Efficacy and Safety of Metoclopramide Nasal Spray Solution in Diabetic Patients With Gastroparesis

A Multicenter, Randomized, Double-Blind, Placebo Controlled, Parallel Group, Dose-Ranging Clinical Study to Evaluate the Efficacy and Safety of Metoclopramide Nasal Spray Solution in Diabetic Subjects With Gastroparesis

To evaluate the safety and the effectiveness of two doses of metoclopramide nasal spray solution, 10 mg and 14 mg, compared to placebo in reducing the symptoms of diabetic gastroparesis.

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus; Diabetes; Gastroparesis; Delayed Gastric Emptying; Diabetic Gastroparesis
• Intervention / Treatment: Drug: metoclopramide; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 287
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Dothan, Alabama, United States, 36305
      • Digestive Specialists of the Southeast
    • Huntsville, Alabama, United States, 35801
      • Medical Affiliated Research Center, Inc.
    • Huntsville, Alabama, United States, 35801
      • Clinical Research Associates
  • Arizona
    • Tucson, Arizona, United States, 85710
      • Desert Sun Gastroenterology
  • Arkansas
    • Jonesboro, Arkansas, United States, 72401
      • Clopton Clinic
    • Sherwood, Arkansas, United States, 72120
      • Arkansas Gastroenterology
  • California
    • Beverly Hills, California, United States, 90211
      • Robert M. Karns, MD, a Medical Corporation
    • Long Beach, California, United States, 90822
      • VA Long Beach Healthcare System
    • Los Angeles, California, United States, 90036
      • Impact Clinical Trials
    • Mission Viejo, California, United States, 92691
      • Prime-Care Clinical Research
    • West Hills, California, United States, 91307
      • Infosphere Clinical Research, Inc.
    • Westlake Village, California, United States, 91361
      • Westlake Medical Research
  • Florida
    • Boynton Beach, Florida, United States, 33426
      • Consultants for Clinical Research of South Florida
    • Clearwater, Florida, United States, 33756
      • Innovative Research of West Florida, Inc.
    • Inverness, Florida, United States, 34452
      • Nature Coast Clinical Research
    • Jacksonville, Florida, United States, 32256
      • Borland-Groover Clinic
    • Miami, Florida, United States, 33183
      • International Research Associates, LLC
    • Miami, Florida, United States, 33155
      • AppleMed Research, Inc.
  • Georgia
    • Conyers, Georgia, United States, 30013
      • Newton Medical Center
    • Marietta, Georgia, United States, 30060
      • Gastrointestinal Specialists of Georgia
  • Illinois
    • Rockford, Illinois, United States, 61107
      • Rockford Gastroenterology Associates
  • Indiana
    • Anderson, Indiana, United States, 46016
      • Saint John's Research Institute
  • Kansas
    • Topeka, Kansas, United States, 66606
      • Cotton-O'Neil Clinical Research Center
    • Wichita, Kansas, United States, 67203
      • Professional Research Network of Kansas
  • Louisiana
    • Monroe, Louisiana, United States, 71201
      • Delta Research Partners, LLC
  • Maryland
    • Chevy Chase, Maryland, United States, 20815
      • Metropolitan Gastroenterology Group
    • Laurel, Maryland, United States, 20707
      • Maryland Digestive Disease Research, Llc
    • Towson, Maryland, United States, 21204
      • Endoscopic Microsurgery Associates
