Pharmacokinetics, Safety, and Efficacy of Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Disoproxil Fumarate Single Tablet Regimen (STR) in Adolescents

• Sponsor: Gilead Sciences (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01721109
• Collaborator: (none)
• Enrollment: 50
• Locations: 18
• Arm: 1
• Actual Duration (Months): 61.8
• Patients Per Site: 2.8
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

The primary objectives of this study are to evaluate the steady-state pharmacokinetics (PK) and confirm the dose of the elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate (EVG/COBI/FTC/TDF) single-tablet regimen (STR) (Part A) and to evaluate the safety and tolerability of EVG/COBI/FTC/TDF STR through Week 48 (Part B) in HIV-1 infected, antiretroviral (ARV) treatment-naive adolescents.

A total of 50 adolescent participants (12 to < 18 years of age) will be enrolled to receive

EVG/COBI/FTC/TDF as follows:

• Part A: Twelve to 16 eligible participants will be enrolled to evaluate steady-state PK, and confirm the dose, with the intent to enroll at least 4 participants 12 to < 15 and at least 4 participants 15 to < 18 years of age.

• Part B: Following confirmation of EVG exposure in at least 12 participants from Part A, 34 to 38 participants in addition to those enrolled in Part A will be enrolled to evaluate the safety, tolerability, and antiviral activity of EVG/COBI/FTC/TDF STR.

Condition or Disease	Intervention/Treatment	Phase
Acquired Immunodeficiency Syndrome; HIV Infections	Drug: EVG/COBI/FTC/TDF	Phase 2/Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 50 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 2/3, Open-Label Study of the Pharmacokinetics, Safety, and Antiviral Activity of the Elvitegravir/ Cobicistat/Emtricitabine/Tenofovir Disoproxil Fumarate Single Tablet Regimen (STR) in HIV-1 Infected Antiretroviral Treatment-Naive Adolescents
• Actual Study Start Date: Dec 6, 2012
• Actual Primary Completion Date: Oct 22, 2015
• Actual Study Completion Date: Jan 29, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: EVG/COBI/FTC/TDF Participants will receive treatment for 48 weeks and then had the option to enter an Extension Phase to receive EVG/COBI/FTC/TDF until 1) the age of 18, 2) EVG/COBI/FTC/TDF becomes commercially available in the country the participant is enrolled, or 3) Gilead elects to terminate the development of EVG/COBI/FTC/TDF in that country.	Drug: EVG/COBI/FTC/TDF; 150/150/200/300 mg STR administered orally once daily with food; Other Names: Stribild®

Outcome Measures

Primary Outcome Measures

1. For Part A, Pharmacokinetic (PK) Parameter: AUCtau of EVG [Predose, 2, 4, 4.5, 5, 8, and 12 hours postdose on Day 10]

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

2. Incidence of Treatment-Emergent Serious Adverse Events (SAEs) and All Treatment-Emergent Adverse Events (AEs) [Up to Week 48 plus 30 days]

Secondary Outcome Measures

1. For Part A, PK Parameter: Ctau of EVG, FTC, Tenofovir (TFV), and COBI [Predose, 2, 4, 4.5, 5, 8, and 12 hours postdose on Day 10]

   Ctau is defined as the observed drug concentration at the end of the dosing interval.

2. For Part A, PK Parameter: Cmax of EVG, FTC, TFV, and COBI [Predose, 2, 4, 4.5, 5, 8, and 12 hours postdose on Day 10]

   Cmax is defined as the maximum concentration of drug.

