Trial Outcomes & Findings for Study Evaluating Interferon And CCI-779 In Advanced Renal Cell Carcinoma (NCT NCT00065468)

Last Updated: 2012-10-25

Results Overview

Overall survival is the duration from randomization to death. For participants who are alive, overall survival is censored at the last contact.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

626 participants

Primary outcome timeframe

Baseline up to Month 80

Results posted on

2012-10-25

Participant Flow

Participant milestones

Participant milestones
Measure	Interferon Alfa Interferon Alfa (Roferon) 3 million units (MU) subcutaneously 3 times per week for 1 week, then 9 MU subcutaneously 3 times per week for 1 week, then 18 MU subcutaneously 3 times per week until disease progression or treatment withdrawal	Temsirolimus Temsirolimus (CCI-779) 25 milligrams (mg) intravenously (IV) once per week until disease progression or treatment withdrawal	Interferon Alfa and Temsirolimus Interferon Alfa (Roferon) 6 MU subcutaneously 3 times per week and Temsirolimus (CCI-779) 15 mg IV once per week until disease progression or treatment withdrawal
Overall Study STARTED	207	209	210
Overall Study Received Treatment	200	208	208
Overall Study COMPLETED	0	0	0
Overall Study NOT COMPLETED	207	209	210

Reasons for withdrawal

Reasons for withdrawal
Measure	Interferon Alfa Interferon Alfa (Roferon) 3 million units (MU) subcutaneously 3 times per week for 1 week, then 9 MU subcutaneously 3 times per week for 1 week, then 18 MU subcutaneously 3 times per week until disease progression or treatment withdrawal	Temsirolimus Temsirolimus (CCI-779) 25 milligrams (mg) intravenously (IV) once per week until disease progression or treatment withdrawal	Interferon Alfa and Temsirolimus Interferon Alfa (Roferon) 6 MU subcutaneously 3 times per week and Temsirolimus (CCI-779) 15 mg IV once per week until disease progression or treatment withdrawal
Overall Study Death	172	169	171
Overall Study Withdrawal by Subject	3	4	5
Overall Study Lost to Follow-up	5	3	2
Overall Study Discontinuation of study by Sponsor	13	9	13
Overall Study Disease progression	0	0	1
Overall Study Other	14	24	18

Baseline Characteristics

Study Evaluating Interferon And CCI-779 In Advanced Renal Cell Carcinoma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Interferon Alfa n=207 Participants Interferon Alfa (Roferon) 3 million units (MU) subcutaneously 3 times per week for 1 week, then 9 MU subcutaneously 3 times per week for 1 week, then 18 MU subcutaneously 3 times per week until disease progression or treatment withdrawal	Temsirolimus n=209 Participants Temsirolimus (CCI-779) 25 milligrams (mg) intravenously (IV) once per week until disease progression or treatment withdrawal	Interferon Alfa and Temsirolimus n=210 Participants Interferon Alfa (Roferon) 6 MU subcutaneously 3 times per week and Temsirolimus (CCI-779) 15 mg IV once per week until disease progression or treatment withdrawal	Total n=626 Participants Total of all reporting groups
Age Continuous	59.2 years STANDARD_DEVIATION 10.4 • n=5 Participants	58.7 years STANDARD_DEVIATION 10.0 • n=7 Participants	59.3 years STANDARD_DEVIATION 9.8 • n=5 Participants	59.1 years STANDARD_DEVIATION 10.1 • n=4 Participants
Sex: Female, Male Female	59 Participants n=5 Participants	70 Participants n=7 Participants	65 Participants n=5 Participants	194 Participants n=4 Participants
Sex: Female, Male Male	148 Participants n=5 Participants	139 Participants n=7 Participants	145 Participants n=5 Participants	432 Participants n=4 Participants

PRIMARY outcome

Timeframe: Baseline up to Month 80

Population: Intent-to-treat (ITT) Population: all randomized participants

Overall survival is the duration from randomization to death. For participants who are alive, overall survival is censored at the last contact.

