Diabetic Gastroparesis
Conditions
Keywords
Gastroparesis, Diabetic, Delayed gastric emptying, Gastric stasis, Nausea, Vomiting, Bloating, Abdominal pain, Early satiety, Gastropathy
Brief summary
The purpose of this study is provide confirmation of the safety and efficacy of Metoclopramide Nasal Spray compared to placebo in reducing the symptoms of diabetic gastroparesis in adult women.
Detailed description
Diabetic women with clinical symptoms attributed to diabetic gastroparesis and documentation of delayed gastric emptying who meet the protocol-specified entry criteria will be randomized to Metoclopramide Nasal Spray 10 mg or placebo administered as a single intranasal spray four (4) times daily; 30 minutes before meals and at bedtime for a total of four (4) weeks.
Interventions
nasal spray formulation of metoclopramide
DRUGPlacebo Nasal Spray
nasal spray formulation with vehicle only
Sponsors
Evoke Pharma
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Non pregnant, non lactating female subjects between the ages of 18 and 75 years * Willingness and ability to give written informed consent * The ability to read, understand and speak English * Prior diagnosis of Type 1 or Type 2 diabetes * Diagnosis of diabetic gastroparesis with confirmation of delayed gastric emptying * A mean daily gastroparesis symptom score of ≥1.4 and ≤3.5 prior to randomization * Subjects of childbearing potential must agree to use contraception * Willingness to discontinue current treatment for diabetic gastroparesis and to avoid all proscribed (excluded) medications, as specified by the protocol, for the duration of the study
Exclusion criteria
* Gastric bypass, gastric banding, gastric pacemaker, post surgical causes of gastroparesis and disorders known to be associated with abnormal gastrointestinal motility * 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 * A history of, or physical findings suggestive of, tardive dyskinesia * A history of epilepsy or currently using and unwilling or unable stop other drugs known to be associated with extrapyramidal reactions at screening * A history of allergy to any of the ingredients in the study drug formulation * A history of organ transplant, chronic pancreatitis, gross malabsorptive syndromes, celiac disease, active inflammatory bowel disease (IBD), or symptomatic irritable bowel syndrome (IBS) * Malignancy (with the exception of treated squamous cell or basal cell carcinoma of the skin) currently present, initially diagnosed or recurring within five (5) years of screening * Renal dysfunction calculated as creatinine clearance (CrCl) \<40 mL/min at screening * Hemoglobin A1c \>11.5% at screening * Subjects who are trying to conceive, are pregnant, or are lactating
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Gastroparesis Symptom Assessment (GSA), a Patient Reported Outcome Measure | Baseline Period to Week 4 of the Treatment Period | Change from the Baseline Period to Week 4 of the Treatment Period in the mean daily Gastroparesis Symptom Assessment (GSA) total score for subjects receiving Metoclopramide Nasal Spray 10 mg versus subjects receiving placebo. The GSA minimum value is 0 (no symptoms) and the maximum value is 4 (very severe symptoms). A higher score is a worse outcome. |
Countries
United States
Participant flow
Recruitment details
Recruitment Period: 27 March 2014 to 27 May 2016 Types of Location: Medical Clinics, University-Based Practices Screening Period consisted of Washout Period, Qualification Period and Baseline Period. Mean daily Gastroparesis Symptom Assessment (GSA) total score ≥ 1.4 and ≤ 3.5 was required during Qualification and Baseline periods
Pre-assignment details
613 participants Screened, 205 participants completed and randomized to treatment. Negative Gastric Emptying Scintigraphy 129 Inclusion/Exclusion Failed 213 Withdrawal by participant 25 Other Reasons 41
Participants by arm
| Arm | Count |
|---|---|
| 10 mg Metoclopramide Nasal Spray Metoclopramide Nasal Spray 10 mg, 30 minutes before meals and at bedtime (QID) for 4 weeks
Metoclopramide Nasal Spray: nasal spray formulation of metoclopramide | 102 |
