Pharmacokinetics of Entospletinib in Adults With Normal and Impaired Liver Function

• Sponsor: Gilead Sciences (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02521376
• Collaborator: (none)
• Enrollment: 56
• Locations: 6
• Arms: 3
• Actual Duration (Months): 23.3
• Patients Per Site: 9.3
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

The primary objective of this study is to evaluate the pharmacokinetics of entospletinib (ENTO) and/or its metabolites (if applicable) in participants with impaired hepatic function (stratified by smoking status, as appropriate) relative to matched, healthy controls.

Condition or Disease	Intervention/Treatment	Phase
Oncology	Drug: Entospletinib	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 56 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 1, Open-Label, Multiple Dose Study to Evaluate the Pharmacokinetics of Entospletinib in Subjects With Normal and Impaired Hepatic Function
• Actual Study Start Date: Nov 16, 2015
• Actual Primary Completion Date: Oct 25, 2017
• Actual Study Completion Date: Oct 25, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cohort 1 (Moderate Hepatic Impairment) Entospletinib administered twice daily on Days 1-4, and 1 morning dose only on Day 5.	Drug: Entospletinib; Entospletinib 100 mg tablet administered orally; Other Names: GS-9973
Experimental: Cohort 2 (Severe Hepatic Impairment) Entospletinib administered twice daily on Days 1-4, and 1 morning dose only on Day 5.	Drug: Entospletinib; Entospletinib 100 mg tablet administered orally; Other Names: GS-9973
Experimental: Cohort 3 (Mild Hepatic Impairment) Entospletinib administered twice daily on Days 1-4, and 1 morning dose only on Day 5.	Drug: Entospletinib; Entospletinib 100 mg tablet administered orally; Other Names: GS-9973

Outcome Measures

Primary Outcome Measures

1. Pharmacokinetic (PK) Parameter: AUCtau of ENTO [0 (predose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36, 48, 60, 72, 84, and 96 hours postdose on Day 5]

   AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval).

2. Pharmacokinetic (PK) Parameter: Cmax of ENTO [0 (predose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36, 48, 60, 72, 84, and 96 hours postdose on Day 5]

   Cmax is defined as the maximum concentration of drug.

Secondary Outcome Measures

1. Percentage of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs) [Baseline up to Day 9 plus 30 days]

   TEAEs are defined as events that meet one of the following criteria: Any adverse events (AEs) with onset date of on or after the study drug start date and no later than 30 days after permanent discontinuation of study drug or Any AEs leading to premature discontinuation of study drug.

2. Percentage of Participants Experiencing Treatment-Emergent Laboratory Abnormalities [Baseline up to Day 9 plus 30 days]

   Treatment-emergent laboratory abnormalities were defined as values that increase at least one toxicity grade from baseline. The most severe graded abnormality from all tests was counted for each subject.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Key Inclusion Criteria:

• Calculated body mass index from 18 to 40 kg/m^2

• Not pregnant

• Normal electrocardiogram

• Participants with impaired liver function must be sufficiently healthy based upon medical history and physical examination, vital signs, and screening laboratory evaluations.

Key Exclusion Criteria:

• Participation in another clinical study (current or within last 30 days)

• HIV, hepatitis B virus, or active hepatitis C virus infection

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Clinical Pharmacology of Miami, Inc. (CPMI)	Miami	Florida	United States
2	Orlando Clinical Research Center	Orlando	Florida	United States
3	DaVita Clinical Research	Minneapolis	Minnesota	United States
4	The Texas Liver Institute	San Antonio	Texas	United States
5	APEX GmBH	Munich		Germany
6	Auckland Clinical Studies	Auckland		New Zealand

Sponsors and Collaborators

• Gilead Sciences

Investigators

• Study Director: Gilead Study Director, Gilead Sciences

Study Documents (Full-Text)

• Study Protocol: Original - Jul 28, 2015
• Study Protocol: Amendment 1 - Oct 16, 2015
• Study Protocol: Amendment 2 - Jul 1, 2016
• Study Protocol: Amendment 3 - Aug 26, 2016
• Study Protocol: Amendment 4 - Nov 30, 2016
• Statistical Analysis Plan - Aug 30, 2018

More Information

Publications

None provided.