3. For Part A, PK Parameter: AUCtau of FTC, TFV, and COBI [Predose, 2, 4, 4.5, 5, 8, and 12 hours postdose on Day 10]

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

4. Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Weeks 24 and 48 as Defined by the FDA Snapshot Analysis [Weeks 24 and 48]

5. Percentage of Participants With HIV-1 RNA < 400 Copies/mL at Weeks 24 and 48 as Defined by the FDA Snapshot Analysis [Weeks 24 and 48]

6. Change From Baseline in Plasma log10 HIV-1 RNA at Weeks 24 and 48 [Baseline; Weeks 24 and 48]

7. Change From Baseline in CD4+ Cell Count at Weeks 24 and 48 [Baseline; Weeks 24 and 48]

8. Change From Baseline in CD4 Percentage at Weeks 24 and 48 [Baseline; Weeks 24 and 48]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 12 Years to 17 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Key Inclusion Criteria:

• 12 years to < 18 years of age at baseline

• Able to give written assent prior to any screening evaluations

• Parent or guardian able to give written informed consent prior to any screening evaluations and willing to comply with study requirements

• Plasma HIV-1 RNA levels of ≥ 1,000 copies/mL

• CD4+ cell count > 100 cells/µL

• Weight ≥ 35 kg (77 lbs)

• Screening genotype report must show sensitivity to FTC and TDF

• Able to swallow oral tablets

• Adequate renal function

• Clinically normal ECG

• Documented screening for active pulmonary tuberculosis per local standard of care within 6 months of a screening visit

• Hepatic transaminases ≤ 5 x upper limit of normal

• Total bilirubin ≤ 1.5 mg/dL, or normal direct bilirubin

• Individuals with a positive Hepatitis B surface antigen screening test can participate in the study, providing that alternate therapy (other than TDF) for chronic Hepatitis B infection is available as a part of local standard of care

• Adequate hematologic function

• Negative serum pregnancy test for all females

• Males and females of childbearing potential must agree to utilize highly effective contraception methods while on study treatment or agree to abstain from heterosexual intercourse throughout the study period and for 30 days following the last dose of study drug

• Males must agree to utilize a highly effective method of contraception during heterosexual intercourse throughout the study period and for 30 days following discontinuation of investigational medicinal product

• Must be willing and able to comply with all study requirements

• Life expectancy ≥ 1 year

Key Exclusion Criteria:

• A new AIDS-defining condition diagnosed within the 30 days prior to screening

• Prior treatment with any approved or investigational or experimental anti HIV-1 drug for any length of time (other than that given for prevention of mother-to-child transmission)

• Evidence of active pulmonary or extra-pulmonary tuberculosis disease within 3 months of the screening visit

• Anticipated to require rifamycin treatment for mycobacterial infection while participating in the study. Note: prophylactic Isoniazid (INH) therapy for latent tuberculosis (TB) treatment is allowed.

• Individuals experiencing decompensated cirrhosis

• Pregnant or lactating females

• Have any serious or active medical or psychiatric illness which would interfere with treatment, assessment, or compliance with the protocol. This would include uncontrolled renal, cardiac, hematological, hepatic, pulmonary, endocrine, central nervous, gastrointestinal, vascular, metabolic, immunodeficiency disorders, active infection, or malignancy that are clinically significant or requiring treatment within 30 days prior to the study dosing.

• Current alcohol or substance abuse that will potentially interfere with compliance

• Have history of significant drug sensitivity or drug allergy

• Known hypersensitivity to the study drugs, the metabolites or formulation excipients

• Have been treated with immunosuppressant therapies or chemotherapeutic agents within 3 months of study screening or expected to receive these agents during the study

• A history of malignancy within the past 5 years or ongoing malignancy other than cutaneous Kaposi's sarcoma, basal cell carcinoma, or resected, non-invasive cutaneous squamous carcinoma

• Have previously participated in an investigational trial involving administration of any investigational agent within 30 days prior to the study dosing

• Participation in any other clinical trial without prior approval from sponsor is prohibited while participating in this trial

• Receiving ongoing therapy with any disallowed medications, including drugs not to be used with EVG, COBI, FTC, TDF or individuals with any known allergies to the excipients of EVG/COBI/FTC/TDF STR tablets

