A Randomized, Double-Blind, Placebo-Controlled Multicenter Phase II Study to Evaluate the Safety and Efficacy and Dose Response of 28 Days of Once-Daily Dosing of the Oral Motilin Receptor Agonist GSK962040, in Type I and II Diabetic Male and Female Subjects with Gastroparesis

Phase 1

• Conditions: Diabetic gastroparesis; MedDRA version: 14.1Level: PTClassification code 10051153Term: Diabetic gastroparesisSystem Organ Class: 10017947 - Gastrointestinal disorders

• Registration Number: EUCTR2010-023186-21-BE
• Lead Sponsor: GlaxoSmithKline Research and Development Ltd

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2010-12-14
• Last Update Posted: 21 August 2017

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 80

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 < LLN at 90 or 120 min
4. Patient must have a > 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 < 450 msec or QTc < 480 msec in patients with Bundle Branch Block based on single or average QTc value of triplicate values obtained over a brief recording period.
12. Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
13. AST and ALT < 2xULN; alkaline phosphatase and bilirubin = 1.5xULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).
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

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.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified