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

NCT ID: NCT00861809

Last Updated: 2017-01-30

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 11 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-06-30
• Study Completion Date: 2010-11-30

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.

Conditions

Gastroparesis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

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.

Group Type: EXPERIMENTAL

GSK962040 25 mg

Intervention Type: DRUG

25 mg

Placebo

Intervention Type: DRUG

placebo comparator

GSK962040 50 mg

Intervention Type: DRUG

50 mg

GSK962040 1250 mg

Intervention Type: DRUG

125 mg

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.

Group Type: EXPERIMENTAL

GSK962040 25 mg

Intervention Type: DRUG

25 mg

Placebo

Intervention Type: DRUG

placebo comparator

GSK962040 50 mg

Intervention Type: DRUG

50 mg

GSK962040 1250 mg

Intervention Type: DRUG

125 mg

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.

Group Type: EXPERIMENTAL

GSK962040 25 mg

Intervention Type: DRUG

25 mg

Placebo

Intervention Type: DRUG

placebo comparator

GSK962040 50 mg

Intervention Type: DRUG

50 mg

GSK962040 1250 mg

Intervention Type: DRUG

125 mg

Interventions

GSK962040 25 mg

25 mg

Intervention Type: DRUG

Placebo

placebo comparator

Intervention Type: DRUG

GSK962040 50 mg

50 mg

Intervention Type: DRUG

GSK962040 1250 mg

125 mg

Intervention Type: DRUG

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

GlaxoSmithKline

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

GSK Clinical Trials

Role: STUDY_DIRECTOR

GlaxoSmithKline

Locations

GSK Investigational Site

Leuven, , Belgium

GSK Investigational Site

Stockholm, , Sweden

Countries

Belgium; Sweden

References

Hellstrom PM, Tack J, Johnson LV, Hacquoil K, Barton ME, Richards DB, Alpers DH, Sanger GJ, Dukes GE. The pharmacodynamics, safety and pharmacokinetics of single doses of the motilin agonist, camicinal, in type 1 diabetes mellitus with slow gastric emptying. Br J Pharmacol. 2016 Jun;173(11):1768-77. doi: 10.1111/bph.13475. Epub 2016 Apr 13.

Reference Type: DERIVED

PMID: 26924243 (View on PubMed)

Study Documents

Document Type: Study Protocol

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Document Type: Dataset Specification

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Document Type: Individual Participant Data Set

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Document Type: Annotated Case Report Form

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Document Type: Clinical Study Report

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Document Type: Statistical Analysis Plan

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Document Type: Informed Consent Form

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Related Links

https://www.clinicalstudydatarequest.com

Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

Other Identifiers

111809

Identifier Type: -

Identifier Source: org_study_id