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	East Bay AIDS Center Medical Group	Oakland	California	United States	94609
2	University of South Florida - Department of Pediatrics	Tampa	Florida	United States	33606
3	University of Chicago	Chicago	Illinois	United States	60637
4	Montefiore Medical Center	Bronx	New York	United States	10467
5	New York University School of Medicine	New York	New York	United States	10016
6	St. Christopher's Hospital for Children	Philadelphia	Pennsylvania	United States	19134
7	St. Jude Children's Research Hospital	Memphis	Tennessee	United States	38105
8	Rahima Moosa Mother and Child Hospital (Wits)	Johannesburg	Gauteng	South Africa	2112
9	Dr Latiff Private Practice	Durban	Kwazulu-Natal	South Africa	4001
10	Desmond Tutu HIV Research Centre	Cape Town		South Africa	7925
11	Mpati Medical Center	Dundee		South Africa	3000
12	Clinical HIV Research Unit	Johannesburg		South Africa	2092
13	Perinatal HIV Research Unit	Soweto		South Africa	2013
14	University of Stellenbosch	Stellenbosch		South Africa	7602
15	The HIV Netherlands Australia Thailand Research Collaboration (HIV-NAT)	Bangkok		Thailand	10330
16	Siriraj Hospital, Mahidol University	Bangkok		Thailand	10700
17	Queen Savang Vadhana Memorial Hospital	Chon Buri		Thailand	20110
18	Srinakarind Hospital	Khon Kaen		Thailand	40002

Sponsors and Collaborators

• Gilead Sciences

Investigators

• Study Director: Gilead Study Director, Gilead Sciences

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Gilead Sciences
• ClinicalTrials.gov Identifier: NCT01721109
• Other Study ID Numbers: GS-US-236-0112; 2015-000313-40
• First Posted: Nov 4, 2012
• Last Update Posted: Aug 17, 2018
• Last Verified: Jul 1, 2018

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Gilead Sciences: Adolescents; HIV-1; HIV; Treatment Naive
• Additional relevant MeSH terms: HIV Infections; Acquired Immunodeficiency Syndrome; Immunologic Deficiency Syndromes; Elvitegravir, Cobicistat, Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination

Study Results

Participant Flow

Recruitment Details	Participants were enrolled at study sites in the United States, South Africa, and Thailand. The first participant was screened on 06 December 2012. The last study visit occurred on 29 January 2018.
Pre-assignment Detail	56 participants were screened.

Arm/Group Title	EVG/COBI/FTC/TDF
Arm/Group Description	Elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate (EVG/COBI/FTC/TDF) (150/150/200/300 mg) single-tablet regimen (STR) administered orally once daily with food for 48 weeks, followed by EVG/COBI/FTC/TDF (150/150/200/300 mg) during the optional extension phase.
Period Title: Overall Study
STARTED	50
COMPLETED	43
NOT COMPLETED	7

Baseline Characteristics

Arm/Group Title	EVG/COBI/FTC/TDF
Arm/Group Description	EVG/COBI/FTC/TDF (150/150/200/300 mg) STR administered orally once daily with food for 48 weeks, followed by EVG/COBI/FTC/TDF (150/150/200/300 mg) during the optional extension phase
Overall Participants	50
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	15 (1.5)
Sex: Female, Male (Count of Participants)
Female	15 30%
Male	35 70%
Race/Ethnicity, Customized (Count of Participants)
Asian	14 28%
Black	34 68%
White	1 2%
Other	1 2%
Race/Ethnicity, Customized (Count of Participants)
Hispanic or Latino	2 4%
Not Hispanic or Latino	47 94%
Not Permitted	1 2%
Region of Enrollment (Count of Participants)
United States	14 28%
South Africa	22 44%
Thailand	14 28%
HIV-1 RNA (log10 copies/mL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [log10 copies/mL]	4.60 (0.551)
HIV-1 RNA Category (Count of Participants)
≤ 100,000 copies/mL	40 80%
> 100,000 copies/mL	10 20%
CD4 Cell Count (cells/µL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [cells/µL]	399 (127.6)
CD4 Cell Count Category (Count of Participants)
≤ 199 cells/µL	2 4%
200 ≥ and ≤ 349 cells/µL	16 32%
350 ≥ and ≤ 499 cells/µL	22 44%
≥ 500 cells/µL	10 20%

