The Effect of Single Doses of the Motilin Receptor Agonist GSK962040 in Type I Diabetic Patients With Gastroparesis

A Multicenter, Double-Blind, Randomized Placebo-Controlled Phase II Study to Evaluate the Pharmacodynamics, Safety, Tolerability, and PK of Single Doses of the Oral Motilin Receptor Agonist GSK962040, in Type 1 Diabetic Male and Female Patients With Gastroparesis

Sponsors

Lead Sponsor: GlaxoSmithKline

Source GlaxoSmithKline
Brief 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.

Overall Status Completed
Start Date June 2009
Completion Date November 2010
Primary Completion Date November 2010
Phase Phase 2
Study Type Interventional
Primary Outcome
Measure Time Frame
Gastric emptying, as measured by the 13C octanoic acid breath test (Gastric half emptying time (t1/2b), Duration of the lag time (tlag), Gastric evacuation coefficient (GEC)) 1.5 h post dose to 5.5 h post dose
Safety and tolerability of GSK962040 (Change from baseline and number of patients outside the normal range for blood pressure, heart rate, 12-lead ECG parameters) 2 h post dose
Pharmacokinetic parameters of GSK962040: Cmax, Tmax, AUC(0-t), AUC(0-inf) for single-dose, CL/F, V/F, and, if possible, half-life 24 h post dose
Safety and tolerability of GSK962040 (Adverse events) 6 weeks
Safety and tolerability of GSK962040 (Change from baseline in clinical chemistry and hematology parameters) 24 h post dose
Secondary Outcome
Measure Time Frame
Bowel movement parameters (Time to first bowel movement after first dose, Bowel movement count, Stool consistency (Bristol Stool Form scale)) 24 h post dose
PK/PD relationship of PP, plasma glucagon, GLP-1, and ghrelin after a single dose of GSK962040. 0-6 h post dose
Plasma glucose 24 h post dose
Food intake 24 h post dose
Enrollment 11
Condition
Intervention

Intervention Type: Drug

Intervention Name: GSK962040 25 mg

Description: 25 mg

Intervention Type: Drug

Intervention Name: Placebo

Description: placebo comparator

Intervention Type: Drug

Intervention Name: GSK962040 50 mg

Description: 50 mg

Intervention Type: Drug

Intervention Name: GSK962040 1250 mg

Description: 125 mg

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.

Gender: All

Minimum Age: 18 Years

Maximum Age: 70 Years

Healthy Volunteers: No

Overall Official
Last Name Role Affiliation
GSK Clinical Trials Study Director GlaxoSmithKline
Location
Facility:
GSK Investigational Site | Leuven, 3000, Belgium
GSK Investigational Site | Stockholm, SE-171 76, Sweden
Location Countries

Belgium

Sweden

Verification Date

January 2017

Responsible Party

Type: Sponsor

Keywords
Has Expanded Access No
Condition Browse
Number Of Arms 3
Arm Group

Label: Cohort 1 Period 1

Type: Experimental

Description: All patients will receive placebo and 2 of the 3 possible doses of GSK962040 in a randomized, double blind, placebo controlled, incomplete block, three period crossover design.

Label: Cohort 1 Period 2

Type: Experimental

Description: All patients will receive placebo and 2 of the 3 possible doses of GSK962040 in a randomized, double blind, placebo controlled, incomplete block, three period crossover design.

Label: Cohort 1 Period 3

Type: Experimental

Description: All patients will receive placebo and 2 of the 3 possible doses of GSK962040 in a randomized, double blind, placebo controlled, incomplete block, three period crossover design.

Patient Data Yes
Study Design Info

Allocation: Randomized

Intervention Model: Crossover Assignment

Primary Purpose: Treatment

Masking: Triple (Participant, Investigator, Outcomes Assessor)

Source: ClinicalTrials.gov