Trial Outcomes & Findings for Roll-Over Protocol To Provide Atv And/Or Truvada For Extended Access (NCT NCT01003990)

Last Updated: 2017-05-11

Results Overview

AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Treatment-related=having certain, probable, possible, or missing relationship to study drug. Grade (Gr) 1=Mild, Gr 2=Moderate, Gr 3=Severe, Gr 4= Potentially Life-threatening or disabling. AIDS Defining Diagnosis ( CDC Class C AIDS Events) are identified from HIV Related Diagnosis.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

710 participants

Primary outcome timeframe

Date of First Dose to 30 days post the last dose; approximately 405 weeks)

Results posted on

2017-05-11

Participant Flow

710 participants were enrolled, 709 were treated. The participant who did not receive treatment was enrolled in error having been assigned to efavirenz in the parent study AI424034 (only subjects assigned to ATV rolled over into AI424077).

Participant milestones

Participant milestones
Measure	Atazanavir (ATV) Atazanavir: Tablets, Oral, 400 mg (2 x 200 mg capsules), once daily with food, indefinitely	Atazanavir/Ritonavir (ATV/RTV) Ritonavir-boosted Atazanavir (ATV/RTV 300/100 mg). Tablets administered orally once daily (QD) with food, indefinitely. Ritonavir: 100 mg QD Atazanavir: 300 mg QD (3 x 100 mg capsules, or 2 x 150 mg capsules)	Lopinavir/Ritonavir (LPV/RTV) Ritonavir-boosted Lopinavir (LPV/RTV 400/100 mg) administered twice a day (BID) with Tenofovir/ Emtricitabine (TDF/FTC). Lopinavir: 400 mg BID Ritonavir: 100 mg BID Tenofovir/Emtricitabine: Tablets, Oral, 300/200 mg, once daily (QD) with food, indefinitely (one tablet with 300 mg - 200 mg QD)
Overall Study STARTED	459	154	96
Overall Study COMPLETED	367	103	53
Overall Study NOT COMPLETED	92	51	43

Reasons for withdrawal

Reasons for withdrawal
Measure	Atazanavir (ATV) Atazanavir: Tablets, Oral, 400 mg (2 x 200 mg capsules), once daily with food, indefinitely	Atazanavir/Ritonavir (ATV/RTV) Ritonavir-boosted Atazanavir (ATV/RTV 300/100 mg). Tablets administered orally once daily (QD) with food, indefinitely. Ritonavir: 100 mg QD Atazanavir: 300 mg QD (3 x 100 mg capsules, or 2 x 150 mg capsules)	Lopinavir/Ritonavir (LPV/RTV) Ritonavir-boosted Lopinavir (LPV/RTV 400/100 mg) administered twice a day (BID) with Tenofovir/ Emtricitabine (TDF/FTC). Lopinavir: 400 mg BID Ritonavir: 100 mg BID Tenofovir/Emtricitabine: Tablets, Oral, 300/200 mg, once daily (QD) with food, indefinitely (one tablet with 300 mg - 200 mg QD)
Overall Study Adverse Event	8	5	11
Overall Study Death	0	8	1
Overall Study Lack of Efficacy	10	2	3
Overall Study Lost to Follow-up	30	12	7
Overall Study Reasons Not Identified	14	13	8
Overall Study Poor/Non-compliance	4	3	2
Overall Study Pregnancy	10	2	4
Overall Study No Longer Met Study Criteria	4	1	0
Overall Study Subject Withdrew Consent	12	5	7

