Pomalidomide and Dexamethasone With or Without Ixazomib i... | NCT02004275

ID	Type	Description	Link
NCI-2013-01702	Registry Identifier	Clinical Trial Reporting Program
U10CA031946	U.S. NIH Grant/Contract		View source

Name	Class
National Cancer Institute (NCI)	NIH
Celgene Corporation	INDUSTRY
Millennium Pharmaceuticals, Inc.	INDUSTRY

Description Module

Detailed Description

PRIMARY OBJECTIVES:

I. To establish the maximum tolerated dose (MTD) for combination therapy pomalidomide/dexamethasone/ixazomib. (Phase I) II. To assess whether the combination of pomalidomide/dexamethasone/ixazomib improves progression-free survival (PFS) relative to pomalidomide/dexamethasone. (Phase II)

SECONDARY OBJECTIVES:

I. To determine dose-limiting toxicities (DLTs). (Phase I) II. To analyze type and grade of all serious adverse events (SAEs). (Phase I) III. To analyze type and grade of all adverse events (AEs). (Phase I) IV. To analyze the reason for and incidence of dose modifications/omissions/delays. (Phase I) V. To assess preliminary evidence of clinical efficacy. (Phase I) VI. To assess whether the overall response rate (ORR), partial response (PR), very good partial response (VGPR), complete response (CR) or stringent CR (sCR) rate differ with respect to treatment regimen. (Phase II) VII. To assess the clinical benefit rate (CBR: minimal response [MR] + ORR) for pomalidomide/dexamethasone/ixazomib compared to pomalidomide/dexamethasone. (Phase II) VIII. To assess the disease control rate (DCR: stable disease [SD] + CBR) for pomalidomide/dexamethasone/ixazomib compared to pomalidomide/dexamethasone. (Phase II) IX. For those patients achieving a PR or better, we will assess whether the combination of pomalidomide/dexamethasone/ixazomib increases the duration of response (DOR) compared to pomalidomide/dexamethasone. (Phase II) X. To assess whether the combination of pomalidomide/dexamethasone/ixazomib improves overall survival (OS) compared to those taking pomalidomide/dexamethasone alone. (Phase II) XI. To assess time to next treatment (TNT) for patients taking pomalidomide/dexamethasone/ixazomib compared to those on pomalidomide/dexamethasone. (Phase II) XII. To evaluate the safety of pomalidomide/dexamethasone/ixazomib compared with pomalidomide/dexamethasone. (Phase II) XIII. For patients on the pomalidomide/dexamethasone arm who opt to cross-over to the pomalidomide/dexamethasone/ixazomib arm, assessment of response rate (ORR, CBR, DCR), DOR, TNT, PFS and OS will be evaluated from date of cross-over. (Phase II) XIV. To determine if baseline level of perceived fatigue and overall quality of life (QOL) is associated with OS. (Phase II)

OUTLINE: This is a phase I, dose-escalation study of pomalidomide and ixazomib followed by a phase II study.

After completion of study treatment, patients are followed up every 4 weeks until disease progression and then every 3 months for 3 years.

Label	Type	Description	Intervention Names
Arm I (pomalidomide, dexamethasone)	Experimental	Patients receive pomalidomide PO QD on days 1-21 and dexamethasone PO QD on days 1, 8, 15, and 22. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients achieving disease progression may cross over to Arm II.	Drug: pomalidomide Drug: dexamethasone
Arm II (pomalidomide, dexamethasone, ixazomib)	Experimental	Patients receive pomalidomide, dexamethasone, and ixazomib as in Phase I. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Drug: pomalidomide Drug: ixazomib Drug: dexamethasone

Name	Type	Description	Arm Group Labels	Other Names
pomalidomide	Drug	given PO	Arm I (pomalidomide, dexamethasone) Arm II (pomalidomide, dexamethasone, ixazomib)

Measure	Description	Time Frame
Maximum Tolerated Dose (MTD) of Pomalidomide and Ixazomib, Determined According to Incidence of Dose Limiting Toxicity (DLT) Graded Using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 (Phase I)	For this protocol, dose-limiting toxicity (DLT) will be defined by the following adverse events at least possibly related to study therapy: Grade 3 or higher non-hematologic toxicity, with the following exceptions: Alopecia is not expected but would not be considered a DLT. Nausea, vomiting and diarrhea will only be considered a DLT if it cannot be adequately managed with optimal supportive care. Grade 3 or 4 hyperglycemia due to dexamethasone will only be considered a DLT if it cannot be controlled with appropriate therapy Grade 4 hematologic toxicity, with the following exceptions: Grade 4 lymphopenia is expected with this regimen and will not be construed as a DLT. Grade 4 neutropenia will only be considered a DLT if it lasts longer than 7 days despite appropriate supportive care. Grade 4 thrombocytopenia will only be considered a DLT if it lasts longer than 7 days or is associated with greater then or equal to grade 3 bleeding event	28 days
Progression Free Survival (PFS) (Phase II)	progression-free survival (PFS), defined as the time from randomization to the date the International Myeloma Working Group (IMWG) criteria for disease progression is met. If a patient initiates another anti-cancer treatment prior to disease progression, they will be censored at the date of initiation of this treatment. Patients will be randomized to treatment using the Pocock-Simon algorithm balancing the distribution of the following stratification factors between the two treatment arms: 1) ISS 1-2 disease vs. ISS 3 disease (current ISS stage based off screening beta 2 microglobulin and albumin) 2) High risk cytogenetics features: yes vs. no High risk cytogenetics features include: del(1p), gain of 1q, t(4;14), t(14;16), t(14; 20), del(17p) 3) Prior treatment with a proteasome inhibitor: yes vs. no	3 years

Measure	Description	Time Frame
Incidence and Type of Dose Limiting Toxicities (DLTs) Graded According to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 (Phase I)	These events are reported in the adverse events section of this report.	44.5 months
Incidence of Dose Reductions/Delays (Phase I)

Eligibility Module

Eligibility Criteria

Histologically confirmed diagnosis of symptomatic multiple myeloma; relapsed disease is myeloma that has previously responded to prior therapy (MR or better) and subsequently progressed
Patient must have measurable disease or non-measurable disease, defined as one or more of the following holding true:
- Measurable disease:
  - Serum M-protein >= 1.0 g/dL (>= 0.5 g/dL for IgA or IgM myeloma) and/or
  - Urine M-protein >= 200 mg/24 hours and/or
  - Involved serum free light chain level >= 10 mg/dL AND an abnormal serum free light chain ratio
- For non-measurable disease:
  - Baseline marrow burden of myeloma of at least 30%
Progression on lenalidomide as part of first line therapy (lenalidomide-refractory disease)

* Lenalidomide-refractory disease is defined as disease progression on or progression within 60 days of the last dose of a lenalidomide-based treatment; patients should have received at least 2 cycles of a lenalidomide-based regimen to be evaluable for refractoriness; examples: 1) progression on lenalidomide maintenance therapy after initial induction +/- consolidation; 2) initial response followed by progression on continuous lenalidomide-dexamethasone +/- elotuzumab or daratumumab
Pomalidomide naive disease
Proteasome inhibitor naive or sensitive disease; proteasome inhibitor sensitive disease is defined as a PR or better to prior proteasome inhibitor-based therapy that is maintained for >= 60 days from the last dose of the proteasome inhibitor