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
  • Minnesota
    • Plymouth, Minnesota, United States, 55446
      • Plymouth Clinic
  • Mississippi
    • Jackson, Mississippi, United States, 39202
      • CRC of Jackson, LLC
    • Jackson, Mississippi, United States, 39202
      • Gastrointestional Associates
    • Tupelo, Mississippi, United States, 38801
      • Digestive Health Specialists
  • Missouri
    • Kansas City, Missouri, United States, 64131
      • Kansas City Gastroenterology & Hepatology
    • Mexico, Missouri, United States, 65265
      • Center for Digestive and Liver Diseases, Inc.
  • New Mexico
    • Albuquerque, New Mexico, United States, 87108
      • Lovelace Scientific Resources, Inc.
  • New York
    • New York, New York, United States, 10004
      • Medex Healthcare Research, Inc.
    • New York, New York, United States, 10075
      • Research Associates of New York
    • Poughkeepsie, New York, United States, 12601
      • Gastroenterology Associates
  • North Carolina
    • Fayetteville, North Carolina, United States, 28304
      • Cumberland Research Associates
    • Greensboro, North Carolina, United States, 27406
      • LeBauer Research Associates
    • Raleigh, North Carolina, United States, 27612
      • Wake Research Associates
    • Wilmington, North Carolina, United States, 28401
      • Hanover Medical Specialists
    • Winston-Salem, North Carolina, United States, 27103
      • Piedmont Medical Research
  • Ohio
    • Akron, Ohio, United States, 44302
      • AGA
    • Cincinnati, Ohio, United States, 45224
      • Hightop Medical Research Center
    • Cincinnati, Ohio, United States, 45211
      • Consultants for Clinical Research
    • Mentor, Ohio, United States, 44060
      • Great Lakes Gastroenterology
  • Pennsylvania
    • Lancaster, Pennsylvania, United States, 17604
      • Regional Gastroenterology Associates of Lancaster, Ltd.
    • Limerick, Pennsylvania, United States, 19468
      • PMA Medical Specialists
  • Tennessee
    • Germantown, Tennessee, United States, 38138
      • Memphis Gastroenterology Group
    • Jackson, Tennessee, United States, 37805
      • HCCA Clinical Research Solutions
    • Jackson, Tennessee, United States, 38301
      • Medical Specialty Clinic Research
    • Kingsport, Tennessee, United States, 37660
      • Holston Medical Group, PC
  • Texas
    • Austin, Texas, United States, 78759
      • Lovelace Scientific Resources
    • Baytown (Houston), Texas, United States, 77521
      • Jacinto Medical Group
    • Houston, Texas, United States, 77034
      • Dynamed Clinical Research
    • Plano, Texas, United States, 75075
      • Digestive Health Associates of Texas, P.A.
    • San Antonio, Texas, United States, 78258
      • Theda Oaks Endoscopy Center
    • Tyler, Texas, United States, 75702
      • Trinity Health Care
  • Virginia
    • Charlottesville, Virginia, United States, 22911
      • Charlottesville Medical Research
    • Chesapeake, Virginia, United States, 23320
      • Gastroenterology Associates of Tidewater
    • Norfolk, Virginia, United States, 23502
      • Digestive and Liver Disease Specialists
    • Virginia Beach, Virginia, United States, 23454
      • Gastroenterology, Ltd.
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53215
      • Wisconsin Center for Advanced Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria

