Multicenter Study to Evaluate the Efficacy and Safety of Metoclopramide Nasal Spray in Men With Diabetic Gastroparesis

• Sponsor: Evoke Pharma (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02025751
• Collaborator: (none)
• Enrollment: 53
• Locations: 49
• Arms: 2
• Actual Duration (Months): 30
• Patients Per Site: 1.1
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

The purpose of this study is evaluate the safety and efficacy of Metoclopramide Nasal Spray compared to placebo in reducing the symptoms of diabetic gastroparesis in adult men.

Condition or Disease	Intervention/Treatment	Phase
Diabetic Gastroparesis	Drug: Metoclopramide Nasal Spray; Drug: Placebo Nasal Spray	Phase 3

Detailed Description

Diabetic men 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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 53 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Phase 3 Companion Study of Intranasal Metoclopramide in Men With Symptomatic Diabetic Gastroparesis
• Actual Study Start Date: Apr 1, 2014
• Actual Primary Completion Date: Aug 1, 2016
• Actual Study Completion Date: Oct 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Metoclopramide Nasal Spray Metoclopramide Nasal Spray 10 mg, 30 minutes before meals and at bedtime (QID) for 4 weeks	Drug: Metoclopramide Nasal Spray; One 10 mg spray dose 30 minutes before meals and before bed for 28 days (QID)
Placebo Comparator: Placebo Nasal Spray Placebo Nasal Spray 30 minutes before meals and at bedtime (QID) for 4 weeks	Drug: Placebo Nasal Spray; One placebo spray dose 30 minutes before meals and before bed for 28 days (QID); Other Names: Vehicle

Outcome Measures

Primary Outcome Measures

1. Gastroparesis Symptom Assessment (GSA), a Patient Reported Outcome Measure [Change from the Baseline Period to Week 4 in Daily Total Score (Intent-to Treat Population)]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Male 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

• 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

• 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Birmingham Gasteroenterology Associates, P.C.	Birmingham	Alabama	United States	35209
2	Digestive Specialists of the Southeast	Dothan	Alabama	United States	36305
3	Clinical Research Associates	Huntsville	Alabama	United States	35801
4	Central Arizone Medical Associates/Clinical Research Advantage	Mesa	Arizona	United States	85206
5	Preferred Research Partners	Little Rock	Arkansas	United States	72211
6	Arkansas Gastroenterology	Sherwood	Arkansas	United States	72120
7	Precision Research Institute, LLC	Chula Vista	California	United States	91910
8	John Muir Physician Network Clinical Research Center	Concord	California	United States	94520
9	Precision Research Institute, LLC	San Diego	California	United States	92114
10	The Center for Gastrointestinal Disorders	Hollywood	Florida	United States	33021
11	Nature Coast Clinical Research	Inverness	Florida	United States	34452
12	International Research Associates, LLC	Miami	Florida	United States	33183
13	Advanced Medical Research	Port Orange	Florida	United States	32127
14	Tri-County Research	Athens	Georgia	United States	30606
15	Digestive Healthcare of Georgia	Atlanta	Georgia	United States	30309
16	Newton Medical Center	Conyers	Georgia	United States	30013
17	Gastrointestinal Specialists of Georgia, PC	Marietta	Georgia	United States	30060
18	Atlanta Gastroenterology Associates	Marietta	Georgia	United States	30067
19	Southwest Gastroenterology	Oak Lawn	Illinois	United States	60453
20	Indiana University Health UH 1634	Indianapolis	Indiana	United States	46202
21	Professional Research Network of Kansas	Wichita	Kansas	United States	67203
22	Gastroenterology Associates, LLC	Baton Rouge	Louisiana	United States	70809
23	Delta Research Partners, LLC	Monroe	Louisiana	United States	71201
24	Clinical Research Institute of Michigan	Chesterfield	Michigan	United States	48047
25	Center for Digestive Health	Troy	Michigan	United States	48098
26	Gastroenterology Associates of Western Michigan	Wyoming	Michigan	United States	49519
27	Kansas City Gastroenterology & Hepatology	Kansas City	Missouri	United States	64131
28	Dartmouth-Hitchcock Medical Center	Lebanon	New Hampshire	United States	03756
29	The Gastroenterology Group of South Jersey	Vineland	New Jersey	United States	08360
30	Lovelace Scientific Resources, Inc.	Albuquerque	New Mexico	United States	87108
31	Premier Medical Group of the Hudson, PC	Poughkeepsie	New York	United States	12601
32	Cumberland Research Associates	Fayetteville	North Carolina	United States	28304
33	LeBauer Research Associates	Greensboro	North Carolina	United States	27406
34	Kinston Medical Specialist Clinical Research Office	Kinston	North Carolina	United States	28501
35	Wake Research Associates	Raleigh	North Carolina	United States	27612
36	PMG Research of Salisbury	Salisbury	North Carolina	United States	28144
37	Piedmont Medical Research	Winston-Salem	North Carolina	United States	27103
38	Dayton Gastroenterology	Beavercreek	Ohio	United States	45440
39	Temple University	Philadelphia	Pennsylvania	United States	19140
40	HCCA Clinical Research Solutions	Jackson	Tennessee	United States	37805
41	Gastroenterology Associates	Kingsport	Tennessee	United States	37660
42	Quality Medical Research	Nashville	Tennessee	United States	37211
43	Texas Clinical Research Institute	Arlington	Texas	United States	76012
44	Lovelace Scientific Resources	Austin	Texas	United States	78758
45	Texas Tech University Health Sciences Center	El Paso	Texas	United States	79905
46	Burke Internal Medicine	Burke	Virginia	United States	22015
47	Manassas Clinical Research	Manassas	Virginia	United States	20110
48	National Clinical Research	Norfolk	Virginia	United States	23502
49	Wisconsin Center for Advanced Research	Milwaukee	Wisconsin	United States	53215

