A Multiple Dose Study of LY3023703 in Healthy Participants

• Sponsor: Eli Lilly and Company (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01849055
• Collaborator: (none)
• Enrollment: 48
• Location: 1
• Arms: 3
• Duration (Months): 7
• Patients Per Site Per Month: 6.8

Study Details

Study Description

Brief Summary

This is a study of LY3023703 in healthy participants. The purposes of this study are to look at safety, how well the study drug is tolerated, how much of the study drug gets into the blood stream and how long it takes the body to remove the study drug. The effects of LY3023703 on blood pressure after 28 days of dosing will be studied. Information about any side effects that occur will be collected. The study is expected to last 21 weeks.

Condition or Disease	Intervention/Treatment	Phase
Healthy Volunteers	Drug: Placebo; Drug: LY3023703; Drug: Celecoxib	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 48 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Basic Science
• Official Title: A Multiple-Dose, Dose-Escalation Study to Evaluate the Safety and Tolerability of LY3023703 in Healthy Subjects
• Study Start Date: May 1, 2013
• Actual Primary Completion Date: Dec 1, 2013
• Actual Study Completion Date: Dec 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo Placebo matching LY3023703 administered orally, once daily (QD), for 28 days	Drug: Placebo; Administered orally
Experimental: LY3023703 Escalating doses (2.5 milligram [mg] up to 30 mg) of LY3023703 administered orally, QD, for 28 days	Drug: LY3023703; Administered orally
Active Comparator: Celecoxib 400 mg celecoxib administered orally, QD, for 28 days. (Positive control.)	Drug: Celecoxib; Administered orally

Outcome Measures

Primary Outcome Measures

1. Number of Participants With One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration [Baseline to Study Completion (up to 74 Days)]

   A summary of serious and all other non-serious adverse events (AE), regardless of possible study drug relatedness, is located in the Reported Adverse Events module.

Secondary Outcome Measures

1. Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve [AUC(0-24)] of LY3023703 [Post-First Dose on Days 1-28 (Time Frame: Day 1: -0.5, 1, 2, 4, 8, 12, 24 hours; Days 5, 12, 20: -0.5 hours; Day 28: -0.5, 1, 2, 4, 8, 12, 24 hours.)]

2. Pharmacokinetics: Maximum Concentration (Cmax) of LY3023703 [Post first dose on Day 1 through Day 28 (Time Frame: Day 1: -0.5, 1, 2, 4, 8, 12, 24 hours; Days 5, 12, 20: -0.5 hours; Day 28: -0.5, 1, 2, 4, 8, 12, 24 hours.)]

3. Pharmacokinetics: Time of Maximum Concentration (Tmax) of LY3023703 [Post first dose on Day 1 through Day 28 (Time Frame: Day 1: -0.5, 1, 2, 4, 8, 12, 24 hours; Days 5, 12, 20: -0.5 hours; Day 28: -0.5, 1, 2, 4, 8, 12, 24 hours.)]

4. Change From Baseline to Day 27 in Blood Pressure (BP) [Baseline, Day 27]

   The Day 27 change from Day -1 was analyzed by using analysis of covariance (ANCOVA) with treatment as a fixed effect and baseline Day -1 as a covariate. The treatment mean, difference to placebo, and difference to celecoxib were output with corresponding 90% confidence intervals.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 60 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Overtly healthy individuals based on the history and physical examinations as determined by the investigator

• Are normotensive (defined as supine systolic blood pressure [BP] less than 140 millimeters of mercury [mm Hg] and diastolic BP less than 90 mm Hg without the use of any antihypertensives) or results that are judged to be not clinically significant by the investigator

Exclusion Criteria:

• Have presence of clinically significant active bleeding or history of bleeding diathesis at the time of screening

• Have presence of active peptic ulcer disease, gastro-intestinal (GI) bleeding, chronic gastritis, inflammatory bowel disease, or chronic diarrhea

• Have evidence of other chronic liver disease

• Have any use of nonsteroidal anti-inflammatory drugs (NSAIDs), celecoxib, aspirin, or acetaminophen (at doses greater than 1 gram per day [g/day] within 14 days of admission

• Have greater than 1 plus pretibial pitting edema or 2 plus ankle or pedal edema

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.	Evansville	Indiana	United States	47710

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: NCT01849055
• Other Study ID Numbers: 14708; I6H-MC-MCBB
• First Posted: May 8, 2013
• Last Update Posted: Dec 14, 2018
• Last Verified: Jul 1, 2018