• Responsible Party: Gilead Sciences
• ClinicalTrials.gov Identifier: NCT02521376
• Other Study ID Numbers: GS-US-339-1631; 2016-003266-98
• First Posted: Aug 13, 2015
• Last Update Posted: Jul 26, 2019
• Last Verified: May 1, 2019

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Neoplasms

Study Results

Participant Flow

Recruitment Details	Participants were enrolled at study sites in United States, New Zealand, and Germany. The first participant was screened on 16 November 2015. The last study visit occurred on 25 October 2017.
Pre-assignment Detail	102 participants were screened.

Arm/Group Title	Severe Hepatic Impairment	Moderate Hepatic Impairment	Mild Hepatic Impairment	Healthy Control
Arm/Group Description	Participants with severe hepatic impairment received entospletinib (ENTO) 100 mg tablet twice daily on Days 1-4, and 1 morning dose only on Day 5.	Participants with moderate hepatic impairment received ENTO 100 mg tablet twice daily on Days 1-4, and 1 morning dose only on Day 5.	Participants with mild hepatic impairment received ENTO 100 mg tablet twice daily on Days 1-4, and 1 morning dose only on Day 5.	Participants with normal hepatic function received ENTO 100 mg tablet twice daily on Days 1-4, and 1 morning dose only on Day 5.
Period Title: Overall Study
STARTED	8	18	10	20
COMPLETED	7	18	10	20
NOT COMPLETED	1	0	0	0

Baseline Characteristics

Arm/Group Title	Severe Hepatic Impairment	Moderate Hepatic Impairment	Mild Hepatic Impairment	Healthy Control	Total
Arm/Group Description	Participants with severe hepatic impairment received entospletinib (ENTO) 100 mg tablet twice daily on Days 1-4, and 1 morning dose only on Day 5.	Participants with moderate hepatic impairment received ENTO 100 mg tablet twice daily on Days 1-4, and 1 morning dose only on Day 5.	Participants with mild hepatic impairment received ENTO 100 mg tablet twice daily on Days 1-4, and 1 morning dose only on Day 5.	Participants with normal hepatic function received ENTO 100 mg tablet twice daily on Days 1-4, and 1 morning dose only on Day 5.	Total of all reporting groups
Overall Participants	7	18	10	20	55
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	56 (10.6)	59 (8.5)	58 (11.4)	56 (9.3)	57 (9.4)
Sex: Female, Male (Count of Participants)
Female	1 14.3%	4 22.2%	5 50%	5 25%	15 27.3%
Male	6 85.7%	14 77.8%	5 50%	15 75%	40 72.7%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	3 42.9%	5 27.8%	3 30%	9 45%	20 36.4%
Not Hispanic or Latino	4 57.1%	13 72.2%	7 70%	11 55%	35 63.6%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	1 5%	1 1.8%
Asian	0 0%	0 0%	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%	0 0%
Black or African American	0 0%	1 5.6%	1 10%	2 10%	4 7.3%
White	7 100%	17 94.4%	9 90%	17 85%	50 90.9%
More than one race	0 0%	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%
Region of Enrollment (Count of Participants)
New Zealand	1 14.3%	0 0%	1 10%	0 0%	2 3.6%
United States	5 71.4%	17 94.4%	8 80%	19 95%	49 89.1%
Germany	1 14.3%	1 5.6%	1 10%	1 5%	4 7.3%

Outcome Measures

1. Primary Outcome

Title	Pharmacokinetic (PK) Parameter: AUCtau of ENTO
Description	AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval).
Time Frame	0 (predose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36, 48, 60, 72, 84, and 96 hours postdose on Day 5

Outcome Measure Data

Analysis Population Description

Participants in the PK Analysis Set (all enrolled participants who received at least one dose of ENTO and had at least one evaluable PK concentration data value reported by the PK lab) with available data were analyzed. Healthy control participants may participate in more than one cohorts.

