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

NCT00845858 | Completed Phase 2 Results

• 1 other identifier: METO-IN-002
• Study Type: interventional
• Target: 287
• Locations: 1 country
• Sites: 65

Brief Summary

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.

Conditions

Gastroparesis; Diabetic Gastroparesis; Diabetes; Diabetes Mellitus; Delayed Gastric Emptying

Keywords

Gastroparesis; Diabetic Gastroparesis; Diabetes; Diabetes Mellitus; Delayed Gastric Emptying

Outcome Measures

Primary Outcomes (1)

• 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). 1. Nausea (feeling sick to your stomach as if you were going to vomit or throw up) 2. Early satiety (not able to finish a normal sized meal) 3. Bloating (feeling like you need to loosen clothes) 4. 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 Outcomes (1)

• 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.

  4 weeks

Study Arms (3)

Metoclopramide Nasal Spray 10 mg

ACTIVE COMPARATOR

Drug: metoclopramide

Metoclopramide Nasal Spray 14 mg

ACTIVE COMPARATOR

Drug: metoclopramide

Placebo Nasal Spray

PLACEBO COMPARATOR

Drug: Placebo

Interventions

metoclopramide DRUG

30 minutes before meals and at bedtime for 4 weeks

Also known as: Reglan

Metoclopramide Nasal Spray 10 mg; Metoclopramide Nasal Spray 14 mg

Placebo DRUG

30 minutes before meals and at bedtime

Placebo Nasal Spray

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male subjects and non-pregnant, non-lactating female subjects between the ages of 18 and 75 years (inclusive)
• Willing and able to give written informed consent to participate in the study
• Ability to read and understand English
• Diagnosis of Type 1 or Type 2 diabetes
• Diagnosis of diabetic gastroparesis previously documented
• A mean daily GCSI-DD score of ≥2 and ≤4 for the 7 days prior to the Randomization Visit (Visit 3, Day 0)
• 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)
• 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
• Willingness to discontinue current treatment for diabetic gastroparesis and to avoid all medications specified by the protocol for the duration of the study

You may not qualify if:

• 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
• 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
• History of or physical findings suggestive of tardive dyskinesia
• 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)
• History of allergy to any of the ingredients in the study drug formulation; metoclopramide, citric acid, sodium citrate, benzalkonium chloride, EDTA, or sorbitol
• History of organ transplant, chronic pancreatitis, gross malabsorptive syndromes, celiac disease, or inflammatory bowel disease
• Malignancy (with the exception of basal cell carcinoma of the skin) currently present, initially diagnosed or recurring within 5 years of enrollment
• 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
• Have renal dysfunction calculated as creatinine clearance (CrCl) \< 40 mL/min at Screening (Visit 1)
• Have a hemoglobin A1c \> 12.5% at Screening (Visit 1)
• 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
• 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)
• 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)
• 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)
• Female subjects who are trying to conceive, are pregnant, or are lactating

Sponsors & Collaborators

• Evoke Pharma: lead

Study Sites (65)

Digestive Specialists of the Southeast

Dothan, Alabama, 36305, United States

Location

Clinical Research Associates

Huntsville, Alabama, 35801, United States

Location

Medical Affiliated Research Center, Inc.

Huntsville, Alabama, 35801, United States

Location

Desert Sun Gastroenterology

Tucson, Arizona, 85710, United States

Location

Clopton Clinic

Jonesboro, Arkansas, 72401, United States

Location

Arkansas Gastroenterology

Sherwood, Arkansas, 72120, United States

Location

Robert M. Karns, MD, a Medical Corporation

Beverly Hills, California, 90211, United States

Location

VA Long Beach Healthcare System

Long Beach, California, 90822, United States

Location

Impact Clinical Trials

Los Angeles, California, 90036, United States

Location

Prime-Care Clinical Research

Mission Viejo, California, 92691, United States

Location

Infosphere Clinical Research, Inc.

West Hills, California, 91307, United States

Location

Westlake Medical Research

Westlake Village, California, 91361, United States

Location

Consultants for Clinical Research of South Florida

Boynton Beach, Florida, 33426, United States

Location

Innovative Research of West Florida, Inc.

Clearwater, Florida, 33756, United States

Location

Nature Coast Clinical Research

Inverness, Florida, 34452, United States

Location

Borland-Groover Clinic

Jacksonville, Florida, 32256, United States

Location

AppleMed Research, Inc.

