Efficacy and Safety of Metoclopramide Nasal Spray Solution in Diabetic Patients With Gastroparesis
Condition: Gastroparesis; Diabetic Gastroparesis; Diabetes; Diabetes Mellitus; Delayed Gastric Emptying
MeSH terms: Gastroparesis; Diabetes Mellitus
Intervention: metoclopramide; Placebo
Intervention description: 30 minutes before meals and at bedtime for 4 weeks; 30 minutes before meals and at bedtime
Intervention MeSH terms: Metoclopramide
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 287.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No
Keywords: Gastroparesis; Diabetic Gastroparesis; Diabetes; Diabetes Mellitus; Delayed Gastric Emptying

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