Outcome Measures

1. Primary Outcome

Title	For Part A, Pharmacokinetic (PK) Parameter: AUCtau of EVG
Description	AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval).
Time Frame	Predose, 2, 4, 4.5, 5, 8, and 12 hours postdose on Day 10

Outcome Measure Data

Analysis Population Description

PK Substudy Analysis Set: all enrolled and treated participants from Part A who had evaluable steady-state pharmacokinetic profiles of the respective analyte of interest at the Day 10 intensive PK visit.

Arm/Group Title	EVG/COBI/FTC/TDF
Arm/Group Description	EVG/COBI/FTC/TDF (150/150/200/300 mg) STR administered orally once daily with food for 48 weeks, followed by EVG/COBI/FTC/TDF (150/150/200/300 mg) during the optional extension phase
Measure Participants	14
Mean (Standard Deviation) [ng•h/mL]	31620.9 (13978.07)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	EVG/COBI/FTC/TDF
	Comments
	Type of Statistical Test	Equivalence
	Comments	A sample size of 14 participants was estimated to provide over 95% power to show pharmacokinetic equivalence between adult and adolescent participants. EVG population PK from historical adult data was used for comparison. The inter-subject standard deviation (natural log scale) of EVG AUCtau observed in the population PK data was 0.31 (historical data).
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric least squares mean ratio
	Estimated Value	1.3029
	Confidence Interval	(2-Sided) 90%; 1.0479 to 1.6200
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Primary Outcome

Title	Incidence of Treatment-Emergent Serious Adverse Events (SAEs) and All Treatment-Emergent Adverse Events (AEs)
Time Frame	Up to Week 48 plus 30 days

Outcome Measure Data

Analysis Population Description

Safety Analysis Set: all participants who received at least 1 dose of study drug.

Arm/Group Title	EVG/COBI/FTC/TDF
Arm/Group Description	EVG/COBI/FTC/TDF (150/150/200/300 mg) STR administered orally once daily with food for 48 weeks, followed by EVG/COBI/FTC/TDF (150/150/200/300 mg) during the optional extension phase
Measure Participants	50
SAEs	4 8%
AEs	45 90%

3. Secondary Outcome

Title	For Part A, PK Parameter: Ctau of EVG, FTC, Tenofovir (TFV), and COBI
Description	Ctau is defined as the observed drug concentration at the end of the dosing interval.
Time Frame	Predose, 2, 4, 4.5, 5, 8, and 12 hours postdose on Day 10

Outcome Measure Data

Analysis Population Description

PK Substudy Analysis Set: all enrolled and treated participants from Part A who had evaluable steady-state pharmacokinetic profiles of the respective analyte of interest at the Day 10 intensive PK visit.

Arm/Group Title	EVG/COBI/FTC/TDF
Arm/Group Description	EVG/COBI/FTC/TDF (150/150/200/300 mg) STR administered orally once daily with food for 48 weeks, followed by EVG/COBI/FTC/TDF (150/150/200/300 mg) during the optional extension phase
Measure Participants	14
EVG	579.3 (455.20)
FTC	102.6 (30.85)
TFV	86.6 (23.58)
COBI	39.7 (68.52)

4. Secondary Outcome

Title	For Part A, PK Parameter: Cmax of EVG, FTC, TFV, and COBI
Description	Cmax is defined as the maximum concentration of drug.
Time Frame	Predose, 2, 4, 4.5, 5, 8, and 12 hours postdose on Day 10

Outcome Measure Data

Analysis Population Description

PK Substudy Analysis Set: all enrolled and treated participants from Part A who had evaluable steady-state pharmacokinetic profiles of the respective analyte of interest at the Day 10 intensive PK visit.

