Diabetic gastroparesis MedDRA version: 14.1 Level: PT Classification code 10051153 Term: Diabetic gastroparesis System Organ Class: 10017947 - Gastrointestinal disorders
Conditions
Interventions
Product Name: GSK962040
Product Code: GSK962040
Pharmaceutical Form: Tablet
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use
Sponsors
GlaxoSmithKline Research and Development Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Type I or II Diabetes Mellitus (HbA1C = 11.0%) 2. Male or female between 18 and 80 years of age, inclusive. 3. Patient has gastroparesis at screening. A patient is eligible if one of the following criteria are met: • Gastric half-time of emptying > upper limit of normal as determined by 13C-oral breath test • % 13C dose recovered or = 3 month history of relevant symptoms of gastroparesis (e.g., chronic post-prandial fullness, early satiety, post-prandial nausea), patients will have a mean of the daily scores over a minimum of 7 days indicating > or = mild (2) post-prandial fullness as assessed using the GCSI-DD during the screening period prior to randomization. 5. A female patient is eligible to participate if she is of: • Non-childbearing potential defined as pre-menopausal females with a documented tubal ligation or hysterectomy; or postmenopausal defined as 12 months of spontaneous amenorrhea [in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) > 40 MlU/mL, or a value consistent with the local laboratory standard value, is confirmatory. • Child-bearing potential and agrees to use one of the contraception methods listed in Section 8.1 for an appropriate period of time (as determined by the product label or investigator) prior to the start of dosing to sufficiently minimize the risk of pregnancy at that point. Female patients must agree to use contraception for at least 5 days following the last dose of study medication. 6. Male patients must agree to use one of the contraception methods listed in Section 8.1. This criterion must be followed from the time of the first dose of study medication through at least 5 days after the last dose of study medication. 7. BMI >18 and = 40.0 kg/m2 (inclusive). 8. Patient has never had a gastrectomy, nor major gastric surgical procedure or any evidence of bowel obstruction or strictures within the previous 12 months 9. Dosage of any concomitant medications has been stable for at least 3 weeks, except for routine adjustments in daily insulin treatments. 10. Estimated (or measured) glomerular filtration rate = 30 mL/min. 11. QTcB or QTcF 1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin =65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1.Patient has acute severe gastroenteritis 2.Patient has a gastric pacemaker 3. Patient is on chronic enteral (e.g., feeding tube) or parenteral feeding 4.Patient has pronounced dehydration 5.Recent (last 6 weeks) history of poor control of diabetes e.g. hypoglycaemia requiring medical intervention, diabetic ketoacidosis, admission for control diabetes or complications of diabetes 6.Patient has evidence of severe cardiovascular autonomic neuropathy (e.g. history of recurrent syncope in the last 6 months) 7.Patient has a history of eating disorders (anorexia nervosa, binge eating, bulimia) 8.Use of medications potentially influencing upper gastrointestinal motility or appetite within one week of the study (e.g., prokinetic drugs, macrolide antibiotics (erythromycin), GLP-1 mimetics) 9.Regular opiate use 10.Use of prohibited medications listed in Section 9.2 within the restricted timeframe relative to the first dose of study medication. 11.History or presence of clinically significant gastro-intestinal, hepatic or renal disease or other condition that would in the opinion of the investigator or medical monitor make the subject unsuitable for inclusion in this clinical study. 12.The patient has participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day in the current study: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer). 13.History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy that, in the opinion of the investigator or GSK Medical Monitor, contraindicates their participation. 14.Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56 day time-period. 15.Pregnant females as determined by positive serum or urine hCG test (from the first urine of the day) at screening or prior to dosing. 16.Lactating females. 17.Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones). 18.A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening 19. Patient has a history of dysphagia. 20. Patient has had intrapyloric botox injections. • A patient would be eligible if the botox treatment was in the past (> 6 months previously) and was not being repeated.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To investigate the pharmacodynamic effect of 28 days of repeated doses of GSK962040 on gastric emptying of an isotope-labelled test meal, as measured by the 13C-oral breath test (OBT) in DM subjects with gastroparesis;Secondary Objective: •To investigare safety and tolerability of 28 days of repeated doses of GSK962040 in DM subjects with gastroparesis. To explore the effect of 28 days of repeated doses of GSK962040 on upper gastrointestinal symptoms •To investigate the pharmacodynamic effect of 28 days of repeated doses of GSK962040 on stool frequency and consistency in DM subjects with gastroparesis. •To investigate the relationship of gastric emptying response to symptom response. •To investigate the pharmacokinetics of 28 days of repeated doses of GSK962040 in DM subjects with gastroparesis. •To investigate the relationship between PK and PD markers, including gastric emptying parameters following the 13C-oral breath test, stool frequency and consistency, and GI symptoms (GCSI-DD) following 28 days of repeated doses of GSK962040. •To determine the effect of GSK962040 on total bowel transit, gastric emptying, small bowel transit and colonic transit as determined by the wireless motility capsule (WMC). ;Primary end point(s): •Gastric emptying, as measured by the 13C-OBT: •Gastric half emptying time (GEt1/2) | — |
Countries
Belgium, Sweden, United Kingdom
Outcome results
None listed