Trial Outcomes & Findings for Sorafenib Dose Ramp-Up in Hepatocellular Carcinoma (HCC) (NCT NCT01203787)

NCT ID: NCT01203787

Last Updated: 2015-03-05

Results Overview

This outcome measure table shows the median cumulative dose delivered to the subjects randomized to the standard dosing regimen (N=63) and ramp-up regimen (N=57) at 4 months of treatment.

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 120 participants
• Primary outcome timeframe: 4 months-1/12/2010-1/27/14
• Results posted on: 2015-03-05

Participant Flow

Participant milestones

Measure	Sorafenib Standard Dosing Regimen Sorafenib 400 mg (2 tablets of 200 mg) twice daily until end of treatment or week 24	Sorafenib Ramp-Up Regimen 200 mg daily from Day 0-Day 13 200 mg twice daily from Day 14-Day 20 600 mg daily from Day 21-Day 27 400 mg twice daily beginning Day 28 until end of treatment or Week 24
Overall Study STARTED	63	57
Overall Study COMPLETED	32	30
Overall Study NOT COMPLETED	31	27

Reasons for withdrawal

Measure	Sorafenib Standard Dosing Regimen Sorafenib 400 mg (2 tablets of 200 mg) twice daily until end of treatment or week 24	Sorafenib Ramp-Up Regimen 200 mg daily from Day 0-Day 13 200 mg twice daily from Day 14-Day 20 600 mg daily from Day 21-Day 27 400 mg twice daily beginning Day 28 until end of treatment or Week 24
Overall Study Death	12	10
Overall Study Withdrawal by Subject	6	2
Overall Study Lost to Follow-up	2	0
Overall Study Adverse Event	11	15

Baseline Characteristics

Sorafenib Dose Ramp-Up in Hepatocellular Carcinoma (HCC)

Baseline characteristics by cohort

Measure	Sorafenib Standard Dosing Regimen n=63 Participants Sorafenib 400 mg (2 tablets of 200 mg) twice daily until end of treatment or week 24	Sorafenib Ramp-Up Regimen n=57 Participants 200 mg daily from Day 0-Day 13, 200 mg twice daily from Day 14-Day 20, 600 mg daily from Day 21-Day 27, 400 mg twice daily beginning Day 28 until end of treatment or Week 24	Total n=120 Participants Total of all reporting groups
Age, Categorical <=18 years	00 Participants n=5 Participants	00 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	39 Participants n=5 Participants	30 Participants n=7 Participants	69 Participants n=5 Participants
Age, Categorical >=65 years	24 Participants n=5 Participants	27 Participants n=7 Participants	51 Participants n=5 Participants
Age, Continuous	62.0 years STANDARD_DEVIATION 6.8 • n=5 Participants	63.5 years STANDARD_DEVIATION 7.5 • n=7 Participants	62.7 years STANDARD_DEVIATION 7.2 • n=5 Participants
Sex: Female, Male Female	12 Participants n=5 Participants	10 Participants n=7 Participants	22 Participants n=5 Participants
Sex: Female, Male Male	51 Participants n=5 Participants	47 Participants n=7 Participants	98 Participants n=5 Participants
Region of Enrollment United States	63 participants n=5 Participants	57 participants n=7 Participants	120 participants n=5 Participants

PRIMARY outcome

Timeframe: 4 months-1/12/2010-1/27/14

This outcome measure table shows the median cumulative dose delivered to the subjects randomized to the standard dosing regimen (N=63) and ramp-up regimen (N=57) at 4 months of treatment.

Outcome measures

Measure	Sorafenib Standard Dosing Regimen n=63 Participants Sorafenib 400 mg (2 tablets of 200 mg) twice daily until end of treatment or week 24	Sorafenib Ramp-Up Regimen n=57 Participants 200 mg daily from Day 0-Day 13 200 mg twice daily from Day 14-Day 20 600 mg daily from Day 21-Day 27 400 mg twice daily beginning Day 28 until end of treatment or Week 24
Total (Cumulative) Dose Delivery of Sorafenib	49800 mg Interval 800.0 to 107600.0	38000 mg Interval 800.0 to 92400.0

PRIMARY outcome

Timeframe: 11/22/2010-1/27/14

Table below shows mean cumulative dose of sorafenib for each of the dosing regimens.

