Trial Outcomes & Findings for Bicalutamide With or Without Akt Inhibitor MK2206 in Treating Patients With Previously Treated Prostate Cancer (NCT NCT01251861)

Last Updated: 2025-12-11

Results Overview

The proportion of patients with undetectable PSA level (\< 0.2 ng/mL) at 44 weeks, defined as number of patients with undetectable PSA level at 44 weeks divided by number of patients randomized.

Recruitment status

ACTIVE_NOT_RECRUITING

Study phase

PHASE2

Target enrollment

108 participants

Primary outcome timeframe

44 weeks

Results posted on

2025-12-11

Participant Flow

This study was activated on December 23, 2010 and closed to accrual on September 20, 2013 with a final accrual of 108 patients from 24 participating sites.

Participant milestones

Participant milestones
Measure	Arm A (Observation and Bicalutamide) Patients undergo observation on weeks 1-12. Patients then receive bicalutamide PO QD on weeks 13-44. Patients with a PSA decline of \>= 50% may continue on bicalutamide until week 72 in the absence of disease progression or unacceptable toxicity.	Arm B (Akt Inhibitor MK2206 and Bicalutamide) Patients receive Akt inhibitor MK2206 PO once per week on weeks 1-44 and bicalutamide PO QD on weeks 13-44. Patients with a PSA decline of \>= 50% may continue on Akt inhibitor MK2206 and bicalutamide until week 72 in the absence of disease progression or unacceptable toxicity.
Overall Study STARTED	54	54
Overall Study Pts Who Received Protocol Therapy	50	53
Overall Study Pts w/ Follow-up PSA Lower Than Baseline	49	47
Overall Study Pts With PSA Response	44	36
Overall Study COMPLETED	36	26
Overall Study NOT COMPLETED	18	28

Reasons for withdrawal

Reasons for withdrawal
Measure	Arm A (Observation and Bicalutamide) Patients undergo observation on weeks 1-12. Patients then receive bicalutamide PO QD on weeks 13-44. Patients with a PSA decline of \>= 50% may continue on bicalutamide until week 72 in the absence of disease progression or unacceptable toxicity.	Arm B (Akt Inhibitor MK2206 and Bicalutamide) Patients receive Akt inhibitor MK2206 PO once per week on weeks 1-44 and bicalutamide PO QD on weeks 13-44. Patients with a PSA decline of \>= 50% may continue on Akt inhibitor MK2206 and bicalutamide until week 72 in the absence of disease progression or unacceptable toxicity.
Overall Study Disease progression	6	6
Overall Study Adverse Event	2	17
Overall Study Withdrawal by Subject	2	2
Overall Study Alternative therapy	1	0
Overall Study Other complicating disease	0	1
Overall Study Physician Decision	1	0
Overall Study Continued treatment beyond 18 cycles	1	0
Overall Study Other	1	0
Overall Study Never started therapy	4	1
Overall Study Potential interaction of drugs	0	1

Baseline Characteristics

Bicalutamide With or Without Akt Inhibitor MK2206 in Treating Patients With Previously Treated Prostate Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Arm A (Observation and Bicalutamide) n=54 Participants Patients undergo observation on weeks 1-12. Patients then receive bicalutamide PO QD on weeks 13-44. Patients with a PSA decline of \>= 50% may continue on bicalutamide until week 72 in the absence of disease progression or unacceptable toxicity.	Arm B (Akt Inhibitor MK2206 and Bicalutamide) n=54 Participants Patients receive Akt inhibitor MK2206 PO once per week on weeks 1-44 and bicalutamide PO QD on weeks 13-44. Patients with a PSA decline of \>= 50% may continue on Akt inhibitor MK2206 and bicalutamide until week 72 in the absence of disease progression or unacceptable toxicity.	Total n=108 Participants Total of all reporting groups
Age, Continuous	66 years n=237 Participants	67 years n=243 Participants	66 years n=480 Participants
Sex: Female, Male Female	0 Participants n=237 Participants	0 Participants n=243 Participants	0 Participants n=480 Participants
Sex: Female, Male Male	54 Participants n=237 Participants	54 Participants n=243 Participants	108 Participants n=480 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=237 Participants	0 Participants n=243 Participants	0 Participants n=480 Participants
Race (NIH/OMB) Asian	0 Participants n=237 Participants	1 Participants n=243 Participants	1 Participants n=480 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=237 Participants	0 Participants n=243 Participants	0 Participants n=480 Participants
Race (NIH/OMB) Black or African American	4 Participants n=237 Participants	5 Participants n=243 Participants	9 Participants n=480 Participants
Race (NIH/OMB) White	50 Participants n=237 Participants	48 Participants n=243 Participants	98 Participants n=480 Participants
Race (NIH/OMB) More than one race	0 Participants n=237 Participants	0 Participants n=243 Participants	0 Participants n=480 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=237 Participants	0 Participants n=243 Participants	0 Participants n=480 Participants

