Trial Outcomes & Findings for Selumetinib and Akt Inhibitor MK2206 or mFOLFOX Therapy Comprising Oxaliplatin and Fluorouracil in Treating Patients With Metastatic Pancreatic Cancer Previously Treated With Chemotherapy (NCT NCT01658943)

Last Updated: 2016-03-09

Results Overview

From date of registration to date of death due to any cause. Patients last known to be alive are censored at date of last contact.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

137 participants

Primary outcome timeframe

Up to 3 years

Results posted on

2016-03-09

Participant Flow

Participant milestones

Participant milestones
Measure	mFOLFOX Patients receive 85 mg/m\^2 oxaliplatin IV over 2 hours on days 1 and 15 and 2,400 mg/m\^2 fluorouracil IV over 46-48 hours on days 1-2 and 15-16. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.	MK2206 and Selumetinib Patients receive 135 mg MK2206 PO on days 1, 8, 15, and 22, and 100 mg selumetinib PO daily on days 1-28. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.
Overall Study STARTED	70	67
Overall Study Eligible	63	58
Overall Study Eligible and Began Protocol Therapy	62	58
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	70	67

Reasons for withdrawal

Reasons for withdrawal
Measure	mFOLFOX Patients receive 85 mg/m\^2 oxaliplatin IV over 2 hours on days 1 and 15 and 2,400 mg/m\^2 fluorouracil IV over 46-48 hours on days 1-2 and 15-16. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.	MK2206 and Selumetinib Patients receive 135 mg MK2206 PO on days 1, 8, 15, and 22, and 100 mg selumetinib PO daily on days 1-28. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.
Overall Study Adverse Event	6	13
Overall Study Withdrawal by Subject	9	2
Overall Study Progression/Relapse	39	40
Overall Study Death	4	2
Overall Study not protocol specified	4	1
Overall Study Not eligible	7	9
Overall Study Withdrew prior to beginning protocol Tx	1	0

Baseline Characteristics

Selumetinib and Akt Inhibitor MK2206 or mFOLFOX Therapy Comprising Oxaliplatin and Fluorouracil in Treating Patients With Metastatic Pancreatic Cancer Previously Treated With Chemotherapy

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	mFOLFOX n=62 Participants Patients receive 85 mg/m\^2 oxaliplatin IV over 2 hours on days 1 and 15 and 2,400 mg/m\^2 fluorouracil IV over 46-48 hours on days 1-2 and 15-16. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.	MK2206 and Selumetinib n=58 Participants Patients receive 135 mg MK2206 PO on days 1, 8, 15, and 22, and 100 mg selumetinib PO daily on days 1-28. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.	Total n=120 Participants Total of all reporting groups
Age, Continuous	65.6 years n=5 Participants	69.4 years n=7 Participants	67.3 years n=5 Participants
Sex: Female, Male Female	40 Participants n=5 Participants	23 Participants n=7 Participants	63 Participants n=5 Participants
Sex: Female, Male Male	22 Participants n=5 Participants	35 Participants n=7 Participants	57 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	3 Participants n=5 Participants	1 Participants n=7 Participants	4 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	59 Participants n=5 Participants	57 Participants n=7 Participants	116 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	4 Participants n=5 Participants	4 Participants n=7 Participants	8 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) Black or African American	7 Participants n=5 Participants	4 Participants n=7 Participants	11 Participants n=5 Participants
Race (NIH/OMB) White	50 Participants n=5 Participants	49 Participants n=7 Participants	99 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Prior Systemic Therapy 4 months or less	23 participants n=5 Participants	22 participants n=7 Participants	45 participants n=5 Participants
Prior Systemic Therapy more than 4 months	39 participants n=5 Participants	36 participants n=7 Participants	75 participants n=5 Participants
Liver Metastasis Yes	39 participants n=5 Participants	43 participants n=7 Participants	82 participants n=5 Participants
Liver Metastasis No	23 participants n=5 Participants	15 participants n=7 Participants	38 participants n=5 Participants

PRIMARY outcome

Timeframe: Up to 3 years

Population: Eligible and analyzable patients.

From date of registration to date of death due to any cause. Patients last known to be alive are censored at date of last contact.