Outcome measures

Outcome measures
Measure	Interferon Alfa n=207 Participants Interferon Alfa (Roferon) 3 million units (MU) subcutaneously 3 times per week for 1 week, then 9 MU subcutaneously 3 times per week for 1 week, then 18 MU subcutaneously 3 times per week until disease progression or treatment withdrawal	Temsirolimus n=209 Participants Temsirolimus (CCI-779) 25 milligrams (mg) intravenously (IV) once per week until disease progression or treatment withdrawal	Interferon Alfa and Temsirolimus n=210 Participants Interferon Alfa (Roferon) 6 MU subcutaneously 3 times per week and Temsirolimus (CCI-779) 15 mg IV once per week until disease progression or treatment withdrawal
Overall Survival (OS)	7.3 months Interval 6.1 to 8.8	10.9 months Interval 8.6 to 12.7	8.4 months Interval 6.6 to 10.3

SECONDARY outcome

Timeframe: Baseline, monthly until tumor progression or death (up to Month 80)

Population: ITT

PFS based on Independent Central Review Assessment. The period from randomization until disease progression, death or date of last contact.

Outcome measures

Outcome measures
Measure	Interferon Alfa n=207 Participants Interferon Alfa (Roferon) 3 million units (MU) subcutaneously 3 times per week for 1 week, then 9 MU subcutaneously 3 times per week for 1 week, then 18 MU subcutaneously 3 times per week until disease progression or treatment withdrawal	Temsirolimus n=209 Participants Temsirolimus (CCI-779) 25 milligrams (mg) intravenously (IV) once per week until disease progression or treatment withdrawal	Interferon Alfa and Temsirolimus n=210 Participants Interferon Alfa (Roferon) 6 MU subcutaneously 3 times per week and Temsirolimus (CCI-779) 15 mg IV once per week until disease progression or treatment withdrawal
Progression-Free Survival (PFS)	3.2 months Interval 2.2 to 4.0	5.6 months Interval 3.9 to 7.2	4.9 months Interval 3.9 to 6.0

SECONDARY outcome

Timeframe: Baseline, every 2 months until tumor progression or death (up to Month 80)

Population: ITT

Percentage of participants with objective response based assessment of confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST). CR was the disappearance of all target lesions and non target lesions. PR was at least a 30 percent (%) decrease in sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD.

Outcome measures

Outcome measures
Measure	Interferon Alfa n=207 Participants Interferon Alfa (Roferon) 3 million units (MU) subcutaneously 3 times per week for 1 week, then 9 MU subcutaneously 3 times per week for 1 week, then 18 MU subcutaneously 3 times per week until disease progression or treatment withdrawal	Temsirolimus n=209 Participants Temsirolimus (CCI-779) 25 milligrams (mg) intravenously (IV) once per week until disease progression or treatment withdrawal	Interferon Alfa and Temsirolimus n=210 Participants Interferon Alfa (Roferon) 6 MU subcutaneously 3 times per week and Temsirolimus (CCI-779) 15 mg IV once per week until disease progression or treatment withdrawal
Percentage of Participants With Objective Response	5.3 percentage of participants Interval 2.3 to 8.4	9.1 percentage of participants Interval 5.2 to 13.0	9.5 percentage of participants Interval 5.6 to 13.5

SECONDARY outcome

Timeframe: Baseline, every 2 months until tumor progression or death (up to Month 80)

Population: ITT

Clinical benefit: confirmed CR or PR or had stable disease (SD) lasting at least 24 weeks. CR was the disappearance of all target lesions and non target lesions. PR was at least a 30% decrease in sum of the LD of target lesions, taking as reference the baseline sum LD. SD was having neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD.

Outcome measures

Outcome measures
Measure	Interferon Alfa n=207 Participants Interferon Alfa (Roferon) 3 million units (MU) subcutaneously 3 times per week for 1 week, then 9 MU subcutaneously 3 times per week for 1 week, then 18 MU subcutaneously 3 times per week until disease progression or treatment withdrawal	Temsirolimus n=209 Participants Temsirolimus (CCI-779) 25 milligrams (mg) intravenously (IV) once per week until disease progression or treatment withdrawal	Interferon Alfa and Temsirolimus n=210 Participants Interferon Alfa (Roferon) 6 MU subcutaneously 3 times per week and Temsirolimus (CCI-779) 15 mg IV once per week until disease progression or treatment withdrawal
Percentage of Participants With Clinical Benefit	16.4 percentage of participants Interval 11.4 to 21.5	34.0 percentage of participants Interval 27.6 to 40.4	30.0 percentage of participants Interval 23.8 to 36.2

SECONDARY outcome

Timeframe: Baseline, every month until tumor progression or death (up to Month 80)

Population: ITT subset of participants who had a response

DR: Time from first documentation of objective tumor response to first date that recurrence or progressive disease (PD) was objectively documented, taking as a reference for PD, the smallest sum LD recorded since randomization.

