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

NCT00861809 | Completed Phase 2

• 1 other identifier: 111809
• Study Type: interventional
• Target: 11
• Locations: 2 countries
• Sites: 2

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

Keywords

single dose; gut motility; Type I Diabetes Mellitus patients; tolerability; phase II; 13C octanoic acid breath test; pharmacodynamics; gastric emtpying; pharmacokinetics

Outcome Measures

Primary Outcomes (5)

• 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 Outcomes (4)

• 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

Study Arms (3)

Cohort 1 Period 1

EXPERIMENTAL

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; Drug: Placebo; Drug: GSK962040 50 mg; Drug: GSK962040 1250 mg

Cohort 1 Period 2

EXPERIMENTAL

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; Drug: Placebo; Drug: GSK962040 50 mg; Drug: GSK962040 1250 mg

Cohort 1 Period 3

EXPERIMENTAL

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; Drug: Placebo; Drug: GSK962040 50 mg; Drug: GSK962040 1250 mg

Interventions

GSK962040 25 mg DRUG

25 mg

Cohort 1 Period 1; Cohort 1 Period 2; Cohort 1 Period 3

Placebo DRUG

placebo comparator

Cohort 1 Period 1; Cohort 1 Period 2; Cohort 1 Period 3

GSK962040 50 mg DRUG

50 mg

Cohort 1 Period 1; Cohort 1 Period 2; Cohort 1 Period 3

GSK962040 1250 mg DRUG

125 mg

Cohort 1 Period 1; Cohort 1 Period 2; Cohort 1 Period 3

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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%)

You may not qualify if:

• 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.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (2)

GSK Investigational Site

Leuven, 3000, Belgium

Location

GSK Investigational Site

Stockholm, SE-171 76, Sweden

Location

Related Publications (1)

• 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.

  PMID: 26924243 DERIVED

Related Links

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

MeSH Terms

Conditions

Gastroparesis

Interventions

N-(3-fluorophenyl)-1-((4-(((3S)-3-methyl-1-piperazinyl)methyl)phenyl)acetyl)-4-piperidinamine

Condition Hierarchy (Ancestors)

Stomach Diseases; Gastrointestinal Diseases; Digestive System Diseases; Paralysis; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 26, 2009
• First Posted: March 13, 2009
• Study Start: June 1, 2009
• Primary Completion: November 1, 2010
• Study Completion: November 1, 2010
• Last Updated: January 30, 2017

Record last verified: 2017-01

Data Sharing

• IPD Sharing: Will share

Locations

BE (1); SE (1)