• Additional relevant MeSH terms: Celecoxib

Study Results

Participant Flow

Arm/Group Title	Placebo	2.5 mg LY3023703	7.5 mg LY3023703	15 mg LY3023703	30 mg LY3023703	400 mg Celecoxib
Arm/Group Description	Placebo administered by mouth (PO), once a day (QD), for 28 days	2.5 milligram (mg) LY3023703 administered PO, QD, for 28 days	7.5 mg LY3023703 administered PO, QD, for 28 days	15 mg LY3023703 administered PO, QD, for 28 days	30 mg LY3023703 administered PO, QD, for 28 days	400 mg celecoxib administered PO, QD, for 28 days
Period Title: Overall Study
STARTED	8	8	8	8	8	8
COMPLETED	8	8	7	8	8	8
NOT COMPLETED	0	0	1	0	0	0

Baseline Characteristics

Arm/Group Title	Placebo	2.5 mg LY3023703	7.5 mg LY3023703	15 mg LY3023703	30 mg LY3023703	400 mg Celecoxib	Total
Arm/Group Description	Placebo administered PO, QD, for 28 days	2.5 mg LY3023703 administered PO, QD, for 28 days	7.5 mg LY3023703 administered PO, QD, for 28 days	15 mg LY3023703 administered PO, QD, for 28 days	30 mg LY3023703 administered PO, QD, for 28 days	400 mg celecoxib administered PO, QD, for 28 days	Total of all reporting groups
Overall Participants	8	8	8	8	8	8	48
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	37.8 (10.6)	43.0 (11.7)	37.9 (12.6)	41.4 (10.4)	39.0 (7.7)	39.1 (6.8)	39.7 (9.8)
Sex: Female, Male (Count of Participants)
Female	1 12.5%	3 37.5%	1 12.5%	0 0%	1 12.5%	1 12.5%	7 14.6%
Male	7 87.5%	5 62.5%	7 87.5%	8 100%	7 87.5%	7 87.5%	41 85.4%
Race/Ethnicity, Customized (Count of Participants)
American Indian/Alaska Native	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%	0 0%	2 25%	0 0%	2 4.2%
Black/African American	3 37.5%	2 25%	3 37.5%	2 25%	3 37.5%	5 62.5%	18 37.5%
Multiple	0 0%	0 0%	1 12.5%	2 25%	0 0%	0 0%	3 6.3%
Native Hawaiian/Pacific Islander	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
White	5 62.5%	6 75%	4 50%	4 50%	3 37.5%	3 37.5%	25 52.1%
Region of Enrollment (Count of Participants)
United States	8 100%	8 100%	8 100%	8 100%	8 100%	8 100%	48 100%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration
Description	A summary of serious and all other non-serious adverse events (AE), regardless of possible study drug relatedness, is located in the Reported Adverse Events module.
Time Frame	Baseline to Study Completion (up to 74 Days)

Outcome Measure Data

Analysis Population Description

Randomized participants who reported an AE that met any of the serious criteria.

Arm/Group Title	Placebo	2.5 mg LY3023703	7.5 mg LY3023703	15 mg LY3023703	30 mg LY3023703	400 mg Celecoxib
Arm/Group Description	Placebo administered PO, QD, for 28 days	2.5 mg LY3023703 administered PO, QD, for 28 days	7.5 mg LY3023703 administered PO, QD, for 28 days	15 mg LY3023703 administered PO, QD, for 28 days	30 mg LY3023703 administered PO, QD, for 28 days	400 mg celecoxib administered PO, QD, for 28 days
Measure Participants	8	8	8	8	8	8
Count of Participants [Participants]	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%

2. Secondary Outcome

Title	Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve [AUC(0-24)] of LY3023703
Time Frame	Post-First Dose on Days 1-28 (Time Frame: Day 1: -0.5, 1, 2, 4, 8, 12, 24 hours; Days 5, 12, 20: -0.5 hours; Day 28: -0.5, 1, 2, 4, 8, 12, 24 hours.)

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least one dose of the study medication and had evaluable PK data.

Arm/Group Title	2.5 mg LY3023703	7.5 mg LY3023703	15 mg LY3023703	30 mg LY3023703
Arm/Group Description	2.5 mg LY3023703 administered PO, QD, for 28 days	7.5 mg LY3023703 administered PO, QD, for 28 days	15 mg LY3023703 administered PO, QD, for 28 days	30 mg LY3023703 administered PO, QD, for 28 days
Measure Participants	8	8	8	8
Single Oral Dose (Day 1)	332 (41.4)	1140 (31.7)	2300 (12.4)	5290 (24.0)
Multiple Oral Doses (Day 28)	300 (39.3)	1340 (43.7)	2880 (19.2)	8520 (24.7)

3. Secondary Outcome

Title	Pharmacokinetics: Maximum Concentration (Cmax) of LY3023703
Time Frame	Post first dose on Day 1 through Day 28 (Time Frame: Day 1: -0.5, 1, 2, 4, 8, 12, 24 hours; Days 5, 12, 20: -0.5 hours; Day 28: -0.5, 1, 2, 4, 8, 12, 24 hours.)