Outcome measures

Measure	Sorafenib Standard Dosing Regimen n=63 Participants Sorafenib 400 mg (2 tablets of 200 mg) twice daily until end of treatment or week 24	Sorafenib Ramp-Up Regimen n=57 Participants 200 mg daily from Day 0-Day 13 200 mg twice daily from Day 14-Day 20 600 mg daily from Day 21-Day 27 400 mg twice daily beginning Day 28 until end of treatment or Week 24
Cumulative Dose of Sorafenib	53692 mg Standard Deviation 33411	41523 mg Standard Deviation 28783

SECONDARY outcome

Timeframe: Baseline-End of Treatment (11/22/2010-3/10/2014)

Population: The total number of CTCAE (Common Terminology Criteria) grade 3 adverse events was collected for each dosing regimen

Safety of Sorafenib was assessed by the frequency and severity of adverse events according to NCI-CTCAE grading

Outcome measures

Measure	Sorafenib Standard Dosing Regimen n=63 Participants Sorafenib 400 mg (2 tablets of 200 mg) twice daily until end of treatment or week 24	Sorafenib Ramp-Up Regimen n=57 Participants 200 mg daily from Day 0-Day 13 200 mg twice daily from Day 14-Day 20 600 mg daily from Day 21-Day 27 400 mg twice daily beginning Day 28 until end of treatment or Week 24
Safety and Efficacy of Sorafenib Dosing Regimens	92 Grade 3 adverse events	101 Grade 3 adverse events

SECONDARY outcome

Timeframe: 11/22/2010-3/10/2014

The total number of CTCAE (Common Terminology Criteria) grade 4 adverse events was collected for each dosing regimen beginning at baseline until Week 24/Early Termination Visit.

Outcome measures

Measure	Sorafenib Standard Dosing Regimen n=63 Participants Sorafenib 400 mg (2 tablets of 200 mg) twice daily until end of treatment or week 24	Sorafenib Ramp-Up Regimen n=57 Participants 200 mg daily from Day 0-Day 13 200 mg twice daily from Day 14-Day 20 600 mg daily from Day 21-Day 27 400 mg twice daily beginning Day 28 until end of treatment or Week 24
Safety of Dosing Regimens as Assessed by the Frequency and Severity of Adverse Events According to National Cancer Institute- CTCAE	19 Grade 4 adverse events	15 Grade 4 adverse events

SECONDARY outcome

Timeframe: 11/22/2010-3/10/2014

The total number of CTCAE (Common Terminology Criteria) grade 5 adverse events was collected for each dosing regimen beginning at baseline through 6 months of treatment.

Outcome measures

Measure	Sorafenib Standard Dosing Regimen n=63 Participants Sorafenib 400 mg (2 tablets of 200 mg) twice daily until end of treatment or week 24	Sorafenib Ramp-Up Regimen n=57 Participants 200 mg daily from Day 0-Day 13 200 mg twice daily from Day 14-Day 20 600 mg daily from Day 21-Day 27 400 mg twice daily beginning Day 28 until end of treatment or Week 24
Frequency and Severity of Adverse Events According to National Cancer Institute- CTCAE	9 Grade 5 Adverse Events	8 Grade 5 Adverse Events

SECONDARY outcome

Timeframe: Baseline-End of Treatment (11/22/2010-3/10/2014)

Outcome measures

Measure	Sorafenib Standard Dosing Regimen n=63 Participants Sorafenib 400 mg (2 tablets of 200 mg) twice daily until end of treatment or week 24	Sorafenib Ramp-Up Regimen n=57 Participants 200 mg daily from Day 0-Day 13 200 mg twice daily from Day 14-Day 20 600 mg daily from Day 21-Day 27 400 mg twice daily beginning Day 28 until end of treatment or Week 24
Number of Subjects With Dose Interruptions	29 participants	20 participants

SECONDARY outcome

Timeframe: 11/22/2010-3/10/2014

Outcome measures

Measure	Sorafenib Standard Dosing Regimen n=63 Participants Sorafenib 400 mg (2 tablets of 200 mg) twice daily until end of treatment or week 24	Sorafenib Ramp-Up Regimen n=57 Participants 200 mg daily from Day 0-Day 13 200 mg twice daily from Day 14-Day 20 600 mg daily from Day 21-Day 27 400 mg twice daily beginning Day 28 until end of treatment or Week 24
Number of Subjects With Dose Reductions	40 participants	34 participants

