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

• Sponsor: Evoke Pharma (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00845858
• Collaborator: (none)
• Enrollment: 287
• Locations: 65
• Arms: 3
• Duration (Months): 32
• Patients Per Site: 4.4
• Patients Per Site Per Month: 0.1

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Gastroparesis; Diabetic Gastroparesis; Diabetes; Diabetes Mellitus; Delayed Gastric Emptying	Drug: metoclopramide; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 287 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, 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
• Study Start Date: Apr 1, 2009
• Actual Primary Completion Date: Dec 1, 2011
• Actual Study Completion Date: Dec 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Metoclopramide Nasal Spray 10 mg	Drug: metoclopramide; 30 minutes before meals and at bedtime for 4 weeks; Other Names: Reglan
Active Comparator: Metoclopramide Nasal Spray 14 mg	Drug: metoclopramide; 30 minutes before meals and at bedtime for 4 weeks; Other Names: Reglan
Placebo Comparator: Placebo Nasal Spray	Drug: Placebo; 30 minutes before meals and at bedtime

Outcome Measures

Primary Outcome Measures

1. 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). Nausea (feeling sick to your stomach as if you were going to vomit or throw up) Early satiety (not able to finish a normal sized meal) Bloating (feeling like you need to loosen clothes) 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

1. 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). Nausea (feeling sick to your stomach as if you were going to vomit or throw up) Early satiety (not able to finish a normal sized meal) Bloating (feeling like you need to loosen clothes) 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Digestive Specialists of the Southeast	Dothan	Alabama	United States	36305
2	Clinical Research Associates	Huntsville	Alabama	United States	35801
3	Medical Affiliated Research Center, Inc.	Huntsville	Alabama	United States	35801
4	Desert Sun Gastroenterology	Tucson	Arizona	United States	85710
5	Clopton Clinic	Jonesboro	Arkansas	United States	72401
6	Arkansas Gastroenterology	Sherwood	Arkansas	United States	72120
7	Robert M. Karns, MD, a Medical Corporation	Beverly Hills	California	United States	90211
8	VA Long Beach Healthcare System	Long Beach	California	United States	90822
9	Impact Clinical Trials	Los Angeles	California	United States	90036
10	Prime-Care Clinical Research	Mission Viejo	California	United States	92691
11	Infosphere Clinical Research, Inc.	West Hills	California	United States	91307
12	Westlake Medical Research	Westlake Village	California	United States	91361
13	Consultants for Clinical Research of South Florida	Boynton Beach	Florida	United States	33426
14	Innovative Research of West Florida, Inc.	Clearwater	Florida	United States	33756
15	Nature Coast Clinical Research	Inverness	Florida	United States	34452
16	Borland-Groover Clinic	Jacksonville	Florida	United States	32256
17	AppleMed Research, Inc.	Miami	Florida	United States	33155
18	International Research Associates, LLC	Miami	Florida	United States	33183
19	Newton Medical Center	Conyers	Georgia	United States	30013
20	Gastrointestinal Specialists of Georgia	Marietta	Georgia	United States	30060
21	Rockford Gastroenterology Associates	Rockford	Illinois	United States	61107
22	Saint John's Research Institute	Anderson	Indiana	United States	46016
23	Cotton-O'Neil Clinical Research Center	Topeka	Kansas	United States	66606
24	Professional Research Network of Kansas	Wichita	Kansas	United States	67203
25	Delta Research Partners, LLC	Monroe	Louisiana	United States	71201
26	Metropolitan Gastroenterology Group	Chevy Chase	Maryland	United States	20815
27	Maryland Digestive Disease Research, LLC	Laurel	Maryland	United States	20707
28	Endoscopic Microsurgery Associates	Towson	Maryland	United States	21204
29	Massachusetts General Hospital	Boston	Massachusetts	United States	02114
30	Plymouth Clinic	Plymouth	Minnesota	United States	55446
31	CRC of Jackson, LLC	Jackson	Mississippi	United States	39202
32	Gastrointestional Associates	Jackson	Mississippi	United States	39202
33	Digestive Health Specialists	Tupelo	Mississippi	United States	38801
34	Kansas City Gastroenterology & Hepatology	Kansas City	Missouri	United States	64131
35	Center for Digestive and Liver Diseases, Inc.	Mexico	Missouri	United States	65265
36	Lovelace Scientific Resources, Inc.	Albuquerque	New Mexico	United States	87108
37	Medex Healthcare Research, Inc.	New York	New York	United States	10004
38	Research Associates of New York	New York	New York	United States	10075
39	Gastroenterology Associates	Poughkeepsie	New York	United States	12601
40	Cumberland Research Associates	Fayetteville	North Carolina	United States	28304
41	LeBauer Research Associates	Greensboro	North Carolina	United States	27406
42	Wake Research Associates	Raleigh	North Carolina	United States	27612
43	Hanover Medical Specialists	Wilmington	North Carolina	United States	28401
44	Piedmont Medical Research	Winston-Salem	North Carolina	United States	27103
45	AGA	Akron	Ohio	United States	44302
46	Consultants for Clinical Research	Cincinnati	Ohio	United States	45211
47	Hightop Medical Research Center	Cincinnati	Ohio	United States	45224
48	Great Lakes Gastroenterology	Mentor	Ohio	United States	44060
49	Regional Gastroenterology Associates of Lancaster, Ltd.	Lancaster	Pennsylvania	United States	17604
50	PMA Medical Specialists	Limerick	Pennsylvania	United States	19468
51	Memphis Gastroenterology Group	Germantown	Tennessee	United States	38138
52	HCCA Clinical Research Solutions	Jackson	Tennessee	United States	37805
53	Medical Specialty Clinic Research	Jackson	Tennessee	United States	38301
54	Holston Medical Group, PC	Kingsport	Tennessee	United States	37660
55	Lovelace Scientific Resources	Austin	Texas	United States	78759
56	Jacinto Medical Group	Baytown (Houston)	Texas	United States	77521
57	Dynamed Clinical Research	Houston	Texas	United States	77034
58	Digestive Health Associates of Texas, P.A.	Plano	Texas	United States	75075
59	Theda Oaks Endoscopy Center	San Antonio	Texas	United States	78258
60	Trinity Health Care	Tyler	Texas	United States	75702
61	Charlottesville Medical Research	Charlottesville	Virginia	United States	22911
62	Gastroenterology Associates of Tidewater	Chesapeake	Virginia	United States	23320
63	Digestive and Liver Disease Specialists	Norfolk	Virginia	United States	23502
64	Gastroenterology, Ltd.	Virginia Beach	Virginia	United States	23454
65	Wisconsin Center for Advanced Research	Milwaukee	Wisconsin	United States	53215