Arm/Group Title	EVG/COBI/FTC/TDF
Arm/Group Description	EVG/COBI/FTC/TDF (150/150/200/300 mg) STR administered orally once daily with food for 48 weeks, followed by EVG/COBI/FTC/TDF (150/150/200/300 mg) during the optional extension phase
Measure Participants	14
EVG	2624.3 (1239.64)
FTC	2217.4 (664.64)
TFV	438.5 (170.69)
COBI	1500.4 (975.29)

5. Secondary Outcome

Title	For Part A, PK Parameter: AUCtau of FTC, TFV, and COBI
Description	AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval).
Time Frame	Predose, 2, 4, 4.5, 5, 8, and 12 hours postdose on Day 10

Outcome Measure Data

Analysis Population Description

PK Substudy Analysis Set: all enrolled and treated participants from Part A who had evaluable steady-state pharmacokinetic profiles of the respective analyte of interest at the Day 10 intensive PK visit.

Arm/Group Title	EVG/COBI/FTC/TDF
Arm/Group Description	EVG/COBI/FTC/TDF (150/150/200/300 mg) STR administered orally once daily with food for 48 weeks, followed by EVG/COBI/FTC/TDF (150/150/200/300 mg) during the optional extension phase
Measure Participants	14
FTC	15136.5 (4702.06)
TFV	4450.7 (1312.27)
COBI	11884.8 (11220.94)

6. Secondary Outcome

Title	Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Weeks 24 and 48 as Defined by the FDA Snapshot Analysis
Time Frame	Weeks 24 and 48

Outcome Measure Data

Analysis Population Description

Full Analysis Set: all participants who were enrolled in the study and received at least 1 dose of study drug.

Arm/Group Title	EVG/COBI/FTC/TDF
Arm/Group Description	EVG/COBI/FTC/TDF (150/150/200/300 mg) STR administered orally once daily with food for 48 weeks, followed by EVG/COBI/FTC/TDF (150/150/200/300 mg) during the optional extension phase
Measure Participants	50
Week 24	88.0 176%
Week 48	88.0 176%

7. Secondary Outcome

Title	Percentage of Participants With HIV-1 RNA < 400 Copies/mL at Weeks 24 and 48 as Defined by the FDA Snapshot Analysis
Time Frame	Weeks 24 and 48

Outcome Measure Data

Analysis Population Description

Full Analysis Set: all participants who were enrolled in the study and received at least 1 dose of study drug.

Arm/Group Title	EVG/COBI/FTC/TDF
Arm/Group Description	EVG/COBI/FTC/TDF (150/150/200/300 mg) STR administered orally once daily with food for 48 weeks, followed by EVG/COBI/FTC/TDF (150/150/200/300 mg) during the optional extension phase
Measure Participants	50
Week 24	94.0 188%
Week 48	92.0 184%

8. Secondary Outcome

Title	Change From Baseline in Plasma log10 HIV-1 RNA at Weeks 24 and 48
Time Frame	Baseline; Weeks 24 and 48

Outcome Measure Data

Analysis Population Description

Full Analysis Set: all participants who were enrolled in the study and received at least 1 dose of study drug.

Arm/Group Title	EVG/COBI/FTC/TDF
Arm/Group Description	EVG/COBI/FTC/TDF (150/150/200/300 mg) STR administered orally once daily with food for 48 weeks, followed by EVG/COBI/FTC/TDF (150/150/200/300 mg) during the optional extension phase
Measure Participants	50
Change at Week 24	-3.08 (0.922)
Change at Week 48	-3.16 (0.705)

9. Secondary Outcome

Title	Change From Baseline in CD4+ Cell Count at Weeks 24 and 48
Time Frame	Baseline; Weeks 24 and 48

Outcome Measure Data

Analysis Population Description

Participants in the Full Analysis Set with available data were analyzed.

Arm/Group Title	EVG/COBI/FTC/TDF
Arm/Group Description	EVG/COBI/FTC/TDF (150/150/200/300 mg) STR administered orally once daily with food for 48 weeks, followed by EVG/COBI/FTC/TDF (150/150/200/300 mg) during the optional extension phase
Measure Participants	49
Change at Week 24	178 (165.4)
Change at Week 48	229 (245.3)

10. Secondary Outcome

Title	Change From Baseline in CD4 Percentage at Weeks 24 and 48
Time Frame	Baseline; Weeks 24 and 48

Outcome Measure Data

Analysis Population Description

Participants in the Full Analysis Set with available data were analyzed.