Adverse Events

Sorafenib Standard Dosing Regimen

Serious events: 16 serious events

Other events: 62 other events

Deaths: 0 deaths

Sorafenib Ramp-Up Regimen

Serious events: 13 serious events

Other events: 57 other events

Deaths: 0 deaths

Serious adverse events

Measure	Sorafenib Standard Dosing Regimen n=63 participants at risk Sorafenib 400 mg (2 tablets of 200 mg) twice daily until end of treatment or week 24	Sorafenib Ramp-Up Regimen n=57 participants at risk 200 mg daily from Day 0-Day 13 200 mg twice daily from Day 14-Day 20 600 mg daily from Day 21-Day 27 400 mg twice daily beginning Day 28 until end of treatment or Week 24
Gastrointestinal disorders Abdominal pain	1.6% 1/63 • Number of events 1 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	0.00% 0/57 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Skin and subcutaneous tissue disorders Abrasion	1.6% 1/63 • Number of events 1 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	0.00% 0/57 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Cardiac disorders Acute congestive heart failure	1.6% 1/63 • Number of events 1 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	0.00% 0/57 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Renal and urinary disorders Acute renal failure	4.8% 3/63 • Number of events 3 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	0.00% 0/57 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Blood and lymphatic system disorders Anemia	3.2% 2/63 • Number of events 2 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	0.00% 0/57 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Hepatobiliary disorders Ascites	1.6% 1/63 • Number of events 1 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	1.8% 1/57 • Number of events 2 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Hepatobiliary disorders Biliary obstruction	1.6% 1/63 • Number of events 1 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	0.00% 0/57 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Ear and labyrinth disorders Blurred vision	0.00% 0/63 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	1.8% 1/57 • Number of events 1 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Cardiac disorders Chest pain	1.6% 1/63 • Number of events 1 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	0.00% 0/57 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Cardiac disorders Cardiac arrest	1.6% 1/63 • Number of events 1 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	0.00% 0/57 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Infections and infestations Cellulitis	1.6% 1/63 • Number of events 1 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	0.00% 0/57 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Hepatobiliary disorders Decompensated liver failure	1.6% 1/63 • Number of events 1 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	0.00% 0/57 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Metabolism and nutrition disorders Dehydration	3.2% 2/63 • Number of events 2 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	1.8% 1/57 • Number of events 1 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
General disorders Deterioration of condition	0.00% 0/63 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	1.8% 1/57 • Number of events 1 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Nervous system disorders Dizziness	1.6% 1/63 • Number of events 1 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	0.00% 0/57 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Injury, poisoning and procedural complications Drug toxicity	1.6% 1/63 • Number of events 1 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	0.00% 0/57 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Hepatobiliary disorders Encephalopathy	9.5% 6/63 • Number of events 6 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	1.8% 1/57 • Number of events 1 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Metabolism and nutrition disorders Failure to thrive	1.6% 1/63 • Number of events 1 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	0.00% 0/57 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Cardiac disorders Hypertension	0.00% 0/63 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	1.8% 1/57 • Number of events 1 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Cardiac disorders Hypotension	4.8% 3/63 • Number of events 3 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	0.00% 0/57 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
General disorders Hypothermia	1.6% 1/63 • Number of events 1 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	0.00% 0/57 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Infections and infestations Influenza	1.6% 1/63 • Number of events 1 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	0.00% 0/57 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Hepatobiliary disorders Liver failure	0.00% 0/63 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	7.0% 4/57 • Number of events 4 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Infections and infestations Meningitis	1.6% 1/63 • Number of events 1 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	0.00% 0/57 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Gastrointestinal disorders Nausea	1.6% 1/63 • Number of events 1 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	0.00% 0/57 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Nervous system disorders Vertigo	0.00% 0/63 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	1.8% 1/57 • Number of events 1 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Respiratory, thoracic and mediastinal disorders Pleural effusion	1.6% 1/63 • Number of events 1 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	1.8% 1/57 • Number of events 1 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Infections and infestations Pneumonia	1.6% 1/63 • Number of events 1 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	1.8% 1/57 • Number of events 1 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Injury, poisoning and procedural complications Post-embolization syndrome	4.8% 3/63 • Number of events 3 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	0.00% 0/57 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	1.6% 1/63 • Number of events 1 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	0.00% 0/57 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Respiratory, thoracic and mediastinal disorders Respiratory failure	3.2% 2/63 • Number of events 2 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	1.8% 1/57 • Number of events 1 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Musculoskeletal and connective tissue disorders Rib fracture	1.6% 1/63 • Number of events 1 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	0.00% 0/57 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Infections and infestations Sepsis	3.2% 2/63 • Number of events 2 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	1.8% 1/57 • Number of events 1 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Infections and infestations Spontaneous bacterial perotinitis	1.6% 1/63 • Number of events 1 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	0.00% 0/57 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
General disorders Syncopal episode	1.6% 1/63 • Number of events 1 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	0.00% 0/57 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Blood and lymphatic system disorders Thrombocytopenia	1.6% 1/63 • Number of events 1 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	0.00% 0/57 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Nervous system disorders Unsteady gait	0.00% 0/63 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	1.8% 1/57 • Number of events 1 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Infections and infestations Urinary tract infection	0.00% 0/63 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	1.8% 1/57 • Number of events 1 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Gastrointestinal disorders Upper gastrointestinal bleed	1.6% 1/63 • Number of events 1 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	3.5% 2/57 • Number of events 2 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Gastrointestinal disorders Vomiting	1.6% 1/63 • Number of events 1 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	0.00% 0/57 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.

