SOM230: Pasireotide LAR in Severe Polycystic Liver Disease

• Sponsor: Mayo Clinic (Other)
• Overall Status: Completed
• CT.gov ID: NCT01670110
• Collaborator: (none)
• Enrollment: 48
• Location: 1
• Arms: 2
• Actual Duration (Months): 73
• Patients Per Site Per Month: 0.7

Study Details

Study Description

Brief Summary

The purpose of this study is to compare SOM230 treatment to placebo. The investigators will also assess the efficacy and safety of SOM230 in reducing total liver volume and improving quality of life.

Condition or Disease	Intervention/Treatment	Phase
Somatostatin Analogs; Polycystic Liver Disease; Autosomal Dominant Polycystic Kidney Disease; Autosomal Dominant Polycystic Liver Disease	Drug: Pasireotide LAR; Drug: Placebo	Phase 2

Detailed Description

Pasireotide (SOM230) is a novel multi-receptor-targeted analog that has high affinity for four of the five SST receptor subtypes (SSTr1, SSTr2, SSTr3 and SSTr5); it has a 40-fold higher affinity and 158-fold higher functional activity for the SST5 receptor than octreotide. Because of its broad receptor binding profile, pasireotide may be more potent in Polycystic Liver Disease (PLD) than octreotide. In this randomized double blind placebo controlled trial the investigators will compare SOM230 treatment to placebo for 12 months in patients with PLD. The primary endpoints will be assessed at 12 months and patients receiving placebo then crossed over to SOM230, permitting all participants to receive SOM230 for the subsequent two years. Magnetic resonance imaging (MRI) will be used to assess liver volume - the primary endpoint, which will be assessed at baseline, end of years 1 and 3. This study will assess the efficacy and safety of SOM230 in reducing total liver volume and improving quality of life over 12 months. (The investigators will not be assessing efficacy at 24 months.) The therapy way be effective in PLD but also may prove to be effective for many more patients with Polycystic Kidney Disease (PKD) which will be evaluated using eGFR and kidney volume using MRI.

The investigators plan to add other sub-sites in other locations.

Study Design

• Study Type: Interventional
• Actual Enrollment: 48 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Randomized, Placebo Controlled Clinical Trial of SOM230 (Pasireotide LAR) In Severe Polycystic Liver Disease
• Actual Study Start Date: Aug 1, 2012
• Actual Primary Completion Date: Sep 1, 2018
• Actual Study Completion Date: Sep 1, 2018

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Pasireotide LAR (SOM230) Active Pasireotide LAR	Drug: Pasireotide LAR; Injectible, 60mg per month
Placebo Comparator: placebo injection	Drug: Placebo; To be injected once per month

Outcome Measures

Primary Outcome Measures

1. Change in Liver Volume [baseline , 12 month]

   Percent change was calculated for liver volumes using the equation=[(12 month value-baseline value)/baseline value]*100*12/12 month

2. Change in Kidney Volume [baseline to 12 months]

   Percent change was calculated for kidney volumes using the equation=[(12 month value-baseline value)/baseline value]*100*12/12 month

Secondary Outcome Measures

1. Percentage Change in Estimated Glomerular Filtration Rate (eGFR) [Baseline, 12 months]

   eGFR was measured using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. This value at baseline and 12 months was used to calculate the percentage change by [12 month value-baseline value)/baseline value]*100

2. Percentage Change in Serum Creatinine [Baseline, 12 months]

   Serum creatinine level at baseline and 12 months was used to calculate the percentage change by [12 month value-baseline value)/baseline value]*100

3. Percent Change in Blood Glucose [Baseline, 12 months]

   Blood glucose (mg/dLb) level at baseline and 12 months was used to calculate the percentage change by [12 month value-baseline value)/baseline value]*100

4. Percentage Change in Hemoglobin A1C [Baseline, 12 months]

   Hemoglobin A1C level at baseline and 12 months was used to calculate the percentage change by [12 month value-baseline value)/baseline value]*100

5. Percentage Change in Heart Rate [Baseline, 12 months]

   Heart rate, measured in beats per minute (BPM), at baseline and 12 months was used to calculate the percentage change by [12 month value-baseline value)/baseline value]*100

6. Change in Quality of Life [Baseline, 12 months]

   Measured using the SF-36 health survey, which consist of eight subscales each scored on a range of 0 to 100 (0=worst imaginable, 100=best imaginable). Change calculated from baseline = 12 month value-baseline value

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 100 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Male or female Age ≥ 18 years.