Miami, Florida, 33155, United States

Location

International Research Associates, LLC

Miami, Florida, 33183, United States

Location

Newton Medical Center

Conyers, Georgia, 30013, United States

Location

Gastrointestinal Specialists of Georgia

Marietta, Georgia, 30060, United States

Location

Rockford Gastroenterology Associates

Rockford, Illinois, 61107, United States

Location

Saint John's Research Institute

Anderson, Indiana, 46016, United States

Location

Cotton-O'Neil Clinical Research Center

Topeka, Kansas, 66606, United States

Location

Professional Research Network of Kansas

Wichita, Kansas, 67203, United States

Location

Delta Research Partners, LLC

Monroe, Louisiana, 71201, United States

Location

Metropolitan Gastroenterology Group

Chevy Chase, Maryland, 20815, United States

Location

Maryland Digestive Disease Research, LLC

Laurel, Maryland, 20707, United States

Location

Endoscopic Microsurgery Associates

Towson, Maryland, 21204, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Plymouth Clinic

Plymouth, Minnesota, 55446, United States

Location

CRC of Jackson, LLC

Jackson, Mississippi, 39202, United States

Location

Gastrointestional Associates

Jackson, Mississippi, 39202, United States

Location

Digestive Health Specialists

Tupelo, Mississippi, 38801, United States

Location

Kansas City Gastroenterology & Hepatology

Kansas City, Missouri, 64131, United States

Location

Center for Digestive and Liver Diseases, Inc.

Mexico, Missouri, 65265, United States

Location

Lovelace Scientific Resources, Inc.

Albuquerque, New Mexico, 87108, United States

Location

Medex Healthcare Research, Inc.

New York, New York, 10004, United States

Location

Research Associates of New York

New York, New York, 10075, United States

Location

Gastroenterology Associates

Poughkeepsie, New York, 12601, United States

Location

Cumberland Research Associates

Fayetteville, North Carolina, 28304, United States

Location

LeBauer Research Associates

Greensboro, North Carolina, 27406, United States

Location

Wake Research Associates

Raleigh, North Carolina, 27612, United States

Location

Hanover Medical Specialists

Wilmington, North Carolina, 28401, United States

Location

Piedmont Medical Research

Winston-Salem, North Carolina, 27103, United States

Location

AGA

Akron, Ohio, 44302, United States

Location

Consultants for Clinical Research

Cincinnati, Ohio, 45211, United States

Location

Hightop Medical Research Center

Cincinnati, Ohio, 45224, United States

Location

Great Lakes Gastroenterology

Mentor, Ohio, 44060, United States

Location

Regional Gastroenterology Associates of Lancaster, Ltd.

Lancaster, Pennsylvania, 17604, United States

Location

PMA Medical Specialists

Limerick, Pennsylvania, 19468, United States

Location

Memphis Gastroenterology Group

Germantown, Tennessee, 38138, United States

Location

HCCA Clinical Research Solutions

Jackson, Tennessee, 37805, United States

Location

Medical Specialty Clinic Research

Jackson, Tennessee, 38301, United States

Location

Holston Medical Group, PC

Kingsport, Tennessee, 37660, United States

Location

Lovelace Scientific Resources

Austin, Texas, 78759, United States

Location

Jacinto Medical Group

Baytown (Houston), Texas, 77521, United States

Location

Dynamed Clinical Research

Houston, Texas, 77034, United States

Location

Digestive Health Associates of Texas, P.A.

Plano, Texas, 75075, United States

Location

Theda Oaks Endoscopy Center

San Antonio, Texas, 78258, United States

Location

Trinity Health Care

Tyler, Texas, 75702, United States

Location

Charlottesville Medical Research

Charlottesville, Virginia, 22911, United States

Location

Gastroenterology Associates of Tidewater

Chesapeake, Virginia, 23320, United States

Location

Digestive and Liver Disease Specialists

Norfolk, Virginia, 23502, United States

Location

Gastroenterology, Ltd.

Virginia Beach, Virginia, 23454, United States

Location

Wisconsin Center for Advanced Research

Milwaukee, Wisconsin, 53215, United States

Location

Related Publications (1)

• 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.

  PMID: 25576687 DERIVED

MeSH Terms

Conditions

Gastroparesis; Diabetes Mellitus

Interventions

Metoclopramide

Condition Hierarchy (Ancestors)

Stomach Diseases; Gastrointestinal Diseases; Digestive System Diseases; Paralysis; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Benzamides; Amides; Organic Chemicals; para-Aminobenzoates; Aminobenzoates; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Chlorobenzoates; Hydroxybenzoate Ethers; Hydroxybenzoates; Hydroxy Acids; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Phenyl Ethers; Phenols

Results Point of Contact

• Title: Marilyn R. Carlson
• Organization: Evoke Pharma

mcarlson@evokepharma.com

858-345-1494

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

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

Study Record Dates

• First Submitted: February 17, 2009
• First Posted: February 18, 2009
• Study Start: April 1, 2009
• Primary Completion: December 1, 2011
• Study Completion: December 1, 2011
• Last Updated: June 27, 2014
• Results First Posted: June 17, 2014

Record last verified: 2013-11

Locations

US (65)