Multiple Dose Study of the Safety, Tolerability, Pharmacokinetics and Effect on Renal Potassium Clearance

• Sponsor: Eli Lilly and Company (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01237899
• Collaborator: (none)
• Enrollment: 32
• Location: 1
• Arms: 6
• Duration (Months): 3
• Patients Per Site Per Month: 10.6

Study Details

Study Description

Brief Summary

The purpose of this study is to investigate the safety and tolerability of LY2623091 after multiple oral dosing in healthy men and women of non-childbearing potential. Two cohorts of 16 subjects will participate in 2 dosing periods. Treatment assignment will be double-blind for LY2623091 and placebo (negative control), and open label for eplerenone (positive control).

Condition or Disease	Intervention/Treatment	Phase
Chronic Kidney Disease	Drug: LY2623091; Drug: Placebo; Drug: Eplerenone	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 32 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Other
• Official Title: Study of the Safety, Tolerability, Pharmacokinetics and Effect on Renal Potassium Clearance After Multiple Oral Dosing of LY2623091 in Healthy Volunteers
• Study Start Date: Oct 1, 2010
• Actual Primary Completion Date: Jan 1, 2011
• Actual Study Completion Date: Jan 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1 mg LY2623091 Daily by mouth for 7 days.	Drug: LY2623091; Administered orally.
Experimental: 10 mg LY2623091 Daily by mouth for 7 days.	Drug: LY2623091; Administered orally.
Experimental: 25 mg LY2623091 The anticipated dose of LY2623091 was revised down from the original proposed dose level of 100 mg based on safety and tolerability data. The 25 mg LY2623091 was administered daily by mouth for 7 days.	Drug: LY2623091; Administered orally.
Experimental: 0.3 mg LY2623091 The anticipated dose of LY2623091 was revised down from the original proposed dose level of up to 200 mg. The 0.3 mg LY2623091 was determined based on an interim analysis after the third dose level and was administered daily by mouth for 7 days.	Drug: LY2623091; Administered orally.
Placebo Comparator: Placebo Daily by mouth for 7 days.	Drug: Placebo; Administered orally.
Active Comparator: 50 mg Eplerenone Daily by mouth for 7 days.	Drug: Eplerenone; Administered orally.

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Clinically Significant Effects (Adverse Events) [Baseline through 7 days for each treatment period]

   A summary of serious adverse events and other nonserious adverse events are located in the Reported Adverse Event section.

Secondary Outcome Measures

1. Pharmacodynamics: Serum to Urine Potassium Area Under the Concentration-Time Curve (AUC) Standardized for Urinary Excretion at Day 7 [Day 7: 24 Hour (hr), 48hr and 72hr Postdose]

   A measure of the renal clearance of the potassium ion (K+). The Least Squares (LS) Mean value was adjusted for pre-challenge renal K+ clearance.

2. Pharmacokinetics of LY2623091: Maximal Concentration (Cmax) at Day 6 [Day 6: Predose,1hr, 2hr, 3hr, 4hr, 8hr and 12 hr Postdose]

   Cmax estimated for LY2623091.

3. Pharmacokinetics LY2623091: Area Under the Concentration-Time Curve (AUC) at Day 6 [Day 6: Predose,1hr, 2hr, 3hr, 4hr, 8hr and 12 hr Postdose]

   AUC from time 0, extrapolated to infinity, estimated for LY2623091.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Are healthy men and women of non-childbearing potential as determined by medical history and physical examination.

• Male subjects: Non-vasectomized male subjects must agree to use 2 medically accepted methods of contraception with all sexual partners during the study and for 90 days following the final dosing.

• Female subjects: Female subjects must be of non-childbearing potential due to surgical sterilization (hysterectomy, bilateral oophorectomy or tubal ligation) or menopause. They should be a minimum of 12 months without a menstrual period. Peri-menopausal women who are 6 months without a menstrual period.

• Have given written informed consent prior to any study-specific procedures.

• Are reliable and willing to make themselves available for the duration of the study and are willing to follow site-specific study procedures.