Outcome measures

Outcome measures
Measure	Interferon Alfa n=11 Participants Interferon Alfa (Roferon) 3 million units (MU) subcutaneously 3 times per week for 1 week, then 9 MU subcutaneously 3 times per week for 1 week, then 18 MU subcutaneously 3 times per week until disease progression or treatment withdrawal	Temsirolimus n=19 Participants Temsirolimus (CCI-779) 25 milligrams (mg) intravenously (IV) once per week until disease progression or treatment withdrawal	Interferon Alfa and Temsirolimus n=20 Participants Interferon Alfa (Roferon) 6 MU subcutaneously 3 times per week and Temsirolimus (CCI-779) 15 mg IV once per week until disease progression or treatment withdrawal
Duration of Response (DR)	7.4 months Interval 5.1 to 18.4	11.1 months Interval 9.1 to 13.8	9.3 months Interval 5.8 to 23.1

SECONDARY outcome

Timeframe: Baseline, every month until tumor progression or death (up to Month 80)

Population: ITT

TTF is defined as the time from the date of randomization to the date of PD or death, withdrawal from treatment due to an adverse event (AE), withdrawal of voluntary consent, or lost to follow-up, whichever occurred first, censored at the date of the conclusion of treatment phase.

Outcome measures

Outcome measures
Measure	Interferon Alfa n=207 Participants Interferon Alfa (Roferon) 3 million units (MU) subcutaneously 3 times per week for 1 week, then 9 MU subcutaneously 3 times per week for 1 week, then 18 MU subcutaneously 3 times per week until disease progression or treatment withdrawal	Temsirolimus n=209 Participants Temsirolimus (CCI-779) 25 milligrams (mg) intravenously (IV) once per week until disease progression or treatment withdrawal	Interferon Alfa and Temsirolimus n=210 Participants Interferon Alfa (Roferon) 6 MU subcutaneously 3 times per week and Temsirolimus (CCI-779) 15 mg IV once per week until disease progression or treatment withdrawal
Time to Treatment Failure (TTF)	1.9 months Interval 1.7 to 1.9	3.7 months Interval 3.4 to 3.9	2.5 months Interval 1.9 to 3.6

SECONDARY outcome

Timeframe: Baseline to Month 80

Population: ITT

The Q-Twist is not a score calculated for each participant but is defined only on a by treatment group basis. For each treatment group, it is the weighted sum of the mean durations of the health states Tox, Twist, and Relapse. Tox is defined as time with severe toxicity related to treatment; Twist: time without symptoms or toxic side effects; and Relapse: time after relapse/progression. The mean duration of each health state is calculated based on the area under the Kaplan Meier curve pertaining to that health state. There is no direct method for calculating the "dispersion" of Q-Twist, and it is typically done using bootstrap method for purposes of inference (see, e.g., Glasziou PP, Simes RJ, Gelber RD. Quality adjusted survival analysis. Stat Med 1990; 9: 1259-76). In practice, as apparently in the case with this study, the intermediate values resulting from the bootstrap exercise were not displayed.

Outcome measures

Outcome measures
Measure	Interferon Alfa n=207 Participants Interferon Alfa (Roferon) 3 million units (MU) subcutaneously 3 times per week for 1 week, then 9 MU subcutaneously 3 times per week for 1 week, then 18 MU subcutaneously 3 times per week until disease progression or treatment withdrawal	Temsirolimus n=209 Participants Temsirolimus (CCI-779) 25 milligrams (mg) intravenously (IV) once per week until disease progression or treatment withdrawal	Interferon Alfa and Temsirolimus n=210 Participants Interferon Alfa (Roferon) 6 MU subcutaneously 3 times per week and Temsirolimus (CCI-779) 15 mg IV once per week until disease progression or treatment withdrawal
Quality-adjusted Time Without Symptoms or Toxicity (Q-TWiST)	6.9083 months	8.3707 months	7.4821 months

SECONDARY outcome

Timeframe: Baseline

Population: ITT;(N)=participants with evaluable data. Week 12 and 32 data collected for individual participants but not summarized.