Arm/Group Title	Cohort 1: Moderate Hepatic Impairment Smoking	Cohort 1: Moderate Hepatic Impairment Non-smoking	Cohort 1: Healthy Control Matched to Smoking	Cohort 1: Healthy Control Matched to Non-smoking	Cohort 2: Severe Hepatic Impairment	Cohort 2: Healthy Control	Cohort 3: Mild Hepatic Impairment	Cohort 3: Healthy Control
Arm/Group Description	Participants with moderate hepatic impairment who are smokers received ENTO 100 mg tablet twice daily on Days 1-4, and 1 morning dose only on Day 5.	Participants with moderate hepatic impairment who are non-smokers received ENTO 100 mg tablet twice daily on Days 1-4, and 1 morning dose only on Day 5.	Participants with normal hepatic function who are smokers received ENTO 100 mg tablet twice daily on Days 1-4, and 1 morning dose only on Day 5.	Participants with normal hepatic function who are non-smokers received ENTO 100 mg tablet twice daily on Days 1-4, and 1 morning dose only on Day 5.	Participants with severe hepatic impairment received ENTO 100 mg tablet twice daily on Days 1-4, and 1 morning dose only on Day 5.	Participants with normal hepatic function received ENTO 100 mg tablet twice daily on Days 1-4, and 1 morning dose only on Day 5.	Participants with mild hepatic impairment received ENTO 100 mg tablet twice daily on Days 1-4, and 1 morning dose only on Day 5.	Participants with normal hepatic function received ENTO 100 mg tablet twice daily on Days 1-4, and 1 morning dose only on Day 5.
Measure Participants	9	9	9	9	7	7	10	10
Mean (Standard Deviation) [h*ng/mL]	1788.9 (771.30)	7490.0 (3805.03)	4081.5 (2464.77)	3318.0 (1788.90)	7036.0 (2814.95)	3402.7 (1771.79)	4071.9 (913.47)	4123.0 (1874.33)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Cohort 1: Moderate Hepatic Impairment Smoking, Cohort 1: Healthy Control Matched to Smoking
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric Mean Ratio (GMR)
	Estimated Value	43.69
	Confidence Interval	(2-Sided) 90%; 24.59 to 77.62
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Cohort 1: Moderate Hepatic Impairment Non-smoking, Cohort 1: Healthy Control Matched to Non-smoking
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	GMR
	Estimated Value	233.63
	Confidence Interval	(2-Sided) 90%; 141.85 to 384.79
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Cohort 2: Severe Hepatic Impairment, Cohort 2: Healthy Control
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	GMR
	Estimated Value	219.20
	Confidence Interval	(2-Sided) 90%; 139.74 to 343.84
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Cohort 3: Mild Hepatic Impairment, Cohort 3: Healthy Control
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	GMR
	Estimated Value	108.50
	Confidence Interval	(2-Sided) 90%; 77.20 to 152.48
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Primary Outcome

Title	Pharmacokinetic (PK) Parameter: Cmax of ENTO
Description	Cmax is defined as the maximum concentration of drug.
Time Frame	0 (predose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36, 48, 60, 72, 84, and 96 hours postdose on Day 5

Outcome Measure Data

Analysis Population Description

Participants in the PK Analysis Set with available data were analyzed. Healthy control participants may participate in more than one cohorts.