Sponsors and Collaborators

• Evoke Pharma

Investigators

• Study Director: Marilyn R Carlson, DMD, MD, Evoke Pharma, Inc.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Evoke Pharma
• ClinicalTrials.gov Identifier: NCT02025751
• Other Study ID Numbers: METO-IN-004
• First Posted: Jan 1, 2014
• Last Update Posted: Jul 7, 2020
• Last Verified: Jun 1, 2020

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Evoke Pharma: Diabetes; Gastroparesis; Delayed gastric emptying; Nausea; Vomiting; Bloating; Abdominal pain; Early Satiety; Gastric stasis; Gastropathy
• Additional relevant MeSH terms: Gastroparesis; Metoclopramide

Study Results

Participant Flow

Arm/Group Title	Metoclopramide Nasal Spray	Placebo Nasal Spray
Arm/Group Description	Metoclopramide Nasal Spray 10 mg, 30 minutes before meals and at bedtime (QID) for 4 weeks Metoclopramide Nasal Spray: One 10 mg spray dose 30 minutes before meals and before bed for 28 days (QID)	Placebo Nasal Spray 30 minutes before meals and at bedtime (QID) for 4 weeks Placebo Nasal Spray: One placebo spray dose 30 minutes before meals and before bed for 28 days (QID)
Period Title: Overall Study
STARTED	26	27
COMPLETED	25	24
NOT COMPLETED	1	3

Baseline Characteristics

Arm/Group Title	Metoclopramide Nasal Spray	Placebo Nasal Spray	Total
Arm/Group Description	Metoclopramide Nasal Spray 10 mg, 30 minutes before meals and at bedtime (QID) for 4 weeks Metoclopramide Nasal Spray: One 10 mg spray dose 30 minutes before meals and before bed for 28 days (QID)	Placebo Nasal Spray 30 minutes before meals and at bedtime (QID) for 4 weeks Placebo Nasal Spray: One placebo spray dose 30 minutes before meals and before bed for 28 days (QID)	Total of all reporting groups
Overall Participants	26	27	53
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	24 92.3%	24 88.9%	48 90.6%
>=65 years	2 7.7%	3 11.1%	5 9.4%
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%
Male	26 100%	27 100%	53 100%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	3 11.5%	6 22.2%	9 17%
Not Hispanic or Latino	23 88.5%	21 77.8%	44 83%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	1 3.8%	2 7.4%	3 5.7%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	6 23.1%	3 11.1%	9 17%
White	19 73.1%	22 81.5%	41 77.4%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	26 100%	27 100%	53 100%
Gastroparesis Symptom Assessment (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	2.096 (0.4801)	2.235 (0.4097)	2.167 (0.4468)

