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

Condition(s) targeted: Gastroparesis; Diabetic Gastroparesis; Diabetes; Diabetes Mellitus; Delayed Gastric Emptying

Intervention: metoclopramide (Drug); Placebo (Drug)

Phase: Phase 2

Status: Recruiting

Sponsored by: Evoke Pharma

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.

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 design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Safety/Efficacy Study

Primary outcome: The primary efficacy endpoint is the change from Baseline to the last 7 days during the treatment period in the average GCSI-DD total score, in subjects receiving metoclopramide nasal spray versus subjects receiving placebo.

Secondary outcome: Abdominal pain and discomfort, hours of nausea, vomiting episodes, daily overall symptom severity, PAGI-SYM, use of rescue medication between groups, SF-12, disability scores, and OGS severity and overall treatment scores by subject and investigator

Minimum age: 18 Years. Maximum age: 75 Years. Gender(s): Both.

Criteria:

Inclusion Criteria:

1. Male subjects and non-pregnant, non-lactating female subjects between the ages of 18 and 75 years

2. Willing and able to give written informed consent to participate

3. The ability to read and understand English

4. Prior diagnosis of Type 1 or Type 2 diabetes

5. Diagnosis of diabetic gastroparesis previously documented within the last 12 months

6. A mean daily Gastroparesis Cardinal Symptom Index-Daily Diary (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 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. Disorders known to be associated with abnormal gastrointestinal motility such as gastric ulcer, duodenal ulcer, severe gastritis, gastric cancer, amyloidosis, neuromuscular diseases (including Parkinson's disease), collagen vascular diseases, alcoholism, uremia, malnutrition, and untreated hypothyroidism or post surgical causes

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 any medication known to be associated with tardive dyskinesia

5. History of allergy to any of the ingredients in the study drug formulation

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, untreated hypothyroidism, 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 > 10% at Screening

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; metoclopramide, domperidone, tricyclic antidepressants, macrolide antibiotics, prokinetic agents, cholinergic agents, agents with significant anticholinergic effects, narcotic analgesics, orally administered B-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

13. Clinically significant abnormal findings or a QTc interval > 450 milliseconds (msec) on the Screening Visit electrocardiogram (ECG)

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

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 with the exception of domperidone

Medical Affiliated Research Center, Inc., Huntsville, Alabama 35801, United States; Recruiting
LuAnne Boggs, Phone: 256-533-6603, Email: jgm@marc-research.com
Suresh Karne, MD, Principal Investigator

Westlake Medical Research, Westlake Village, California 91361, United States; Recruiting
Jamie Plocky, Phone: 805-496-3322, Email: jamie@wmresearch.com
Edward B Portnoy, MD, Principal Investigator

Impact Clinical Trials, Los Angeles, California 90036, United States; Recruiting
Yujing Lin, Phone: 310-289-8242, Email: ylin@impactla.org
Lydie Hazan, MD, Principal Investigator

Prime Care Clinical Research, Mission Viejo, California 92691, United States; Recruiting
Lina Khadra, Phone: 949-364-1662, Email: linakhadra@prime-care.org
Marwan Edris, MD, Principal Investigator

Innovative Research of West Florida, Inc., Clearwater, Florida 33756, United States; Recruiting
Susan Snyder, Phone: 727-584-6368, Email: susans@innovativeresearchfl.com
Miguel Trevino, MD, Principal Investigator

AppleMed Research, Inc., Miami, Florida 33155, United States; Recruiting
Carlos Manzano, Phone: 305-667-8434, Email: c26applemed@aol.com
Leonel Perez-Limonte, MD, Principal Investigator

International Research Associates, LLC, Miami, Florida 33183, United States; Recruiting
Yeline Gomez, Phone: 305-670-8830, Ext: 102, Email: ygomez@intrllc.comm
Christian F Breton, MD, Principal Investigator

Nature Coast Clinical Research, Inverness, Florida 34452, United States; Recruiting
Kimberly Siddell, Phone: 352-341-2100
Paul Hellstern, MD, Principal Investigator

Cotton-O'Neil Clinical Research Center, Topeka, Kansas 66606, United States; Recruiting
Sherrie Stottlemire, Phone: 785-270-4856, Email: sstottle@stormontvail.org
Thomas Welton, MD, Principal Investigator