EQ-5D: participant rated questionnaire to assess health-related quality of life in terms of a single index value. EQ-5D index measured 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Range of EQ-5D index score = -0.594 to 1 where higher scores indicated a better health state.

Outcome measures

Outcome measures
Measure	Interferon Alfa n=197 Participants Interferon Alfa (Roferon) 3 million units (MU) subcutaneously 3 times per week for 1 week, then 9 MU subcutaneously 3 times per week for 1 week, then 18 MU subcutaneously 3 times per week until disease progression or treatment withdrawal	Temsirolimus n=204 Participants Temsirolimus (CCI-779) 25 milligrams (mg) intravenously (IV) once per week until disease progression or treatment withdrawal	Interferon Alfa and Temsirolimus n=197 Participants Interferon Alfa (Roferon) 6 MU subcutaneously 3 times per week and Temsirolimus (CCI-779) 15 mg IV once per week until disease progression or treatment withdrawal
European Quality of Life Health Questionnaire (EQ-5D) - Index Score	0.656 units on a scale Interval -0.319 to 1.0	0.689 units on a scale Interval -0.181 to 1.0	0.689 units on a scale Interval -0.239 to 1.0

Adverse Events

Interferon Alfa

Serious events: 99 serious events

Other events: 197 other events

Deaths: 0 deaths

Temsirolimus

Serious events: 82 serious events

Other events: 208 other events

Deaths: 0 deaths

Interferon Alfa and Temsirolimus

Serious events: 122 serious events

Other events: 205 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Pfizer ClinicalTrials.gov Call Center

Pfizer, Inc.

Phone: 1-800-718-1021

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
Publication restrictions are in place