Sponsors and Collaborators

• Evoke Pharma

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Evoke Pharma
• ClinicalTrials.gov Identifier: NCT00845858
• Other Study ID Numbers: METO-IN-002
• First Posted: Feb 18, 2009
• Last Update Posted: Jun 27, 2014
• Last Verified: Nov 1, 2013

• Keywords provided by Evoke Pharma: Gastroparesis; Diabetic Gastroparesis; Diabetes; Diabetes Mellitus; Delayed Gastric Emptying
• Additional relevant MeSH terms: Gastroparesis; Diabetes Mellitus; Metoclopramide

Study Results

Participant Flow

Arm/Group Title	Metoclopramide Nasal Spray 10 mg	Metoclopramide Nasal Spray 14 mg	Placebo Nasal Spray
Arm/Group Description	metoclopramide: 30 minutes before meals and at bedtime for 4 weeks	metoclopramide: 30 minutes before meals and at bedtime for 4 weeks	Placebo: 30 minutes before meals and at bedtime
Period Title: Overall Study
STARTED	96	96	95
COMPLETED	88	84	87
NOT COMPLETED	8	12	8

Baseline Characteristics

Arm/Group Title	Metoclopramide Nasal Spray 10 mg	Metoclopramide Nasal Spray 14 mg	Placebo Nasal Spray	Total
Arm/Group Description	metoclopramide: 30 minutes before meals and at bedtime for 4 weeks	metoclopramide: 30 minutes before meals and at bedtime for 4 weeks	Placebo: 30 minutes before meals and at bedtime	Total of all reporting groups
Overall Participants	96	96	95	287
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	51.6 (12.13)	50.3 (12.40)	52.4 (10.03)	51.4 (11.56)
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	81 84.4%	83 86.5%	85 89.5%	249 86.8%
>=65 years	15 15.6%	13 13.5%	10 10.5%	38 13.2%
Sex: Female, Male (Count of Participants)
Female	65 67.7%	70 72.9%	68 71.6%	203 70.7%
Male	31 32.3%	26 27.1%	27 28.4%	84 29.3%
Region of Enrollment (participants) [Number]
United States	96 100%	96 100%	95 100%	287 100%

Outcome Measures

1. Primary Outcome

Title	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.
Description	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). Nausea (feeling sick to your stomach as if you were going to vomit or throw up) Early satiety (not able to finish a normal sized meal) Bloating (feeling like you need to loosen clothes) 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