• Have a body mass index (BMI) of between 19 and 32.5 kilograms per square meter (kg/m^2).

• Have clinical laboratory test results within the normal reference range for the population or study site, or test results with acceptable deviations that are judged by the Investigator not to be clinically significant.

• Have venous access sufficient to allow blood sampling per the protocol.

• Have serum potassium levels within the normal range.

• Are nonsmokers or smokers of less than or equal to 10 cigarettes per day.

Exclusion Criteria:

• Are currently enrolled in, or have discontinued, within 60 days inclusive, a clinical trial involving an investigational drug, device or an off-label use of an approved drug, or are concurrently enrolled in any other type of medical research judged to be scientifically or medically incompatible with this study. Subjects who meet any of these criteria may be enrolled in this study but they cannot be dosed until at least 60 days following the last day of the previous investigational trial.

• Have previously completed or withdrawn from this study or any other study investigating LY2623091.

• Have a history or presence of medical illness including but not limited to any cardiovascular, hepatic, respiratory, hematological, endocrine or neurological disease, or any clinically significant laboratory abnormality that is of a serious medical problem that would preclude study participation.

• Have an abnormality in the 12-lead electrocardiogram (ECG), which increases the risks associated with participation in the study.

• Are unwilling or unable to comply with the use of an electronic data capture system.

• Show evidence of human immunodeficiency virus (HIV) and/or positive human HIV antibodies, hepatitis C and/or positive hepatitis C antibody or hepatitis B and/or positive hepatitis B surface antigen.

• Use and/or intend to use any medication for a medical condition that is not compatible with Inclusion Criterion. For medications that may be used in "healthy" subjects (example given: preventative and/or naturopathic agents, temporary symptom-relieving medications, and so forth) the following constraints must be observed:

• No use of vasoactive drugs (example given: diuretics, antihypertensive agents, phosphodiesterase inhibitors, erectile dysfunction medications, nasal decongestants, et cetera) or systemic glucocorticoids within 7 days of first dosing and/or anticipated use during the study.

• No use of acetaminophen/paracetamol or non-steroidal anti-inflammatory drugs (NSAIDs) within 24 hours of first dosing and/or anticipated use during the study. Aspirin may not be used at doses greater than 100 milligrams per day (mg/day) within 7days of first dosing and/or anticipated use during the study.

• No use of herbal or nutritional products within 7 days of first dosing and/or anticipated use during the study.

• Have donated blood of more than 50 milliliters (mL) within the last 60 days.

• Have an average weekly alcohol intake that exceeds 21 units per week and/or subjects unwilling to stop alcohol within 48 hours of study enrollment and for the duration of the study.

• Have an abnormally high blood pressure (supine or standing) defined as diastolic blood pressure greater than 95 millimeters of mercury (mmHg) and /or systolic blood pressure greater than 150 mmHg, confirmed by at least 1 repeat measurement.

• Have serum potassium greater than the upper limit of normal.

• Regularly use known drugs of abuse or show positive findings for such use on urinary drug screening.

• Consumption of natural licorice and/or natural licorice-containing products and/or grapefruit and/or grapefruit juice within 7 days of first dosing and/or anticipated consumption during the study.

• Consumption of methylxanthine-containing beverages and/or foods (example: coffee, tea, caffeinated soft drinks, chocolate) within 4 days of first dosing and/or anticipated consumption during the study.

• Are unwilling to abstain from salt-substitutes containing potassium for the duration of the study.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Zuidlaren		Netherlands	9471 GP

Sponsors and Collaborators

• Eli Lilly and Company

Investigators

• Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern Time (UTC/GMT - 5 hours, EST), Eli Lilly and Company

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Eli Lilly and Company
• ClinicalTrials.gov Identifier: NCT01237899
• Other Study ID Numbers: 14121; I4M-MC-MRAB
• First Posted: Nov 10, 2010
• Last Update Posted: Jun 3, 2019
• Last Verified: Feb 1, 2019