Restriction type: OTHER

Serious adverse events
Measure	Interferon Alfa n=200 participants at risk Interferon Alfa (Roferon) 3 million units (MU) subcutaneously 3 times per week for 1 week, then 9 MU subcutaneously 3 times per week for 1 week, then 18 MU subcutaneously 3 times per week until disease progression or treatment withdrawal	Temsirolimus n=208 participants at risk Temsirolimus (CCI-779) 25 milligrams (mg) intravenously (IV) once per week until disease progression or treatment withdrawal	Interferon Alfa and Temsirolimus n=208 participants at risk Interferon Alfa (Roferon) 6 MU subcutaneously 3 times per week and Temsirolimus (CCI-779) 15 mg IV once per week until disease progression or treatment withdrawal
Cardiac disorders SHOCK	0.00% 0/200 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/208 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.	0.48% 1/208 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.
Cardiac disorders TACHYCARDIA SINUS	0.00% 0/200 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.	0.48% 1/208 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/208 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.
Cardiac disorders ANGINA PECTORIS	0.00% 0/200 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/208 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.	0.48% 1/208 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.
Cardiac disorders CARDIOMYOPATHY	0.00% 0/200 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/208 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.	0.48% 1/208 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.
Metabolism and nutrition disorders HYPERGLYCEMIA	0.00% 0/200 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.	2.9% 6/208 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/208 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.
Cardiac disorders CEREBRAL HEMORRHAGE	0.00% 0/200 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/208 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.	0.48% 1/208 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.
Cardiac disorders CEREBRAL ISCHEMIA	0.00% 0/200 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/208 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.	0.48% 1/208 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.
Cardiac disorders CEREBROVASCULAR DISORDER	0.50% 1/200 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/208 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/208 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.
Cardiac disorders HEART ARREST	0.00% 0/200 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/208 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.	0.48% 1/208 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.
Cardiac disorders HEMORRHAGE	0.50% 1/200 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/208 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.	0.96% 2/208 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.
Cardiac disorders HYPOTENSION	1.0% 2/200 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/208 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.	0.96% 2/208 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.
Cardiac disorders HYPOVOLEMIA	0.50% 1/200 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/208 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/208 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.
Cardiac disorders POSTURAL HYPOTENSION 1	0.50% 1/200 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/208 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/208 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.
Cardiac disorders THROMBOSIS	0.00% 0/200 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/208 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.	0.48% 1/208 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.
Cardiac disorders VASCULAR DISORDER	0.50% 1/200 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/208 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/208 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders STOMATITIS	0.00% 0/200 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.	1.4% 3/208 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.	1.9% 4/208 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders GASTROINTESTINAL HEMORRHAGE	0.00% 0/200 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.	0.96% 2/208 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/208 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders NAUSEA	1.5% 3/200 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.	0.96% 2/208 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.	0.96% 2/208 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders VOMITING	1.5% 3/200 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.	0.96% 2/208 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.	0.48% 1/208 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders DIARRHEA	0.50% 1/200 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.	0.48% 1/208 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.	2.9% 6/208 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders GASTROINTESTINAL DISORDER	0.50% 1/200 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.	0.48% 1/208 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/208 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders ILEUS	0.00% 0/200 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.	0.48% 1/208 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.	0.48% 1/208 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders INTESTINAL PERFORATION	0.00% 0/200 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.	0.48% 1/208 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/208 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders MUCOSITIS	0.00% 0/200 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.	0.48% 1/208 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.	0.96% 2/208 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders ANOREXIA	0.50% 1/200 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/208 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.	1.4% 3/208 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders COLITIS	0.00% 0/200 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/208 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.	0.48% 1/208 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders CONSTIPATION	0.50% 1/200 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/208 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.	0.48% 1/208 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders GASTROENTERITIS	0.00% 0/200 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/208 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.	0.48% 1/208 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders HEMATEMESIS	0.50% 1/200 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/208 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/208 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders HEMORRHAGIC GASTRITIS	0.00% 0/200 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/208 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.	0.48% 1/208 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders HEPATIC FAILURE	0.50% 1/200 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/208 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/208 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders HEPATITIS	0.50% 1/200 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/208 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/208 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders INTESTINAL OBSTRUCTION	0.50% 1/200 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/208 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.	0.48% 1/208 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders LIVER FATTY DEPOSIT	0.50% 1/200 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/208 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/208 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders MELENA	0.50% 1/200 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/208 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/208 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders PROCTITIS	0.00% 0/200 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/208 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.	0.48% 1/208 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders RECTAL HEMORRHAGE	0.00% 0/200 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/208 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.	0.48% 1/208 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.
Endocrine disorders DIABETES MELLITUS	0.00% 0/200 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.	0.96% 2/208 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/208 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.
Endocrine disorders THYROID CARCINOMA	0.50% 1/200 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/208 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/208 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.
Blood and lymphatic system disorders ANEMIA	6.0% 12/200 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.	5.3% 11/208 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.	9.6% 20/208 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.