* A patient who receives induction therapy with lenalidomide, bortezomib and dexamethasone and achieves a PR or better but subsequently progresses on continued lenalidomide or lenalidomide-dexamethasone would be eligible provided the progression occurs 60 days or more after discontinuation of the bortezomib; similarly, ixazomib exposure is allowed provided they meet the definition of proteasome inhibitor sensitive disease
1 prior line of systemic therapy for multiple myeloma, where a line of therapy for myeloma is defined as 1 or more planned cycles of single agent or combination therapy, as well as a planned series of treatment regimens administered in a sequential manner (e.g. lenalidomide, bortezomib and dexamethasone induction therapy for 4 cycles followed by autologous stem cell transplantation and then lenalidomide maintenance therapy would be considered 1 line of prior therapy); a new line of therapy begins when a planned therapy is modified to include other treatment agents (alone or in combination) as a result of disease progression, disease relapse or treatment-related toxicity (e.g. a patient is progressing in the face of lenalidomide maintenance therapy and has bortezomib and dexamethasone added into their regimen); a new line of therapy also begins when a planned treatment-free interval is interrupted by the need to start treatment due to disease relapse/progression (e.g. a patient with relapsed myeloma achieves a partial response after a planned 8 cycles of cyclophosphamide, bortezomib and dexamethasone, enjoys an 8-month period off therapy but then experiences disease progression requiring re-initiation of therapy)
Allogeneic stem cell transplantation is allowed provided the patient is >= 1 year from transplant at time of registration, is not on immunosuppressive therapy to treat/prevent graft-versus-host disease, has no evidence of active graft versus host disease, and no evidence of active infection
No other chemotherapy or radiation therapy within 14 days prior to registration
No investigational therapy within 14 days prior to registration
No major surgery within 28 days prior to registration
No G-CSF (filgrastim) or GM-CSF (sargramostim) within 7 days of registration or pegfilgrastim within 14 days of registration to meet eligibility criteria
No platelet transfusions within 7 days of registration to meet eligibility criteria; Note: red blood cell transfusions are allowed at any time
A female of childbearing potential is a sexually mature female who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months)
- Women of childbearing potential:
  - Must have a negative serum or urine pregnancy test with a sensitivity of at least 25 mlU/ml no more than 14 days prior to registration and must agree to repeat this test within 24 hours of starting pomalidomide
  - Must either commit to complete abstinence from heterosexual contact or begin TWO acceptable methods of birth control, one highly effective method and one additional effective (barrier) method, AT THE SAME TIME, before starting pomalidomide
  - Must agree to ongoing pregnancy testing
  - Must agree to not become pregnant or breast feed a child during treatment on this protocol
- Men must practice complete abstinence or agree to use a condom during sexual contact with a female of childbearing potential, even if they have had a successful vasectomy
- Note: All participants must be counseled at a minimum of every 28 days about pregnancy precautions and risks of fetal exposure
Eastern Cooperative Oncology Group (ECOG) performance status 0-2
Absolute neutrophil count (ANC) >= 1.0 x 10^9/L
Platelet count >= 50 x 10^9/L
Calculated (Calc.) creatinine clearance >= 30 mL/min; calculated utilizing the Cockcroft-Gault formula or 24-hour urine collection
Total bilirubin < 1.5 x upper limits of normal (ULN)
Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 2.5 x upper limits of normal (ULN)
Note: G-CSF and platelet transfusions cannot be used to increase counts to meet eligibility criteria
Patients cannot have:
- Central nerve system involvement
- Primary refractory multiple myeloma, where primary refractory multiple myeloma is defined as disease that is nonresponsive - patients who have never achieved a minimal response (MR) or better - with any therapy over the course of their disease; it includes patients who never achieve MR or better in whom there is no significant change in M-protein and no evidence of clinical progression as well as patients who meet criteria for true progressive disease (PD)
- Primary or secondary plasma cell leukemia
- Light-chain (AL) amyloidosis or polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome
- Known active hepatitis C based on:
  - +hepatitis C virus (HCV) antibody (confirmed)
  - +HCV RNA
  - Liver disease with history of positive serology
  - Note: patients with a prior history of hepatitis C that has been successfully eradicated with antiviral therapy are eligible
- Known hepatitis B surface antigen positivity
- Previous hypersensitivity to any of the components of the study treatment
- Prior history of erythema multiforme with thalidomide or lenalidomide treatment
=< grade 2 peripheral neuropathy
Adequate cardiac function, defined as:
- No electrocardiogram (EKG) evidence of acute ischemia
- No EKG evidence of active, clinically significant conduction system abnormalities
- No EKG evidence of > grade 2 (> 480 ms) corrected QT (QTc) prolongation
- Prior to study entry, any EKG abnormality at screening not felt to put the patient at risk has to be documented by the investigator as not medically significant
- No uncontrolled angina or severe ventricular arrhythmias
- No clinically significant pericardial disease
- No history of myocardial infarction within 6 months prior to registration
- No class 3 or higher New York Heart Association congestive heart failure
No strong inducers of cytochrome P450 (CYP) 3A4 or CYP1A2 or strong inhibitors of CYP3A4 or CYP1A2 within 14 days prior to registration
- Note: Ixazomib is a substrate of CYP3A4 and CYP1A2
Patients with human immunodeficiency virus (HIV) infection are eligible, provided they meet the following:
- No history of acquired immunodeficiency syndrome (AIDS)-defining conditions or other HIV related illness
- Cluster of differentiation (CD)4+ cells nadirs > 350/mm^3 within 28 days prior to registration
- Treatment sensitive HIV and, if on anti-HIV therapy, HIV viral load < 50 copies/mm^3 within 28 days prior to registration
- Note: HIV+ patients who enroll on this study and are assigned to treatment with ixazomib may need to modify their anti-retroviral therapy prior to receiving protocol therapy if they are on strong inducers or potent inhibitors of cytochrome P450 3A4
RE-REGISTRATION ELIGIBILITY CRITERIA (STEP 2): Patients randomized to Arm 1 may opt to switch to the 3-drug regimen following disease progression; these patients must be re-registered to the study and meet the eligibility criteria below
RE-REGISTRATION ELIGIBILITY CRITERIA (STEP 2): Patient must have measurable disease or non-measurable disease after progression on pomalidomide + dexamethasone, defined as one or more of the following holding true:

* Measurable disease:
- Serum M-protein >= 0.5 g/dL and/or
- Urine M-protein >= 200 mg/24 hours and/or
- Involved serum free light chain level >= 10 mg/dL AND an abnormal serum free light chain ratio
  
  * For non-measurable disease:
- Marrow burden of myeloma of at least 30%
RE-REGISTRATION ELIGIBILITY CRITERIA (STEP 2):
- Women of childbearing potential:
  
  ** Must have a negative serum or urine pregnancy test within 72 hours prior to re-registration
  
  ** Must either commit to complete abstinence from heterosexual contact or begin TWO acceptable methods of birth control, one highly effective method and one additional effective (barrier) method, AT THE SAME TIME, before starting pomalidomide
  
  ** Must agree to ongoing pregnancy testing
  
  ** Must agree to not become pregnant or breast feed a child during treatment on this protocol
- Men must practice complete abstinence or agree to use a condom during sexual contact with a female of childbearing potential, even if they have had a successful vasectomy
- Note: All participants must be counseled at a minimum of every 28 days about pregnancy precautions and risks of fetal exposure
RE-REGISTRATION ELIGIBILITY CRITERIA (STEP 2): ECOG performance status 0-2
RE-REGISTRATION ELIGIBILITY CRITERIA (STEP 2): Absolute neutrophil count (ANC) >= 1.0 x 10^9/L
RE-REGISTRATION ELIGIBILITY CRITERIA (STEP 2): Platelet count >= 50 x 10^9/L
RE-REGISTRATION ELIGIBILITY CRITERIA (STEP 2): Calc. creatinine clearance >= 30 mL/min