Baseline Characteristics

Roll-Over Protocol To Provide Atv And/Or Truvada For Extended Access

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Atazanavir (ATV) n=459 Participants Atazanavir: Tablets, Oral, 400 mg (2 x 200 mg capsules), once daily with food, indefinitely	Atazanavir/Ritonavir (ATV/RTV) n=154 Participants Ritonavir-boosted Atazanavir (ATV/RTV 300/100 mg). Tablets administered orally once daily (QD) with food, indefinitely. Ritonavir: 100 mg QD Atazanavir: 300 mg QD (3 x 100 mg capsules, or 2 x 150 mg capsules)	Lopinavir/Ritonavir (LPV/RTV) n=96 Participants Ritonavir-boosted Lopinavir (LPV/RTV 400/100 mg) administered twice a day (BID) with Tenofovir/ Emtricitabine (TDF/FTC). Lopinavir: 400 mg BID Ritonavir: 100 mg BID Tenofovir/Emtricitabine: Tablets, Oral, 300/200 mg, once daily (QD) with food, indefinitely (one tablet with 300 mg - 200 mg QD)	Total n=709 Participants Total of all reporting groups
Age, Continuous	36.6 years STANDARD_DEVIATION 9.00 • n=99 Participants	35.9 years STANDARD_DEVIATION 8.81 • n=107 Participants	37.6 years STANDARD_DEVIATION 10.16 • n=206 Participants	36.6 years STANDARD_DEVIATION 9.12 • n=7 Participants
Sex: Female, Male Female	172 Participants n=99 Participants	54 Participants n=107 Participants	30 Participants n=206 Participants	256 Participants n=7 Participants
Sex: Female, Male Male	287 Participants n=99 Participants	100 Participants n=107 Participants	66 Participants n=206 Participants	453 Participants n=7 Participants
Race/Ethnicity, Customized White	158 Participants n=99 Participants	34 Participants n=107 Participants	18 Participants n=206 Participants	210 Participants n=7 Participants
Race/Ethnicity, Customized Black or African American	112 Participants n=99 Participants	25 Participants n=107 Participants	2 Participants n=206 Participants	139 Participants n=7 Participants
Race/Ethnicity, Customized American Indian/Alaska Native	1 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	1 Participants n=7 Participants
Race/Ethnicity, Customized Asian	53 Participants n=99 Participants	13 Participants n=107 Participants	18 Participants n=206 Participants	84 Participants n=7 Participants
Race/Ethnicity, Customized Other	135 Participants n=99 Participants	82 Participants n=107 Participants	58 Participants n=206 Participants	275 Participants n=7 Participants

PRIMARY outcome

Timeframe: Date of First Dose to 30 days post the last dose; approximately 405 weeks)

Population: All Treated Participants

Outcome measures

Outcome measures
Measure	Atazanavir (ATV) n=459 Participants Atazanavir: Tablets, Oral, 400 mg (2 x 200 mg capsules), once daily with food, indefinitely	Atazanavir/Ritonavir (ATV/RTV) n=154 Participants Ritonavir-boosted Atazanavir (ATV/RTV 300/100 mg). Tablets administered orally once daily (QD) with food, indefinitely. Ritonavir: 100 mg QD Atazanavir: 300 mg QD (3 x 100 mg capsules, or 2 x 150 mg capsules)	Lopinavir/Ritonavir (LPV/RTV) n=96 Participants Ritonavir-boosted Lopinavir (LPV/RTV 400/100 mg) administered twice a day (BID) with Tenofovir/ Emtricitabine (TDF/FTC). Lopinavir: 400 mg BID Ritonavir: 100 mg BID Tenofovir/Emtricitabine: Tablets, Oral, 300/200 mg, once daily (QD) with food, indefinitely (one tablet with 300 mg - 200 mg QD)
Number of Participants With Serious Adverse Events (SAEs), Treatment Related SAEs, Treatment Related Adverse Events (AEs), AEs Leading to Discontinuation of Study Therapy, Grade 3 to Grade 4 AEs, Grade 3 to Grade 4 AEs, CDC Class C AIDS Events, or Death AEs Leading to Discontinuation of Study Therapy	8 Participants	5 Participants	11 Participants
Number of Participants With Serious Adverse Events (SAEs), Treatment Related SAEs, Treatment Related Adverse Events (AEs), AEs Leading to Discontinuation of Study Therapy, Grade 3 to Grade 4 AEs, Grade 3 to Grade 4 AEs, CDC Class C AIDS Events, or Death SAEs	35 Participants	19 Participants	12 Participants
Number of Participants With Serious Adverse Events (SAEs), Treatment Related SAEs, Treatment Related Adverse Events (AEs), AEs Leading to Discontinuation of Study Therapy, Grade 3 to Grade 4 AEs, Grade 3 to Grade 4 AEs, CDC Class C AIDS Events, or Death Treatment Related SAEs	4 Participants	1 Participants	0 Participants
Number of Participants With Serious Adverse Events (SAEs), Treatment Related SAEs, Treatment Related Adverse Events (AEs), AEs Leading to Discontinuation of Study Therapy, Grade 3 to Grade 4 AEs, Grade 3 to Grade 4 AEs, CDC Class C AIDS Events, or Death Treatment Related AEs of Any Grade	180 Participants	49 Participants	34 Participants
Number of Participants With Serious Adverse Events (SAEs), Treatment Related SAEs, Treatment Related Adverse Events (AEs), AEs Leading to Discontinuation of Study Therapy, Grade 3 to Grade 4 AEs, Grade 3 to Grade 4 AEs, CDC Class C AIDS Events, or Death Grade 2 to Grade 4 AEs	102 Participants	28 Participants	19 Participants
Number of Participants With Serious Adverse Events (SAEs), Treatment Related SAEs, Treatment Related Adverse Events (AEs), AEs Leading to Discontinuation of Study Therapy, Grade 3 to Grade 4 AEs, Grade 3 to Grade 4 AEs, CDC Class C AIDS Events, or Death Grade 3 to Grade 4 AEs	72 Participants	27 Participants	15 Participants
Number of Participants With Serious Adverse Events (SAEs), Treatment Related SAEs, Treatment Related Adverse Events (AEs), AEs Leading to Discontinuation of Study Therapy, Grade 3 to Grade 4 AEs, Grade 3 to Grade 4 AEs, CDC Class C AIDS Events, or Death CDC Class C AIDS Events	2 Participants	0 Participants	0 Participants
Number of Participants With Serious Adverse Events (SAEs), Treatment Related SAEs, Treatment Related Adverse Events (AEs), AEs Leading to Discontinuation of Study Therapy, Grade 3 to Grade 4 AEs, Grade 3 to Grade 4 AEs, CDC Class C AIDS Events, or Death Deaths	2 Participants	7 Participants	1 Participants