1. Male subjects and non-pregnant, non-lactating female subjects between the ages of 18 and 75 years (inclusive)
2. Willing and able to give written informed consent to participate in the study
3. Ability to read and understand English
4. Diagnosis of Type 1 or Type 2 diabetes
5. Diagnosis of diabetic gastroparesis previously documented
6. A mean daily GCSI-DD score of ≥2 and ≤4 for the 7 days prior to the Randomization Visit (Visit 3, Day 0)
7. Female subjects of childbearing potential, defined as not surgically sterile or at least 2 years postmenopausal, must agree to use one of the following forms of contraception from Screening through the last dose of study drug: hormonal (oral, implant, or injection) begun >30 days prior to screening, barrier (condom, diaphragm, or cervical cap with spermicide), intrauterine device (IUD), or vasectomized partner (6-months minimum)
8. No clinically significant abnormal findings on the physical examination, medical history, or clinical laboratory results (with the exception of lipid profile, glucose and hemoglobin A1c) during screening which, in the opinion of the Investigator, would jeopardize the safety of the subject or impact the validity of the study results
9. Willingness to discontinue current treatment for diabetic gastroparesis and to avoid all medications specified by the protocol for the duration of the study

Exclusion Criteria

1. Gastric bypass and gastric banding, gastric pacemakers, post-surgical causes of gastroparesis and disorders known to be associated with abnormal gastrointestinal motility such as active gastric ulcer, active duodenal ulcer, active severe gastritis, gastric cancer, amyloidosis, neuromuscular diseases (including Parkinson's disease), collagen vascular diseases, alcoholism, uremia, malnutrition, and untreated hypothyroidism
2. A history of allergic or adverse responses, including, but not limited to, acute dystonic reactions and tardive dyskinesia to metoclopramide or any comparable or similar product
3. History of or physical findings suggestive of tardive dyskinesia
4. Currently using and unwilling or unable to stop any medication known to be associated with tardive dyskinesia (See Study Reference Manual) prior to Washout (Visit 2)
5. History of allergy to any of the ingredients in the study drug formulation; metoclopramide, citric acid, sodium citrate, benzalkonium chloride, EDTA, or sorbitol
6. History of organ transplant, chronic pancreatitis, gross malabsorptive syndromes, celiac disease, or inflammatory bowel disease
7. Malignancy (with the exception of basal cell carcinoma of the skin) currently present, initially diagnosed or recurring within 5 years of enrollment
8. History of other clinically significant renal, hepatic, neurologic, hematologic, oncologic, pulmonary, psychiatric, cardiovascular or infectious disease, or any other condition which, in the opinion of the Investigator, would jeopardize the safety of the subject or impact the validity of the study results
9. Have renal dysfunction calculated as creatinine clearance (CrCl) < 40 mL/min at Screening (Visit 1)
10. Have a hemoglobin A1c > 12.5% at Screening (Visit 1)
11. Inability or unwillingness to stop using the following agents for 7 days during the Washout Period (Day -7 to Day -1) prior to Randomization (Visit 3, Day 0) and refrain from their use for the 4-week study period; oral and parenteral formulations of metoclopramide, domperidone, tricyclic antidepressants, macrolide antibiotics, prokinetic agents, cholinergic agents, agents with significant anticholinergic effects, narcotic analgesics, orally administered β agonists, spasmolytics, dopamine agonists, monoamine oxidase inhibitors, herbal supplements, fiber or bulking products, and laxatives
12. Use of neurotoxins (e.g., botulinum type A or B) as a treatment for gastroparesis or delayed gastric emptying within 6 months of Screening (Visit 1)
13. Clinically significant abnormal finding or a QTc interval >450 milliseconds (msec) on ECGs obtained at Screening (Visit 1) OR pre- or post-dose at Randomization (Visit 3)
14. Inability or unwillingness to stop using medications associated with Torsades de Pointes or a prolonged QT interval for 30 days prior to the initial symptom assessment and refrain from their use for the 4-week study period (see Study Reference Manual)
15. Female subjects who are trying to conceive, are pregnant, or are lactating
16. Positive serum human chorionic gonadotropin (HCG) pregnancy test at Screening or a positive HCG urine test on Day 0 prior to administration of study drug for women of childbearing potential
17. History of alcohol or drug abuse within the year prior to the Screening Visit, or current known evidence of substance dependence or abuse
18. Participation in a clinical (investigational) trial or receipt of a non-FDA approved therapy within 30 days prior to the Screening Visit (Visit 1) with the exception of domperidone

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Metoclopramide Nasal Spray 10 mg	Drug: metoclopramide; 30 minutes before meals and at bedtime for 4 weeks; Other Names: Reglan
ACTIVE_COMPARATOR: Metoclopramide Nasal Spray 14 mg	Drug: metoclopramide; 30 minutes before meals and at bedtime for 4 weeks; Other Names: Reglan
PLACEBO_COMPARATOR: Placebo Nasal Spray	Drug: Placebo; 30 minutes before meals and at bedtime