Other adverse events

Measure	Sorafenib Standard Dosing Regimen n=63 participants at risk Sorafenib 400 mg (2 tablets of 200 mg) twice daily until end of treatment or week 24	Sorafenib Ramp-Up Regimen n=57 participants at risk 200 mg daily from Day 0-Day 13 200 mg twice daily from Day 14-Day 20 600 mg daily from Day 21-Day 27 400 mg twice daily beginning Day 28 until end of treatment or Week 24
Hepatobiliary disorders total hyperbilirubinemia	50.8% 32/63 • Number of events 50 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	59.6% 34/57 • Number of events 53 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Gastrointestinal disorders umbilical hernia	0.00% 0/63 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	1.8% 1/57 • Number of events 1 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Gastrointestinal disorders abdominal bloating	1.6% 1/63 • Number of events 1 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	0.00% 0/57 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Gastrointestinal disorders abdominal cramps	0.00% 0/63 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	8.8% 5/57 • Number of events 6 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Gastrointestinal disorders abdominal pain	27.0% 17/63 • Number of events 22 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	36.8% 21/57 • Number of events 26 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Skin and subcutaneous tissue disorders abscess	3.2% 2/63 • Number of events 2 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	0.00% 0/57 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Immune system disorders allergic rhinitis	1.6% 1/63 • Number of events 1 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	0.00% 0/57 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Skin and subcutaneous tissue disorders alopecia	20.6% 13/63 • Number of events 13 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	12.3% 7/57 • Number of events 7 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Hepatobiliary disorders ammonia elevation	3.2% 2/63 • Number of events 2 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	0.00% 0/57 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Gastrointestinal disorders amylase elevation	11.1% 7/63 • Number of events 11 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	10.5% 6/57 • Number of events 6 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Blood and lymphatic system disorders anemia	28.6% 18/63 • Number of events 26 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	28.1% 16/57 • Number of events 19 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Musculoskeletal and connective tissue disorders ankle pain	0.00% 0/63 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	1.8% 1/57 • Number of events 1 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Gastrointestinal disorders anorexia	27.0% 17/63 • Number of events 20 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	22.8% 13/57 • Number of events 13 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Psychiatric disorders anxiety	3.2% 2/63 • Number of events 2 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	0.00% 0/57 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Cardiac disorders aortic stenosis	1.6% 1/63 • Number of events 1 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	0.00% 0/57 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Nervous system disorders arm paresthesia	1.6% 1/63 • Number of events 1 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	0.00% 0/57 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Musculoskeletal and connective tissue disorders arthralgias	1.6% 1/63 • Number of events 2 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	7.0% 4/57 • Number of events 4 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Hepatobiliary disorders ascites	14.3% 9/63 • Number of events 9 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	15.8% 9/57 • Number of events 10 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Hepatobiliary disorders asterexis	0.00% 0/63 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	1.8% 1/57 • Number of events 1 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Hepatobiliary disorders ast elevation	1.6% 1/63 • Number of events 1 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	0.00% 0/57 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Cardiac disorders atypical chest pain	1.6% 1/63 • Number of events 1 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	0.00% 0/57 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Musculoskeletal and connective tissue disorders back pain	3.2% 2/63 • Number of events 2 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	3.5% 2/57 • Number of events 2 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Renal and urinary disorders bacteuria	0.00% 0/63 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	1.8% 1/57 • Number of events 1 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Gastrointestinal disorders bezoar	1.6% 1/63 • Number of events 1 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	0.00% 0/57 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
General disorders bleeding gums	6.3% 4/63 • Number of events 5 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	0.00% 0/57 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Skin and subcutaneous tissue disorders blister	3.2% 2/63 • Number of events 2 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	0.00% 0/57 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Eye disorders blurred vision	0.00% 0/63 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	5.3% 3/57 • Number of events 3 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Cardiac disorders bradycardia	1.6% 1/63 • Number of events 1 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	0.00% 0/57 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Respiratory, thoracic and mediastinal disorders bronchitis	1.6% 1/63 • Number of events 1 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	1.8% 1/57 • Number of events 1 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Skin and subcutaneous tissue disorders bruising	1.6% 1/63 • Number of events 1 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	0.00% 0/57 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Infections and infestations cellulitis	3.2% 2/63 • Number of events 2 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	0.00% 0/57 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Eye disorders Cataract	1.6% 1/63 • Number of events 1 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	1.8% 1/57 • Number of events 1 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Cardiac disorders chest pain	0.00% 0/63 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	7.0% 4/57 • Number of events 4 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