Arm/Group Title	Cohort 1: Moderate Hepatic Impairment Smoking	Cohort 1: Moderate Hepatic Impairment Non-smoking	Cohort 1: Healthy Control Matched to Smoking	Cohort 1: Healthy Control Matched to Non-smoking	Cohort 2: Severe Hepatic Impairment	Cohort 2: Healthy Control	Cohort 3: Mild Hepatic Impairment	Cohort 3: Healthy Control
Arm/Group Description	Participants with moderate hepatic impairment who are smokers received ENTO 100 mg tablet twice daily on Days 1-4, and 1 morning dose only on Day 5.	Participants with moderate hepatic impairment who are non-smokers received ENTO 100 mg tablet twice daily on Days 1-4, and 1 morning dose only on Day 5.	Participants with normal hepatic function who are smokers received ENTO 100 mg tablet twice daily on Days 1-4, and 1 morning dose only on Day 5.	Participants with normal hepatic function who are non-smokers received ENTO 100 mg tablet twice daily on Days 1-4, and 1 morning dose only on Day 5.	Participants with severe hepatic impairment received ENTO 100 mg tablet twice daily on Days 1-4, and 1 morning dose only on Day 5.	Participants with normal hepatic function received ENTO 100 mg tablet twice daily on Days 1-4, and 1 morning dose only on Day 5.	Participants with mild hepatic impairment received ENTO 100 mg tablet twice daily on Days 1-4, and 1 morning dose only on Day 5.	Participants with normal hepatic function received ENTO 100 mg tablet twice daily on Days 1-4, and 1 morning dose only on Day 5.
Measure Participants	9	9	9	9	7	7	10	10
Mean (Standard Deviation) [ng/mL]	313.1 (122.39)	1007.3 (480.63)	582.3 (326.04)	497.4 (292.67)	837.7 (326.52)	521.1 (280.65)	569.8 (166.56)	590.5 (326.08)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Cohort 1: Moderate Hepatic Impairment Smoking, Cohort 1: Healthy Control Matched to Smoking
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	GMR
	Estimated Value	55.71
	Confidence Interval	(2-Sided) 90%; 34.70 to 89.42
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Cohort 1: Moderate Hepatic Impairment Non-smoking, Cohort 1: Healthy Control Matched to Non-smoking
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	GMR
	Estimated Value	211.94
	Confidence Interval	(2-Sided) 90%; 132.49 to 339.03
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Cohort 2: Severe Hepatic Impairment, Cohort 2: Healthy Control
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	GMR
	Estimated Value	171.33
	Confidence Interval	(2-Sided) 90%; 108.17 to 271.37
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Cohort 3: Mild Hepatic Impairment, Cohort 3: Healthy Control
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	GMR
	Estimated Value	107.35
	Confidence Interval	(2-Sided) 90%; 72.71 to 158.51
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Percentage of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs)
Description	TEAEs are defined as events that meet one of the following criteria: Any adverse events (AEs) with onset date of on or after the study drug start date and no later than 30 days after permanent discontinuation of study drug or Any AEs leading to premature discontinuation of study drug.
Time Frame	Baseline up to Day 9 plus 30 days

Outcome Measure Data

Analysis Population Description

Safety Analysis Set included all randomized participants who received at least one dose of study drug.

Arm/Group Title	Severe Hepatic Impairment	Moderate Hepatic Impairment	Mild Hepatic Impairment	Healthy Control
Arm/Group Description	Participants with severe hepatic impairment received entospletinib (ENTO) 100 mg tablet twice daily on Days 1-4, and 1 morning dose only on Day 5.	Participants with moderate hepatic impairment received ENTO 100 mg tablet twice daily on Days 1-4, and 1 morning dose only on Day 5.	Participants with mild hepatic impairment received ENTO 100 mg tablet twice daily on Days 1-4, and 1 morning dose only on Day 5.	Participants with normal hepatic function received ENTO 100 mg tablet twice daily on Days 1-4, and 1 morning dose only on Day 5.
Measure Participants	7	18	10	20
Number [percentage of participants]	14.3 204.3%	22.3 123.9%	30.0 300%	30.0 150%

4. Secondary Outcome

Title	Percentage of Participants Experiencing Treatment-Emergent Laboratory Abnormalities
Description	Treatment-emergent laboratory abnormalities were defined as values that increase at least one toxicity grade from baseline. The most severe graded abnormality from all tests was counted for each subject.
Time Frame	Baseline up to Day 9 plus 30 days

Outcome Measure Data

Analysis Population Description

Participants in the Safety Analysis Set were analyzed.

Arm/Group Title	Severe Hepatic Impairment	Moderate Hepatic Impairment	Mild Hepatic Impairment	Healthy Control
Arm/Group Description	Participants with severe hepatic impairment received entospletinib (ENTO) 100 mg tablet twice daily on Days 1-4, and 1 morning dose only on Day 5.	Participants with moderate hepatic impairment received ENTO 100 mg tablet twice daily on Days 1-4, and 1 morning dose only on Day 5.	Participants with mild hepatic impairment received ENTO 100 mg tablet twice daily on Days 1-4, and 1 morning dose only on Day 5.	Participants with normal hepatic function received ENTO 100 mg tablet twice daily on Days 1-4, and 1 morning dose only on Day 5.
Measure Participants	7	18	10	20
Number [percentage of participants]	100.0 1428.6%	88.9 493.9%	60.0 600%	50.0 250%