Outcome Measure Data

Analysis Population Description

ITT

Arm/Group Title	Metoclopramide Nasal Spray 10 mg	Metoclopramide Nasal Spray 14 mg	Placebo Nasal Spray
Arm/Group Description	metoclopramide: 30 minutes before meals and at bedtime for 4 weeks	metoclopramide: 30 minutes before meals and at bedtime for 4 weeks	Placebo: 30 minutes before meals and at bedtime
Measure Participants	96	96	95
Mean (Standard Deviation) [units on a scale]	-1.2 (1.18)	-1.2 (0.94)	-1.0 (0.89)

2. Other Pre-specified Outcome

Title	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.
Description	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). Nausea (feeling sick to your stomach as if you were going to vomit or throw up) Early satiety (not able to finish a normal sized meal) Bloating (feeling like you need to loosen clothes) 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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Female-Metoclopramide Nasal Spray 10 mg	Female-Metoclopramide Nasal Spray 14 mg	Female-Placebo Nasal Spray
Arm/Group Description	metoclopramide: 30 minutes before meals and at bedtime for 4 weeks	metoclopramide: 30 minutes before meals and at bedtime for 4 weeks	Placebo: 30 minutes before meals and at bedtime
Measure Participants	65	70	68
Mean (Standard Deviation) [units on a scale]	-1.2 (1.18)	-1.3 (0.98)	-0.8 (0.79)