PRIMARY outcome

Timeframe: 44 weeks

Population: All randomized patients are included in this analysis.

The proportion of patients with undetectable PSA level (\< 0.2 ng/mL) at 44 weeks, defined as number of patients with undetectable PSA level at 44 weeks divided by number of patients randomized.

Outcome measures

Outcome measures
Measure	Arm A (Observation and Bicalutamide) n=54 Participants Patients undergo observation on weeks 1-12. Patients then receive bicalutamide PO QD on weeks 13-44. Patients with a PSA decline of \>= 50% may continue on bicalutamide until week 72 in the absence of disease progression or unacceptable toxicity.	Arm B (Akt Inhibitor MK2206 and Bicalutamide) n=54 Participants Patients receive Akt inhibitor MK2206 PO once per week on weeks 1-44 and bicalutamide PO QD on weeks 13-44. Patients with a PSA decline of \>= 50% may continue on Akt inhibitor MK2206 and bicalutamide until week 72 in the absence of disease progression or unacceptable toxicity.
The Proportion of Patients With Undetectable PSA Level (< 0.2 ng/mL) at 44 Weeks	0.093 proportion of participants Interval 0.046 to 0.165	0.148 proportion of participants Interval 0.088 to 0.23

SECONDARY outcome

Timeframe: 44 weeks

Population: All randomized patients are included in the analysis.

Proportion of patients with PSA decline \> 85% at 44 weeks from baseline, defined as number of patients with PSA decline \> 85% at 44 weeks from baseline divided by number of patients randomized.

Outcome measures

Outcome measures
Measure	Arm A (Observation and Bicalutamide) n=54 Participants Patients undergo observation on weeks 1-12. Patients then receive bicalutamide PO QD on weeks 13-44. Patients with a PSA decline of \>= 50% may continue on bicalutamide until week 72 in the absence of disease progression or unacceptable toxicity.	Arm B (Akt Inhibitor MK2206 and Bicalutamide) n=54 Participants Patients receive Akt inhibitor MK2206 PO once per week on weeks 1-44 and bicalutamide PO QD on weeks 13-44. Patients with a PSA decline of \>= 50% may continue on Akt inhibitor MK2206 and bicalutamide until week 72 in the absence of disease progression or unacceptable toxicity.
Proportion of Patients With PSA Decline > 85% at 44 Weeks	0.296 proportion of participants Interval 0.18 to 0.436	0.426 proportion of participants Interval 0.292 to 0.568

SECONDARY outcome

Timeframe: Assessed every 3 months for 2 years, every 6 months for 3 years, and then annually up to 10 years

Population: All randomized patients

PSA complete response (CR) is defined as a PSA \<0.2 ng/mL confirmed on two consecutive additional determinations taken at least 4 weeks apart. PSA partial response (PR) is defined as a reduction in PSA ≥ 50% from baseline without evidence of progression (confirmed on two consecutive additional determinations taken at least 4 weeks apart). Either CR or PR is considered as a PSA response.