• Keywords provided by Eli Lilly and Company: Kidney; Renal
• Additional relevant MeSH terms: Kidney Diseases; Renal Insufficiency, Chronic; Eplerenone

Study Results

Participant Flow

Arm/Group Title	1 mg LY2623091 First Then 25 mg LY2623091	1 mg LY2623091 First Then Placebo	1 mg LY2623091 First Then 50 mg Eplerenone	50 mg Eplerenone First Then 25 mg LY2623091	50 mg Eplerenone First Then Placebo	Placebo First Then 25 mg LY2623091	10 mg LY2623091 First Then 0.3 mg LY2623091	10 mg LY2623091 First Then Placebo	10 mg LY2623091 First Then 50 mg Eplerenone	50 mg Eplerenone First Then 0.3 mg LY2623091	Placebo Then 0.3 mg LY2623091
Arm/Group Description	1 mg LY2623091 daily by mouth for 7 days, followed by a minimum 7-day washout period before receiving 25 mg LY2623091 daily by mouth for 7 days.	1 mg LY2623091 daily by mouth for 7 days, followed by a minimum 7-day washout period before receiving placebo daily by mouth for 7 days.	1 mg LY2623091 daily by mouth for 7 days, followed by a minimum 7-day washout period before receiving 50 mg eplerenone daily by mouth for 7 days.	50 mg eplerenone daily by mouth for 7 days, followed by a minimum 7-day washout period before receiving 25 mg LY2623091 daily by mouth for 7 days.	50 mg eplerenone daily by mouth for 7 days, followed by a minimum 7-day washout period before receiving placebo daily by mouth for 7 days.	Placebo daily by mouth for 7 days, followed by a minimum 7-day washout period before receiving 25 mg LY2623091 daily by mouth for 7 days.	10 mg LY2623091 daily by mouth for 7 days, followed by a minimum 7-day washout period before 0.3 mg LY2623091 daily by mouth for 7 days.	10 mg LY2623091 daily by mouth for 7 days, followed by a minimum 7-day washout period before receiving placebo daily by mouth for 7 days.	10 mg LY2623091 daily by mouth for 7 days, followed by a minimum 7-day washout period before receiving 50 mg eplerenone daily by mouth for 7 days.	50 mg eplerenone daily by mouth for 7 days, followed by a minimum 7-day washout period before receiving 0.3 mg LY2623091 daily by mouth for 7 days.	Placebo daily by mouth for 7 days, followed by a minimum 7-day washout period before receiving 0.3 mg LY2623091 daily by mouth for 7 days.
Period Title: First Dosing Period
STARTED	1	3	4	3	2	4	1	3	4	3	4
COMPLETED	1	3	4	3	2	4	1	3	4	3	4
NOT COMPLETED	0	0	0	0	0	0	0	0	0	0	0
Period Title: First Dosing Period
STARTED	1	3	4	3	2	4	1	3	4	3	4
COMPLETED	1	3	3	3	2	4	1	3	4	3	4
NOT COMPLETED	0	0	1	0	0	0	0	0	0	0	0
Period Title: First Dosing Period
STARTED	1	3	3	3	2	4	1	3	4	3	4
COMPLETED	1	3	3	3	2	4	1	3	4	3	4
NOT COMPLETED	0	0	0	0	0	0	0	0	0	0	0

