraceptive implant or depot injection, contraceptive patch, intrauterine device (IUD), condom and spermicidal agent, or diaphragm and spermicidal agent, or agree upon continuous abstinence from heterosexual sexual contact and be willing to continue this contraception. 3. Subject has a history of chronic constipation for at least 6 months before the Screening Visit and reports an average of =65 years) yes F.1.3.1 Number of subjects for this age range 12
Exclusion criteria
Exclusion criteria: Subjects are excluded from the study if any of the following exclusion criteria are met. 1. Subjects in whom constipation is thought to be drug-induced. 2. Body mass index >37.0kg/m². 3. Subjects suffering from secondary causes of chronic constipation, such as. – Endocrine disorders, e.g. hypopituitarism, hypothyroidism, hypercalcemia, pseudo hypoparathyroidism, pheochromocytoma or glucagon-producing tumors, unless these are controlled by appropriate medical therapy; – Metabolic disorders, e.g. porphyria, uremia, hypokaliemia or amyloid neuropathy, unless these are controlled by appropriate medical therapy; – Neurological disorders, e.g. Parkinson’s disease, cerebral tumors, cerebrovascular accidents, multiple sclerosis, meningocele, aganglionosis, hypoganglionosis, hyper-ganglionosis, autonomic neuropathy or neuropathy due to chemotherapy, spinal cord injury, Chaga’s disease, or major depression; – Surgery. Note: if a subject was having chronic constipation prior to the onset of a condition listed above and the constipation has not been worsened by this condition, the subject is eligible for screening; however, if the constipation has started after the onset of 1 of the above conditions and the relation between both cannot be excluded (i.e. it is not certain whether it is secondary to it or not), or when the constipation has worsened after the onset of 1 of the above conditions, the subject is not allowed to be screened for this study. 4. Subjects with insulin-dependent diabetes mellitus, irrespective of whether the constipation started prior to or after the onset of diabetes. 5. Rectal evacuation disorder/outlet obstruction. If data are not available regarding rectal evacuation disorder/outlet obstruction, a clinical evaluation should be performed at screening. 6. Subjects with intestinal perforation or obstruction due to structural or functional disorder of the gut wall, obstructive ileus, severe inflammatory conditions of the intestinal tract, such as Crohn’s disease, ulcerative colitis, or toxic megacolon/megarectum. When polyps, cancer, stricture, or other structural or organic disease are found at the endoscopic examination in conjunction with the manometry catheter placement or if it is clinically indicated that a repeat colonoscopy/sigmoidoscopy is needed to rule out or treat such abnormalities, the subject should be a screen failure. 7. Severe renal impairment (calculated creatinine clearance <30mL/min) or requiring dialysis. 8. Subjects with clinically significant abnormalities at the physical examination, or in hematology and biochemistry tests performed at the Screening Visit, as judged by the Investigator. 9. Subjects with a history of alcohol or drug abuse in the previous 6 months, or a positive screen for alcohol or drugs of abuse. 10. Use of another investigational product (or active enrollment in another drug or vaccine clinical study) within 30 days prior to receiving the first dose of investigational product within this study. 11. Substantial changes in eating habits within 30 days prior to receiving the first dose of investigational product, as assessed by the Investigator. 12. An inability to follow a standardized diet and meal schedule, including consumption of clear liquids and a low fat meal, as required during the study. 13. Prior screen failure, randomization, or enrollment in this study. 14. Subjects with clinically significant cardiac, vascular, liver, pulmonary, endocrine, neurolog
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate differences in pharmacodynamic effects of prucalopride and PEG 3350 + electrolytes on the number of colonic HAPC during a 12-hour intraluminal manometry in chronically constipated subjects.;Secondary Objective: • To evaluate the association between motility parameters and number and consistency of bowel movements in chronically constipated subjects receiving a single dose of prucalopride and 2 doses of PEG 3350 + electrolytes • To explore the relationship between plasma concentrations and pharmacodynamic endpoints in chronically constipated subjects. • To collect pharmacogenomic data in chronically constipated subjects for exploratory purposes. ;Primary end point(s): • The number of HAPCs during the 12 hours after treatment initiation.;Timepoint(s) of evaluation of this end point: 12-hour period following AM dosing. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • The area under the curve of all HAPCs during the 12 hours after treatment initiation • The mean amplitude of HAPC (mmHg), duration (s), and propagation velocity (cm/s) • Motility index (number of antro- vs. retro-grade complete propagating waves) • Number and consistency of bowel movements on Day 1 as assessed by the Bristol Stool Scale • Time between occurrence of BM and last HAPC preceding that BM • Time to first HAPC and time to first BM after intake of investigational product on Day 1 • Time to catheter expulsion for those subjects that expel the catheter prematurely. ;Timepoint(s) of evaluation of this end point: 12-hour period following AM dosing | — |
Countries
Belgium, United Kingdom, United States
Contacts
Public ContactMedical Communications
Shire-Movetis
Outcome results
None listed