Outcome measures

Outcome measures
Measure	Arm A (Observation and Bicalutamide) n=54 Participants Patients undergo observation on weeks 1-12. Patients then receive bicalutamide PO QD on weeks 13-44. Patients with a PSA decline of \>= 50% may continue on bicalutamide until week 72 in the absence of disease progression or unacceptable toxicity.	Arm B (Akt Inhibitor MK2206 and Bicalutamide) n=54 Participants Patients receive Akt inhibitor MK2206 PO once per week on weeks 1-44 and bicalutamide PO QD on weeks 13-44. Patients with a PSA decline of \>= 50% may continue on Akt inhibitor MK2206 and bicalutamide until week 72 in the absence of disease progression or unacceptable toxicity.
Proportion of Patients With PSA Response	0.815 proportion of participants Interval 0.686 to 0.908	0.667 proportion of participants Interval 0.525 to 0.789

SECONDARY outcome

Timeframe: Assessed every 3 months for 2 years, every 6 months for 3 years, and then annually up to 10 years

Population: All randomized patients

Time to PSA progression was defined as the time from randomization to PSA progression or date of last disease assessment showing progression-free. Development of clinical progression is also considered as an event. * For patients (pts) who achieved a ≥ 50% decline in PSA (confirmed on two consecutive determinations taken at least 4 weeks apart), progression is defined as an increase in PSA by 50% above baseline or nadir, whichever is lowest, confirmed by a 2nd PSA rise at least two weeks later. The PSA rise must be \>= 5 ng/mL. * For pts with an undetectable PSA nadir (\< 0.2 ng/mL confirmed on two consecutive determinations taken at least 4 weeks apart), progression is defined as PSA ≥ 0.2 ng/mL confirmed by a 2nd PSA rise at least 2 weeks later. * For pts whose PSA has not decreased by 50%, progression is defined as an increase in PSA of ≥ 50% of baseline or nadir PSA, whichever is lowest, confirmed by a repeat PSA at least 2 weeks later. The PSA must have risen by \>= 5 ng/mL

Outcome measures

Outcome measures
Measure	Arm A (Observation and Bicalutamide) n=54 Participants Patients undergo observation on weeks 1-12. Patients then receive bicalutamide PO QD on weeks 13-44. Patients with a PSA decline of \>= 50% may continue on bicalutamide until week 72 in the absence of disease progression or unacceptable toxicity.	Arm B (Akt Inhibitor MK2206 and Bicalutamide) n=54 Participants Patients receive Akt inhibitor MK2206 PO once per week on weeks 1-44 and bicalutamide PO QD on weeks 13-44. Patients with a PSA decline of \>= 50% may continue on Akt inhibitor MK2206 and bicalutamide until week 72 in the absence of disease progression or unacceptable toxicity.
Time to PSA Progression	25.8 months Interval 21.0 to 37.7	24.3 months Interval 19.1 to 30.1

SECONDARY outcome

Timeframe: Assessed every 3 months for 2 years, every 6 months for 3 years, and then annually up to 10 years

Population: Only patients who received protocol therapy and had follow-up PSA level lower than baseline PSA were included.

Time to PSA nadir was defined as the time from randomization to the date that PSA nadir, the lowest PSA value achieved after randomization, was documented. This analysis was performed among patients whose PSA level decreased after randomization compared to baseline.

Outcome measures

Outcome measures
Measure	Arm A (Observation and Bicalutamide) n=49 Participants Patients undergo observation on weeks 1-12. Patients then receive bicalutamide PO QD on weeks 13-44. Patients with a PSA decline of \>= 50% may continue on bicalutamide until week 72 in the absence of disease progression or unacceptable toxicity.	Arm B (Akt Inhibitor MK2206 and Bicalutamide) n=47 Participants Patients receive Akt inhibitor MK2206 PO once per week on weeks 1-44 and bicalutamide PO QD on weeks 13-44. Patients with a PSA decline of \>= 50% may continue on Akt inhibitor MK2206 and bicalutamide until week 72 in the absence of disease progression or unacceptable toxicity.
Time to PSA Nadir	7.7 months Interval 1.1 to 22.0	6.7 months Interval 0.3 to 19.3

SECONDARY outcome

Timeframe: Assessed every 3 months for 2 years, every 6 months for 3 years, and then annually up to 10 years

Population: Patients with PSA response (CR or PR)

Duration of PSA response was defined as the time from the date PSA criteria were met for complete response (CR) or partial response (PR), whichever status was recorded first, to the date of PSA progression. Patients without documented PSA progression were censored at the date of last disease assessment. Duration of PSA response is analyzed among responders (PSA CR or PR).