Baseline Characteristics

Arm/Group Title	1 mg LY2623091 First Then 25 mg LY2623091	1 mg LY2623091 First Then Placebo	1 mg LY2623091 First Then 50 mg Eplerenone	50 mg Eplerenone First Then 25 mg LY2623091	50 mg Eplerenone First Then Placebo	Placebo First Then 25 mg LY2623091	10 mg LY2623091 First Then 0.3 mg LY2623091	10 mg LY2623091 First Then Placebo	10 mg LY2623091 First Then 50 mg Eplerenone	50 mg Eplerenone First Then 0.3 mg LY2623091	Placebo Then 0.3 mg LY2623091	Total
Arm/Group Description	1 mg LY2623091 daily by mouth for 7 days, followed by a minimum 7-day washout period before receiving 25 mg LY2623091 daily by mouth for 7 days.	1 mg LY2623091 daily by mouth for 7 days, followed by a minimum 7-day washout period before receiving placebo daily by mouth for 7 days.	1 mg LY2623091 daily by mouth for 7 days, followed by a minimum 7-day washout period before receiving 50 mg eplerenone daily by mouth for 7 days.	50 mg eplerenone daily by mouth for 7 days, followed by a minimum 7-day washout period before receiving 25 mg LY2623091 daily by mouth for 7 days.	50 mg eplerenone daily by mouth for 7 days, followed by a minimum 7-day washout period before receiving placebo daily by mouth for 7 days.	Placebo daily by mouth for 7 days, followed by a minimum 7-day washout period before receiving 25 mg LY2623091 daily by mouth for 7 days.	10 mg LY2623091 daily by mouth for 7 days, followed by a minimum 7-day washout period before 0.3 mg LY2623091 daily by mouth for 7 days.	10 mg LY2623091 daily by mouth for 7 days, followed by a minimum 7-day washout period before receiving placebo daily by mouth for 7 days.	10 mg LY2623091 daily by mouth for 7 days, followed by a minimum 7-day washout period before receiving 50 mg eplerenone daily by mouth for 7 days.	50 mg eplerenone daily by mouth for 7 days, followed by a minimum 7-day washout period before receiving 0.3 mg LY2623091 daily by mouth for 7 days.	Placebo daily by mouth for 7 days, followed by a minimum 7-day washout period before receiving 0.3 mg LY2623091 daily by mouth for 7 days.	Total of all reporting groups
Overall Participants	1	3	4	3	2	4	1	3	4	3	4	32
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	1 100%	3 100%	4 100%	3 100%	2 100%	4 100%	1 100%	3 100%	4 100%	3 100%	4 100%	32 100%
>=65 years	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	0 0%	1 33.3%	0 0%	0 0%	0 0%	2 50%	0 0%	0 0%	0 0%	0 0%	0 0%	3 9.4%
Male	1 100%	2 66.7%	4 100%	3 100%	2 100%	2 50%	1 100%	3 100%	4 100%	3 100%	4 100%	29 90.6%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Not Hispanic or Latino	1 100%	3 100%	4 100%	3 100%	2 100%	4 100%	1 100%	3 100%	4 100%	3 100%	4 100%	32 100%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Race/Ethnicity, Customized (Count of Participants)
Asian	0 0%	1 33.3%	0 0%	0 0%	0 0%	0 0%	0 0%	1 33.3%	0 0%	0 0%	0 0%	2 6.3%
White	1 100%	2 66.7%	4 100%	3 100%	2 100%	4 100%	1 100%	2 66.7%	4 100%	3 100%	4 100%	30 93.8%
Region of Enrollment (Count of Participants)
Netherlands	1 100%	3 100%	4 100%	3 100%	2 100%	4 100%	1 100%	3 100%	4 100%	3 100%	4 100%	32 100%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Clinically Significant Effects (Adverse Events)
Description	A summary of serious adverse events and other nonserious adverse events are located in the Reported Adverse Event section.
Time Frame	Baseline through 7 days for each treatment period

Outcome Measure Data

Analysis Population Description

All participants who received at least 1 dose of study drug.

Arm/Group Title	Placebo	0.3 mg LY2623091	1 mg LY2623091	10 mg LY2623091	25 mg LY2623091	50 mg Eplerenone
Arm/Group Description	Daily by mouth for 7 days.	Daily by mouth for 7 days.	Daily by mouth for 7 days.	Daily by mouth for 7 days.	Daily by mouth for 7 days.	Daily by mouth for 7 days.
Measure Participants	16	8	8	8	8	15
Serious Adverse Events	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Nonserious Adverse Events	6 600%	2 66.7%	5 125%	4 133.3%	6 300%	9 225%

2. Secondary Outcome

Title	Pharmacodynamics: Serum to Urine Potassium Area Under the Concentration-Time Curve (AUC) Standardized for Urinary Excretion at Day 7
Description	A measure of the renal clearance of the potassium ion (K+). The Least Squares (LS) Mean value was adjusted for pre-challenge renal K+ clearance.
Time Frame	Day 7: 24 Hour (hr), 48hr and 72hr Postdose

Outcome Measure Data

Analysis Population Description

All participants who received at least 1 dose of study drug and for whom the data are considered sufficient and interpretable.