* Calculated utilizing the Cockcroft-Gault formula or 24-hour urine collection
RE-REGISTRATION ELIGIBILITY CRITERIA (STEP 2): Total bilirubin < 1.5 x upper limits of normal (ULN)
RE-REGISTRATION ELIGIBILITY CRITERIA (STEP 2): AST and ALT < 2.5 x upper limits of normal (ULN)
RE-REGISTRATION ELIGIBILITY CRITERIA (STEP 2): Note: G-CSF and platelet transfusions cannot be used to increase counts to meet eligibility criteria
RE-REGISTRATION ELIGIBILITY CRITERIA (STEP 2): =< grade 2 peripheral neuropathy
RE-REGISTRATION ELIGIBILITY CRITERIA (STEP 2): No strong inducers of cytochrome P450 (CYP) 3A4 or CYP1A2 or strong inhibitors of CYP3A4 or CYP1A2 * Note: Ixazomib is a substrate of CYP3A4 and CYP1A2

Name	Affiliation	Role
Peter Voorhees, MD	University of North Carolina, Chapel Hill	Study Chair

Facility	Status	City	State	ZIP	Country	Contacts
Anchorage Associates in Radiation Medicine		Anchorage	Alaska	98508	United States
Anchorage Radiation Therapy Center

PubMed Identifier	Type	Citation	Retractions
39058954	Derived	Voorhees P, Suman V, Efebera Y, Raje N, Tuchman S, Rodriguez C, Laubach J, Bova-Solem M, Carlisle D, Usmani S, McCarthy P, Richardson PG. Alliance A061202: ixazomib, pomalidomide, and dexamethasone for patients with lenalidomide-refractory MM in first relapse. Blood Adv. 2024 Oct 8;8(19):5039-5050. doi: 10.1182/bloodadvances.2024013623.
34559902	Derived	Voorhees PM, Suman VJ, Tuchman SA, Laubach JP, Hassoun H, Efebera YA, Mulkey F, Bova-Solem M, Santo K, Carlisle D, McCarthy PL, Richardson PG. A phase I/II study of ixazomib, pomalidomide, and dexamethasone for lenalidomide and proteasome inhibitor refractory multiple myeloma (Alliance A061202). Am J Hematol. 2021 Dec 1;96(12):1595-1603. doi: 10.1002/ajh.26361. Epub 2021 Oct 6.

ID	Title	Description
FG000	Arm I (Pomalidomide, Dexamethasone)	Patients receive 4mg of pomalidomide PO QD on days 1-21 and 40mg dexamethasone PO QD on days 1, 8, 15, and 22. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients achieving disease progression may cross over to Arm II.
FG001

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot_SAP	Yes	Yes	No	Study Protocol and Statistical Analysis Plan	Aug 17, 2022

Arm/Group Information

ID	Title	Description
BG000	Phase II Arm I (Pomalidomide, Dexamethasone)	Patients receive pomalidomide PO QD on days 1-21 and dexamethasone PO QD on days 1, 8, 15, and 22. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients achieving disease progression may cross over to Arm II.
BG001	Phase II Arm II (Pomalidomide, Dexamethasone, Ixazomib)	Patients receive pomalidomide, dexamethasone, and ixazomib as in Phase I. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
BG002	Phase 1 Dose Level 1	A 3 + 3 phase I dose escalation design was used to examine the safety profile and establish the MTD of IXA when given in combination with POM-DEX. Protocol therapy was administered over a 28-day cycle. IXA was given at a dose of 2.3 up to 4 mg by mouth on days 1, 8, and 15; POM at 2 up to 4 mg daily by mouth on days 1-21; and DEX 20 mg (age > 75 years) or 40 mg (age ≤ 75) by mouth on days 1, 8, 15, and 22 (Table 1). A new cycle of treatment was not to begin until the ANC was ≥ 1.0 × 109/L, platelets ≥ 50 × 109/L, and all other adverse events (AEs) had improved to grade 1 or baseline. Treatment continued until PD, the emergence of unacceptable toxicity, or patient request to discontinue protocol treatment. Dose Level 1 was 2mg POM-DEX and 3mg IXA.
BG003	Phase 1 Dose Level 2	A 3 + 3 phase I dose escalation design was used to examine the safety profile and establish the MTD of IXA when given in combination with POM-DEX. Protocol therapy was administered over a 28-day cycle. IXA was given at a dose of 2.3 up to 4 mg by mouth on days 1, 8, and 15; POM at 2 up to 4 mg daily by mouth on days 1-21; and DEX 20 mg (age > 75 years) or 40 mg (age ≤ 75) by mouth on days 1, 8, 15, and 22 (Table 1). A new cycle of treatment was not to begin until the ANC was ≥ 1.0 × 109/L, platelets ≥ 50 × 109/L, and all other adverse events (AEs) had improved to grade 1 or baseline. Treatment continued until PD, the emergence of unacceptable toxicity, or patient request to discontinue protocol treatment. Dose Level 2 was 3mg POM-DEX and 3mg IXA.
BG004	Phase 1 Dose Level 3	A 3 + 3 phase I dose escalation design was used to examine the safety profile and establish the MTD of IXA when given in combination with POM-DEX. Protocol therapy was administered over a 28-day cycle. IXA was given at a dose of 2.3 up to 4 mg by mouth on days 1, 8, and 15; POM at 2 up to 4 mg daily by mouth on days 1-21; and DEX 20 mg (age > 75 years) or 40 mg (age ≤ 75) by mouth on days 1, 8, 15, and 22 (Table 1). A new cycle of treatment was not to begin until the ANC was ≥ 1.0 × 109/L, platelets ≥ 50 × 109/L, and all other adverse events (AEs) had improved to grade 1 or baseline. Treatment continued until PD, the emergence of unacceptable toxicity, or patient request to discontinue protocol treatment. Dose Level 3 was 4mg POM-DEX and 3mg IXA.
BG005	Phase 1 Dose Level 4	A 3 + 3 phase I dose escalation design was used to examine the safety profile and establish the MTD of IXA when given in combination with POM-DEX. Protocol therapy was administered over a 28-day cycle. IXA was given at a dose of 2.3 up to 4 mg by mouth on days 1, 8, and 15; POM at 2 up to 4 mg daily by mouth on days 1-21; and DEX 20 mg (age > 75 years) or 40 mg (age ≤ 75) by mouth on days 1, 8, 15, and 22 (Table 1). A new cycle of treatment was not to begin until the ANC was ≥ 1.0 × 109/L, platelets ≥ 50 × 109/L, and all other adverse events (AEs) had improved to grade 1 or baseline. Treatment continued until PD, the emergence of unacceptable toxicity, or patient request to discontinue protocol treatment. Dose Level 4 was 4mg POM-DEX and 4mg IXA.
BG006	Total	Total of all reporting groups

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Maximum Tolerated Dose (MTD) of Pomalidomide and Ixazomib, Determined According to Incidence of Dose Limiting Toxicity (DLT) Graded Using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 (Phase I)

For this protocol, dose-limiting toxicity (DLT) will be defined by the following adverse events at least possibly related to study therapy: Grade 3 or higher non-hematologic toxicity, with the following exceptions: Alopecia is not expected but would not be considered a DLT. Nausea, vomiting and diarrhea will only be considered a DLT if it cannot be adequately managed with optimal supportive care. Grade 3 or 4 hyperglycemia due to dexamethasone will only be considered a DLT if it cannot be controlled with appropriate therapy Grade 4 hematologic toxicity, with the following exceptions: Grade 4 lymphopenia is expected with this regimen and will not be construed as a DLT. Grade 4 neutropenia will only be considered a DLT if it lasts longer than 7 days despite appropriate supportive care. Grade 4 thrombocytopenia will only be considered a DLT if it lasts longer than 7 days or is associated with greater then or equal to grade 3 bleeding event