General disorders chills	1.6% 1/63 • Number of events 1 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	3.5% 2/57 • Number of events 2 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Respiratory, thoracic and mediastinal disorders chronic obstructive pulmonary disease	0.00% 0/63 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	1.8% 1/57 • Number of events 1 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Gastrointestinal disorders cholecystitis	1.6% 1/63 • Number of events 1 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	0.00% 0/57 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Gastrointestinal disorders cholelithiasis	1.6% 1/63 • Number of events 1 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	0.00% 0/57 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Endocrine disorders cold intolerance	1.6% 1/63 • Number of events 1 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	0.00% 0/57 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Musculoskeletal and connective tissue disorders collar bone pain	0.00% 0/63 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	1.8% 1/57 • Number of events 1 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Eye disorders conjunctival hemorrhage	1.6% 1/63 • Number of events 1 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	0.00% 0/57 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Eye disorders conjunctivitis	1.6% 1/63 • Number of events 1 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	0.00% 0/57 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Gastrointestinal disorders constipation	6.3% 4/63 • Number of events 4 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	10.5% 6/57 • Number of events 7 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Skin and subcutaneous tissue disorders contusion	0.00% 0/63 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	1.8% 1/57 • Number of events 2 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Respiratory, thoracic and mediastinal disorders cough	3.2% 2/63 • Number of events 2 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	3.5% 2/57 • Number of events 2 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Renal and urinary disorders creatinine elevation	1.6% 1/63 • Number of events 1 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	0.00% 0/57 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Skin and subcutaneous tissue disorders decubitus ulcer	0.00% 0/63 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	1.8% 1/57 • Number of events 1 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
General disorders dehydration	1.6% 1/63 • Number of events 1 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	0.00% 0/57 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Psychiatric disorders depression	9.5% 6/63 • Number of events 6 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	1.8% 1/57 • Number of events 1 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Endocrine disorders Diabetic neuropathy	1.6% 1/63 • Number of events 1 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	0.00% 0/57 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Endocrine disorders diabetes	1.6% 1/63 • Number of events 1 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	0.00% 0/57 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Gastrointestinal disorders diarrhea	38.1% 24/63 • Number of events 30 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	40.4% 23/57 • Number of events 28 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Respiratory, thoracic and mediastinal disorders diminished breath sounds	0.00% 0/63 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	1.8% 1/57 • Number of events 1 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Blood and lymphatic system disorders direct hyperbilirubinemia	38.1% 24/63 • Number of events 44 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	52.6% 30/57 • Number of events 51 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Nervous system disorders dizziness	3.2% 2/63 • Number of events 2 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	3.5% 2/57 • Number of events 2 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Gastrointestinal disorders dry mouth	4.8% 3/63 • Number of events 3 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	3.5% 2/57 • Number of events 2 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Skin and subcutaneous tissue disorders dry skin	3.2% 2/63 • Number of events 2 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	3.5% 2/57 • Number of events 2 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Gastrointestinal disorders dysgeusia	0.00% 0/63 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	1.8% 1/57 • Number of events 1 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Gastrointestinal disorders dyspepsia	4.8% 3/63 • Number of events 3 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	1.8% 1/57 • Number of events 1 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Gastrointestinal disorders dysphagia	1.6% 1/63 • Number of events 2 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	1.8% 1/57 • Number of events 1 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Respiratory, thoracic and mediastinal disorders dysphonia	6.3% 4/63 • Number of events 5 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	14.0% 8/57 • Number of events 8 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Ear and labyrinth disorders ear fullness	1.6% 1/63 • Number of events 1 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	1.8% 1/57 • Number of events 1 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Ear and labyrinth disorders ear pain	0.00% 0/63 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	1.8% 1/57 • Number of events 1 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Gastrointestinal disorders early satiety	3.2% 2/63 • Number of events 2 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	0.00% 0/57 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Cardiac disorders edema	9.5% 6/63 • Number of events 6 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	7.0% 4/57 • Number of events 4 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Hepatobiliary disorders elevated INR	30.2% 19/63 • Number of events 24 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	26.3% 15/57 • Number of events 16 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Hepatobiliary disorders encephalopathy	17.5% 11/63 • Number of events 11 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	12.3% 7/57 • Number of events 7 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
General disorders epistaxis	4.8% 3/63 • Number of events 3 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	1.8% 1/57 • Number of events 1 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Skin and subcutaneous tissue disorders erythema	1.6% 1/63 • Number of events 1 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	0.00% 0/57 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Nervous system disorders face/mouth sensitivity	1.6% 1/63 • Number of events 1 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	0.00% 0/57 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Nervous system disorders facial droop	1.6% 1/63 • Number of events 1 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	0.00% 0/57 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
General disorders fatigue	34.9% 22/63 • Number of events 26 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	54.4% 31/57 • Number of events 37 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Gastrointestinal disorders fecal incontinence	1.6% 1/63 • Number of events 1 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	0.00% 0/57 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Infections and infestations fever	12.7% 8/63 • Number of events 10 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	3.5% 2/57 • Number of events 2 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Gastrointestinal disorders flatulence	1.6% 1/63 • Number of events 1 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	0.00% 0/57 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