Arm/Group Title	Placebo	0.3 mg LY2623091	1 mg LY2623091	10 mg LY2623091	25 mg LY2623091	50 mg Eplerenone
Arm/Group Description	Daily by mouth for 7 days.	Daily by mouth for 7 days.	Daily by mouth for 7 days.	Daily by mouth for 7 days.	Daily by mouth for 7 days.	Daily by mouth for 7 days.
Measure Participants	16	8	8	7	6	15
Least Squares Mean (95% Confidence Interval) [liter per hour (L/h)]	2.098	1.940	1.981	1.788	1.551	1.838

3. Secondary Outcome

Title	Pharmacokinetics of LY2623091: Maximal Concentration (Cmax) at Day 6
Description	Cmax estimated for LY2623091.
Time Frame	Day 6: Predose,1hr, 2hr, 3hr, 4hr, 8hr and 12 hr Postdose

Outcome Measure Data

Analysis Population Description

All participants who received at least 1 dose of study drug and for whom the data are considered sufficient and interpretable.

Arm/Group Title	0.3 mg LY2623091	1 mg LY2623091	10 mg LY2623091	25 mg LY2623091
Arm/Group Description	Daily by mouth for 7 days.	Daily by mouth for 7 days.	Daily by mouth for 7 days.	Daily by mouth for 7 days.
Measure Participants	8	8	8	8
Mean (Standard Deviation) [nanograms per milliliter (ng/mL)]	7.57 (0.776)	27.5 (5.19)	324 (55.2)	812 (106)

4. Secondary Outcome

Title	Pharmacokinetics LY2623091: Area Under the Concentration-Time Curve (AUC) at Day 6
Description	AUC from time 0, extrapolated to infinity, estimated for LY2623091.
Time Frame	Day 6: Predose,1hr, 2hr, 3hr, 4hr, 8hr and 12 hr Postdose

Outcome Measure Data

Analysis Population Description

All participants who received at least 1 dose of study drug and for whom the data are considered sufficient and interpretable.

Arm/Group Title	0.3 mg LY2623091	1 mg LY2623091	10 mg LY2623091	25 mg LY2623091
Arm/Group Description	Daily by mouth for 7 days.	Daily by mouth for 7 days.	Daily by mouth for 7 days.	Daily by mouth for 7 days.
Measure Participants	8	8	8	8
Mean (Standard Deviation) [microgram*hour per milliliter (µg*h/mL)]	0.123 (0.0141)	0.444 (0.0741)	5.50 (1.08)	13.7 (2.37)

