Clinical trial NCT00845858: Efficacy and Safety of Metoclopramide Nasal Spray Solution in Diabetic Patients With Gastroparesis
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Gastroparesis
Diabetic Gastroparesis
Diabetes
Diabetes Mellitus
Delayed Gastric Emptying
Keywords: Gastroparesis
Diabetic Gastroparesis
Diabetes
Diabetes Mellitus
Delayed Gastric Emptying
Lead sponsor: Evoke Pharma
Sponsor class: INDUSTRY
First posted: 2009-02-18
Enrollment: 287
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: 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.
timeFrame: 4 weeks
Secondary outcomes:
Other outcomes:
measure: 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.
timeFrame: 4 weeks
Locations:
city: Dothan
country: United States
facility: Digestive Specialists of the Southeast
state: Alabama
city: Huntsville
country: United States
facility: Clinical Research Associates
state: Alabama
city: Huntsville
country: United States
facility: Medical Affiliated Research Center, Inc.
state: Alabama
city: Tucson
country: United States
facility: Desert Sun Gastroenterology
state: Arizona
city: Jonesboro
country: United States
facility: Clopton Clinic
state: Arkansas
city: Sherwood
country: United States
facility: Arkansas Gastroenterology
state: Arkansas
city: Beverly Hills
country: United States
facility: Robert M. Karns, MD, a Medical Corporation
state: California
city: Long Beach
country: United States
facility: VA Long Beach Healthcare System
state: California
city: Los Angeles
country: United States
facility: Impact Clinical Trials
state: California
city: Mission Viejo
country: United States
facility: Prime-Care Clinical Research
state: California
city: West Hills
country: United States
facility: Infosphere Clinical Research, Inc.
state: California
city: Westlake Village
country: United States
facility: Westlake Medical Research
state: California
city: Boynton Beach
country: United States
facility: Consultants for Clinical Research of South Florida
state: Florida
city: Clearwater
country: United States
facility: Innovative Research of West Florida, Inc.
state: Florida
city: Inverness
country: United States
facility: Nature Coast Clinical Research
state: Florida
city: Jacksonville
country: United States
facility: Borland-Groover Clinic
state: Florida
city: Miami
country: United States
facility: AppleMed Research, Inc.
state: Florida
city: Miami
country: United States
facility: International Research Associates, LLC
state: Florida
city: Conyers
country: United States
facility: Newton Medical Center
state: Georgia
city: Marietta
country: United States
facility: Gastrointestinal Specialists of Georgia
state: Georgia
city: Rockford
country: United States
facility: Rockford Gastroenterology Associates
state: Illinois
city: Anderson
country: United States
facility: Saint John's Research Institute
state: Indiana
city: Topeka
country: United States
facility: Cotton-O'Neil Clinical Research Center
state: Kansas
city: Wichita
country: United States
facility: Professional Research Network of Kansas
state: Kansas
city: Monroe
country: United States
facility: Delta Research Partners, LLC
state: Louisiana
city: Chevy Chase
country: United States
facility: Metropolitan Gastroenterology Group
state: Maryland
city: Laurel
country: United States
facility: Maryland Digestive Disease Research, LLC
state: Maryland
city: Towson
country: United States
facility: Endoscopic Microsurgery Associates
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Plymouth
country: United States
facility: Plymouth Clinic
state: Minnesota
city: Jackson
country: United States
facility: CRC of Jackson, LLC
state: Mississippi
city: Jackson
country: United States
facility: Gastrointestional Associates
state: Mississippi
city: Tupelo
country: United States
facility: Digestive Health Specialists
state: Mississippi
city: Kansas City
country: United States
facility: Kansas City Gastroenterology & Hepatology
state: Missouri
city: Mexico
country: United States
facility: Center for Digestive and Liver Diseases, Inc.
state: Missouri
city: Albuquerque
country: United States
facility: Lovelace Scientific Resources, Inc.
state: New Mexico
city: New York
country: United States
facility: Medex Healthcare Research, Inc.
state: New York
city: New York
country: United States
facility: Research Associates of New York
state: New York
city: Poughkeepsie
country: United States
facility: Gastroenterology Associates
state: New York
city: Fayetteville
country: United States
facility: Cumberland Research Associates
state: North Carolina
city: Greensboro
country: United States
facility: LeBauer Research Associates
state: North Carolina
city: Raleigh
country: United States
facility: Wake Research Associates
state: North Carolina
city: Wilmington
country: United States
facility: Hanover Medical Specialists
state: North Carolina
city: Winston-Salem
country: United States
facility: Piedmont Medical Research
state: North Carolina
city: Akron
country: United States
facility: AGA
state: Ohio
city: Cincinnati
country: United States
facility: Consultants for Clinical Research
state: Ohio
city: Cincinnati
country: United States
facility: Hightop Medical Research Center
state: Ohio
city: Mentor
country: United States
facility: Great Lakes Gastroenterology
state: Ohio
city: Lancaster
country: United States
facility: Regional Gastroenterology Associates of Lancaster, Ltd.
state: Pennsylvania
city: Limerick
country: United States
facility: PMA Medical Specialists
state: Pennsylvania
city: Germantown
country: United States
facility: Memphis Gastroenterology Group
state: Tennessee
city: Jackson
country: United States
facility: HCCA Clinical Research Solutions
state: Tennessee
city: Jackson
country: United States
facility: Medical Specialty Clinic Research
state: Tennessee
city: Kingsport
country: United States
facility: Holston Medical Group, PC
state: Tennessee
city: Austin
country: United States
facility: Lovelace Scientific Resources
state: Texas
city: Baytown (Houston)
country: United States
facility: Jacinto Medical Group
state: Texas
city: Houston
country: United States
facility: Dynamed Clinical Research
state: Texas
city: Plano
country: United States
facility: Digestive Health Associates of Texas, P.A.
state: Texas
city: San Antonio
country: United States
facility: Theda Oaks Endoscopy Center
state: Texas
city: Tyler
country: United States
facility: Trinity Health Care
state: Texas
city: Charlottesville
country: United States
facility: Charlottesville Medical Research
state: Virginia
city: Chesapeake
country: United States
facility: Gastroenterology Associates of Tidewater
state: Virginia
city: Norfolk
country: United States
facility: Digestive and Liver Disease Specialists
state: Virginia
city: Virginia Beach
country: United States
facility: Gastroenterology, Ltd.
state: Virginia
city: Milwaukee
country: United States
facility: Wisconsin Center for Advanced Research
state: Wisconsin
Study officials:
References:
citation: 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.