Posted

Number

participants with DLT

28 days

ID	Title	Description
OG000	Phase 1 Dose Level 1	A 3 + 3 phase I dose escalation design was used to examine the safety profile and establish the MTD of IXA when given in combination with POM-DEX. Protocol therapy was administered over a 28-day cycle. IXA was given at a dose of 2.3 up to 4 mg by mouth on days 1, 8, and 15; POM at 2 up to 4 mg daily by mouth on days 1-21; and DEX 20 mg (age > 75 years) or 40 mg (age ≤ 75) by mouth on days 1, 8, 15, and 22 (Table 1). A new cycle of treatment was not to begin until the ANC was ≥ 1.0 × 109/L, platelets ≥ 50 × 109/L, and all other adverse events (AEs) had improved to grade 1 or baseline. Treatment continued until PD, the emergence of unacceptable toxicity, or patient request to discontinue protocol treatment. Dose Level 1 was 2mg POM-DEX and 3mg IXA.
OG001	Phase 1 Dose Level 2	A 3 + 3 phase I dose escalation design was used to examine the safety profile and establish the MTD of IXA when given in combination with POM-DEX. Protocol therapy was administered over a 28-day cycle. IXA was given at a dose of 2.3 up to 4 mg by mouth on days 1, 8, and 15; POM at 2 up to 4 mg daily by mouth on days 1-21; and DEX 20 mg (age > 75 years) or 40 mg (age ≤ 75) by mouth on days 1, 8, 15, and 22 (Table 1). A new cycle of treatment was not to begin until the ANC was ≥ 1.0 × 109/L, platelets ≥ 50 × 109/L, and all other adverse events (AEs) had improved to grade 1 or baseline. Treatment continued until PD, the emergence of unacceptable toxicity, or patient request to discontinue protocol treatment. Dose Level 2 was 3mg POM-DEX and 3mg IXA.
OG002	Phase 1 Dose Level 3	A 3 + 3 phase I dose escalation design was used to examine the safety profile and establish the MTD of IXA when given in combination with POM-DEX. Protocol therapy was administered over a 28-day cycle. IXA was given at a dose of 2.3 up to 4 mg by mouth on days 1, 8, and 15; POM at 2 up to 4 mg daily by mouth on days 1-21; and DEX 20 mg (age > 75 years) or 40 mg (age ≤ 75) by mouth on days 1, 8, 15, and 22 (Table 1). A new cycle of treatment was not to begin until the ANC was ≥ 1.0 × 109/L, platelets ≥ 50 × 109/L, and all other adverse events (AEs) had improved to grade 1 or baseline. Treatment continued until PD, the emergence of unacceptable toxicity, or patient request to discontinue protocol treatment. Dose Level 3 was 4mg POM-DEX and 3mg IXA.
OG003

Units	Counts
Participants	OG0003 OG0013 OG0026 OG003

Title

Denominators

Categories

Title	Measurements
	OG0000 OG0010 OG0021 OG003

Primary

Progression Free Survival (PFS) (Phase II)

progression-free survival (PFS), defined as the time from randomization to the date the International Myeloma Working Group (IMWG) criteria for disease progression is met. If a patient initiates another anti-cancer treatment prior to disease progression, they will be censored at the date of initiation of this treatment. Patients will be randomized to treatment using the Pocock-Simon algorithm balancing the distribution of the following stratification factors between the two treatment arms: 1) ISS 1-2 disease vs. ISS 3 disease (current ISS stage based off screening beta 2 microglobulin and albumin) 2) High risk cytogenetics features: yes vs. no High risk cytogenetics features include: del(1p), gain of 1q, t(4;14), t(14;16), t(14; 20), del(17p) 3) Prior treatment with a proteasome inhibitor: yes vs. no

All eligible phase 2 patients were included in this analysis

Posted

Median

95% Confidence Interval

days

3 years

ID	Title	Description
OG000	Phase II Arm I (Pomalidomide, Dexamethasone)	Patients receive pomalidomide PO QD on days 1-21 and dexamethasone PO QD on days 1, 8, 15, and 22. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients achieving disease progression may cross over to Arm II.
OG001	Phase II Arm II (Pomalidomide, Dexamethasone, Ixazomib)	Patients receive pomalidomide, dexamethasone, and ixazomib as in Phase I. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Secondary

Incidence and Type of Dose Limiting Toxicities (DLTs) Graded According to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 (Phase I)

These events are reported in the adverse events section of this report.

All enrolled phase 1 patients that were eligible and treated per protocol were evaluated for dose limiting toxicities. This excludes two dose level 2 patients, one dose level 3 patient and 5 dose level 4 patients.

Posted

Number

participants with DLT

44.5 months

ID	Title	Description
OG000	Phase 1 Dose Level 1	A 3 + 3 phase I dose escalation design was used to examine the safety profile and establish the MTD of IXA when given in combination with POM-DEX. Protocol therapy was administered over a 28-day cycle. IXA was given at a dose of 2.3 up to 4 mg by mouth on days 1, 8, and 15; POM at 2 up to 4 mg daily by mouth on days 1-21; and DEX 20 mg (age > 75 years) or 40 mg (age ≤ 75) by mouth on days 1, 8, 15, and 22 (Table 1). A new cycle of treatment was not to begin until the ANC was ≥ 1.0 × 109/L, platelets ≥ 50 × 109/L, and all other adverse events (AEs) had improved to grade 1 or baseline. Treatment continued until PD, the emergence of unacceptable toxicity, or patient request to discontinue protocol treatment. Dose Level 1 was 2mg POM-DEX and 3mg IXA.
OG001	Phase 1 Dose Level 2	A 3 + 3 phase I dose escalation design was used to examine the safety profile and establish the MTD of IXA when given in combination with POM-DEX. Protocol therapy was administered over a 28-day cycle. IXA was given at a dose of 2.3 up to 4 mg by mouth on days 1, 8, and 15; POM at 2 up to 4 mg daily by mouth on days 1-21; and DEX 20 mg (age > 75 years) or 40 mg (age ≤ 75) by mouth on days 1, 8, 15, and 22 (Table 1). A new cycle of treatment was not to begin until the ANC was ≥ 1.0 × 109/L, platelets ≥ 50 × 109/L, and all other adverse events (AEs) had improved to grade 1 or baseline. Treatment continued until PD, the emergence of unacceptable toxicity, or patient request to discontinue protocol treatment. Dose Level 2 was 3mg POM-DEX and 3mg IXA.

