the effect of single doses of the motilin receptor agonist gsk962040 in type i diabetic patients with gastroparesis

Conditions: Gastroparesis

Summary: the purpose of this study is to assess the pharmacodynamic effects (gastric emptying), safety, tolerability, and pharmacokinetics of single doses of gsk962040 in type 1 diabetic patients with gastroparesis.


Eligibility criteria:
inclusion criteria: * controlled type 1 diabetes mellitus (glucose \< 250 mg/dl) with onset \< 30 years of age. * male or female between 18 and 70 years of age, inclusive. * patient has documented diagnosis of moderate to severe gastroparesis (\> 30% at 2 h as determined by scintigraphy; or t1/2b \> 109 min as determined by 13c-octanoic acid breath test). all of the following apply: * confirmed delayed gastric emptying (properly conducted gastric emptying assessments within last 6 months acceptable) and a minimum 3 month history of relevant symptoms for gastroparesis (e.g., chronic postprandial fullness, postprandial nausea, vomiting) * a female patient is eligible to participate if she is of: * non-childbearing potential * child-bearing potential and agrees to use contraception for at least 4 days following the last dose of study medication. * male patients must agree to use contraception from the time of the first dose of study medication through at least 4 days after the last dose of study medication. * body weight ≤110 kg and bmi \< 32.0 kg/m2 (inclusive). * patient has never had a gastrectomy, nor major gastric surgical procedure or any evidence of bowel obstruction within the previous 12 months * dosage of any concomitant medications has been stable for at least 3 weeks, except for routine adjustments in daily insulin treatments * hba1c level is ≤ 10.0% * calculated creatinine clearance \> or equal to 50 ml/min * qtcb or qtcf \< 450 msec or qtc\<480msec in patients with bundle branch block based on single or average qtc value of triplicate values obtained over a brief recording period. * ast, alt, alkaline phosphatase and bilirubin ≤ 1.5xuln (isolated bilirubin \>1.5xuln is acceptable if bilirubin is fractionated and direct bilirubin \<35%) * capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form. exclusion criteria: * patient has acute severe gastroenteritis * patient has a gastric pacemaker * patient is on chronic parenteral feeding * patient has daily persistent severe vomiting * patient has pronounced dehydration * patient has had clinical diabetic ketoacidosis in last 4 weeks * patient has a history of eating disorders (anorexia nervosa, binge eating, bulimia) * use of medications potentially influencing upper gastrointestinal motility or appetite within one week of the study (e.g., prokinetic drugs, macrolide antibiotics (erythromycin)) * patient is taking opiates. * use of prohibited medications listed in section 9.2 within the restricted timeframe relative to the first dose of study medication. * history or presence of clinically significant gastro-intestinal, hepatic or renal disease or other condition known to interfere with the absorption, distribution, metabolism or excretion of drugs. * presence of thyroid dysfunction (note: patients with abnormal tsh at screening/baseline are not eligible. patients with a history of hypothyroidism on a stable dose of thyroid replacement therapy are eligible to participate in the study). * 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). * 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. * where participation in the study would result in donation of blood or blood products in excess of 500 ml within a 56 day period. * pregnant females as determined by positive serum or urine hcg test (from the first urine of the day) at screening or prior to dosing. * lactating or pregnant females. * unwillingness or inability to follow the procedures outlined in the protocol. * patients deemed unable to comply with the procedures outlined in the protocol may be excluded at the investigator's discretion. * for male volunteers: an unwillingness of the male patient to comply with the contraception requirements listed in section 8.1, from the time of the first dose of study medication until at least 4 days following administration of the last dose of study medication. * a positive pre-study hepatitis b surface antigen or positive hepatitis c antibody result within 3 months of screening.

Keywords: single dose gut motility type i diabetes mellitus patients tolerability phase ii 13c octanoic acid breath test pharmacodynamics gastric emtpying pharmacokinetics