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

Diabetes Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00845858
• Other study ID #: METO-IN-002
• Status: Completed
• Phase: Phase 2
• First received: February 17, 2009
• Last updated: June 17, 2014
• Start date: April 2009
• Est. completion date: December 2011

Study information

• Verified date: November 2013
• Source: Evoke Pharma
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 287
• Est. completion date: December 2011
• Est. primary completion date: December 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

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 ß 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 Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Delayed Gastric Emptying
• Diabetes
• Diabetes Mellitus
• Diabetic Gastroparesis
• Gastroparesis

Intervention

Drug:
• metoclopramide
30 minutes before meals and at bedtime for 4 weeks
• Placebo
30 minutes before meals and at bedtime

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Evoke Pharma

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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	No
Primary	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	No