| Placebo Nasal Spray Placebo Nasal Spray 30 minutes before meals and at bedtime (QID) for 4 weeks
Placebo Nasal Spray: nasal spray formulation with vehicle only | 103 |
| Total | 205 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 5 | 0 |
| Overall Study | Lost to Follow-up | 2 | 0 |
| Overall Study | Post-dose QTcB > 270 msec | 0 | 1 |
| Overall Study | Protocol Violation | 1 | 1 |
| Overall Study | Withdrawal by Subject | 3 | 2 |
Baseline characteristics
| Characteristic | 10 mg Metoclopramide Nasal Spray | Total | Placebo Nasal Spray |
|---|---|---|---|
| Age, Categorical Age (years) <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Age (years) >=65 years | 15 Participants | 28 Participants | 13 Participants |
| Age, Categorical Age (years) Between 18 and 65 years | 87 Participants | 177 Participants | 90 Participants |
| Age, Continuous | 52.9 Years STANDARD_DEVIATION 11.6 | 52.7 Years STANDARD_DEVIATION 11.2 | 52.5 Years STANDARD_DEVIATION 10.9 |
| Baseline Mean Daily GSA Score | 2.28 units on a scale STANDARD_DEVIATION 0.518 | 2.29 units on a scale STANDARD_DEVIATION 0.53 | 2.30 units on a scale STANDARD_DEVIATION 0.552 |
| Co-Existing Complications of Diabetes Any Complication | 38 Participants | 79 Participants | 41 Participants |
| Co-Existing Complications of Diabetes Diabetic Retinopathy | 7 Participants | 9 Participants | 2 Participants |
| Co-Existing Complications of Diabetes Nephropathy | 2 Participants | 3 Participants | 1 Participants |
| Co-Existing Complications of Diabetes Neuropathy | 35 Participants | 74 Participants | 39 Participants |
| Co-Existing Complications of Diabetes No Complications | 64 Participants | 124 Participants | 60 Participants |
| Co-Existing Complications of Diabetes Peripheral Vascular Disease/Amputation | 2 Participants | 5 Participants | 3 Participants |
| Current Diabetes Mellitus Treatment Diet | 30 Participants | 63 Participants | 33 Participants |
| Current Diabetes Mellitus Treatment Insulin | 51 Participants | 105 Participants | 54 Participants |
| Current Diabetes Mellitus Treatment None | 0 Participants | 1 Participants | 1 Participants |
| Current Diabetes Mellitus Treatment Oral Diabetic Medications | 69 Participants | 143 Participants | 74 Participants |
| Current Diabetes Mellitus Treatment Other | 11 Participants | 28 Participants | 17 Participants |
| Diabetes Mellitus Duration | 12.4 years STANDARD_DEVIATION 10.51 | 12.9 years STANDARD_DEVIATION 10.7 | 13.4 years STANDARD_DEVIATION 10.9 |
| Diabetes Mellitus Type Type 1 | 13 Participants | 24 Participants | 11 Participants |
| Diabetes Mellitus Type Type 2 | 89 Participants | 181 Participants | 92 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 11 Participants | 25 Participants | 14 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 91 Participants | 180 Participants | 89 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Qualification Mean Daily GSA Score | 2.259 units on a scale STANDARD_DEVIATION 0.481 | 2.251 units on a scale STANDARD_DEVIATION 0.483 | 2.242 units on a scale STANDARD_DEVIATION 0.487 |
| Race (NIH/OMB) American Indian or Alaska Native | 2 Participants | 5 Participants | 3 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 2 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 20 Participants | 57 Participants | 37 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 78 Participants | 141 Participants | 63 Participants |
| Region of Enrollment United States | 102 Participants | 205 Participants | 103 Participants |
| Sex: Female, Male Female | 102 Participants | 205 Participants | 103 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 102 | 0 / 103 |
| other Total, other adverse events | 21 / 102 | 36 / 103 |
| serious Total, serious adverse events | 3 / 102 | 2 / 103 |
Outcome results
Primary
Gastroparesis Symptom Assessment (GSA), a Patient Reported Outcome Measure
Change from the Baseline Period to Week 4 of the Treatment Period in the mean daily Gastroparesis Symptom Assessment (GSA) total score for subjects receiving Metoclopramide Nasal Spray 10 mg versus subjects receiving placebo. The GSA minimum value is 0 (no symptoms) and the maximum value is 4 (very severe symptoms). A higher score is a worse outcome.