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least one dose of the study medication and had evaluable PK data.

Arm/Group Title	2.5 mg LY3023703	7.5 mg LY3023703	15 mg LY3023703	30 mg LY3023703
Arm/Group Description	2.5 mg LY3023703 administered PO, QD, for 28 days	7.5 mg LY3023703 administered PO, QD, for 28 days	15 mg LY3023703 administered PO, QD, for 28 days	30 mg LY3023703 administered PO, QD, for 28 days
Measure Participants	8	8	8	8
Single Oral Dose (Day 1)	42.6 (25.2)	126 (35.2)	228 (25.6)	556 (30.1)
Multiple Oral Doses (Day 28)	41.9 (47.5)	151 (47.0)	243 (28.3)	711 (26.2)

4. Secondary Outcome

Title	Pharmacokinetics: Time of Maximum Concentration (Tmax) of LY3023703
Time Frame	Post first dose on Day 1 through Day 28 (Time Frame: Day 1: -0.5, 1, 2, 4, 8, 12, 24 hours; Days 5, 12, 20: -0.5 hours; Day 28: -0.5, 1, 2, 4, 8, 12, 24 hours.)

Outcome Measure Data

Analysis Population Description

All randomly assigned participants who received at least one dose of the study medication and had evaluable PK data.

Arm/Group Title	2.5 mg LY3023703	7.5 mg LY3023703	15 mg LY3023703	30 mg LY3023703
Arm/Group Description	2.5 mg LY3023703 administered PO, QD, for 28 days	7.5 mg LY3023703 administered PO, QD, for 28 days	15 mg LY3023703 administered PO, QD, for 28 days	30 mg LY3023703 administered PO, QD, for 28 days
Measure Participants	8	8	8	8
Single Oral Dose (Day 1)	2.01	3.00	4.00	4.00
Multiple Oral Doses (Day 28)	2.00	2.00	4.00	4.00

5. Secondary Outcome

Title	Change From Baseline to Day 27 in Blood Pressure (BP)
Description	The Day 27 change from Day -1 was analyzed by using analysis of covariance (ANCOVA) with treatment as a fixed effect and baseline Day -1 as a covariate. The treatment mean, difference to placebo, and difference to celecoxib were output with corresponding 90% confidence intervals.
Time Frame	Baseline, Day 27

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least one dose of study treatment and had evaluable data.

Arm/Group Title	Placebo	2.5 mg LY3023703	7.5 mg LY3023703	15 mg LY3023703	30 mg LY3023703	400 mg Celecoxib
Arm/Group Description	Placebo administered PO, QD, for 28 days	2.5 mg LY3023703 administered PO, QD, for 28 days	7.5 mg LY3023703 administered PO, QD, for 28 days	15 mg LY3023703 administered PO, QD, for 28 days	30 mg LY3023703 administered PO, QD, for 28 days	400 mg celecoxib administered PO, QD, for 28 days
Measure Participants	8	8	8	8	8	8
Systolic Blood Pressure (SBP)	-1.45	-2.67	-2.54	-2.99	-2.98	-5.29
Diastolic Blood Pressure (DBP)	0.28	-0.11	-0.83	-0.68	-1.22	-2.24