• Diagnosis of PLD associated with ADPKD (meeting the Modified Ravine's criteria) or isolated ADPLD (defined by the criteria described by Reynolds et al)

• Severe PLD defined as a liver volume >4000mL or symptomatic disease due to mass effects from hepatic cysts (must be able to undergo MRI or CT scan to determine this).

• Not a candidate for or declining surgical intervention.

• Capable of providing informed consent.

• Life expectancy ≥ 12 weeks

• Patients with a known history of impaired fasting blood glucose (glucose >100 and <126) may be included at the discretion of the PI. These patients should be monitored closely throughout the trial and antihyperglycemic treatment adjusted as necessary. Patients that are deemed non eligible due to elevated glucose can be re-screened after adequate medical treatment.

• Adequate end organ function as defined by:

• Adequate bone marrow function:

• WBC ≥ 2.5 x 109/L

• Absolute Neutrophil Count (ANC) ≥ 1.5 x 109/L

• Platelets ≥ 100 x 109/L

• Hb ≥ 9 g/dL

• No evidence of significant liver disease:

• Serum bilirubin ≤1.5 x ULN

• INR < 1.3

• ALT and AST ≤ 2 x ULN

• Estimated glomerular filtration rate (eGFR) >30 ml/min/m2

• Serum amylase and lipase ≤ 1.5 x ULN

• Alkaline phosphatase ≤ 2.5 x ULN

• Written informed consent obtained prior to any screening procedures

• Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests and other study procedures

Exclusion Criteria:

• Patients will be considered ineligible for this study if they meet any of the following criteria:

• Patients with a known hypersensitivity to SST analogs or any component of the pasireotide LAR or SQ formulations.

• Patients with known malabsorption syndrome, short bowel or chologenic diarrhea not controlled by specific therapeutic means.

• Patients with abnormal coagulation (PT or a PTT elevated by 30% above normal limits).

• Patients on continuous anticoagulation therapy. Patients who were on anticoagulant therapy must complete a washout period of at least 10 days and have confirmed normal coagulation parameters before study inclusion.

• Patients with symptomatic cholelithiasis.

• Patients who are not biochemically euthyroid.

• Patients with known history of hypothyroidism are eligible if they are on adequate and stable re-placement thyroid hormone therapy for at least 3 months.

• Serum magnesium ≥ ULN

• QT-related exclusion criteria:

• QTcF at screening > 470 msec

• Patients with a history of syncope or family history of idiopathic sudden death

• Patients who have sustained or clinically significant cardiac arrhythmias

• Risk factors for Torsades de Pointes such as hypokalemia, hypomagnesemia, cardiac failure, clinically significant/symptomatic bradycardia, or high-grade AV block

• Patients with concomitant disease(s) that could prolong QT such as autonomic neuropathy (caused by diabetes, or Parkinson's disease), HIV, cirrhosis, uncontrolled hypothyroidism or cardiac failure

• Family history of long QT syndrome

• Concomitant medications known to prolong the QT interval.

• Potassium < or = to 3.5

• Patients who have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study such as:

• Patients who have Uncontrolled diabetes as defined by HbA1c>8%* despite adequate therapy

• Patients with the presence of active or suspected acute or chronic uncontrolled infection or with a history of immunodeficiency, including a positive HIV test result (ELISA and Western blot). An HIV test will not be required; however, previous medical history will be reviewed.

• Non-malignant medical illnesses that are uncontrolled or whose control may be jeopardized by the treatment with this study treatment.

• Liver disease such as cirrhosis, decompensated liver disease, chronic active hepatitis or chronic persistent hepatitis.

• Baseline ALT or AST >3x ULN

• Patients with life-threatening autoimmune and ischemic disorders.

• Uncontrolled hypertension

• Patients who have a history of a primary malignancy, with the exception of locally excised non-melanoma skin cancer and carcinoma in situ of uterine cervix. (Patients who have had no evidence of disease from primary cancer for 3 or more years are allowed to participate in the study.)