Adverse Events

Atazanavir (ATV)

Serious events: 35 serious events

Other events: 284 other events

Deaths: 2 deaths

Atazanavir/Ritonavir (ATV/RTV)

Serious events: 19 serious events

Other events: 92 other events

Deaths: 7 deaths

Lopinavir/Ritonavir (LPV/RTV)

Serious events: 12 serious events

Other events: 57 other events

Deaths: 1 deaths

Serious adverse events

Other adverse events

Additional Information

Bristol-Myers Squibb Study Director

Bristol-Myers Squibb

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Bristol-Myers Squibb Co. agreements with investigators vary; constant is our right to embargo communications regarding trial results prior to public release for a period ≤60 days from submittal for review. We will not prohibit investigators from publishing, but will prohibit the disclosure of previously undisclosed confidential information other than study results, and request postponement of single-center publications until after disclosure of the clinical trial's primary publication.
Publication restrictions are in place

Restriction type: OTHER

Measure	Atazanavir (ATV) n=459 participants at risk Atazanavir: Tablets, Oral, 400 mg (2 x 200 mg capsules), once daily with food, indefinitely	Atazanavir/Ritonavir (ATV/RTV) n=154 participants at risk Ritonavir-boosted Atazanavir (ATV/RTV 300/100 mg). Tablets administered orally once daily (QD) with food, indefinitely. Ritonavir: 100 mg QD; Atazanavir: 300 mg QD (3 x 100 mg capsules, or 2 x 150 mg capsules)	Lopinavir/Ritonavir (LPV/RTV) n=96 participants at risk Ritonavir-boosted Lopinavir (LPV/RTV 400/100 mg) administered twice a day (BID) with Tenofovir/ Emtricitabine (TDF/FTC). Lopinavir: 400 mg BID; Ritonavir: 100 mg BID; Tenofovir/Emtricitabine: Tablets, Oral, 300/200 mg, once daily (QD) with food, indefinitely (one tablet with 300 mg - 200 mg QD)
Investigations Alanine aminotransferase increased	5.9% 27/459 • Date of first dose to date of last dose plus 30 days; approx. 680 weeks All Treated Participants Study Initiated: November 13, 2002 Study Completion: February 16, 2016	3.2% 5/154 • Date of first dose to date of last dose plus 30 days; approx. 680 weeks All Treated Participants Study Initiated: November 13, 2002 Study Completion: February 16, 2016	3.1% 3/96 • Date of first dose to date of last dose plus 30 days; approx. 680 weeks All Treated Participants Study Initiated: November 13, 2002 Study Completion: February 16, 2016
Hepatobiliary disorders Hyperbilirubinaemia	9.8% 45/459 • Date of first dose to date of last dose plus 30 days; approx. 680 weeks All Treated Participants Study Initiated: November 13, 2002 Study Completion: February 16, 2016	1.9% 3/154 • Date of first dose to date of last dose plus 30 days; approx. 680 weeks All Treated Participants Study Initiated: November 13, 2002 Study Completion: February 16, 2016	1.0% 1/96 • Date of first dose to date of last dose plus 30 days; approx. 680 weeks All Treated Participants Study Initiated: November 13, 2002 Study Completion: February 16, 2016
Infections and infestations Nasopharyngitis	11.1% 51/459 • Date of first dose to date of last dose plus 30 days; approx. 680 weeks All Treated Participants Study Initiated: November 13, 2002 Study Completion: February 16, 2016	20.8% 32/154 • Date of first dose to date of last dose plus 30 days; approx. 680 weeks All Treated Participants Study Initiated: November 13, 2002 Study Completion: February 16, 2016	25.0% 24/96 • Date of first dose to date of last dose plus 30 days; approx. 680 weeks All Treated Participants Study Initiated: November 13, 2002 Study Completion: February 16, 2016
Respiratory, thoracic and mediastinal disorders Cough	2.6% 12/459 • Date of first dose to date of last dose plus 30 days; approx. 680 weeks All Treated Participants Study Initiated: November 13, 2002 Study Completion: February 16, 2016	4.5% 7/154 • Date of first dose to date of last dose plus 30 days; approx. 680 weeks All Treated Participants Study Initiated: November 13, 2002 Study Completion: February 16, 2016	6.2% 6/96 • Date of first dose to date of last dose plus 30 days; approx. 680 weeks All Treated Participants Study Initiated: November 13, 2002 Study Completion: February 16, 2016