Time frame: Baseline Period to Week 4 of the Treatment Period
Population: Intent-to-Treat (ITT) Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 10 mg Metoclopramide Nasal Spray | Gastroparesis Symptom Assessment (GSA), a Patient Reported Outcome Measure | -0.925 score on a scale | Standard Deviation 0.935 |
| Placebo Nasal Spray | Gastroparesis Symptom Assessment (GSA), a Patient Reported Outcome Measure | -0.896 score on a scale | Standard Deviation 0.947 |
p-value: 0.881ANCOVA
Post Hoc
Gastroparesis Symptom Assessment (GSA)
Change from the Baseline Period to Weeks 1, 2, 3 and 4 of the Treatment Period in the mean daily Gastroparesis Symptom Assessment (GSA) total score in subjects with moderate to severe symptoms at Baseline (GSA score greater than 2.7) receiving Metoclopramide Nasal Spray 10 mg versus subjects receiving placebo. The GSA minimum value is 0 (no symptoms) and the maximum value is 4 (very severe symptoms). A higher score is a worse outcome.
Time frame: Baseline Period to Weeks 1, 2, 3 and 4 of the Treatment Period
Population: Subjects in the intent-to-treat population with moderate to severe disease (symptoms) at Baseline (i.e., baseline GSA scores higher than 2.7 on the 0-4 scale). Results presented are Weeks 1, 2, 3 and 4 compared to the Baseline Period.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 10 mg Metoclopramide Nasal Spray | Gastroparesis Symptom Assessment (GSA) | Week 3 of Treatment compared to Baseline Period | -1.095 score on a scale | Standard Deviation 0.912 |
| 10 mg Metoclopramide Nasal Spray | Gastroparesis Symptom Assessment (GSA) | Week 2 of Treatment compared to Baseline Period | -0.949 score on a scale | Standard Deviation 0.864 |
| 10 mg Metoclopramide Nasal Spray | Gastroparesis Symptom Assessment (GSA) | Week 4 of Treatment compared to Baseline Period | -1.218 score on a scale | Standard Deviation 0.991 |
| 10 mg Metoclopramide Nasal Spray | Gastroparesis Symptom Assessment (GSA) | Week 1 of Treatment compared to Baseline Period | -0.587 score on a scale | Standard Deviation 0.52 |
| Placebo Nasal Spray | Gastroparesis Symptom Assessment (GSA) | Week 4 of Treatment compared to Baseline Period | -0.857 score on a scale | Standard Deviation 0.938 |
| Placebo Nasal Spray | Gastroparesis Symptom Assessment (GSA) | Week 2 of Treatment compared to Baseline Period | -0.616 score on a scale | Standard Deviation 0.635 |
| Placebo Nasal Spray | Gastroparesis Symptom Assessment (GSA) | Week 3 of Treatment compared to Baseline Period | -0.750 score on a scale | Standard Deviation 0.785 |
| Placebo Nasal Spray | Gastroparesis Symptom Assessment (GSA) | Week 1 of Treatment compared to Baseline Period | -0.388 score on a scale | Standard Deviation 0.444 |
Comparison: Change in mean daily GSA total score from Baseline to Week 1: metoclopramide nasal spray minus placebo.p-value: 0.036ANCOVA
Comparison: Change in mean daily GSA total score from Baseline to Week 2: metoclopramide nasal spray minus placebop-value: 0.025ANCOVA
Comparison: Change in mean daily GSA total score from Baseline to Week 3: metoclopramide nasal spray minus placebo.p-value: 0.039ANCOVA
Comparison: Change in mean daily GSA total score from Baseline to Week 4: metoclopramide nasal spray minus placebo.p-value: 0.085ANCOVA