Arm/Group Title	EVG/COBI/FTC/TDF
Arm/Group Description	EVG/COBI/FTC/TDF (150/150/200/300 mg) STR administered orally once daily with food for 48 weeks, followed by EVG/COBI/FTC/TDF (150/150/200/300 mg) during the optional extension phase
Measure Participants	49
Change at Week 24	7.4 (4.70)
Change at Week 48	8.1 (5.34)

Adverse Events

Time Frame	Baseline up to the last dose date plus 30 days (maximum exposure: 250.7 weeks)
Adverse Event Reporting Description	Safety Analysis Set: all participants who received at least 1 dose of study drug.
Arm/Group Title	EVG/COBI/FTC/TDF
Arm/Group Description	EVG/COBI/FTC/TDF (150/150/200/300 mg) STR administered orally once daily with food for 48 weeks, followed by EVG/COBI/FTC/TDF (150/150/200/300 mg) during the optional extension phase
All Cause Mortality
	EVG/COBI/FTC/TDF
	Affected / at Risk (%)	# Events
Total	0/50 (0%)
Serious Adverse Events
	EVG/COBI/FTC/TDF
	Affected / at Risk (%)	# Events
Total	5/50 (10%)
Blood and lymphatic system disorders
Anaemia	1/50 (2%)
Gastrointestinal disorders
Food poisoning	1/50 (2%)
Haemorrhoids	1/50 (2%)
Immune system disorders
Immune reconstitution inflammatory syndrome	1/50 (2%)
Infections and infestations
Disseminated tuberculosis	1/50 (2%)
Gastroenteritis shigella	1/50 (2%)
Oral candidiasis	1/50 (2%)
Pneumonia	1/50 (2%)
Metabolism and nutrition disorders
Dehydration	1/50 (2%)
Psychiatric disorders
Suicidal behaviour	1/50 (2%)
Renal and urinary disorders
Acute kidney injury	1/50 (2%)
Respiratory, thoracic and mediastinal disorders
Asthma	1/50 (2%)
Other (Not Including Serious) Adverse Events
	EVG/COBI/FTC/TDF
	Affected / at Risk (%)	# Events
Total	46/50 (92%)
Gastrointestinal disorders
Diarrhoea	8/50 (16%)
Haemorrhoids	4/50 (8%)
Nausea	8/50 (16%)
Toothache	3/50 (6%)
Vomiting	10/50 (20%)
General disorders
Pyrexia	3/50 (6%)
Infections and infestations
Bronchitis	4/50 (8%)
Influenza	3/50 (6%)
Nasopharyngitis	4/50 (8%)
Oral herpes	3/50 (6%)
Oropharyngeal gonococcal infection	3/50 (6%)
Pharyngitis	6/50 (12%)
Proctitis gonococcal	3/50 (6%)
Respiratory tract infection viral	3/50 (6%)
Secondary syphilis	3/50 (6%)
Tonsillitis	3/50 (6%)
Upper respiratory tract infection	18/50 (36%)
Urinary tract infection	3/50 (6%)
Injury, poisoning and procedural complications
Skin abrasion	3/50 (6%)
Investigations
Weight decreased	4/50 (8%)
Metabolism and nutrition disorders
Decreased appetite	3/50 (6%)
Vitamin D deficiency	9/50 (18%)
Musculoskeletal and connective tissue disorders
Myalgia	3/50 (6%)
Nervous system disorders
Dizziness	4/50 (8%)
Headache	12/50 (24%)
Skin and subcutaneous tissue disorders
Acne	8/50 (16%)
Dermatitis	3/50 (6%)
Dermatitis contact	3/50 (6%)
Rash	4/50 (8%)

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