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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00861809
First received: February 26, 2009
Last updated: August 2, 2012
Last verified: July 2012
  Purpose

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.


Condition Intervention Phase
Gastroparesis
Drug: GSK962040 25 mg
Drug: Placebo
Drug: GSK962040 50 mg
Drug: GSK962040 1250 mg
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official 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

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: Yes ]
  • 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 ] [ Designated as safety issue: No ]
  • Safety and tolerability of GSK962040 (Adverse events) [ Time Frame: 6 weeks ] [ Designated as safety issue: Yes ]
  • Safety and tolerability of GSK962040 (Change from baseline in clinical chemistry and hematology parameters) [ Time Frame: 24 h post dose ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
  • PK/PD relationship of PP, plasma glucagon, GLP-1, and ghrelin after a single dose of GSK962040. [ Time Frame: 0-6 h post dose ] [ Designated as safety issue: No ]
  • Plasma glucose [ Time Frame: 24 h post dose ] [ Designated as safety issue: No ]
  • Food intake [ Time Frame: 24 h post dose ] [ Designated as safety issue: No ]

Enrollment: 11
Study Start Date: June 2009
Study Completion Date: November 2010
Primary Completion Date: November 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cohort 1 Period 1
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.
Drug: GSK962040 25 mg
25 mg
Drug: Placebo
placebo comparator
Drug: GSK962040 50 mg
50 mg
Drug: GSK962040 1250 mg
125 mg
Experimental: Cohort 1 Period 2
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.
Drug: GSK962040 25 mg
25 mg
Drug: Placebo
placebo comparator
Drug: GSK962040 50 mg
50 mg
Drug: GSK962040 1250 mg
125 mg
Experimental: Cohort 1 Period 3
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.
Drug: GSK962040 25 mg
25 mg
Drug: Placebo
placebo comparator
Drug: GSK962040 50 mg
50 mg
Drug: GSK962040 1250 mg
125 mg

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00861809

Locations
Belgium
GSK Investigational Site
Leuven, Belgium, 3000
Sweden
GSK Investigational Site
Stockholm, Sweden, SE-171 76
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT00861809     History of Changes
Other Study ID Numbers: 111809
Study First Received: February 26, 2009
Last Updated: August 2, 2012
Health Authority: Sweden: Regional Ethical Review Board
Belgium: Institutional Review Board
Belgium: Federal Agency for Medicines and Health Products, FAMHP
Sweden: Medical Products Agency

Keywords provided by GlaxoSmithKline:
single dose
gut motility
Type I Diabetes Mellitus patients
tolerability
phase II
13C octanoic acid breath test
pharmacodynamics
gastric emtpying
pharmacokinetics

Additional relevant MeSH terms:
Gastroparesis
Stomach Diseases
Gastrointestinal Diseases
Digestive System Diseases
Paralysis
Neurologic Manifestations
Signs and Symptoms

ClinicalTrials.gov processed this record on April 15, 2014