Metabolism and nutrition disorders Hypertriglyceridaemia	1.3% 6/459 • Date of first dose to date of last dose plus 30 days; approx. 680 weeks All Treated Participants Study Initiated: November 13, 2002 Study Completion: February 16, 2016	4.5% 7/154 • Date of first dose to date of last dose plus 30 days; approx. 680 weeks All Treated Participants Study Initiated: November 13, 2002 Study Completion: February 16, 2016	12.5% 12/96 • Date of first dose to date of last dose plus 30 days; approx. 680 weeks All Treated Participants Study Initiated: November 13, 2002 Study Completion: February 16, 2016
Musculoskeletal and connective tissue disorders Back pain	5.9% 27/459 • Date of first dose to date of last dose plus 30 days; approx. 680 weeks All Treated Participants Study Initiated: November 13, 2002 Study Completion: February 16, 2016	8.4% 13/154 • Date of first dose to date of last dose plus 30 days; approx. 680 weeks All Treated Participants Study Initiated: November 13, 2002 Study Completion: February 16, 2016	12.5% 12/96 • Date of first dose to date of last dose plus 30 days; approx. 680 weeks All Treated Participants Study Initiated: November 13, 2002 Study Completion: February 16, 2016
Gastrointestinal disorders Diarrhoea	10.2% 47/459 • Date of first dose to date of last dose plus 30 days; approx. 680 weeks All Treated Participants Study Initiated: November 13, 2002 Study Completion: February 16, 2016	14.3% 22/154 • Date of first dose to date of last dose plus 30 days; approx. 680 weeks All Treated Participants Study Initiated: November 13, 2002 Study Completion: February 16, 2016	12.5% 12/96 • Date of first dose to date of last dose plus 30 days; approx. 680 weeks All Treated Participants Study Initiated: November 13, 2002 Study Completion: February 16, 2016
Infections and infestations Urinary tract infection	2.4% 11/459 • Date of first dose to date of last dose plus 30 days; approx. 680 weeks All Treated Participants Study Initiated: November 13, 2002 Study Completion: February 16, 2016	7.1% 11/154 • Date of first dose to date of last dose plus 30 days; approx. 680 weeks All Treated Participants Study Initiated: November 13, 2002 Study Completion: February 16, 2016	2.1% 2/96 • Date of first dose to date of last dose plus 30 days; approx. 680 weeks All Treated Participants Study Initiated: November 13, 2002 Study Completion: February 16, 2016
Gastrointestinal disorders Abdominal pain upper	2.8% 13/459 • Date of first dose to date of last dose plus 30 days; approx. 680 weeks All Treated Participants Study Initiated: November 13, 2002 Study Completion: February 16, 2016	1.3% 2/154 • Date of first dose to date of last dose plus 30 days; approx. 680 weeks All Treated Participants Study Initiated: November 13, 2002 Study Completion: February 16, 2016	6.2% 6/96 • Date of first dose to date of last dose plus 30 days; approx. 680 weeks All Treated Participants Study Initiated: November 13, 2002 Study Completion: February 16, 2016
Infections and infestations Influenza	7.0% 32/459 • Date of first dose to date of last dose plus 30 days; approx. 680 weeks All Treated Participants Study Initiated: November 13, 2002 Study Completion: February 16, 2016	10.4% 16/154 • Date of first dose to date of last dose plus 30 days; approx. 680 weeks All Treated Participants Study Initiated: November 13, 2002 Study Completion: February 16, 2016	6.2% 6/96 • Date of first dose to date of last dose plus 30 days; approx. 680 weeks All Treated Participants Study Initiated: November 13, 2002 Study Completion: February 16, 2016
