Delayed Gastric Emptying, Diabetes, Diabetes Mellitus, Diabetic Gastroparesis, Gastroparesis
Conditions
Keywords
Gastroparesis, Diabetic Gastroparesis, Diabetes, Diabetes Mellitus, Delayed Gastric Emptying
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.
Interventions
DRUGmetoclopramide
30 minutes before meals and at bedtime for 4 weeks
DRUGPlacebo
30 minutes before meals and at bedtime
Sponsors
Evoke Pharma
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. | 4 weeks | 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
| Measure | Time frame | Description |
|---|---|---|
| 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. | 4 weeks | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Metoclopramide Nasal Spray 10 mg metoclopramide: 30 minutes before meals and at bedtime for 4 weeks | 96 |
| Metoclopramide Nasal Spray 14 mg metoclopramide: 30 minutes before meals and at bedtime for 4 weeks | 96 |
| Placebo Nasal Spray Placebo: 30 minutes before meals and at bedtime | 95 |
| Total | 287 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 3 | 8 | 4 |
| Overall Study | not eligible | 0 | 3 | 2 |
| Overall Study | Protocol Violation | 0 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 5 | 1 | 1 |
Baseline characteristics
| Characteristic | Metoclopramide Nasal Spray 10 mg | Metoclopramide Nasal Spray 14 mg | Placebo Nasal Spray | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 15 Participants | 13 Participants | 10 Participants | 38 Participants |
| Age, Categorical Between 18 and 65 years | 81 Participants | 83 Participants | 85 Participants | 249 Participants |
| Age, Continuous | 51.6 years STANDARD_DEVIATION 12.13 | 50.3 years STANDARD_DEVIATION 12.4 | 52.4 years STANDARD_DEVIATION 10.03 | 51.4 years STANDARD_DEVIATION 11.56 |
| Region of Enrollment United States | 96 participants | 96 participants | 95 participants | 287 participants |
| Sex: Female, Male Female | 65 Participants | 70 Participants | 68 Participants | 203 Participants |
| Sex: Female, Male Male | 31 Participants | 26 Participants | 27 Participants | 84 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 53 / 95 | 57 / 95 | 53 / 95 |
| serious Total, serious adverse events | 0 / 95 | 2 / 95 | 3 / 95 |
Outcome results
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). 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.
Time frame: 4 weeks
Population: ITT
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Metoclopramide Nasal Spray 10 mg | 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. | -1.2 units on a scale | Standard Deviation 1.18 |
| Metoclopramide Nasal Spray 14 mg | 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. | -1.2 units on a scale | Standard Deviation 0.94 |
| Placebo Nasal Spray | 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. | -1.0 units on a scale | Standard Deviation 0.89 |
Other Pre-specified
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). 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.
Time frame: 4 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Metoclopramide Nasal Spray 10 mg | 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. | -1.2 units on a scale | Standard Deviation 1.18 |
| Metoclopramide Nasal Spray 14 mg | 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. | -1.3 units on a scale | Standard Deviation 0.98 |
| Placebo Nasal Spray | 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. | -0.8 units on a scale | Standard Deviation 0.79 |