Outcome measures

Outcome measures
Measure	mFOLFOX n=62 Participants Patients receive 85 mg/m\^2 oxaliplatin IV over 2 hours on days 1 and 15 and 2,400 mg/m\^2 fluorouracil IV over 46-48 hours on days 1-2 and 15-16. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.	MK2206 and Selumetinib n=58 Participants Patients receive 135 mg MK2206 PO on days 1, 8, 15, and 22, and 100 mg selumetinib PO daily on days 1-28. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.
Overall Survival	6.7 months Interval 6.0 to 8.3	3.9 months Interval 3.5 to 4.6

SECONDARY outcome

Timeframe: Up to 3 years

Population: Eligible patients who received any treatment and were assessed for adverse events are included in this summary.

Only adverse events that are possibly, probably or definitely related to study drug are reported.

Outcome measures

Outcome measures
Measure	mFOLFOX n=62 Participants Patients receive 85 mg/m\^2 oxaliplatin IV over 2 hours on days 1 and 15 and 2,400 mg/m\^2 fluorouracil IV over 46-48 hours on days 1-2 and 15-16. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.	MK2206 and Selumetinib n=57 Participants Patients receive 135 mg MK2206 PO on days 1, 8, 15, and 22, and 100 mg selumetinib PO daily on days 1-28. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.
Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug Abdominal pain	1 Participants	0 Participants
Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug Alanine aminotransferase increased	0 Participants	4 Participants
Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug Alkaline phosphatase increased	0 Participants	2 Participants
Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug Anemia	2 Participants	3 Participants
Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug Anorexia	1 Participants	1 Participants
Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug Aspartate aminotransferase increased	0 Participants	3 Participants
Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug Blood bilirubin increased	1 Participants	0 Participants
Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug Cognitive disturbance	0 Participants	1 Participants
Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug Dehydration	1 Participants	6 Participants
Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug Device related infection	1 Participants	0 Participants
Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug Diarrhea	4 Participants	4 Participants
Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug Edema face	0 Participants	1 Participants
Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug Encephalopathy	0 Participants	1 Participants
Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug Erythema multiforme	0 Participants	1 Participants
Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug Erythroderma	0 Participants	1 Participants
Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug Fatigue	8 Participants	7 Participants
Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug Generalized muscle weakness	0 Participants	1 Participants
Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug Hepatic failure	0 Participants	1 Participants
Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug Hyperglycemia	1 Participants	7 Participants
Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug Hypertension	2 Participants	5 Participants
Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug Hypokalemia	1 Participants	1 Participants
Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug Hypomagnesemia	1 Participants	0 Participants
Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug Hyponatremia	1 Participants	4 Participants
Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug Hypophosphatemia	0 Participants	1 Participants
Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug Hypotension	1 Participants	1 Participants
Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug Hypoxia	0 Participants	1 Participants
Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug Left ventricular systolic dysfunction	0 Participants	1 Participants
Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug Lung infection	1 Participants	1 Participants
Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug Lymphocyte count decreased	8 Participants	0 Participants
Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug Mucositis oral	1 Participants	4 Participants
Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug Multi-organ failure	0 Participants	1 Participants
Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug Nausea	3 Participants	0 Participants
Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug Neoplasms benign, malignant and unspecified	0 Participants	2 Participants
Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug Neutrophil count decreased	4 Participants	0 Participants
Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug Platelet count decreased	1 Participants	0 Participants
Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug Rash acneiform	0 Participants	5 Participants
Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug Rash maculo-papular	0 Participants	7 Participants
Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug Skin infection	0 Participants	1 Participants
Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug Soft tissue infection	0 Participants	1 Participants
Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug Stevens-Johnson syndrome	0 Participants	1 Participants
Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug Syncope	0 Participants	1 Participants
Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug Vomiting	3 Participants	1 Participants
Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug Weight loss	1 Participants	0 Participants
Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug White blood cell decreased	2 Participants	0 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to 3 years

Population: Eligible and analyzable patients.

From date of registration to date of first documentation of progression or symptomatic deterioration, or death due to any cause. Patients last known to be alive and progression free are censored at date of last contact.