Professional Research Network of Kansas, Wichita, Kansas 67203, United States; Recruiting
Cindy James, Phone: 316-838-7700, Email: cjames@prnofkansas.com
Dennis Buth, MD, Principal Investigator

CRC of Jackson, LLC, Jackson, Mississippi 39202, United States; Recruiting
Suzanne Griffith, Phone: 601-714-3261, Email: sgriffith@mbhs.org
Charles E Hall, MD, Principal Investigator

Gastrointestional Associates, Jackson, Mississippi 39202, United States; Recruiting
Donna Darwin, RN, Phone: 601-863-0395, Email: donna.darwin@gastrodocs.net
Billy Long, MD, Principal Investigator

Digestive Health Specialists, Tupelo, Mississippi 38801, United States; Recruiting
Lori Johnson, RN, Phone: 662-680-5654, Email: lcjohnson@nmhs.net
Stephen Amann, MD, Principal Investigator

Center for Digestive and Liver Diseases, Inc., Mexico, Missouri 65265, United States; Recruiting
Amy Bakke, Phone: 573-581-7196, Email: amy@gutdoc.us
Glen L Gordon, MD,FACP,FACG, Principal Investigator

Lovelace Scientific Resources, Inc., Albuquerque, New Mexico 87108, United States; Recruiting
Jeanie Tovrea, Phone: 505-348-9636, Email: jtovrea@lrri.org
Martin Conway, MD, Principal Investigator

Medical Research Associates, New York, New York 10075, United States; Recruiting
Robby Kirshoff, Phone: 212-996-1105, Email: robert.kirshoff@nyga.md
Lawrence B Cohen, Principal Investigator

Medex Healthcare Research, Inc., New York, New York 10004, United States; Recruiting
Emily Shaw, Phone: 646-722-6214, Email: Emily.shaw@medexhealth.net
David Pulver, MD, Principal Investigator

Wake Research Associates, Raleigh, North Carolina 27612, United States; Recruiting
Marsha Peery, RN, Phone: 919-781-2514, Email: mpeery@wakeresearch.com
Charles Barish, MD, Principal Investigator

Cumberland Research Associates, Fayetteville, North Carolina 28304, United States; Recruiting
Angela Person, Phone: 910-484-8163, Email: aperson@cumberlandresearchassociates.com
Valli Kodali, MD, Principal Investigator

Piedmont Medical Research, Winston-Salem, North Carolina 27103, United States; Recruiting
Janet Shuping, Phone: 336-760-8062, Email: jshuping@pmg-research.com
Robert Holmes, MD, Principal Investigator

Hanover Medical Specialists, Wilmington, North Carolina 28401, United States; Recruiting
Carol Lewis, Phone: 910-763-0131, Email: clewis@hmnsdocs.com
Frederick Opper, MD, Principal Investigator

Hightop Medical Research Center, Cincinnati, Ohio 45224, United States; Recruiting
Linda Fidelholtz, Phone: 513-681-0606
James Fidelholtz, MD, Principal Investigator

AGA, Akron, Ohio 44302, United States; Recruiting
Nina Thacker, Phone: 330-344-6728, Email: akrongastro42@aol.com
Thomas LoIudice, MD, Principal Investigator

Holston Medical Group, PC, Kingsport, Tennessee 37660, United States; Recruiting
Karen Coleman, Phone: 423-578-1568, Email: kec@hmgkpt.com
Emily Morawski, MD, Principal Investigator

Memphis Gastroenterology Group, Germantown, Tennessee 38138, United States; Recruiting
Rochelle McLarty, Phone: 901-747-3630, Ext: 342, Email: rochelle.mclarty@scresearch.net
Lawrence Wruble, MD, Principal Investigator

Lovelace Scientific Resources, Austin, Texas 78759, United States; Recruiting
Rick Gonzales, Phone: 512-795-9404, Email: rdgonzales@lrri.org
William Howland, MD, Principal Investigator

Jacinto Medical Group, Baytown (Houston), Texas 77521, United States; Recruiting
Fawaz Yousufuddin, Phone: 281-425-3805, Email: fyousuf@jacintomedical.com
Croline Johnston, MD, Principal Investigator

Starting date: April 2009
Last updated: July 30, 2009