• History of pancreatitis

• Patients with a known history of hepatitis B or C

• Presence of Hepatitis B surface antigen (HbsAg)

• Presence of Hepatitis C antibody (anti-HCV)

• Patients with a history of, or current, alcohol misuse/abuse within the past 12 months

• Known gallbladder or bile duct disease, acute or chronic pancreatitis

• Patients who have any current or prior medical condition that may interfere with the conduct of the study or the evaluation of its results in the opinion of the Investigator or the Sponsor's Medical Monitor

• Use of an investigational drug within 1 month prior to dosing

• Patients with a history of non-compliance to medical regimens or who are considered potentially unreliable or will not be able to complete the entire study

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Mayo Clinic	Rochester	Minnesota	United States	55905

Sponsors and Collaborators

• Mayo Clinic

Investigators

• Principal Investigator: Marie C Hogan, MD PhD, Mayo Clinic

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Oct 14, 2014

More Information

Additional Information:

• Mayo Clinic Clinical Trials

Publications

None provided.

• Responsible Party: Marie Hogan, Assistant Professor of Medicine, Mayo Clinic
• ClinicalTrials.gov Identifier: NCT01670110
• Other Study ID Numbers: 11-007405
• First Posted: Aug 21, 2012
• Last Update Posted: May 1, 2020
• Last Verified: Apr 1, 2020

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Marie Hogan, Assistant Professor of Medicine, Mayo Clinic: Polycystic Liver Disease; Autosomal dominant polycystic kidney disease; Autosomal dominant polycystic liver disease; Somatostatin analogs; Pasireotide LAR; SOM230
• Additional relevant MeSH terms: Cysts; Arthrogryposis; Liver Diseases; Kidney Diseases; Polycystic Kidney Diseases; Polycystic Kidney, Autosomal Dominant; Pasireotide

Study Results

Participant Flow

Arm/Group Title	Pasireotide LAR (SOM230)	Placebo Injection
Arm/Group Description	Active Pasireotide LAR Pasireotide LAR: Injectible, 60mg per month	Placebo: To be injected once per month
Period Title: Overall Study
STARTED	33	15
COMPLETED	29	12
NOT COMPLETED	4	3

Baseline Characteristics

Arm/Group Title	Pasireotide LAR (SOM230)	Placebo Injection	Total
Arm/Group Description	Active Pasireotide LAR Pasireotide LAR: Injectible, 60mg per month	Placebo: To be injected once per month	Total of all reporting groups
Overall Participants	33	15	48
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	50.16 (8.63)	51.40 (7.97)	50.55 (8.37)
Sex: Female, Male (Count of Participants)
Female	31 93.9%	12 80%	43 89.6%
Male	2 6.1%	3 20%	5 10.4%
Race/Ethnicity, Customized (Count of Participants)
White	29 87.9%	15 100%	44 91.7%
African American	1 3%	0 0%	1 2.1%
Other	3 9.1%	0 0%	3 6.3%
Region of Enrollment (participants) [Number]
United States	33 100%	15 100%	48 100%

Outcome Measures

1. Primary Outcome

Title	Change in Liver Volume
Description	Percent change was calculated for liver volumes using the equation=[(12 month value-baseline value)/baseline value]*100*12/12 month
Time Frame	baseline , 12 month

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Pasireotide LAR (SOM230)	Placebo Injection
Arm/Group Description	Active Pasireotide LAR Pasireotide LAR: Injectible, 60mg per month	Placebo: To be injected once per month
Measure Participants	29	12
Mean (Standard Deviation) [percentage of change]	-3.36 (7.33)	6.29 (6.97)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pasireotide LAR (SOM230), Placebo Injection
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.001
	Comments
	Method	ANCOVA
	Comments

2. Primary Outcome

Title	Change in Kidney Volume
Description	Percent change was calculated for kidney volumes using the equation=[(12 month value-baseline value)/baseline value]*100*12/12 month
Time Frame	baseline to 12 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Pasireotide LAR (SOM230)	Placebo Injection
Arm/Group Description	Active Pasireotide LAR Pasireotide LAR: Injectible, 60mg per month	Placebo: To be injected once per month
Measure Participants	29	12
Mean (Standard Deviation) [percentage of change]	-1.37 (3.52)	3.85 (4.49)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pasireotide LAR (SOM230), Placebo Injection
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.003
	Comments
	Method	ANCOVA
	Comments