Outcome measures

Outcome measures
Measure	mFOLFOX n=62 Participants Patients receive 85 mg/m\^2 oxaliplatin IV over 2 hours on days 1 and 15 and 2,400 mg/m\^2 fluorouracil IV over 46-48 hours on days 1-2 and 15-16. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.	MK2206 and Selumetinib n=58 Participants Patients receive 135 mg MK2206 PO on days 1, 8, 15, and 22, and 100 mg selumetinib PO daily on days 1-28. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.
Progression-free Survival	2.0 months Interval 1.8 to 2.9	1.9 months Interval 1.8 to 2.1

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to 3 years

Population: All eligible and analyzable patients with measurable disease.

Confirmed response (CR) is two or more objective statuses of CR a minimum of four weeks apart documented before progression or symptomatic deterioration. Partial response (PR) is two or more objective statuses of PR or better a minimum of four weeks apart documented before progression or symptomatic deterioration. Unconfirmed CR is one objective status of CR documented before progression or symptomatic deterioration but not qualifying as CR or PR. Unconfirmed PR is one objective status of PR documented before progression or symptomatic deterioration but not qualifying as CR, PR or unconfirmed CR.

Outcome measures

Outcome measures
Measure	mFOLFOX n=57 Participants Patients receive 85 mg/m\^2 oxaliplatin IV over 2 hours on days 1 and 15 and 2,400 mg/m\^2 fluorouracil IV over 46-48 hours on days 1-2 and 15-16. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.	MK2206 and Selumetinib n=55 Participants Patients receive 135 mg MK2206 PO on days 1, 8, 15, and 22, and 100 mg selumetinib PO daily on days 1-28. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.
Objective Response Rate Partial Response	4 participants	0 participants
Objective Response Rate Unconfirmed Partial Response	1 participants	1 participants
Objective Response Rate Stable/No response	14 participants	12 participants
Objective Response Rate Increasing disease	29 participants	34 participants
Objective Response Rate Symptomatic Deterioration	3 participants	2 participants
Objective Response Rate Assessment Inadequate	6 participants	6 participants