Outcome measures

Outcome measures
Measure	Arm A (Observation and Bicalutamide) n=44 Participants Patients undergo observation on weeks 1-12. Patients then receive bicalutamide PO QD on weeks 13-44. Patients with a PSA decline of \>= 50% may continue on bicalutamide until week 72 in the absence of disease progression or unacceptable toxicity.	Arm B (Akt Inhibitor MK2206 and Bicalutamide) n=36 Participants Patients receive Akt inhibitor MK2206 PO once per week on weeks 1-44 and bicalutamide PO QD on weeks 13-44. Patients with a PSA decline of \>= 50% may continue on Akt inhibitor MK2206 and bicalutamide until week 72 in the absence of disease progression or unacceptable toxicity.
Duration of PSA Response	20.6 months Interval 17.0 to 34.7	25.3 months Interval 17.6 to 37.5

SECONDARY outcome

Timeframe: Baseline (pre-randomization)

Population: All randomized patients

PSA slopes were assessed by multiple PSA values prior to randomization. Linear regression was used to calculate PSA slope using natural log-transformed PSA values on the time of PSA measurements for each patient.

Outcome measures

Outcome measures
Measure	Arm A (Observation and Bicalutamide) n=54 Participants Patients undergo observation on weeks 1-12. Patients then receive bicalutamide PO QD on weeks 13-44. Patients with a PSA decline of \>= 50% may continue on bicalutamide until week 72 in the absence of disease progression or unacceptable toxicity.	Arm B (Akt Inhibitor MK2206 and Bicalutamide) n=54 Participants Patients receive Akt inhibitor MK2206 PO once per week on weeks 1-44 and bicalutamide PO QD on weeks 13-44. Patients with a PSA decline of \>= 50% may continue on Akt inhibitor MK2206 and bicalutamide until week 72 in the absence of disease progression or unacceptable toxicity.
PSA Slope Prior to Randomization	0.20 ln(PSA)/month Standard Deviation 0.16	0.20 ln(PSA)/month Standard Deviation 0.13

SECONDARY outcome

Timeframe: After randomization and prior to starting bicalutamide

Population: Patients with follow-up PSA measurement before starting bicalutamide.

PSA slopes were assessed by multiple PSA values from randomization to starting bicalutamide treatment. Linear regression was used to calculate PSA slope using natural log-transformed PSA values on the time of PSA measurements for each patient.

Outcome measures

Outcome measures
Measure	Arm A (Observation and Bicalutamide) n=49 Participants Patients undergo observation on weeks 1-12. Patients then receive bicalutamide PO QD on weeks 13-44. Patients with a PSA decline of \>= 50% may continue on bicalutamide until week 72 in the absence of disease progression or unacceptable toxicity.	Arm B (Akt Inhibitor MK2206 and Bicalutamide) n=53 Participants Patients receive Akt inhibitor MK2206 PO once per week on weeks 1-44 and bicalutamide PO QD on weeks 13-44. Patients with a PSA decline of \>= 50% may continue on Akt inhibitor MK2206 and bicalutamide until week 72 in the absence of disease progression or unacceptable toxicity.
PSA Slope After Randomization and Before Starting Bicalutamide	0.10 ln(PSA)/month Standard Deviation 0.14	0.06 ln(PSA)/month Standard Deviation 0.23

SECONDARY outcome

Timeframe: Assessed every 3 months for 2 years, every 6 months for 3 years, and then annually up to 10 years

Population: Patients with follow-up PSA measurement after starting bicalutamide.

PSA slopes were assessed by multiple PSA values after starting bicalutamide treatment. Linear regression was used to calculate PSA slope using natural log-transformed PSA values on the time of PSA measurements for each patient.