Secondary

Incidence of Dose Reductions/Delays (Phase I)

Posted

Count of Participants

Participants

39 months

ID	Title	Description
OG000	Phase 1 Dose Level 1	A 3 + 3 phase I dose escalation design was used to examine the safety profile and establish the MTD of IXA when given in combination with POM-DEX. Protocol therapy was administered over a 28-day cycle. IXA was given at a dose of 2.3 up to 4 mg by mouth on days 1, 8, and 15; POM at 2 up to 4 mg daily by mouth on days 1-21; and DEX 20 mg (age > 75 years) or 40 mg (age ≤ 75) by mouth on days 1, 8, 15, and 22 (Table 1). A new cycle of treatment was not to begin until the ANC was ≥ 1.0 × 109/L, platelets ≥ 50 × 109/L, and all other adverse events (AEs) had improved to grade 1 or baseline. Treatment continued until PD, the emergence of unacceptable toxicity, or patient request to discontinue protocol treatment. Dose Level 1 was 2mg POM-DEX and 3mg IXA.
OG001	Phase 1 Dose Level 2	A 3 + 3 phase I dose escalation design was used to examine the safety profile and establish the MTD of IXA when given in combination with POM-DEX. Protocol therapy was administered over a 28-day cycle. IXA was given at a dose of 2.3 up to 4 mg by mouth on days 1, 8, and 15; POM at 2 up to 4 mg daily by mouth on days 1-21; and DEX 20 mg (age > 75 years) or 40 mg (age ≤ 75) by mouth on days 1, 8, 15, and 22 (Table 1). A new cycle of treatment was not to begin until the ANC was ≥ 1.0 × 109/L, platelets ≥ 50 × 109/L, and all other adverse events (AEs) had improved to grade 1 or baseline. Treatment continued until PD, the emergence of unacceptable toxicity, or patient request to discontinue protocol treatment. Dose Level 2 was 3mg POM-DEX and 3mg IXA.

Secondary

Overall Response Rate (ORR)

ORR is defined as partial response (PR), very good partial response (VGPR), complete response (CR), or stringent complete response (sCR) according to International Myeloma Working Group (IMWG) Uniform Response Criteria

All eligible and treated Phase II patients were included in analysis. Phase I patients were excluded from response analysis.

Posted

Number

95% Confidence Interval

proportion of participants

3 years

ID	Title	Description
OG000	Arm I (Pomalidomide, Dexamethasone)	Patients receive pomalidomide PO QD on days 1-21 and dexamethasone PO QD on days 1, 8, 15, and 22. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients achieving disease progression may cross over to Arm II.
OG001	Arm II (Pomalidomide, Dexamethasone, Ixazomib)	Patients receive pomalidomide, dexamethasone, and ixazomib as in Phase I. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Units	Counts
Participants

Secondary

Clinical Benefit Rate (CBR)

Disease response status is based on the IMWG criteria being held for two consecutive evaluations at least 4 weeks apart. Clinical benefit rate (CBR) is defined as proportion of patients with minimal response (MR) and better according to International Myeloma Working Group (IMWG) Uniform Response Criteria (Phase II)

Posted

Number

95% Confidence Interval

proportion of participants

3 years

ID	Title	Description
OG000	Phase II Arm I (Pomalidomide, Dexamethasone)	Patients receive pomalidomide PO QD on days 1-21 and dexamethasone PO QD on days 1, 8, 15, and 22. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients achieving disease progression may cross over to Arm II.
OG001	Phase II Arm II (Pomalidomide, Dexamethasone, Ixazomib)	Patients receive pomalidomide, dexamethasone, and ixazomib as in Phase I. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Units	Counts
Participants

Secondary

Disease Control Rate (DCR), Defined as Stable Disease (SD) and Better According to International Myeloma Working Group (IMWG) Uniform Response Criteria (Phase II)

Proportion of patients that went two of more cycles of treatment without discontinuing treatment for progression or intolerability.

Posted

Number

95% Confidence Interval

proportion of partcipants

42 days

ID	Title	Description
OG000	Phase II Arm I (Pomalidomide, Dexamethasone)	Patients receive pomalidomide PO QD on days 1-21 and dexamethasone PO QD on days 1, 8, 15, and 22. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients achieving disease progression may cross over to Arm II.
OG001	Phase II Arm II (Pomalidomide, Dexamethasone, Ixazomib)	Patients receive pomalidomide, dexamethasone, and ixazomib as in Phase I. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Units	Counts
Participants	OG000

Secondary

Duration of Response (DOR), Calculated for All Patients Achieving an Objective Response, Partial Response (PR) or Better (Phase II)

All eligible phase 2 responders

Posted

Median

95% Confidence Interval

Months

Up to 3 years

ID	Title	Description
OG000	Phase II Arm I (Pomalidomide, Dexamethasone)	Patients receive pomalidomide PO QD on days 1-21 and dexamethasone PO QD on days 1, 8, 15, and 22. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients achieving disease progression may cross over to Arm II.
OG001	Phase II Arm II (Pomalidomide, Dexamethasone, Ixazomib)	Patients receive pomalidomide, dexamethasone, and ixazomib as in Phase I. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Units	Counts
Participants	OG000

Secondary

Overall Survival (OS) (Phase II)

Overall survival was analyzed from the time of registration to the date of death or last known date living. Due to median OS time not being reached due to lack of deaths at the time of this report by either arm, the 2 year OS rate has been reported. This analysis censors living patients at 2 years.

Posted

Number

95% Confidence Interval

proportion of patients alive

2 years

ID	Title	Description
OG000	Phase II Arm I (Pomalidomide, Dexamethasone)	Patients receive pomalidomide PO QD on days 1-21 and dexamethasone PO QD on days 1, 8, 15, and 22. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients achieving disease progression may cross over to Arm II.
OG001	Phase II Arm II (Pomalidomide, Dexamethasone, Ixazomib)	Patients receive pomalidomide, dexamethasone, and ixazomib as in Phase I. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Units	Counts
Participants

Secondary

Time to Next Treatment (TNT) (Phase II)

Not Posted

Apr 2024

Up to 3 years post-registration

Participants

Secondary

Incidence, Type and Severity of Adverse Events, Graded According to National Cancer Institute (NCI) Common Terminology Criteria Adverse Events (CTCAE) Version 4.0 (Phase II)

The count of paitents that experenced an adverse event is reported in this section. A full table of these events is reported in the adverse event section of this report.

Posted

Count of Participants

Participants

92 months

ID	Title	Description
OG000	Phase II Arm I (Pomalidomide, Dexamethasone)	Patients receive pomalidomide PO QD on days 1-21 and dexamethasone PO QD on days 1, 8, 15, and 22. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients achieving disease progression may cross over to Arm II.
OG001	Phase II Arm II (Pomalidomide, Dexamethasone, Ixazomib) + Crossover Patients From Arm I	Patients receive pomalidomide, dexamethasone, and ixazomib as in Phase I. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
OG002	Phase 1 Dose Level 1	A 3 + 3 phase I dose escalation design was used to examine the safety profile and establish the MTD of IXA when given in combination with POM-DEX. Protocol therapy was administered over a 28-day cycle. IXA was given at a dose of 2.3 up to 4 mg by mouth on days 1, 8, and 15; POM at 2 up to 4 mg daily by mouth on days 1-21; and DEX 20 mg (age > 75 years) or 40 mg (age ≤ 75) by mouth on days 1, 8, 15, and 22 (Table 1). A new cycle of treatment was not to begin until the ANC was ≥ 1.0 × 109/L, platelets ≥ 50 × 109/L, and all other adverse events (AEs) had improved to grade 1 or baseline. Treatment continued until PD, the emergence of unacceptable toxicity, or patient request to discontinue protocol treatment. Dose Level 1 was 2mg POM-DEX and 3mg IXA.

Secondary

Response Rates (Overall Response Rate (ORR), Clinical Benefit Rate (CBR), Disease Control Rate (DCR) for All Patients on the Pomalidomide/Dexamethasone Arm at the Time of Cross-over to Pomalidomide/Dexamethasone/Ixazomib (Phase II)

Posted

Number

95% Confidence Interval

proportion of partcipants

Up to 3 years

ID	Title	Description
OG000	Arm I(Pomalidomide, Dexamethasone)	Patients receive pomalidomide PO QD on days 1-21 and dexamethasone PO QD on days 1, 8, 15, and 22. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients achieving disease progression may cross over to Arm II.