Adverse Events

Time Frame	All adverse events (AEs) (from signing of Informed Consent Form until termination of study drug [28 days]), whether observed by the Investigator, reported by the subject, from laboratory findings, or other means, were captured.
Adverse Event Reporting Description	All AEs were followed in accordance with good medical practice until resolved or fully characterized. AEs that were ongoing at the end of the study were followed for at least 72 hours to determine the status of the event. All serious and related AEs that occurred within 30 days after the last dose of study drug were captured.
Arm/Group Title	Metoclopramide Nasal Spray 10 mg		Metoclopramide Nasal Spray 14 mg		Placebo Nasal Spray
Arm/Group Description	metoclopramide: 30 minutes before meals and at bedtime for 4 weeks		metoclopramide: 30 minutes before meals and at bedtime for 4 weeks		Placebo: 30 minutes before meals and at bedtime
All Cause Mortality
	Metoclopramide Nasal Spray 10 mg		Metoclopramide Nasal Spray 14 mg		Placebo Nasal Spray
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Metoclopramide Nasal Spray 10 mg		Metoclopramide Nasal Spray 14 mg		Placebo Nasal Spray
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/95 (0%)		2/95 (2.1%)		3/95 (3.2%)
General disorders
Non cardiac chest pain	0/95 (0%)	0	0/95 (0%)	0	1/95 (1.1%)	1
Condition aggravated	0/95 (0%)	0	1/95 (1.1%)	1	0/95 (0%)	0
Hepatobiliary disorders
Cholelithiasis	0/95 (0%)	0	1/95 (1.1%)	1	0/95 (0%)	0
Infections and infestations
Kidney infection	0/95 (0%)	0	0/95 (0%)	0	1/95 (1.1%)	1
Metabolism and nutrition disorders
Diabetic Ketoacidosis	0/95 (0%)	0	0/95 (0%)	0	1/95 (1.1%)	1
Respiratory, thoracic and mediastinal disorders
Chronic Obstructive Pulmonary Disease	0/95 (0%)	0	0/95 (0%)	0	1/95 (1.1%)	1
Other (Not Including Serious) Adverse Events
	Metoclopramide Nasal Spray 10 mg		Metoclopramide Nasal Spray 14 mg		Placebo Nasal Spray
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	53/95 (55.8%)		57/95 (60%)		53/95 (55.8%)
Blood and lymphatic system disorders
Lymphadenopathy	2/95 (2.1%)	2	0/95 (0%)	0	1/95 (1.1%)	1
Gastrointestinal disorders
Diarrhoea	3/95 (3.2%)	3	2/95 (2.1%)	2	9/95 (9.5%)	9
Nausea	1/95 (1.1%)	1	4/95 (4.2%)	4	4/95 (4.2%)	4
Dyspesia	2/95 (2.1%)	2	2/95 (2.1%)	2	1/95 (1.1%)	1
Flatulence	1/95 (1.1%)	1	2/95 (2.1%)	2	2/95 (2.1%)	2
Gastrooesophageal Reflux Disease	4/95 (4.2%)	5	0/95 (0%)	0	1/95 (1.1%)	1
Abdominal Pain Lower	2/95 (2.1%)	4	0/95 (0%)	0	2/95 (2.1%)	2
Constipation	1/95 (1.1%)	1	0/95 (0%)	0	2/95 (2.1%)	2
Eructation	0/95 (0%)	0	2/95 (2.1%)	2	1/95 (1.1%)	1
Vomiting	1/95 (1.1%)	1	2/95 (2.1%)	2	0/95 (0%)	0
General disorders
Fatigue	5/95 (5.3%)	5	6/95 (6.3%)	7	1/95 (1.1%)	1
Oedema Peripheral	2/95 (2.1%)	2	0/95 (0%)	0	0/95 (0%)	0
Pain	0/95 (0%)	0	0/95 (0%)	0	2/95 (2.1%)	2
Hyperglycemia	1/95 (1.1%)	1	3/95 (3.2%)	3	1/95 (1.1%)	1
Hypoglycemia	1/95 (1.1%)	1	3/95 (3.2%)	5	1/95 (1.1%)	1
Decreased Appetite	0/95 (0%)	0	2/95 (2.1%)	2	0/95 (0%)	0
Hyperkalaemia	2/95 (2.1%)	2	0/95 (0%)	0	0/95 (0%)	0
Immune system disorders
Seasonal Allergy	0/95 (0%)	0	0/95 (0%)	0	2/95 (2.1%)	2
Infections and infestations
Upper Respiratory Tract Infection	0/95 (0%)	0	2/95 (2.1%)	2	4/95 (4.2%)	4
Nasopharyngitis	3/95 (3.2%)	3	1/95 (1.1%)	1	1/95 (1.1%)	1
Sinusitis	0/95 (0%)	0	1/95 (1.1%)	1	2/95 (2.1%)	2
Injury, poisoning and procedural complications
Muscle Strain	0/95 (0%)	0	2/95 (2.1%)	2	0/95 (0%)	0
Investigations
Blood Glucose Increase	0/95 (0%)	0	1/95 (1.1%)	1	2/95 (2.1%)	2
Electrocardiogram Qt Prolonged	1/95 (1.1%)	1	0/95 (0%)	0	2/95 (2.1%)	2
Aspartate Aminotransferase Increased	2/95 (2.1%)	2	0/95 (0%)	0	0/95 (0%)	0
Glycosylated Haemoglobin Increased	0/95 (0%)	0	0/95 (0%)	0	2/95 (2.1%)	2
Musculoskeletal and connective tissue disorders
Arthralgia	2/95 (2.1%)	2	0/95 (0%)	0	1/95 (1.1%)	1
Nervous system disorders
Dysguesia	12/95 (12.6%)	13	13/95 (13.7%)	14	4/95 (4.2%)	4
Headache	12/95 (12.6%)	13	13/95 (13.7%)	14	11/95 (11.6%)	13
Dizziness	3/95 (3.2%)	3	3/95 (3.2%)	3	2/95 (2.1%)	2
Somnolence	2/95 (2.1%)	2	2/95 (2.1%)	2	0/95 (0%)	0
Tremor	0/95 (0%)	0	2/95 (2.1%)	2	0/95 (0%)	0
Psychiatric disorders
Anxiety	1/95 (1.1%)	1	1/95 (1.1%)	1	2/95 (2.1%)	2
Depression	0/95 (0%)	0	0/95 (0%)	0	3/95 (3.2%)	3
Renal and urinary disorders
Pollakiurua	1/95 (1.1%)	1	2/95 (2.1%)	2	0/95 (0%)	0
Respiratory, thoracic and mediastinal disorders
Epistaxis	2/95 (2.1%)	2	3/95 (3.2%)	4	2/95 (2.1%)	2
Cough	0/95 (0%)	0	3/95 (3.2%)	3	2/95 (2.1%)	2
Nasal Discomfort	3/95 (3.2%)	3	2/95 (2.1%)	2	0/95 (0%)	0
Rhinorrhoea	1/95 (1.1%)	1	3/95 (3.2%)	3	1/95 (1.1%)	1
Throat Irritation	0/95 (0%)	0	3/95 (3.2%)	3	1/95 (1.1%)	1
Nasal Congestion	0/95 (0%)	0	2/95 (2.1%)	2	1/95 (1.1%)	1
Oropharyngeal Pain	2/95 (2.1%)	2	0/95 (0%)	0	1/95 (1.1%)	1
Dry Throat	2/95 (2.1%)	2	0/95 (0%)	0	0/95 (0%)	0
Skin and subcutaneous tissue disorders
Rash	1/95 (1.1%)	1	0/95 (0%)	0	2/95 (2.1%)	2

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.