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

• Register: ClinicalTrials.gov
• Last refreshed on: 16 December 2017
• Main ID: NCT00861809
• Date of registration: 26/02/2009
• Prospective Registration: Yes
• Primary sponsor: GlaxoSmithKline
• Public title: The Effect of Single Doses of the Motilin Receptor Agonist GSK962040 in Type I Diabetic Patients With Gastroparesis
• Scientific title: 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
• Date of first enrolment: June 2009
• Target sample size: 11
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT00861809
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Crossover Assignment. Primary purpose: Treatment. Masking: Triple (Participant, Investigator, Outcomes Assessor).
• Phase: Phase 2

Countries of recruitment

Belgium, Sweden

Contacts

• Name: GSK Clinical Trials
• Affiliation: GlaxoSmithKline

Key inclusion & exclusion 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.



Age minimum: 18 Years
Age maximum: 70 Years
Gender: All

Health Condition(s) or Problem(s) studied

Gastroparesis

Intervention(s)

Drug: Placebo

Drug: GSK962040 50 mg

Drug: GSK962040 1250 mg

Drug: GSK962040 25 mg

Primary Outcome(s)

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)) [Time Frame: 1.5 h post dose to 5.5 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 [Time Frame: 24 h post dose]

Safety and tolerability of GSK962040 (Change from baseline in clinical chemistry and hematology parameters) [Time Frame: 24 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) [Time Frame: 2 h post dose]

Safety and tolerability of GSK962040 (Adverse events) [Time Frame: 6 weeks]

Secondary Outcome(s)

Food intake [Time Frame: 24 h post dose]

Bowel movement parameters (Time to first bowel movement after first dose, Bowel movement count, Stool consistency (Bristol Stool Form scale)) [Time Frame: 24 h post dose]

PK/PD relationship of PP, plasma glucagon, GLP-1, and ghrelin after a single dose of GSK962040. [Time Frame: 0-6 h post dose]

Plasma glucose [Time Frame: 24 h post dose]

Secondary ID(s)

111809

Source(s) of Monetary Support

Please refer to primary and secondary sponsors