Adverse Events

mFOLFOX

Serious events: 2 serious events

Other events: 56 other events

Deaths: 0 deaths

MK2206 and Selumetinib

Serious events: 37 serious events

Other events: 53 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

SWOG Statistician

SWOG Statistical Center

Phone: 206-667-4408

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60

Measure	mFOLFOX n=62 participants at risk Patients receive 85 mg/m\^2 oxaliplatin IV over 2 hours on days 1 and 15 and 2,400 mg/m\^2 fluorouracil IV over 46-48 hours on days 1-2 and 15-16. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.	MK2206 and Selumetinib n=57 participants at risk Patients receive 135 mg MK2206 PO on days 1, 8, 15, and 22, and 100 mg selumetinib PO daily on days 1-28. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.
Blood and lymphatic system disorders Anemia	0.00% 0/62 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	3.5% 2/57 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.
Cardiac disorders Left ventricular systolic dysfunction	0.00% 0/62 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	1.8% 1/57 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.
Cardiac disorders Myocardial infarction	0.00% 0/62 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	1.8% 1/57 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.
Gastrointestinal disorders Abdominal distension	0.00% 0/62 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	1.8% 1/57 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.
Gastrointestinal disorders Abdominal pain	0.00% 0/62 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	1.8% 1/57 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.
Gastrointestinal disorders Colonic perforation	1.6% 1/62 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	0.00% 0/57 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.
Gastrointestinal disorders Constipation	0.00% 0/62 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	3.5% 2/57 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.
Gastrointestinal disorders Diarrhea	0.00% 0/62 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	5.3% 3/57 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.
Gastrointestinal disorders Duodenal perforation	0.00% 0/62 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	1.8% 1/57 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.
Gastrointestinal disorders Dysphagia	0.00% 0/62 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	1.8% 1/57 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.
Gastrointestinal disorders Gastric perforation	0.00% 0/62 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	1.8% 1/57 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.
Gastrointestinal disorders Mucositis oral	0.00% 0/62 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	3.5% 2/57 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.
Gastrointestinal disorders Nausea	0.00% 0/62 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	1.8% 1/57 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.
Gastrointestinal disorders Vomiting	0.00% 0/62 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	3.5% 2/57 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.
General disorders Fatigue	0.00% 0/62 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	3.5% 2/57 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.
General disorders Fever	0.00% 0/62 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	3.5% 2/57 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.
General disorders General disorders and admin site conditions - Other	0.00% 0/62 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	1.8% 1/57 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.
General disorders Multi-organ failure	0.00% 0/62 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	1.8% 1/57 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.
Hepatobiliary disorders Hepatic failure	0.00% 0/62 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	1.8% 1/57 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.
Infections and infestations Infections and infestations-Other	0.00% 0/62 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	3.5% 2/57 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.
Infections and infestations Lung infection	1.6% 1/62 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	1.8% 1/57 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.
Infections and infestations Sepsis	1.6% 1/62 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	3.5% 2/57 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.
Infections and infestations Skin infection	0.00% 0/62 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	1.8% 1/57 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.
Infections and infestations Soft tissue infection	0.00% 0/62 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	1.8% 1/57 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.
Injury, poisoning and procedural complications Intraoperative gastrointestinal injury	0.00% 0/62 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	1.8% 1/57 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.
Injury, poisoning and procedural complications Spinal fracture	0.00% 0/62 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	1.8% 1/57 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.
Investigations Alanine aminotransferase increased	0.00% 0/62 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	1.8% 1/57 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.
Investigations Alkaline phosphatase increased	0.00% 0/62 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	3.5% 2/57 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.
Investigations Aspartate aminotransferase increased	0.00% 0/62 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	1.8% 1/57 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.
Investigations Blood bilirubin increased	0.00% 0/62 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	3.5% 2/57 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.
Investigations Investigations-Other	0.00% 0/62 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	1.8% 1/57 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.
Metabolism and nutrition disorders Anorexia	0.00% 0/62 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	3.5% 2/57 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.
Metabolism and nutrition disorders Dehydration	0.00% 0/62 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	12.3% 7/57 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.
Metabolism and nutrition disorders Hyperglycemia	0.00% 0/62 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	8.8% 5/57 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.
Metabolism and nutrition disorders Hyponatremia	0.00% 0/62 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	3.5% 2/57 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.
Metabolism and nutrition disorders Hypophosphatemia	0.00% 0/62 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	1.8% 1/57 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/62 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	1.8% 1/57 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.
Musculoskeletal and connective tissue disorders Generalized muscle weakness	0.00% 0/62 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	5.3% 3/57 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasms benign, malignant and unspecified - Other	0.00% 0/62 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	17.5% 10/57 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.
Nervous system disorders Cognitive disturbance	0.00% 0/62 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	1.8% 1/57 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.
Nervous system disorders Depressed level of consciousness	0.00% 0/62 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	1.8% 1/57 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.
Nervous system disorders Encephalopathy	0.00% 0/62 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	1.8% 1/57 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.
Nervous system disorders Stroke	0.00% 0/62 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	1.8% 1/57 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.
Nervous system disorders Syncope	0.00% 0/62 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	3.5% 2/57 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.
Respiratory, thoracic and mediastinal disorders Epistaxis	0.00% 0/62 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	1.8% 1/57 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.
Respiratory, thoracic and mediastinal disorders Hypoxia	0.00% 0/62 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	1.8% 1/57 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.
Skin and subcutaneous tissue disorders Erythema multiforme	0.00% 0/62 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	1.8% 1/57 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.
Skin and subcutaneous tissue disorders Erythroderma	0.00% 0/62 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	1.8% 1/57 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.
Skin and subcutaneous tissue disorders Rash acneiform	0.00% 0/62 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	3.5% 2/57 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.
Skin and subcutaneous tissue disorders Rash maculo-papular	0.00% 0/62 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	7.0% 4/57 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.
Skin and subcutaneous tissue disorders Stevens-Johnson syndrome	0.00% 0/62 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	1.8% 1/57 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.
Vascular disorders Hypertension	0.00% 0/62 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	7.0% 4/57 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.
Vascular disorders Hypotension	0.00% 0/62 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	3.5% 2/57 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.
Vascular disorders Thromboembolic event	0.00% 0/62 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	5.3% 3/57 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.
Vascular disorders Visceral arterial ischemia	1.6% 1/62 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.	0.00% 0/57 • Up to 3 years Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.