Units	Counts
Participants	OG00026

Secondary

Progression Free Survival (PFS) for All Patients on the Pomalidomide/Dexamethasone Arm at the Time of Cross-over to Pomalidomide/Dexamethasone/Ixazomib (Phase II)

Arm 1 patients that chose to crossover to Arm 2 treatment (add IXA treatment).

Posted

Median

95% Confidence Interval

months

Up to 3 years post-registration (at crossover)

ID	Title	Description
OG000	Arm I (Pomalidomide, Dexamethasone)	Patients receive pomalidomide PO QD on days 1-21 and dexamethasone PO QD on days 1, 8, 15, and 22. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients achieving disease progression may cross over to Arm II.

Units	Counts
Participants	OG000

Secondary

Baseline Level of Perceived Fatigue and QOL, Assessed Using the Registration Fatigue/Uniscale Assessment Form (Phase II)

Pre-treatment patient-report of fatigue and overall quality of life (based on a 10-point Likert scale). A higher number indicates a better quality of life where 10 is the best outcome and 0 is the worst.

All patients that completed and returned the QoL survey

Posted

Number

participants

baseline

ID	Title	Description
OG000	Arm I (Pomalidomide, Dexamethasone)	Patients receive pomalidomide PO QD on days 1-21 and dexamethasone PO QD on days 1, 8, 15, and 22. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients achieving disease progression may cross over to Arm II.
OG001	Arm II (Pomalidomide, Dexamethasone, Ixazomib)	Patients receive pomalidomide, dexamethasone, and ixazomib as in Phase I. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Units	Counts
Participants

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Phase II Arm I (Pomalidomide, Dexamethasone)	Patients receive pomalidomide PO QD on days 1-21 and dexamethasone PO QD on days 1, 8, 15, and 22. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients achieving disease progression may cross over to Arm II.	7	45	22	45	45	45
EG001	Phase II Arm II (Pomalidomide, Dexamethasone, Ixazomib) + Crossover Patients From Arm I	Patients receive pomalidomide, dexamethasone, and ixazomib as in Phase I. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.	22	76	33	76	76	76
EG002	Phase 1 Dose Level 1	A 3 + 3 phase I dose escalation design was used to examine the safety profile and establish the MTD of IXA when given in combination with POM-DEX. Protocol therapy was administered over a 28-day cycle. IXA was given at a dose of 2.3 up to 4 mg by mouth on days 1, 8, and 15; POM at 2 up to 4 mg daily by mouth on days 1-21; and DEX 20 mg (age > 75 years) or 40 mg (age ≤ 75) by mouth on days 1, 8, 15, and 22 (Table 1). A new cycle of treatment was not to begin until the ANC was ≥ 1.0 × 109/L, platelets ≥ 50 × 109/L, and all other adverse events (AEs) had improved to grade 1 or baseline. Treatment continued until PD, the emergence of unacceptable toxicity, or patient request to discontinue protocol treatment. Dose Level 1 was 2mg POM-DEX and 3mg IXA.	1	3	2	3	3	3
EG003	Phase 1 Dose Level 2	A 3 + 3 phase I dose escalation design was used to examine the safety profile and establish the MTD of IXA when given in combination with POM-DEX. Protocol therapy was administered over a 28-day cycle. IXA was given at a dose of 2.3 up to 4 mg by mouth on days 1, 8, and 15; POM at 2 up to 4 mg daily by mouth on days 1-21; and DEX 20 mg (age > 75 years) or 40 mg (age ≤ 75) by mouth on days 1, 8, 15, and 22 (Table 1). A new cycle of treatment was not to begin until the ANC was ≥ 1.0 × 109/L, platelets ≥ 50 × 109/L, and all other adverse events (AEs) had improved to grade 1 or baseline. Treatment continued until PD, the emergence of unacceptable toxicity, or patient request to discontinue protocol treatment. Dose Level 2 was 3mg POM-DEX and 3mg IXA.	4	5	2	4	4	4
EG004	Phase 1 Dose Level 3	A 3 + 3 phase I dose escalation design was used to examine the safety profile and establish the MTD of IXA when given in combination with POM-DEX. Protocol therapy was administered over a 28-day cycle. IXA was given at a dose of 2.3 up to 4 mg by mouth on days 1, 8, and 15; POM at 2 up to 4 mg daily by mouth on days 1-21; and DEX 20 mg (age > 75 years) or 40 mg (age ≤ 75) by mouth on days 1, 8, 15, and 22 (Table 1). A new cycle of treatment was not to begin until the ANC was ≥ 1.0 × 109/L, platelets ≥ 50 × 109/L, and all other adverse events (AEs) had improved to grade 1 or baseline. Treatment continued until PD, the emergence of unacceptable toxicity, or patient request to discontinue protocol treatment. Dose Level 3 was 4mg POM-DEX and 3mg IXA.	4	7	4	6	6	6
EG005	Phase 1 Dose Level 4	A 3 + 3 phase I dose escalation design was used to examine the safety profile and establish the MTD of IXA when given in combination with POM-DEX. Protocol therapy was administered over a 28-day cycle. IXA was given at a dose of 2.3 up to 4 mg by mouth on days 1, 8, and 15; POM at 2 up to 4 mg daily by mouth on days 1-21; and DEX 20 mg (age > 75 years) or 40 mg (age ≤ 75) by mouth on days 1, 8, 15, and 22 (Table 1). A new cycle of treatment was not to begin until the ANC was ≥ 1.0 × 109/L, platelets ≥ 50 × 109/L, and all other adverse events (AEs) had improved to grade 1 or baseline. Treatment continued until PD, the emergence of unacceptable toxicity, or patient request to discontinue protocol treatment. Dose Level 4 was 4mg POM-DEX and 4mg IXA.	7	11	6	11	11	11