3. Secondary Outcome

Title	Percentage Change in Estimated Glomerular Filtration Rate (eGFR)
Description	eGFR was measured using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. This value at baseline and 12 months was used to calculate the percentage change by [12 month value-baseline value)/baseline value]*100
Time Frame	Baseline, 12 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Pasireotide LAR (SOM230)	Placebo Injection
Arm/Group Description	Active Pasireotide LAR Pasireotide LAR: Injectible, 60mg per month	Placebo: To be injected once per month
Measure Participants	29	12
Mean (Standard Deviation) [percentage of change]	-0.3 (14)	-2.2 (17.7)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pasireotide LAR (SOM230), Placebo Injection
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.79
	Comments
	Method	t-test, 2 sided
	Comments

4. Secondary Outcome

Title	Percentage Change in Serum Creatinine
Description	Serum creatinine level at baseline and 12 months was used to calculate the percentage change by [12 month value-baseline value)/baseline value]*100
Time Frame	Baseline, 12 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Pasireotide LAR (SOM230)	Placebo Injection
Arm/Group Description	Active Pasireotide LAR Pasireotide LAR: Injectible, 60mg per month	Placebo: To be injected once per month
Measure Participants	29	12
Mean (Standard Deviation) [percentage of change]	1.8 (12)	3.4 (15.6)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pasireotide LAR (SOM230), Placebo Injection
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.79
	Comments
	Method	t-test, 2 sided
	Comments

5. Secondary Outcome

Title	Percent Change in Blood Glucose
Description	Blood glucose (mg/dLb) level at baseline and 12 months was used to calculate the percentage change by [12 month value-baseline value)/baseline value]*100
Time Frame	Baseline, 12 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Pasireotide LAR (SOM230)	Placebo Injection
Arm/Group Description	Active Pasireotide LAR Pasireotide LAR: Injectible, 60mg per month	Placebo: To be injected once per month
Measure Participants	29	12
Mean (Standard Deviation) [percentage of change]	39 (30)	2.2 (15.2)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pasireotide LAR (SOM230), Placebo Injection
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.001
	Comments
	Method	t-test, 2 sided
	Comments

6. Secondary Outcome

Title	Percentage Change in Hemoglobin A1C
Description	Hemoglobin A1C level at baseline and 12 months was used to calculate the percentage change by [12 month value-baseline value)/baseline value]*100
Time Frame	Baseline, 12 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Pasireotide LAR (SOM230)	Placebo Injection
Arm/Group Description	Active Pasireotide LAR Pasireotide LAR: Injectible, 60mg per month	Placebo: To be injected once per month
Measure Participants	29	12
Mean (Standard Deviation) [percentage of change]	18 (11)	1.6 (3.3)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pasireotide LAR (SOM230), Placebo Injection
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.001
	Comments
	Method	t-test, 2 sided
	Comments

7. Secondary Outcome

Title	Percentage Change in Heart Rate
Description	Heart rate, measured in beats per minute (BPM), at baseline and 12 months was used to calculate the percentage change by [12 month value-baseline value)/baseline value]*100
Time Frame	Baseline, 12 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Pasireotide LAR (SOM230)	Placebo Injection
Arm/Group Description	Active Pasireotide LAR Pasireotide LAR: Injectible, 60mg per month	Placebo: To be injected once per month
Measure Participants	29	12
Mean (Standard Deviation) [percentage of change]	-0.15 (0.2)	-0.1 (0.1)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pasireotide LAR (SOM230), Placebo Injection
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.73
	Comments
	Method	t-test, 2 sided
	Comments

8. Secondary Outcome

Title	Change in Quality of Life
Description	Measured using the SF-36 health survey, which consist of eight subscales each scored on a range of 0 to 100 (0=worst imaginable, 100=best imaginable). Change calculated from baseline = 12 month value-baseline value
Time Frame	Baseline, 12 months

Outcome Measure Data

Analysis Population Description

Data for 19 participants in the pasireotide LAR (SOM230) group and 9 participants from the placebo injection group was available for analysis.

