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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Evoke Pharma
ClinicalTrials.gov Identifier:
NCT00845858
First received: February 17, 2009
Last updated: June 17, 2014
Last verified: November 2013
  Purpose

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.


Condition Intervention Phase
Gastroparesis
Diabetic Gastroparesis
Diabetes
Diabetes Mellitus
Delayed Gastric Emptying
Drug: metoclopramide
Drug: Placebo
Phase 2

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

Resource links provided by NLM:


Further study details as provided by Evoke Pharma:

Primary Outcome Measures:
  • 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. [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]

    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.



Other Outcome Measures:
  • 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. [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]

    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).

    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.



Enrollment: 287
Study Start Date: April 2009
Study Completion Date: December 2011
Primary Completion Date: December 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Metoclopramide Nasal Spray 10 mg Drug: metoclopramide
30 minutes before meals and at bedtime for 4 weeks
Other Name: Reglan
Active Comparator: Metoclopramide Nasal Spray 14 mg Drug: metoclopramide
30 minutes before meals and at bedtime for 4 weeks
Other Name: Reglan
Placebo Comparator: Placebo Nasal Spray Drug: Placebo
30 minutes before meals and at bedtime

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00845858

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Sponsors and Collaborators
Evoke Pharma
  More Information

No publications provided

Responsible Party: Evoke Pharma
ClinicalTrials.gov Identifier: NCT00845858     History of Changes
Other Study ID Numbers: METO-IN-002
Study First Received: February 17, 2009
Results First Received: April 17, 2014
Last Updated: June 17, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Evoke Pharma:
Gastroparesis
Diabetic Gastroparesis
Diabetes
Diabetes Mellitus
Delayed Gastric Emptying

Additional relevant MeSH terms:
Metoclopramide
Diabetes Mellitus
Gastroparesis
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Stomach Diseases
Gastrointestinal Diseases
Digestive System Diseases
Paralysis
Neurologic Manifestations
Signs and Symptoms
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Gastrointestinal Agents
Dopamine Antagonists
Dopamine Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on August 28, 2014