Adverse Events

Arm/Group Title	Placebo		0.3 mg LY2623091		1 mg LY2623091		10 mg LY2623091		25 mg LY2623091		50 mg Eplerenone
Arm/Group Description	Daily by mouth for 7 days.		Daily by mouth for 7 days.		Daily by mouth for 7 days.		Daily by mouth for 7 days.		Daily by mouth for 7 days.		Daily by mouth for 7 days.
All Cause Mortality
	Placebo		0.3 mg LY2623091		1 mg LY2623091		10 mg LY2623091		25 mg LY2623091		50 mg Eplerenone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo		0.3 mg LY2623091		1 mg LY2623091		10 mg LY2623091		25 mg LY2623091		50 mg Eplerenone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/16 (0%)		0/8 (0%)		0/8 (0%)		0/8 (0%)		0/8 (0%)		0/15 (0%)
Other (Not Including Serious) Adverse Events
	Placebo		0.3 mg LY2623091		1 mg LY2623091		10 mg LY2623091		25 mg LY2623091		50 mg Eplerenone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/16 (37.5%)		2/8 (25%)		5/8 (62.5%)		4/8 (50%)		6/8 (75%)		9/15 (60%)
Cardiac disorders
Palpitations	0/16 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	1/15 (6.7%)	1
Eye disorders
Ocular hyperaemia	0/16 (0%)	0	0/8 (0%)	0	2/8 (25%)	2	0/8 (0%)	0	0/8 (0%)	0	0/15 (0%)	0
Gastrointestinal disorders
Abdominal distension	0/16 (0%)	0	0/8 (0%)	0	1/8 (12.5%)	1	0/8 (0%)	0	0/8 (0%)	0	0/15 (0%)	0
Abdominal pain	0/16 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	2/8 (25%)	2	0/15 (0%)	0
Constipation	0/16 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	1/8 (12.5%)	1	0/8 (0%)	0	0/15 (0%)	0
Diarrhoea	0/16 (0%)	0	1/8 (12.5%)	1	2/8 (25%)	2	0/8 (0%)	0	0/8 (0%)	0	1/15 (6.7%)	2
Flatulence	0/16 (0%)	0	0/8 (0%)	0	1/8 (12.5%)	1	1/8 (12.5%)	1	0/8 (0%)	0	0/15 (0%)	0
Gingivitis	0/16 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	1/8 (12.5%)	1	0/15 (0%)	0
Lip dry	1/16 (6.3%)	1	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/15 (0%)	0
Nausea	1/16 (6.3%)	1	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	2/8 (25%)	2	1/15 (6.7%)	1
Toothache	0/16 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	1/8 (12.5%)	1	0/8 (0%)	0	0/15 (0%)	0
General disorders
Application site irritation	0/16 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	1/8 (12.5%)	1	0/15 (0%)	0
Catheter site related reaction	2/16 (12.5%)	3	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	2/8 (25%)	2	1/15 (6.7%)	1
Fatigue	1/16 (6.3%)	1	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	2/15 (13.3%)	2
Vessel puncture site reaction	0/16 (0%)	0	2/8 (25%)	2	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	1/15 (6.7%)	2
Infections and infestations
Fungal skin infection	0/16 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	1/15 (6.7%)	1
Nasopharyngitis	2/16 (12.5%)	2	1/8 (12.5%)	1	1/8 (12.5%)	1	2/8 (25%)	2	2/8 (25%)	2	3/15 (20%)	3
Injury, poisoning and procedural complications
Skin injury	0/16 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	1/8 (12.5%)	1	0/15 (0%)	0
Musculoskeletal and connective tissue disorders
Arthralgia	0/16 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	1/8 (12.5%)	1	0/15 (0%)	0
Myalgia	0/16 (0%)	0	0/8 (0%)	0	1/8 (12.5%)	1	1/8 (12.5%)	1	0/8 (0%)	0	0/15 (0%)	0
Nervous system disorders
Dizziness	0/16 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	2/8 (25%)	2	2/15 (13.3%)	2
Headache	0/16 (0%)	0	0/8 (0%)	0	1/8 (12.5%)	1	0/8 (0%)	0	2/8 (25%)	2	5/15 (33.3%)	6
Renal and urinary disorders
Pollakiuria	0/16 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	1/15 (6.7%)	1
Reproductive system and breast disorders
Epididymitis	0/16 (0%)	0	0/8 (0%)	0	1/8 (12.5%)	1	0/8 (0%)	0	0/8 (0%)	0	0/15 (0%)	0
Respiratory, thoracic and mediastinal disorders
Cough	0/16 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	1/8 (12.5%)	1	0/8 (0%)	0	0/15 (0%)	0
Dry throat	0/16 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	1/8 (12.5%)	1	0/8 (0%)	0	0/15 (0%)	0
Nasal discomfort	0/16 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	1/8 (12.5%)	1	0/8 (0%)	0	0/15 (0%)	0
Oropharyngeal pain	1/16 (6.3%)	1	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	1/15 (6.7%)	1
Sneezing	1/16 (6.3%)	1	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	1/15 (6.7%)	1

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 more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.