Gastrointestinal disorders Abdominal pain	4.4% 20/459 • Date of first dose to date of last dose plus 30 days; approx. 680 weeks All Treated Participants Study Initiated: November 13, 2002 Study Completion: February 16, 2016	5.2% 8/154 • Date of first dose to date of last dose plus 30 days; approx. 680 weeks All Treated Participants Study Initiated: November 13, 2002 Study Completion: February 16, 2016	4.2% 4/96 • Date of first dose to date of last dose plus 30 days; approx. 680 weeks All Treated Participants Study Initiated: November 13, 2002 Study Completion: February 16, 2016
Investigations Creatinine renal clearance decreased	0.00% 0/459 • Date of first dose to date of last dose plus 30 days; approx. 680 weeks All Treated Participants Study Initiated: November 13, 2002 Study Completion: February 16, 2016	10.4% 16/154 • Date of first dose to date of last dose plus 30 days; approx. 680 weeks All Treated Participants Study Initiated: November 13, 2002 Study Completion: February 16, 2016	8.3% 8/96 • Date of first dose to date of last dose plus 30 days; approx. 680 weeks All Treated Participants Study Initiated: November 13, 2002 Study Completion: February 16, 2016
Nervous system disorders Headache	8.1% 37/459 • Date of first dose to date of last dose plus 30 days; approx. 680 weeks All Treated Participants Study Initiated: November 13, 2002 Study Completion: February 16, 2016	9.7% 15/154 • Date of first dose to date of last dose plus 30 days; approx. 680 weeks All Treated Participants Study Initiated: November 13, 2002 Study Completion: February 16, 2016	8.3% 8/96 • Date of first dose to date of last dose plus 30 days; approx. 680 weeks All Treated Participants Study Initiated: November 13, 2002 Study Completion: February 16, 2016
Hepatobiliary disorders Jaundice	5.2% 24/459 • Date of first dose to date of last dose plus 30 days; approx. 680 weeks All Treated Participants Study Initiated: November 13, 2002 Study Completion: February 16, 2016	3.2% 5/154 • Date of first dose to date of last dose plus 30 days; approx. 680 weeks All Treated Participants Study Initiated: November 13, 2002 Study Completion: February 16, 2016	1.0% 1/96 • Date of first dose to date of last dose plus 30 days; approx. 680 weeks All Treated Participants Study Initiated: November 13, 2002 Study Completion: February 16, 2016
Infections and infestations Upper respiratory tract infection	16.1% 74/459 • Date of first dose to date of last dose plus 30 days; approx. 680 weeks All Treated Participants Study Initiated: November 13, 2002 Study Completion: February 16, 2016	6.5% 10/154 • Date of first dose to date of last dose plus 30 days; approx. 680 weeks All Treated Participants Study Initiated: November 13, 2002 Study Completion: February 16, 2016	4.2% 4/96 • Date of first dose to date of last dose plus 30 days; approx. 680 weeks All Treated Participants Study Initiated: November 13, 2002 Study Completion: February 16, 2016
Respiratory, thoracic and mediastinal disorders Asthma	0.87% 4/459 • Date of first dose to date of last dose plus 30 days; approx. 680 weeks All Treated Participants Study Initiated: November 13, 2002 Study Completion: February 16, 2016	0.65% 1/154 • Date of first dose to date of last dose plus 30 days; approx. 680 weeks All Treated Participants Study Initiated: November 13, 2002 Study Completion: February 16, 2016	6.2% 6/96 • Date of first dose to date of last dose plus 30 days; approx. 680 weeks All Treated Participants Study Initiated: November 13, 2002 Study Completion: February 16, 2016
Investigations Blood bilirubin increased	7.4% 34/459 • Date of first dose to date of last dose plus 30 days; approx. 680 weeks All Treated Participants Study Initiated: November 13, 2002 Study Completion: February 16, 2016	1.9% 3/154 • Date of first dose to date of last dose plus 30 days; approx. 680 weeks All Treated Participants Study Initiated: November 13, 2002 Study Completion: February 16, 2016	1.0% 1/96 • Date of first dose to date of last dose plus 30 days; approx. 680 weeks All Treated Participants Study Initiated: November 13, 2002 Study Completion: February 16, 2016