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, 2.5 mg LY3023703
	Comments	SBP
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-1.22
	Confidence Interval	(2-Sided) 90%; -4.98 to 2.54
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, 7.5 mg LY3023703
	Comments	SBP
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-1.09
	Confidence Interval	(2-Sided) 90%; -4.70 to 2.53
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, 15 mg LY3023703
	Comments	SBP
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-1.54
	Confidence Interval	(2-Sided) 90%; -5.30 to 2.22
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, 30 mg LY3023703
	Comments	SBP
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-1.53
	Confidence Interval	(2-Sided) 90%; -5.16 to 2.10
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Placebo, 400 mg Celecoxib
	Comments	SBP
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-3.84
	Confidence Interval	(2-Sided) 90%; -7.74 to 0.07
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Placebo, 2.5 mg LY3023703
	Comments	DBP
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.38
	Confidence Interval	(2-Sided) 90%; -2.95 to 2.18
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Placebo, 7.5 mg LY3023703
	Comments	DBP
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-1.11
	Confidence Interval	(2-Sided) 90%; -3.69 to 1.48
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Placebo, 15 mg LY3023703
	Comments	DBP
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.95
	Confidence Interval	(2-Sided) 90%; -3.75 to 1.85
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Placebo, 30 mg LY3023703
	Comments	DBP
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-1.49
	Confidence Interval	(2-Sided) 90%; -4.09 to 1.10
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Placebo, 400 mg Celecoxib
	Comments	DBP
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-2.51
	Confidence Interval	(2-Sided) 90%; -5.23 to 0.20
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Arm/Group Title	Placebo		2.5 mg LY3023703		7.5 mg LY3023703		15 mg LY3023703		30 mg LY3023703		400 mg Celecoxib
Arm/Group Description	Placebo administered PO, QD, for 28 days		2.5 mg LY3023703 administered PO, QD, for 28 days		7.5 mg LY3023703 administered PO, QD, for 28 days		15 mg LY3023703 administered PO, QD, for 28 days		30 mg LY3023703 administered PO, QD, for 28 days		400 mg celecoxib administered PO, QD, for 28 days
All Cause Mortality
	Placebo		2.5 mg LY3023703		7.5 mg LY3023703		15 mg LY3023703		30 mg LY3023703		400 mg Celecoxib
	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		2.5 mg LY3023703		7.5 mg LY3023703		15 mg LY3023703		30 mg LY3023703		400 mg Celecoxib
	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	0/8 (0%)		0/8 (0%)		0/8 (0%)		0/8 (0%)		0/8 (0%)		0/8 (0%)
Other (Not Including Serious) Adverse Events
	Placebo		2.5 mg LY3023703		7.5 mg LY3023703		15 mg LY3023703		30 mg LY3023703		400 mg Celecoxib
	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	4/8 (50%)		3/8 (37.5%)		3/8 (37.5%)		4/8 (50%)		5/8 (62.5%)		3/8 (37.5%)
Gastrointestinal disorders
Abdominal discomfort	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	1/8 (12.5%)	1	0/8 (0%)	0	0/8 (0%)	0
Abdominal pain	1/8 (12.5%)	1	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	2/8 (25%)	3	1/8 (12.5%)	1
Constipation	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	1/8 (12.5%)	2	0/8 (0%)	0
Diarrhoea	0/8 (0%)	0	2/8 (25%)	2	0/8 (0%)	0	0/8 (0%)	0	1/8 (12.5%)	1	1/8 (12.5%)	1
Dyspepsia	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	1/8 (12.5%)	1	0/8 (0%)	0	0/8 (0%)	0
Faeces discoloured	1/8 (12.5%)	1	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	1/8 (12.5%)	2	0/8 (0%)	0
Flatulence	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	1/8 (12.5%)	1
Nausea	1/8 (12.5%)	1	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0
Stomatitis	0/8 (0%)	0	0/8 (0%)	0	1/8 (12.5%)	1	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0
General disorders
Non-cardiac chest pain	1/8 (12.5%)	1	1/8 (12.5%)	2	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0
Oedema peripheral	0/8 (0%)	0	0/8 (0%)	0	1/8 (12.5%)	1	0/8 (0%)	0	0/8 (0%)	0	1/8 (12.5%)	1
Infections and infestations
Folliculitis	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	1/8 (12.5%)	1
Injury, poisoning and procedural complications
Arthropod bite	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	1/8 (12.5%)	1	0/8 (0%)	0	0/8 (0%)	0
Thermal burn	0/8 (0%)	0	1/8 (12.5%)	1	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0
Investigations
Blood immunoglobulin e increased	0/8 (0%)	0	1/8 (12.5%)	1	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0
Liver function test abnormal	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	1/8 (12.5%)	1	0/8 (0%)	0
Metabolism and nutrition disorders
Decreased appetite	1/8 (12.5%)	1	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0
Nervous system disorders
Dizziness postural	0/8 (0%)	0	1/8 (12.5%)	1	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0
Headache	3/8 (37.5%)	4	1/8 (12.5%)	2	1/8 (12.5%)	2	1/8 (12.5%)	1	3/8 (37.5%)	4	0/8 (0%)	0
Hypoaesthesia	0/8 (0%)	0	1/8 (12.5%)	1	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0
Reproductive system and breast disorders
Menstruation irregular	0/1 (0%)	0	1/3 (33.3%)	1	0/1 (0%)	0	0/0 (NaN)	0	0/1 (0%)	0	0/1 (0%)	0
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	1/8 (12.5%)	1
Rhinorrhoea	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	1/8 (12.5%)	1	0/8 (0%)	0	0/8 (0%)	0
Skin and subcutaneous tissue disorders
Dermatitis	1/8 (12.5%)	1	2/8 (25%)	2	0/8 (0%)	0	0/8 (0%)	0	1/8 (12.5%)	1	0/8 (0%)	0
Urticaria	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	1/8 (12.5%)	1	0/8 (0%)	0

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.