Arm/Group Title	Pasireotide LAR (SOM230)	Placebo Injection
Arm/Group Description	Active Pasireotide LAR Pasireotide LAR: Injectible, 60mg per month	Placebo: To be injected once per month
Measure Participants	19	9
Physical functioning	4.7 (16)	-1 (8)
Physical role	7.9 (36)	-3 (38)
Bodily pain	5.5 (22)	7 (12)
General health	-6.2 (14)	2 (15)
Vitality	4.5 (14)	-2 (17)
Social functioning	0.0 (18)	-3 (8)
Role emotional	0.0 (22)	11 (5)
Mental health	1.5 (12)	-1.8 (11)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pasireotide LAR (SOM230), Placebo Injection
	Comments	Physical functioning
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.31
	Comments
	Method	t-test, 2 sided
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Pasireotide LAR (SOM230), Placebo Injection
	Comments	Physical role
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.48
	Comments
	Method	t-test, 2 sided
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Pasireotide LAR (SOM230), Placebo Injection
	Comments	Bodily pain
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.89
	Comments
	Method	t-test, 2 sided
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Pasireotide LAR (SOM230), Placebo Injection
	Comments	General health
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.18
	Comments
	Method	t-test, 2 sided
	Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Pasireotide LAR (SOM230), Placebo Injection
	Comments	Vitality
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.28
	Comments
	Method	t-test, 2 sided
	Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Pasireotide LAR (SOM230), Placebo Injection
	Comments	Social functioning
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.66
	Comments
	Method	t-test, 2 sided
	Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Pasireotide LAR (SOM230), Placebo Injection
	Comments	Role emotional
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.43
	Comments
	Method	t-test, 2 sided
	Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Pasireotide LAR (SOM230), Placebo Injection
	Comments	Mental health
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.51
	Comments
	Method	t-test, 2 sided
	Comments

Adverse Events

Time Frame	Adverse Events were collected from baseline to 12 months
Arm/Group Title	Pasireotide LAR (SOM230)		Placebo Injection
Arm/Group Description	Active Pasireotide LAR Pasireotide LAR: Injectible, 60mg per month		Placebo: To be injected once per month
All Cause Mortality
	Pasireotide LAR (SOM230)		Placebo Injection
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/33 (0%)		1/15 (6.7%)
Serious Adverse Events
	Pasireotide LAR (SOM230)		Placebo Injection
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/33 (12.1%)		1/15 (6.7%)
Cardiac disorders
Prolonged QT>480msec	1/33 (3%)	1	0/15 (0%)	0
Gastrointestinal disorders
Abdominal pain	1/33 (3%)	1	0/15 (0%)	0
General disorders
Right upper quadrant pain	1/33 (3%)	1	0/15 (0%)	0
Ascites	1/33 (3%)	1	0/15 (0%)	0
Hepatobiliary disorders
Ruptured liver cyst	1/33 (3%)	1	0/15 (0%)	0
Elevated alkaline phosphatase	1/33 (3%)	1	0/15 (0%)	0
Surgical and medical procedures
Abdominal hernia repair	0/33 (0%)	0	1/15 (6.7%)	1
Other (Not Including Serious) Adverse Events
	Pasireotide LAR (SOM230)		Placebo Injection
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	33/33 (100%)		15/15 (100%)
Cardiac disorders
Bradycardia	10/33 (30.3%)	10	1/15 (6.7%)	1
Endocrine disorders
Diabetes	19/32 (59.4%)	19	1/15 (6.7%)	1
Gastrointestinal disorders
Diarrhea	17/33 (51.5%)	17	8/15 (53.3%)	8
Pain abdomen	11/33 (33.3%)	11	1/15 (6.7%)	1
Nausea	9/33 (27.3%)	9	3/15 (20%)	3
General disorders
Fatigue	13/33 (39.4%)	13	3/15 (20%)	3
Alopecia	9/33 (27.3%)	9	0/15 (0%)	0
Metabolism and nutrition disorders
Hyperglycemia	26/33 (78.8%)	26	4/15 (26.7%)	4
Nervous system disorders
Dizziness	10/33 (30.3%)	10	3/15 (20%)	3
Headache	5/33 (15.2%)	5	3/15 (20%)	3

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE 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.