Outcome Measures

1. Primary Outcome

Title	Gastroparesis Symptom Assessment (GSA), a Patient Reported Outcome Measure
Description	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	Change from the Baseline Period to Week 4 in Daily Total Score (Intent-to Treat Population)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Metoclopramide Nasal Spray	Placebo Nasal Spray
Arm/Group Description	Metoclopramide Nasal Spray 10 mg, 30 minutes before meals and at bedtime (QID) for 4 weeks Metoclopramide Nasal Spray: One 10 mg spray dose 30 minutes before meals and before bed for 28 days (QID)	Placebo Nasal Spray 30 minutes before meals and at bedtime (QID) for 4 weeks Placebo Nasal Spray: One placebo spray dose 30 minutes before meals and before bed for 28 days (QID)
Measure Participants	26	27
Mean (Standard Deviation) [score on a scale]	-0.751 (0.4673)	-0.657 (0.9042)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Metoclopramide Nasal Spray, Placebo Nasal Spray
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.597
	Comments
	Method	ANCOVA
	Comments

Adverse Events

Time Frame	4 weeks
Arm/Group Title	Metoclopramide Nasal Spray		Placebo Nasal Spray
Arm/Group Description	Metoclopramide Nasal Spray 10 mg, 30 minutes before meals and at bedtime (QID) for 4 weeks Metoclopramide Nasal Spray: One 10 mg spray dose 30 minutes before meals and before bed for 28 days (QID)		Placebo Nasal Spray 30 minutes before meals and at bedtime (QID) for 4 weeks Placebo Nasal Spray: One placebo spray dose 30 minutes before meals and before bed for 28 days (QID)
All Cause Mortality
	Metoclopramide Nasal Spray		Placebo Nasal Spray
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/26 (0%)		0/27 (0%)
Serious Adverse Events
	Metoclopramide Nasal Spray		Placebo Nasal Spray
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/26 (0%)		3/27 (11.1%)
Gastrointestinal disorders
Impaired gastric emptying	0/26 (0%)	0	1/27 (3.7%)	1
Infections and infestations
Staphylococcal infection	0/26 (0%)	0	1/27 (3.7%)	1
Metabolism and nutrition disorders
Diabetes mellitus inadequate control	0/26 (0%)	0	1/27 (3.7%)	1
Other (Not Including Serious) Adverse Events
	Metoclopramide Nasal Spray		Placebo Nasal Spray
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	7/26 (26.9%)		3/27 (11.1%)
Gastrointestinal disorders
Abdominal pain	0/26 (0%)	0	1/27 (3.7%)	1
Ascites	1/26 (3.8%)	1	0/27 (0%)	0
Diarrhoea	1/26 (3.8%)	1	0/27 (0%)	0
Nausea	1/26 (3.8%)	1	0/27 (0%)	0
Oesophagitis ulcerative	0/26 (0%)	0	1/27 (3.7%)	1
General disorders
Malaise	0/26 (0%)	0	1/27 (3.7%)	1
Pyrexia	0/26 (0%)	0	1/27 (3.7%)	1
Infections and infestations
Abscess limb	0/26 (0%)	0	1/27 (3.7%)	1
Nasopharyngitis	1/26 (3.8%)	1	0/27 (0%)	0
Injury, poisoning and procedural complications
Ligament sprain	1/26 (3.8%)	1	0/27 (0%)	0
Investigations
Liver palpable	0/26 (0%)	0	1/27 (3.7%)	1
Platelet count decreased	1/26 (3.8%)	1	0/27 (0%)	0
Metabolism and nutrition disorders
Electrolyte imbalance	0/26 (0%)	0	1/27 (3.7%)	1
Hyperglycaemia	1/26 (3.8%)	1	0/27 (0%)	0
Hypoglycaemia	0/26 (0%)	0	1/27 (3.7%)	1
Type 1 diabetes mellitus	0/26 (0%)	0	1/27 (3.7%)	1
Psychiatric disorders
Depression	0/26 (0%)	0	1/27 (3.7%)	1
Renal and urinary disorders
Acute kidney injury	0/26 (0%)	0	1/27 (3.7%)	1
Chronic kidney disease	0/26 (0%)	0	1/27 (3.7%)	1
Respiratory, thoracic and mediastinal disorders
Throat irritation	1/26 (3.8%)	1	1/27 (3.7%)	1
Cough	0/26 (0%)	0	1/27 (3.7%)	1
Epistaxis	1/26 (3.8%)	1	0/27 (0%)	0
Nasal discomfort	1/26 (3.8%)	1	0/27 (0%)	0
Skin and subcutaneous tissue disorders
Dermatitis contact	1/26 (3.8%)	1	0/27 (0%)	0
Vascular disorders
Hypertension	0/26 (0%)	0	1/27 (3.7%)	1

Limitations/Caveats

Study failed to meet recruitment goals (N=150) and was completed after 24 months (N=53). All study visits and assessments were completed. Limited pharmacokinetic (PK) samples so no calculated PK parameters.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.