Outcome measures

Outcome measures
Measure	Arm A (Observation and Bicalutamide) n=48 Participants Patients undergo observation on weeks 1-12. Patients then receive bicalutamide PO QD on weeks 13-44. Patients with a PSA decline of \>= 50% may continue on bicalutamide until week 72 in the absence of disease progression or unacceptable toxicity.	Arm B (Akt Inhibitor MK2206 and Bicalutamide) n=42 Participants Patients receive Akt inhibitor MK2206 PO once per week on weeks 1-44 and bicalutamide PO QD on weeks 13-44. Patients with a PSA decline of \>= 50% may continue on Akt inhibitor MK2206 and bicalutamide until week 72 in the absence of disease progression or unacceptable toxicity.
PSA Slope After Starting Bicalutamide Treatment	-0.57 ln(PSA)/month Standard Deviation 0.96	-0.60 ln(PSA)/month Standard Deviation 0.57

SECONDARY outcome

Timeframe: Assessed every 3 months for 2 years, every 6 months for 3 years, and then annually up to 10 years

Population: All randomized patients

The association between PSA response (responder vs non-responder) and Gleason score (\<7, 7 vs. \>7) was evaluated by logistic regression with adjustment for treatment assignment. Based on the biopsy sample, a Gleason grade is assigned to the most predominant pattern in the biopsy and a second Gleason grade is assigned to the second most predominant pattern. The two grades will then be added together to determine the Gleason score. Gleason scores range from 2-10. The higher the Gleason score, the more aggressive the cancer is likely to be.

Outcome measures

Outcome measures
Measure	Arm A (Observation and Bicalutamide) n=54 Participants Patients undergo observation on weeks 1-12. Patients then receive bicalutamide PO QD on weeks 13-44. Patients with a PSA decline of \>= 50% may continue on bicalutamide until week 72 in the absence of disease progression or unacceptable toxicity.	Arm B (Akt Inhibitor MK2206 and Bicalutamide) n=54 Participants Patients receive Akt inhibitor MK2206 PO once per week on weeks 1-44 and bicalutamide PO QD on weeks 13-44. Patients with a PSA decline of \>= 50% may continue on Akt inhibitor MK2206 and bicalutamide until week 72 in the absence of disease progression or unacceptable toxicity.
The Association Between Gleason Score and PSA Response Gleason score <7 · Responder	9 Participants	7 Participants
The Association Between Gleason Score and PSA Response Gleason score <7 · Non-responder	1 Participants	3 Participants
The Association Between Gleason Score and PSA Response Gleason score =7 · Responder	20 Participants	17 Participants
The Association Between Gleason Score and PSA Response Gleason score =7 · Non-responder	5 Participants	6 Participants
The Association Between Gleason Score and PSA Response Gleason score >7 · Responder	15 Participants	12 Participants
The Association Between Gleason Score and PSA Response Gleason score >7 · Non-responder	4 Participants	9 Participants

SECONDARY outcome

Timeframe: Assessed every 3 months for 2 years, every 6 months for 3 years, and then annually up to 10 years

Population: All randomized patients

The association between PSA response (responder vs non-responder) and prior hormonal therapy (yes vs. no) was evaluated by logistic regression with adjustment for treatment assignment.

Outcome measures

Outcome measures
Measure	Arm A (Observation and Bicalutamide) n=54 Participants Patients undergo observation on weeks 1-12. Patients then receive bicalutamide PO QD on weeks 13-44. Patients with a PSA decline of \>= 50% may continue on bicalutamide until week 72 in the absence of disease progression or unacceptable toxicity.	Arm B (Akt Inhibitor MK2206 and Bicalutamide) n=54 Participants Patients receive Akt inhibitor MK2206 PO once per week on weeks 1-44 and bicalutamide PO QD on weeks 13-44. Patients with a PSA decline of \>= 50% may continue on Akt inhibitor MK2206 and bicalutamide until week 72 in the absence of disease progression or unacceptable toxicity.
The Association Between Prior Hormonal Therapy and PSA Response No prior hormonal therapy · Responder	28 Participants	19 Participants
The Association Between Prior Hormonal Therapy and PSA Response No prior hormonal therapy · Non-responder	3 Participants	10 Participants
The Association Between Prior Hormonal Therapy and PSA Response Received prior hormonal therapy · Responder	16 Participants	17 Participants
The Association Between Prior Hormonal Therapy and PSA Response Received prior hormonal therapy · Non-responder	7 Participants	8 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline