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anemia	Blood and lymphatic system disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected45 at risk EG0013 events3 affected76 at risk EG0021 events1 affected3 at risk EG0030 events0 affected4 at risk EG0043 events1 affected6 at risk EG0050 events0 affected11 at risk
Blood and lymph sys disorders - Oth Spec	Blood and lymphatic system disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected45 at risk EG0011 events1 affected76 at risk EG0020 events0 affected3 at risk EG003
Febrile neutropenia	Blood and lymphatic system disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected45 at risk EG0012 events2 affected76 at risk EG0020 events0 affected3 at risk EG003
Atrial fibrillation	Cardiac disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected45 at risk EG0012 events2 affected76 at risk EG0021 events1 affected3 at risk EG003
Chest pain - cardiac	Cardiac disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected45 at risk EG0010 events0 affected76 at risk EG0020 events0 affected3 at risk EG003
Mitral valve disease	Cardiac disorders	MedDRA 12	Systematic Assessment	EG0002 events1 affected45 at risk EG0010 events0 affected76 at risk EG0020 events0 affected3 at risk EG003
Myocardial infarction	Cardiac disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected45 at risk EG0010 events0 affected76 at risk EG0020 events0 affected3 at risk EG003
Tinnitus	Ear and labyrinth disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected45 at risk EG0010 events0 affected76 at risk EG0021 events1 affected3 at risk EG003
Blurred vision	Eye disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected45 at risk EG0010 events0 affected76 at risk EG0020 events0 affected3 at risk EG003
Abdominal pain	Gastrointestinal disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected45 at risk EG0010 events0 affected76 at risk EG0020 events0 affected3 at risk EG003
Bloating	Gastrointestinal disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected45 at risk EG0010 events0 affected76 at risk EG0020 events0 affected3 at risk EG003
Constipation	Gastrointestinal disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected45 at risk EG0011 events1 affected76 at risk EG0020 events0 affected3 at risk EG003
Diarrhea	Gastrointestinal disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected45 at risk EG0017 events3 affected76 at risk EG0021 events1 affected3 at risk EG003
Enterocolitis	Gastrointestinal disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected45 at risk EG0010 events0 affected76 at risk EG0020 events0 affected3 at risk EG003
Gastrointestinal disorders - Oth spec	Gastrointestinal disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected45 at risk EG0011 events1 affected76 at risk EG0020 events0 affected3 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected45 at risk EG0011 events1 affected76 at risk EG0021 events1 affected3 at risk EG003
Upper gastrointestinal hemorrhage	Gastrointestinal disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected45 at risk EG0011 events1 affected76 at risk EG0020 events0 affected3 at risk EG003
Vomiting	Gastrointestinal disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected45 at risk EG0011 events1 affected76 at risk EG0020 events0 affected3 at risk EG003
Death NOS	General disorders	MedDRA 12	Systematic Assessment	EG0002 events2 affected45 at risk EG0010 events0 affected76 at risk EG0020 events0 affected3 at risk EG003
Fatigue	General disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected45 at risk EG0012 events2 affected76 at risk EG0021 events1 affected3 at risk EG003
Fever	General disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected45 at risk EG0011 events1 affected76 at risk EG0021 events1 affected3 at risk EG003
Flu like symptoms	General disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected45 at risk EG0011 events1 affected76 at risk EG0020 events0 affected3 at risk EG003
Gen disord and admin site conds-Oth spec	General disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected45 at risk EG0016 events4 affected76 at risk EG0020 events0 affected3 at risk EG003
Localized edema	General disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected45 at risk EG0010 events0 affected76 at risk EG0020 events0 affected3 at risk EG003
Non-cardiac chest pain	General disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected45 at risk EG0010 events0 affected76 at risk EG0020 events0 affected3 at risk EG003
Cholecystitis	Hepatobiliary disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected45 at risk EG0010 events0 affected76 at risk EG0020 events0 affected3 at risk EG003
Hepatobiliary disorders - Other, specify	Hepatobiliary disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected45 at risk EG0011 events1 affected76 at risk EG0020 events0 affected3 at risk EG003
Allergic reaction	Immune system disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected45 at risk EG0010 events0 affected76 at risk EG0020 events0 affected3 at risk EG003
Bone infection	Infections and infestations	MedDRA 12	Systematic Assessment	EG0000 events0 affected45 at risk EG0011 events1 affected76 at risk EG0020 events0 affected3 at risk EG003
Bronchial infection	Infections and infestations	MedDRA 12	Systematic Assessment	EG0000 events0 affected45 at risk EG0010 events0 affected76 at risk EG0020 events0 affected3 at risk EG003
Infections and infestations - Oth spec	Infections and infestations	MedDRA 12	Systematic Assessment	EG0005 events3 affected45 at risk EG0017 events5 affected76 at risk EG0021 events1 affected3 at risk EG003
Lung infection	Infections and infestations	MedDRA 12	Systematic Assessment	EG0003 events3 affected45 at risk EG0013 events3 affected76 at risk EG0020 events0 affected3 at risk EG003
Meningitis	Infections and infestations	MedDRA 12	Systematic Assessment	EG0000 events0 affected45 at risk EG0011 events1 affected76 at risk EG0020 events0 affected3 at risk EG003
Sepsis	Infections and infestations	MedDRA 12	Systematic Assessment	EG0000 events0 affected45 at risk EG0012 events2 affected76 at risk EG0020 events0 affected3 at risk EG003
Skin infection	Infections and infestations	MedDRA 12	Systematic Assessment	EG0000 events0 affected45 at risk EG0013 events3 affected76 at risk EG0020 events0 affected3 at risk EG003
Upper respiratory infection	Infections and infestations	MedDRA 12	Systematic Assessment	EG0002 events2 affected45 at risk EG0012 events1 affected76 at risk EG0020 events0 affected3 at risk EG003
Urinary tract infection	Infections and infestations	MedDRA 12	Systematic Assessment	EG0000 events0 affected45 at risk EG0014 events2 affected76 at risk EG0020 events0 affected3 at risk EG003
Wound infection	Infections and infestations	MedDRA 12	Systematic Assessment	EG0000 events0 affected45 at risk EG0011 events1 affected76 at risk EG0020 events0 affected3 at risk EG003
Bruising	Injury, poisoning and procedural complications	MedDRA 12	Systematic Assessment	EG0000 events0 affected45 at risk EG0010 events0 affected76 at risk EG0020 events0 affected3 at risk EG003
Fall	Injury, poisoning and procedural complications	MedDRA 12	Systematic Assessment	EG0001 events1 affected45 at risk EG0012 events2 affected76 at risk EG0020 events0 affected3 at risk EG003
Blood bilirubin increased	Investigations	MedDRA 12	Systematic Assessment	EG0000 events0 affected45 at risk EG0011 events1 affected76 at risk EG0020 events0 affected3 at risk EG003
Creatinine increased	Investigations	MedDRA 12	Systematic Assessment	EG0001 events1 affected45 at risk EG0010 events0 affected76 at risk EG0020 events0 affected3 at risk EG003
Lymphocyte count decreased	Investigations	MedDRA 12	Systematic Assessment	EG0005 events5 affected45 at risk EG0011 events1 affected76 at risk EG0021 events1 affected3 at risk EG003
Neutrophil count decreased	Investigations	MedDRA 12	Systematic Assessment	EG0000 events0 affected45 at risk EG0011 events1 affected76 at risk EG0021 events1 affected3 at risk EG003
Platelet count decreased	Investigations	MedDRA 12	Systematic Assessment	EG0002 events2 affected45 at risk EG0010 events0 affected76 at risk EG0020 events0 affected3 at risk EG003
White blood cell decreased	Investigations	MedDRA 12	Systematic Assessment	EG0001 events1 affected45 at risk EG0012 events2 affected76 at risk EG0020 events0 affected3 at risk EG003
Dehydration	Metabolism and nutrition disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected45 at risk EG0011 events1 affected76 at risk EG0020 events0 affected3 at risk EG003
Hypercalcemia	Metabolism and nutrition disorders	MedDRA 12	Systematic Assessment	EG0002 events2 affected45 at risk EG0010 events0 affected76 at risk EG0020 events0 affected3 at risk EG003
Hypernatremia	Metabolism and nutrition disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected45 at risk EG0010 events0 affected76 at risk EG0020 events0 affected3 at risk EG003
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected45 at risk EG0011 events1 affected76 at risk EG0020 events0 affected3 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected45 at risk EG0011 events1 affected76 at risk EG0020 events0 affected3 at risk EG003
Generalized muscle weakness	Musculoskeletal and connective tissue disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected45 at risk EG0010 events0 affected76 at risk EG0020 events0 affected3 at risk EG003
Muscle weakness lower limb	Musculoskeletal and connective tissue disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected45 at risk EG0011 events1 affected76 at risk EG0020 events0 affected3 at risk EG003
Neck pain	Musculoskeletal and connective tissue disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected45 at risk EG0010 events0 affected76 at risk EG0020 events0 affected3 at risk EG003
Osteonecrosis of jaw	Musculoskeletal and connective tissue disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected45 at risk EG0010 events0 affected76 at risk EG0020 events0 affected3 at risk EG003
Neoplasms benign, mal, uncpec - Oth spec	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 12	Systematic Assessment	EG0002 events2 affected45 at risk EG0012 events2 affected76 at risk EG0020 events0 affected3 at risk EG003
Treatment related secondary malignancy	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 12	Systematic Assessment	EG0006 events2 affected45 at risk EG0013 events1 affected76 at risk EG0020 events0 affected3 at risk EG003
Ataxia	Nervous system disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected45 at risk EG0010 events0 affected76 at risk EG0020 events0 affected3 at risk EG003
Headache	Nervous system disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected45 at risk EG0012 events2 affected76 at risk EG0020 events0 affected3 at risk EG003
Paresthesia	Nervous system disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected45 at risk EG0011 events1 affected76 at risk EG0020 events0 affected3 at risk EG003
Peripheral sensory neuropathy	Nervous system disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected45 at risk EG0010 events0 affected76 at risk EG0021 events1 affected3 at risk EG003
Seizure	Nervous system disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected45 at risk EG0010 events0 affected76 at risk EG0020 events0 affected3 at risk EG003
Stroke	Nervous system disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected45 at risk EG0010 events0 affected76 at risk EG0020 events0 affected3 at risk EG003
Syncope	Nervous system disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected45 at risk EG0011 events1 affected76 at risk EG0020 events0 affected3 at risk EG003
Transient ischemic attacks	Nervous system disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected45 at risk EG0010 events0 affected76 at risk EG0020 events0 affected3 at risk EG003
Agitation	Psychiatric disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected45 at risk EG0010 events0 affected76 at risk EG0020 events0 affected3 at risk EG003
Insomnia	Psychiatric disorders	MedDRA 12	Systematic Assessment	EG0007 events1 affected45 at risk EG0010 events0 affected76 at risk EG0020 events0 affected3 at risk EG003
Acute kidney injury	Renal and urinary disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected45 at risk EG0012 events2 affected76 at risk EG0021 events1 affected3 at risk EG003
Aspiration	Respiratory, thoracic and mediastinal disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected45 at risk EG0010 events0 affected76 at risk EG0020 events0 affected3 at risk EG003
Dyspnea	Respiratory, thoracic and mediastinal disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected45 at risk EG0010 events0 affected76 at risk EG0020 events0 affected3 at risk EG003
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected45 at risk EG0010 events0 affected76 at risk EG0020 events0 affected3 at risk EG003
Hypoxia	Respiratory, thoracic and mediastinal disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected45 at risk EG0011 events1 affected76 at risk EG0020 events0 affected3 at risk EG003
Pneumonitis	Respiratory, thoracic and mediastinal disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected45 at risk EG0012 events2 affected76 at risk EG0020 events0 affected3 at risk EG003
Pulmonary edema	Respiratory, thoracic and mediastinal disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected45 at risk EG0010 events0 affected76 at risk EG0020 events0 affected3 at risk EG003
Resp, thoracic, mediastinal - Oth spec	Respiratory, thoracic and mediastinal disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected45 at risk EG0013 events2 affected76 at risk EG0020 events0 affected3 at risk EG003
Respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected45 at risk EG0010 events0 affected76 at risk EG0020 events0 affected3 at risk EG003
Rash maculo-papular	Skin and subcutaneous tissue disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected45 at risk EG0012 events1 affected76 at risk EG0020 events0 affected3 at risk EG003
Skin and subcut tissue disord - Oth spec	Skin and subcutaneous tissue disorders	MedDRA 12	Systematic Assessment	EG0004 events3 affected45 at risk EG0011 events1 affected76 at risk EG0020 events0 affected3 at risk EG003
Surgical and medical proced - Oth spec	Surgical and medical procedures	MedDRA 12	Systematic Assessment	EG0000 events0 affected45 at risk EG0010 events0 affected76 at risk EG0021 events1 affected3 at risk EG003
Hypotension	Vascular disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected45 at risk EG0012 events2 affected76 at risk EG0020 events0 affected3 at risk EG003
Thromboembolic event	Vascular disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected45 at risk EG0012 events2 affected76 at risk EG0020 events0 affected3 at risk EG003