Other adverse events
Measure	Interferon Alfa n=200 participants at risk Interferon Alfa (Roferon) 3 million units (MU) subcutaneously 3 times per week for 1 week, then 9 MU subcutaneously 3 times per week for 1 week, then 18 MU subcutaneously 3 times per week until disease progression or treatment withdrawal	Temsirolimus n=208 participants at risk Temsirolimus (CCI-779) 25 milligrams (mg) intravenously (IV) once per week until disease progression or treatment withdrawal	Interferon Alfa and Temsirolimus n=208 participants at risk Interferon Alfa (Roferon) 6 MU subcutaneously 3 times per week and Temsirolimus (CCI-779) 15 mg IV once per week until disease progression or treatment withdrawal
Skin and subcutaneous tissue disorders ACNE	1.0% 2/200 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.	10.1% 21/208 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.	3.4% 7/208 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.
Metabolism and nutrition disorders HYPOPHOSPHATEMIA	2.0% 4/200 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.	8.2% 17/208 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.	10.1% 21/208 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.
Skin and subcutaneous tissue disorders EXFOLIATIVE DERMATITIS	0.50% 1/200 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.	7.7% 16/208 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.	2.9% 6/208 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.
Metabolism and nutrition disorders SGOT INCREASED	14.5% 29/200 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.	7.7% 16/208 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.	20.7% 43/208 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders MUCOSITIS	5.0% 10/200 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.	18.8% 39/208 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.	22.1% 46/208 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders VOMITING	28.5% 57/200 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.	18.8% 39/208 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.	28.8% 60/208 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.
General disorders ASTHENIA	63.0% 126/200 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.	50.5% 105/208 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.	61.1% 127/208 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.
General disorders PAIN	15.0% 30/200 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.	26.9% 56/208 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.	19.7% 41/208 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.
General disorders FEVER	49.0% 98/200 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.	23.6% 49/208 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.	60.6% 126/208 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.
General disorders ABDOMINAL PAIN	17.0% 34/200 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.	20.2% 42/208 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.	16.3% 34/208 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.
General disorders BACK PAIN	14.0% 28/200 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.	19.7% 41/208 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.	14.9% 31/208 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.
General disorders CHEST PAIN	9.0% 18/200 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.	16.8% 35/208 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.	11.1% 23/208 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.
General disorders HEADACHE	15.0% 30/200 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.	15.4% 32/208 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.	22.6% 47/208 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.
General disorders INFECTION	5.5% 11/200 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.	13.9% 29/208 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.	15.4% 32/208 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.
General disorders ALLERGIC REACTION	0.50% 1/200 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.	8.7% 18/208 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.	5.3% 11/208 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.
General disorders CHILLS	29.0% 58/200 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.	8.2% 17/208 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.	34.6% 72/208 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.
General disorders FACE EDEMA	0.50% 1/200 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.	7.2% 15/208 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.	4.8% 10/208 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.
General disorders ACCIDENTAL INJURY	4.0% 8/200 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.	6.2% 13/208 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.	5.8% 12/208 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.
General disorders FLU SYNDROME	11.5% 23/200 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.	3.8% 8/208 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.	13.5% 28/208 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.
General disorders LAB TEST ABNORMAL	2.5% 5/200 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.	3.8% 8/208 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.	6.2% 13/208 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.
Cardiac disorders HYPERTENSION	3.5% 7/200 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.	5.8% 12/208 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.	5.8% 12/208 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.
Cardiac disorders HYPOTENSION	5.5% 11/200 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.	4.8% 10/208 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.	3.4% 7/208 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.
Cardiac disorders TACHYCARDIA	5.5% 11/200 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.	4.3% 9/208 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.	8.2% 17/208 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.
Cardiac disorders VASODILATATION	2.5% 5/200 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.	2.4% 5/208 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.	5.8% 12/208 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders NAUSEA	41.0% 82/200 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.	36.5% 76/208 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.	40.4% 84/208 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders ANOREXIA	43.0% 86/200 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.	31.7% 66/208 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.	38.0% 79/208 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders DIARRHEA	19.5% 39/200 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.	27.4% 57/208 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.	26.9% 56/208 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders CONSTIPATION	17.5% 35/200 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.	20.2% 42/208 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.	18.8% 39/208 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders STOMATITIS	3.5% 7/200 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.	19.7% 41/208 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.	20.2% 42/208 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders DRY MOUTH	8.0% 16/200 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.	6.2% 13/208 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.	5.8% 12/208 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders MOUTH ULCERATION	2.5% 5/200 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.	2.9% 6/208 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.	7.2% 15/208 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders ORAL MONILIASIS	2.0% 4/200 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.	2.4% 5/208 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.	7.2% 15/208 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.
Blood and lymphatic system disorders ANEMIA	39.0% 78/200 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.	43.3% 90/208 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.	59.1% 123/208 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.
Blood and lymphatic system disorders THROMBOCYTOPENIA	8.0% 16/200 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.	13.5% 28/208 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.	37.0% 77/208 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.
Blood and lymphatic system disorders NEUTROPENIA	13.0% 26/200 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.	7.2% 15/208 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.	27.4% 57/208 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.
Blood and lymphatic system disorders LEUKOPENIA	17.0% 34/200 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.	6.2% 13/208 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.	31.2% 65/208 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.
Blood and lymphatic system disorders LYMPHOPENIA	8.5% 17/200 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.	5.3% 11/208 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.	13.5% 28/208 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.
Metabolism and nutrition disorders HYPERLIPEMIA	14.5% 29/200 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.	27.4% 57/208 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.	38.5% 80/208 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.
Metabolism and nutrition disorders PERIPHERAL EDEMA	7.5% 15/200 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.	26.0% 54/208 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.	17.3% 36/208 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.
Metabolism and nutrition disorders HYPERCHOLESTEREMIA	4.5% 9/200 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.	24.5% 51/208 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.	26.4% 55/208 The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.