Biospecimen banking for future analysis; no data to be reported

Outcome measures

Outcome data not reported

Adverse Events

Arm A (Observation + Bicalutamide)

Serious events: 1 serious events

Other events: 39 other events

Deaths: 9 deaths

Arm B (MK-2206 + Bicalutamide)

Serious events: 33 serious events

Other events: 52 other events

Deaths: 9 deaths

Serious adverse events

Other adverse events

Additional Information

Study Statistician

ECOG-ACRIN Statistical Office

Phone: 617-632-3012

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60

Measure	Arm A (Observation + Bicalutamide) n=50 participants at risk Patients undergo observation on weeks 1-12. Patients then receive bicalutamide PO QD on weeks 13-44. Patients with a PSA decline of \>= 50% may continue on bicalutamide until week 72 in the absence of disease progression or unacceptable toxicity.	Arm B (MK-2206 + Bicalutamide) n=53 participants at risk Patients receive Akt inhibitor MK2206 PO once per week on weeks 1-44 and bicalutamide PO QD on weeks 13-44. Patients with a PSA decline of \>= 50% may continue on Akt inhibitor MK2206 and bicalutamide until week 72 in the absence of disease progression or unacceptable toxicity.
Blood and lymphatic system disorders Anemia	0.00% 0/50 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment (up to about 76 weeks) All-cause mortality was monitored in all randomized patients and all other adverse events were assessed in participants who received treatment.	1.9% 1/53 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment (up to about 76 weeks) All-cause mortality was monitored in all randomized patients and all other adverse events were assessed in participants who received treatment.
Blood and lymphatic system disorders Blood and lymphatic disorders - Other	0.00% 0/50 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment (up to about 76 weeks) All-cause mortality was monitored in all randomized patients and all other adverse events were assessed in participants who received treatment.	1.9% 1/53 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment (up to about 76 weeks) All-cause mortality was monitored in all randomized patients and all other adverse events were assessed in participants who received treatment.
General disorders Fatigue	0.00% 0/50 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment (up to about 76 weeks) All-cause mortality was monitored in all randomized patients and all other adverse events were assessed in participants who received treatment.	5.7% 3/53 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment (up to about 76 weeks) All-cause mortality was monitored in all randomized patients and all other adverse events were assessed in participants who received treatment.
Skin and subcutaneous tissue disorders Pruritus	0.00% 0/50 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment (up to about 76 weeks) All-cause mortality was monitored in all randomized patients and all other adverse events were assessed in participants who received treatment.	1.9% 1/53 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment (up to about 76 weeks) All-cause mortality was monitored in all randomized patients and all other adverse events were assessed in participants who received treatment.
Skin and subcutaneous tissue disorders Rash maculo-papular	0.00% 0/50 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment (up to about 76 weeks) All-cause mortality was monitored in all randomized patients and all other adverse events were assessed in participants who received treatment.	37.7% 20/53 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment (up to about 76 weeks) All-cause mortality was monitored in all randomized patients and all other adverse events were assessed in participants who received treatment.
Gastrointestinal disorders Hemorrhoids	0.00% 0/50 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment (up to about 76 weeks) All-cause mortality was monitored in all randomized patients and all other adverse events were assessed in participants who received treatment.	1.9% 1/53 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment (up to about 76 weeks) All-cause mortality was monitored in all randomized patients and all other adverse events were assessed in participants who received treatment.
Gastrointestinal disorders Mucositis oral	0.00% 0/50 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment (up to about 76 weeks) All-cause mortality was monitored in all randomized patients and all other adverse events were assessed in participants who received treatment.	3.8% 2/53 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment (up to about 76 weeks) All-cause mortality was monitored in all randomized patients and all other adverse events were assessed in participants who received treatment.
Investigations Alanine aminotransferase increased	2.0% 1/50 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment (up to about 76 weeks) All-cause mortality was monitored in all randomized patients and all other adverse events were assessed in participants who received treatment.	0.00% 0/53 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment (up to about 76 weeks) All-cause mortality was monitored in all randomized patients and all other adverse events were assessed in participants who received treatment.
