Coated MNTX is being developed for the prevention of constipation in patients taking opioids for hip and knee replacement surgery for analgesia (pain relief). This drug is as yet unlicensed for use in humans. Studies in subjects have shown no adverse effects of oral doses of MNTX, indicating that oral MNTX is safe and well tolerated in healthy humans at doses of up to 19.2mg/kg.
Conditions
Interventions
Product Name: Coated Methylnaltrexone
Product Code: MNTX
Pharmaceutical Form: Capsule, hard
Pharmaceutical form of the placebo: Capsule, hard
Sponsors
Norgine International Limited
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Patients over 18 years of age (race, sex and BMI irrelevant), scheduled to undergo elective hip or knee replacement surgery at Ravenscourt Park Hospital. Females must be either surgically sterile as documented by medical records, postmenopausal with no periods for at least one year and an untreated postmenopausal oestradiol level of Not Detected-110 pmol/L and FSH within 21.7 - 153 IU/L (WHO 2nd IRP 78/549) or agreeable to appropriate contraception. Females of child-bearing potential must have a negative urine pregnancy test. Be in good health (to include stable and/or, controlled medical conditions) determined by a medical history, electrocardiogram (12-Lead ECG), haematology, biochemistry and urinalysis. Be in good health (to include stable and/or, controlled medical conditions) as determined by a medical examination by a qualified physician. Have given both verbal and written informed consent to participate in the study. (Consent will be documented by the patient’s dated signature, which will be countersigned and dated by the Investigator or designee, who will have explained the nature, purpose and possible risks of the 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 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Patients who have a history of relevant constipation/ diarrhoea in the last four weeks (constipation defined as no bowel movement in one week; and diarrhoea defined as more than 3 loose bowel movements per day). Patients who have any condition that precludes the use of post-operative morphine PCA (patient controlled analgesia). Patients who have any condition that will make the surgery or peri/ post-operative care non-standard. Patients taking any medication that is on the precluded list (opiate analgesia other than morphine for the first 24hr post-operatively; Any regular laxative use pre and post-operatively (lactulose is allowed 48hrs after surgery as “rescue medication” if clinically needed), prokinetic products, IBS products)). Patients who have had any abdominal operation that may interfere with stool collection. Patients who have any known previous or suspected allergy or reaction to methylnaltrexone or similar drugs. Patients who have participated in another study with an investigational drug or product within 3 months prior to the start of this study. Patients who have, or have had a history of any clinically significant neurological (brain or nerve), gastrointestinal (stomach or bowel), renal (kidney), hepatic (liver), cardiovascular (heart, circulation or blood pressure), psychological, pulmonary (chest and lungs), metabolic, endocrine (hormone), haematological (blood) disease or any other major disorders. Patients who have had a clinically significant acute illness, within 30 days preceding the start of the study. Patients who have any moderate to severe colitis (inflammation of the colon) as this may prevent the absorption of study medication.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Secondary Objective: N/A;Main Objective: The objectives of the study are:-To confirm that 700mg and 70mg coated MNTX are effective at reducing opiate induced constipation in patients undergoing elective joint replacement requiring post-operative opiate analgesia.-To confirm that time to passage of first stool and faecal water content are reliable indicators of reversal of opiate induced constipation.; Primary end point(s): The primary endpoint, time to first stool post-operatively will be analysed with statistical models for survival data like a proportional hazards regression model with an effect for treatment and covariate average duration between stools pre-operatively and stochastic regressor dose of opioids from 0-96 hours. Time to laxative requirement will be accounted for in the model. In order to assess whether the additional use of MNTX will have an impact on the morphine therapy with respect to pain, the other efficacy endpoints of pain scores, dose of opioids from 0-96 hours, rescue analgesic needed and time to rescue analgesic will be analysed with statistical models for survival data, analysis of covariance models or logistic regression models, according to the distribution of the data. The two-sided 95% confidence intervals of the LS means will be examined. For pain scores, parameters like the maximum and the final score as well as the baseline value will be assessed, if applicable. The pharmacokinetic parameter AUC0-96hours will be log-transformed and fit to an analysis of variance (ANOVA) model with an effect for treatment. In addition, the dose-response relationship might be explored. The primary pharmacodynamic endpoint stool water content will be fit to an analysis of covariance model (ANCOVA) with an effect for treatment and covariate stool water content at baseline and stochastic regressor dose of opioids from 0-96 hours. No formal statistical analyses of safety evaluations are planned. | — |
Countries
United Kingdom
Outcome results
None listed