Infections and infestations Bronchitis	7.0% 32/459 • Date of first dose to date of last dose plus 30 days; approx. 680 weeks All Treated Participants Study Initiated: November 13, 2002 Study Completion: February 16, 2016	5.2% 8/154 • Date of first dose to date of last dose plus 30 days; approx. 680 weeks All Treated Participants Study Initiated: November 13, 2002 Study Completion: February 16, 2016	6.2% 6/96 • Date of first dose to date of last dose plus 30 days; approx. 680 weeks All Treated Participants Study Initiated: November 13, 2002 Study Completion: February 16, 2016
Gastrointestinal disorders Gastritis	2.6% 12/459 • Date of first dose to date of last dose plus 30 days; approx. 680 weeks All Treated Participants Study Initiated: November 13, 2002 Study Completion: February 16, 2016	5.2% 8/154 • Date of first dose to date of last dose plus 30 days; approx. 680 weeks All Treated Participants Study Initiated: November 13, 2002 Study Completion: February 16, 2016	3.1% 3/96 • Date of first dose to date of last dose plus 30 days; approx. 680 weeks All Treated Participants Study Initiated: November 13, 2002 Study Completion: February 16, 2016
Gastrointestinal disorders Nausea	4.1% 19/459 • Date of first dose to date of last dose plus 30 days; approx. 680 weeks All Treated Participants Study Initiated: November 13, 2002 Study Completion: February 16, 2016	2.6% 4/154 • Date of first dose to date of last dose plus 30 days; approx. 680 weeks All Treated Participants Study Initiated: November 13, 2002 Study Completion: February 16, 2016	5.2% 5/96 • Date of first dose to date of last dose plus 30 days; approx. 680 weeks All Treated Participants Study Initiated: November 13, 2002 Study Completion: February 16, 2016
Musculoskeletal and connective tissue disorders Arthralgia	4.6% 21/459 • Date of first dose to date of last dose plus 30 days; approx. 680 weeks All Treated Participants Study Initiated: November 13, 2002 Study Completion: February 16, 2016	7.8% 12/154 • Date of first dose to date of last dose plus 30 days; approx. 680 weeks All Treated Participants Study Initiated: November 13, 2002 Study Completion: February 16, 2016	5.2% 5/96 • Date of first dose to date of last dose plus 30 days; approx. 680 weeks All Treated Participants Study Initiated: November 13, 2002 Study Completion: February 16, 2016
Investigations Blood cholesterol increased	0.00% 0/459 • Date of first dose to date of last dose plus 30 days; approx. 680 weeks All Treated Participants Study Initiated: November 13, 2002 Study Completion: February 16, 2016	2.6% 4/154 • Date of first dose to date of last dose plus 30 days; approx. 680 weeks All Treated Participants Study Initiated: November 13, 2002 Study Completion: February 16, 2016	7.3% 7/96 • Date of first dose to date of last dose plus 30 days; approx. 680 weeks All Treated Participants Study Initiated: November 13, 2002 Study Completion: February 16, 2016
Eye disorders Ocular icterus	6.8% 31/459 • Date of first dose to date of last dose plus 30 days; approx. 680 weeks All Treated Participants Study Initiated: November 13, 2002 Study Completion: February 16, 2016	2.6% 4/154 • Date of first dose to date of last dose plus 30 days; approx. 680 weeks All Treated Participants Study Initiated: November 13, 2002 Study Completion: February 16, 2016	0.00% 0/96 • Date of first dose to date of last dose plus 30 days; approx. 680 weeks All Treated Participants Study Initiated: November 13, 2002 Study Completion: February 16, 2016
General disorders Pyrexia	2.6% 12/459 • Date of first dose to date of last dose plus 30 days; approx. 680 weeks All Treated Participants Study Initiated: November 13, 2002 Study Completion: February 16, 2016	5.8% 9/154 • Date of first dose to date of last dose plus 30 days; approx. 680 weeks All Treated Participants Study Initiated: November 13, 2002 Study Completion: February 16, 2016	3.1% 3/96 • Date of first dose to date of last dose plus 30 days; approx. 680 weeks All Treated Participants Study Initiated: November 13, 2002 Study Completion: February 16, 2016