Investigations Aspartate aminotransferase increased	2.0% 1/50 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment (up to about 76 weeks) All-cause mortality was monitored in all randomized patients and all other adverse events were assessed in participants who received treatment.	0.00% 0/53 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment (up to about 76 weeks) All-cause mortality was monitored in all randomized patients and all other adverse events were assessed in participants who received treatment.
Investigations Lymphocyte count decreased	0.00% 0/50 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment (up to about 76 weeks) All-cause mortality was monitored in all randomized patients and all other adverse events were assessed in participants who received treatment.	9.4% 5/53 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment (up to about 76 weeks) All-cause mortality was monitored in all randomized patients and all other adverse events were assessed in participants who received treatment.
Investigations Neutrophil count decreased	0.00% 0/50 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment (up to about 76 weeks) All-cause mortality was monitored in all randomized patients and all other adverse events were assessed in participants who received treatment.	1.9% 1/53 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment (up to about 76 weeks) All-cause mortality was monitored in all randomized patients and all other adverse events were assessed in participants who received treatment.
Investigations White blood cell decreased	0.00% 0/50 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment (up to about 76 weeks) All-cause mortality was monitored in all randomized patients and all other adverse events were assessed in participants who received treatment.	1.9% 1/53 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment (up to about 76 weeks) All-cause mortality was monitored in all randomized patients and all other adverse events were assessed in participants who received treatment.
Metabolism and nutrition disorders Hyperglycemia	0.00% 0/50 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment (up to about 76 weeks) All-cause mortality was monitored in all randomized patients and all other adverse events were assessed in participants who received treatment.	11.3% 6/53 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment (up to about 76 weeks) All-cause mortality was monitored in all randomized patients and all other adverse events were assessed in participants who received treatment.
Metabolism and nutrition disorders Hyponatremia	0.00% 0/50 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment (up to about 76 weeks) All-cause mortality was monitored in all randomized patients and all other adverse events were assessed in participants who received treatment.	3.8% 2/53 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment (up to about 76 weeks) All-cause mortality was monitored in all randomized patients and all other adverse events were assessed in participants who received treatment.
Metabolism and nutrition disorders Hypophosphatemia	0.00% 0/50 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment (up to about 76 weeks) All-cause mortality was monitored in all randomized patients and all other adverse events were assessed in participants who received treatment.	3.8% 2/53 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment (up to about 76 weeks) All-cause mortality was monitored in all randomized patients and all other adverse events were assessed in participants who received treatment.
Musculoskeletal and connective tissue disorders Pain in extremity	0.00% 0/50 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment (up to about 76 weeks) All-cause mortality was monitored in all randomized patients and all other adverse events were assessed in participants who received treatment.	1.9% 1/53 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment (up to about 76 weeks) All-cause mortality was monitored in all randomized patients and all other adverse events were assessed in participants who received treatment.
Nervous system disorders Peripheral sensory neuropathy	0.00% 0/50 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment (up to about 76 weeks) All-cause mortality was monitored in all randomized patients and all other adverse events were assessed in participants who received treatment.	1.9% 1/53 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment (up to about 76 weeks) All-cause mortality was monitored in all randomized patients and all other adverse events were assessed in participants who received treatment.
Vascular disorders Hypertension	0.00% 0/50 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment (up to about 76 weeks) All-cause mortality was monitored in all randomized patients and all other adverse events were assessed in participants who received treatment.	5.7% 3/53 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment (up to about 76 weeks) All-cause mortality was monitored in all randomized patients and all other adverse events were assessed in participants who received treatment.
Vascular disorders Thromboembolic event	0.00% 0/50 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment (up to about 76 weeks) All-cause mortality was monitored in all randomized patients and all other adverse events were assessed in participants who received treatment.	1.9% 1/53 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment (up to about 76 weeks) All-cause mortality was monitored in all randomized patients and all other adverse events were assessed in participants who received treatment.