General disorders flu-like symptoms	0.00% 0/63 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	1.8% 1/57 • Number of events 1 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Infections and infestations gastritis	1.6% 1/63 • Number of events 2 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	3.5% 2/57 • Number of events 2 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Gastrointestinal disorders gastrointestinal bleed	9.5% 6/63 • Number of events 6 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	5.3% 3/57 • Number of events 3 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Gastrointestinal disorders gastroparesis	1.6% 1/63 • Number of events 1 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	0.00% 0/57 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Gastrointestinal disorders g.i disturbance	1.6% 1/63 • Number of events 1 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	0.00% 0/57 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Gastrointestinal disorders glossodynia	0.00% 0/63 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	1.8% 1/57 • Number of events 1 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Musculoskeletal and connective tissue disorders groin pain	4.8% 3/63 • Number of events 3 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	3.5% 2/57 • Number of events 3 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Hepatobiliary disorders gynecomastia	0.00% 0/63 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	3.5% 2/57 • Number of events 3 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Skin and subcutaneous tissue disorders hand-foot reaction	39.7% 25/63 • Number of events 37 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	42.1% 24/57 • Number of events 36 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
General disorders head cold	0.00% 0/63 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	1.8% 1/57 • Number of events 1 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Nervous system disorders headache	7.9% 5/63 • Number of events 5 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	12.3% 7/57 • Number of events 8 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Ear and labyrinth disorders hearing impairment	0.00% 0/63 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	1.8% 1/57 • Number of events 1 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Skin and subcutaneous tissue disorders hematoma	0.00% 0/63 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	1.8% 1/57 • Number of events 1 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Renal and urinary disorders hematuria	0.00% 0/63 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	1.8% 1/57 • Number of events 1 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Injury, poisoning and procedural complications hematuria with catherization	0.00% 0/63 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	1.8% 1/57 • Number of events 1 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Gastrointestinal disorders hemorrhoids	1.6% 1/63 • Number of events 1 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	3.5% 2/57 • Number of events 3 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Hepatobiliary disorders hepatomegaly	3.2% 2/63 • Number of events 2 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	0.00% 0/57 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Gastrointestinal disorders hiccups	3.2% 2/63 • Number of events 2 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	0.00% 0/57 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Cardiac disorders hypertension	50.8% 32/63 • Number of events 56 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	50.9% 29/57 • Number of events 49 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Endocrine disorders hyperglycemia	1.6% 1/63 • Number of events 1 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	0.00% 0/57 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Renal and urinary disorders hyperkalemia	6.3% 4/63 • Number of events 4 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	1.8% 1/57 • Number of events 1 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Hepatobiliary disorders hypoalbuminemia	49.2% 31/63 • Number of events 43 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	47.4% 27/57 • Number of events 37 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Renal and urinary disorders hypokalemia	9.5% 6/63 • Number of events 6 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	1.8% 1/57 • Number of events 1 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Renal and urinary disorders hypomagnesemia	7.9% 5/63 • Number of events 8 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	8.8% 5/57 • Number of events 5 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Renal and urinary disorders hyponatremia	1.6% 1/63 • Number of events 1 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	1.8% 1/57 • Number of events 1 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Renal and urinary disorders hypophosphatemia	36.5% 23/63 • Number of events 37 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	40.4% 23/57 • Number of events 30 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Cardiac disorders hypotension	3.2% 2/63 • Number of events 2 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	3.5% 2/57 • Number of events 2 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Nervous system disorders impaired speech	1.6% 1/63 • Number of events 1 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	0.00% 0/57 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Psychiatric disorders insomnia	6.3% 4/63 • Number of events 4 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	10.5% 6/57 • Number of events 6 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Psychiatric disorders irritability	1.6% 1/63 • Number of events 1 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	0.00% 0/57 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Hepatobiliary disorders jaundice	1.6% 1/63 • Number of events 1 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	1.8% 1/57 • Number of events 1 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Skin and subcutaneous tissue disorders keratosis	0.00% 0/63 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	1.8% 1/57 • Number of events 1 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Renal and urinary disorders kidney injury	1.6% 1/63 • Number of events 1 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	0.00% 0/57 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Musculoskeletal and connective tissue disorders knee pain	0.00% 0/63 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	1.8% 1/57 • Number of events 1 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Hepatobiliary disorders left portal vein thrombosis	0.00% 0/63 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	1.8% 1/57 • Number of events 1 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Musculoskeletal and connective tissue disorders leg pain	1.6% 1/63 • Number of events 1 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	0.00% 0/57 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Hepatobiliary disorders liver failure	9.5% 6/63 • Number of events 6 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	8.8% 5/57 • Number of events 5 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Blood and lymphatic system disorders leukocytosis	0.00% 0/63 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	1.8% 1/57 • Number of events 1 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Blood and lymphatic system disorders leukopenia	31.7% 20/63 • Number of events 29 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	19.3% 11/57 • Number of events 16 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