Adverse Events

Time Frame	First dose date up to Day 9 plus 30 days
Adverse Event Reporting Description	Safety Analysis Set included all randomized participants who received at least one dose of study drug.
Arm/Group Title	Severe Hepatic Impairment		Moderate Hepatic Impairment		Mild Hepatic Impairment		Healthy Control
Arm/Group Description	Participants with severe hepatic impairment received entospletinib (ENTO) 100 mg tablet twice daily on Days 1-4, and 1 morning dose only on Day 5.		Participants with moderate hepatic impairment received ENTO 100 mg tablet twice daily on Days 1-4, and 1 morning dose only on Day 5.		Participants with mild hepatic impairment received ENTO 100 mg tablet twice daily on Days 1-4, and 1 morning dose only on Day 5.		Participants with normal hepatic function received ENTO 100 mg tablet twice daily on Days 1-4, and 1 morning dose only on Day 5.
All Cause Mortality
	Severe Hepatic Impairment		Moderate Hepatic Impairment		Mild Hepatic Impairment		Healthy Control
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/7 (0%)		0/18 (0%)		0/10 (0%)		0/20 (0%)
Serious Adverse Events
	Severe Hepatic Impairment		Moderate Hepatic Impairment		Mild Hepatic Impairment		Healthy Control
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/7 (0%)		0/18 (0%)		0/10 (0%)		0/20 (0%)
Other (Not Including Serious) Adverse Events
	Severe Hepatic Impairment		Moderate Hepatic Impairment		Mild Hepatic Impairment		Healthy Control
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/7 (14.3%)		4/18 (22.2%)		3/10 (30%)		6/20 (30%)
Gastrointestinal disorders
Abdominal distension	0/7 (0%)		1/18 (5.6%)		0/10 (0%)		0/20 (0%)
Constipation	0/7 (0%)		0/18 (0%)		0/10 (0%)		2/20 (10%)
Diarrhoea	1/7 (14.3%)		0/18 (0%)		0/10 (0%)		0/20 (0%)
Dry mouth	0/7 (0%)		0/18 (0%)		1/10 (10%)		0/20 (0%)
Dyspepsia	0/7 (0%)		1/18 (5.6%)		0/10 (0%)		0/20 (0%)
General disorders
Oedema peripheral	0/7 (0%)		0/18 (0%)		0/10 (0%)		1/20 (5%)
Infections and infestations
Infected bite	1/7 (14.3%)		0/18 (0%)		0/10 (0%)		0/20 (0%)
Upper respiratory tract infection	0/7 (0%)		0/18 (0%)		0/10 (0%)		1/20 (5%)
Injury, poisoning and procedural complications
Contusion	0/7 (0%)		0/18 (0%)		0/10 (0%)		1/20 (5%)
Laceration	0/7 (0%)		0/18 (0%)		1/10 (10%)		0/20 (0%)
Musculoskeletal and connective tissue disorders
Flank pain	0/7 (0%)		1/18 (5.6%)		0/10 (0%)		0/20 (0%)
Muscle tightness	0/7 (0%)		0/18 (0%)		1/10 (10%)		0/20 (0%)
Nervous system disorders
Headache	0/7 (0%)		1/18 (5.6%)		1/10 (10%)		4/20 (20%)
Renal and urinary disorders
Chromaturia	0/7 (0%)		1/18 (5.6%)		0/10 (0%)		0/20 (0%)
Skin and subcutaneous tissue disorders
Rash	1/7 (14.3%)		0/18 (0%)		0/10 (0%)		0/20 (0%)
Vascular disorders
Hypotension	0/7 (0%)		0/18 (0%)		0/10 (0%)		1/20 (5%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

After conclusion of the study and without prior written approval from Gilead, investigators in this study may communicate, orally present, or publish in scientific journals or other media only after the following conditions have been met: The results of the study in their entirety have been publicly disclosed by or with the consent of Gilead in an abstract, manuscript, or presentation form; or The study has been completed at all study sites for at least 2 years