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Primary Efficacy Endpoint is the Change From Baseline to Week 4 of the Treatment Period in the Modified Gastroparesis Cardinal Symptom Index-Daily Diary (mGCSI-DD) Total Score.	Change from Baseline to Week 4 of the treatment period in the mGCSI-DD total score in male and female subjects receiving metoclopramide nasal spray versus subjects receiving placebo. The mGCSI-DD is a patient reported outcome measure of gastroparesis symptom severity composed of 4 individual symptoms (listed below) with each symptom graded on a scale from 0 (none) to 5 (very severe).; Nausea (feeling sick to your stomach as if you were going to vomit or throw up); Early satiety (not able to finish a normal sized meal); Bloating (feeling like you need to loosen clothes); Upper abdominal pain (above the navel) The mGCSI-DD daily score is a mean of the 4 individual symptom scores. The total score is a mean of the daily scores for the observation period. A mean change (improvement) of >1 category (for example, moderate to mild or severe to moderate) is considered to be clinically meaningful.	4 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Pre-specified Endpoint is the Change From Baseline to Week 4 of the Treatment Period in the Modified Gastroparesis Cardinal Symptom Index-Daily Diary (mGCSI-DD) Total Score by Gender.	Change from Baseline to Week 4 of the treatment period in the mGCSI-DD total score in Female subjects receiving metoclopramide nasal spray versus Female subjects receiving placebo. The mGCSI-DD is a patient reported outcome measure of gastroparesis symptom severity composed of 4 individual symptoms (listed below) with each symptom graded on a scale from 0 (none) to 5 (very severe).; Nausea (feeling sick to your stomach as if you were going to vomit or throw up); Early satiety (not able to finish a normal sized meal); Bloating (feeling like you need to loosen clothes); Upper abdominal pain (above the navel) The mGCSI-DD daily score is a mean of the 4 individual symptom scores. The total score is a mean of the daily scores for the observation period. A mean change (improvement) of >1 category (for example, moderate to mild or severe to moderate) is considered to be clinically meaningful.	4 weeks

Collaborators and Investigators

• Sponsor: Evoke Pharma

Publications and helpful links

General Publications

• Parkman HP, Carlson MR, Gonyer D. Metoclopramide Nasal Spray Reduces Symptoms of Gastroparesis in Women, but not Men, With Diabetes: Results of a Phase 2B Randomized Study. Clin Gastroenterol Hepatol. 2015 Jul;13(7):1256-1263.e1. doi: 10.1016/j.cgh.2014.12.030. Epub 2015 Jan 7.

Study record dates

Study Major Dates

• Study Start: April 1, 2009
• Primary Completion (ACTUAL): December 1, 2011
• Study Completion (ACTUAL): December 1, 2011

Study Registration Dates

• First Submitted: February 17, 2009
• First Submitted That Met QC Criteria: February 17, 2009
• First Posted (ESTIMATE): February 18, 2009

Study Record Updates

• Last Update Posted (ESTIMATE): June 27, 2014
• Last Update Submitted That Met QC Criteria: June 17, 2014
• Last Verified: November 1, 2013

More Information

Terms related to this study

• Keywords: Diabetes; Diabetes Mellitus; Gastroparesis; Delayed Gastric Emptying; Diabetic Gastroparesis
• Additional Relevant MeSH Terms: Digestive System Diseases; Glucose Metabolism Disorders; Metabolic Diseases; Neurologic Manifestations; Endocrine System Diseases; Gastrointestinal Diseases; Stomach Diseases; Paralysis; Diabetes Mellitus; Gastroparesis; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Antiemetics; Gastrointestinal Agents; Dopamine Agents; Dopamine D2 Receptor Antagonists; Dopamine Antagonists; Metoclopramide
• Other Study ID Numbers: METO-IN-002