General disorders lightheadedness	3.2% 2/63 • Number of events 2 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	0.00% 0/57 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Gastrointestinal disorders lipase elevation	34.9% 22/63 • Number of events 38 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	45.6% 26/57 • Number of events 49 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Blood and lymphatic system disorders lymphodenitis	1.6% 1/63 • Number of events 1 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	0.00% 0/57 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Blood and lymphatic system disorders lymphopenia	0.00% 0/63 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	1.8% 1/57 • Number of events 1 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Metabolism and nutrition disorders malnutrition	0.00% 0/63 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	1.8% 1/57 • Number of events 1 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Psychiatric disorders mood alteration	1.6% 1/63 • Number of events 1 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	0.00% 0/57 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Gastrointestinal disorders mucositis	0.00% 0/63 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	3.5% 2/57 • Number of events 2 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Musculoskeletal and connective tissue disorders muscle cramps	9.5% 6/63 • Number of events 6 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	17.5% 10/57 • Number of events 11 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Infections and infestations MRSA	1.6% 1/63 • Number of events 1 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	0.00% 0/57 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Musculoskeletal and connective tissue disorders myalgia	0.00% 0/63 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	1.8% 1/57 • Number of events 1 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Skin and subcutaneous tissue disorders nail changes	1.6% 1/63 • Number of events 1 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	1.8% 1/57 • Number of events 1 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Musculoskeletal and connective tissue disorders nasal fracture	1.6% 1/63 • Number of events 1 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	0.00% 0/57 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Gastrointestinal disorders nausea	33.3% 21/63 • Number of events 24 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	33.3% 19/57 • Number of events 20 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
General disorders night sweats	0.00% 0/63 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	1.8% 1/57 • Number of events 1 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Musculoskeletal and connective tissue disorders nose tenderness	0.00% 0/63 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	1.8% 1/57 • Number of events 1 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Skin and subcutaneous tissue disorders oral aphthous ulcers	6.3% 4/63 • Number of events 4 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	8.8% 5/57 • Number of events 5 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Gastrointestinal disorders oral hypersensitivity	1.6% 1/63 • Number of events 1 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	3.5% 2/57 • Number of events 2 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Gastrointestinal disorders oral pain	0.00% 0/63 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	1.8% 1/57 • Number of events 1 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Infections and infestations oral thrush	0.00% 0/63 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	1.8% 1/57 • Number of events 1 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Ear and labyrinth disorders otitis media	1.6% 1/63 • Number of events 1 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	0.00% 0/57 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Hepatobiliary disorders palmer erythema	1.6% 1/63 • Number of events 1 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	0.00% 0/57 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Cardiac disorders palpitations	0.00% 0/63 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	1.8% 1/57 • Number of events 1 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Gastrointestinal disorders pancreatitis	1.6% 1/63 • Number of events 1 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	0.00% 0/57 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Blood and lymphatic system disorders pancytopenia	1.6% 1/63 • Number of events 1 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	0.00% 0/57 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Reproductive system and breast disorders pelvic floor dysfunction	0.00% 0/63 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	1.8% 1/57 • Number of events 1 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Gastrointestinal disorders peptic ulcer	1.6% 1/63 • Number of events 1 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	0.00% 0/57 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Gastrointestinal disorders perianal abcess	0.00% 0/63 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	1.8% 1/57 • Number of events 1 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Nervous system disorders peripheral neuropathy	0.00% 0/63 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	1.8% 1/57 • Number of events 1 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Gastrointestinal disorders peritoneal enlarged studding	1.6% 1/63 • Number of events 1 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	0.00% 0/57 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Infections and infestations pneumonia	0.00% 0/63 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	3.5% 2/57 • Number of events 2 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Injury, poisoning and procedural complications post-tace syndrome	3.2% 2/63 • Number of events 3 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	1.8% 1/57 • Number of events 1 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Skin and subcutaneous tissue disorders poison ivy	0.00% 0/63 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	1.8% 1/57 • Number of events 1 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Skin and subcutaneous tissue disorders pruritus	9.5% 6/63 • Number of events 6 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	10.5% 6/57 • Number of events 6 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Musculoskeletal and connective tissue disorders pseudogout	1.6% 1/63 • Number of events 1 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	0.00% 0/57 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Respiratory, thoracic and mediastinal disorders pulmonary edema	0.00% 0/63 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	1.8% 1/57 • Number of events 1 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Skin and subcutaneous tissue disorders rash	19.0% 12/63 • Number of events 13 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	22.8% 13/57 • Number of events 18 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Gastrointestinal disorders rectal fissue	0.00% 0/63 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	1.8% 1/57 • Number of events 1 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Renal and urinary disorders renal failure	1.6% 1/63 • Number of events 1 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	0.00% 0/57 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Infections and infestations ringworm	1.6% 1/63 • Number of events 1 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	0.00% 0/57 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Skin and subcutaneous tissue disorders scalp hypersensitivity	1.6% 1/63 • Number of events 1 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	3.5% 2/57 • Number of events 2 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Nervous system disorders sciatica	1.6% 1/63 • Number of events 1 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	0.00% 0/57 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Reproductive system and breast disorders scortal pain	1.6% 1/63 • Number of events 1 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	0.00% 0/57 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Nervous system disorders seizure like activity	1.6% 1/63 • Number of events 1 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	0.00% 0/57 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Respiratory, thoracic and mediastinal disorders shortness of breath	1.6% 1/63 • Number of events 1 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	7.0% 4/57 • Number of events 4 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Infections and infestations sinusitis	0.00% 0/63 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	3.5% 2/57 • Number of events 2 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) skin cancer	1.6% 1/63 • Number of events 1 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	0.00% 0/57 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Skin and subcutaneous tissue disorders skin excoriation	1.6% 1/63 • Number of events 1 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	0.00% 0/57 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Skin and subcutaneous tissue disorders skin lesions	1.6% 1/63 • Number of events 1 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	0.00% 0/57 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Skin and subcutaneous tissue disorders skin ulcer	0.00% 0/63 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	1.8% 1/57 • Number of events 1 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Infections and infestations skull infection	0.00% 0/63 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	1.8% 1/57 • Number of events 1 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Nervous system disorders somnolence	1.6% 1/63 • Number of events 1 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	1.8% 1/57 • Number of events 1 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Hepatobiliary disorders spider angiomata	1.6% 1/63 • Number of events 1 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	0.00% 0/57 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Musculoskeletal and connective tissue disorders spinal spondolytis	0.00% 0/63 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	1.8% 1/57 • Number of events 1 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Hepatobiliary disorders splenomegaly	1.6% 1/63 • Number of events 1 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	3.5% 2/57 • Number of events 3 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) squamous cell carcinoma	1.6% 1/63 • Number of events 1 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	3.5% 2/57 • Number of events 2 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Infections and infestations stye	0.00% 0/63 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	1.8% 1/57 • Number of events 2 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Cardiac disorders systolic murmur	1.6% 1/63 • Number of events 1 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	0.00% 0/57 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Cardiac disorders tachycardia	1.6% 1/63 • Number of events 1 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	0.00% 0/57 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Skin and subcutaneous tissue disorders telangiectasia	0.00% 0/63 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	3.5% 2/57 • Number of events 2 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Metabolism and nutrition disorders temporal wasting	1.6% 1/63 • Number of events 1 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	0.00% 0/57 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Infections and infestations throat pain	3.2% 2/63 • Number of events 2 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	1.8% 1/57 • Number of events 1 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Blood and lymphatic system disorders thrombocytopenia	47.6% 30/63 • Number of events 41 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	45.6% 26/57 • Number of events 39 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Infections and infestations thrush	1.6% 1/63 • Number of events 1 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	0.00% 0/57 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Ear and labyrinth disorders tinnitus	1.6% 1/63 • Number of events 1 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	0.00% 0/57 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
General disorders tooth pain	1.6% 1/63 • Number of events 1 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	0.00% 0/57 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Nervous system disorders unsteady gait	4.8% 3/63 • Number of events 3 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	3.5% 2/57 • Number of events 2 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Infections and infestations upper respiratory infection	0.00% 0/63 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	1.8% 1/57 • Number of events 1 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Renal and urinary disorders urinary incontinence	3.2% 2/63 • Number of events 2 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	1.8% 1/57 • Number of events 1 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Renal and urinary disorders urinary tract infection	3.2% 2/63 • Number of events 2 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	5.3% 3/57 • Number of events 4 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Cardiac disorders ventricular hypertrophy	1.6% 1/63 • Number of events 1 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	0.00% 0/57 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Nervous system disorders vertigo	0.00% 0/63 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	1.8% 1/57 • Number of events 1 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
Gastrointestinal disorders vomiting	17.5% 11/63 • Number of events 11 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	15.8% 9/57 • Number of events 11 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.
General disorders weight loss	63.5% 40/63 • Number of events 63 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.	49.1% 28/57 • Number of events 39 • Adverse events were collected during 6 months of treatment. First subject randomized 8/29/2011 and last subject completed 6 months of treatment on 3/10/14.

Additional Information

Roniel Cabrera, MD

UNIVERSITY OF FLORIDA

Phone: 352-273-9468

Email: RONIEL.CABRERA@MEDICINE.UFL.EDU

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place