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anemia	Blood and lymphatic system disorders	MedDRA 12	Systematic Assessment	EG000187 events31 affected45 at risk EG001420 events56 affected76 at risk EG0023 events1 affected3 at risk EG0036 events4 affected4 at risk EG00453 events6 affected6 at risk EG005114 events10 affected11 at risk
Blood and lymph sys disorders - Oth Spec	Blood and lymphatic system disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected45 at risk EG0011 events1 affected76 at risk EG0020 events0 affected3 at risk EG003
Febrile neutropenia	Blood and lymphatic system disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected45 at risk EG0010 events0 affected76 at risk EG0020 events0 affected3 at risk EG003
Atrial fibrillation	Cardiac disorders	MedDRA 12	Systematic Assessment	EG0002 events2 affected45 at risk EG00125 events5 affected76 at risk EG0022 events1 affected3 at risk EG003
Atrial flutter	Cardiac disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected45 at risk EG0010 events0 affected76 at risk EG0021 events1 affected3 at risk EG003
Cardiac disorders - Other, specify	Cardiac disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected45 at risk EG0013 events3 affected76 at risk EG0020 events0 affected3 at risk EG003
Chest pain - cardiac	Cardiac disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected45 at risk EG0010 events0 affected76 at risk EG0020 events0 affected3 at risk EG003
Heart failure	Cardiac disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected45 at risk EG0010 events0 affected76 at risk EG0020 events0 affected3 at risk EG003
Palpitations	Cardiac disorders	MedDRA 12	Systematic Assessment	EG0002 events2 affected45 at risk EG0011 events1 affected76 at risk EG0020 events0 affected3 at risk EG003
Paroxysmal atrial tachycardia	Cardiac disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected45 at risk EG0010 events0 affected76 at risk EG0020 events0 affected3 at risk EG003
Sick sinus syndrome	Cardiac disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected45 at risk EG00110 events1 affected76 at risk EG0020 events0 affected3 at risk EG003
Sinus bradycardia	Cardiac disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected45 at risk EG00153 events6 affected76 at risk EG0020 events0 affected3 at risk EG003
Sinus tachycardia	Cardiac disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected45 at risk EG0012 events2 affected76 at risk EG0020 events0 affected3 at risk EG003
Ventricular arrhythmia	Cardiac disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected45 at risk EG0011 events1 affected76 at risk EG0020 events0 affected3 at risk EG003
Ear and labyrinth disorders - Oth spec	Ear and labyrinth disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected45 at risk EG0010 events0 affected76 at risk EG0020 events0 affected3 at risk EG003
Ear pain	Ear and labyrinth disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected45 at risk EG0010 events0 affected76 at risk EG0020 events0 affected3 at risk EG003
Hearing impaired	Ear and labyrinth disorders	MedDRA 12	Systematic Assessment	EG0002 events1 affected45 at risk EG00116 events3 affected76 at risk EG0020 events0 affected3 at risk EG003
Tinnitus	Ear and labyrinth disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected45 at risk EG0014 events1 affected76 at risk EG0020 events0 affected3 at risk EG003
Vertigo	Ear and labyrinth disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected45 at risk EG00112 events4 affected76 at risk EG0021 events1 affected3 at risk EG003
Endocrine disorders - Other, specify	Endocrine disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected45 at risk EG0010 events0 affected76 at risk EG0020 events0 affected3 at risk EG003
Blurred vision	Eye disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected45 at risk EG00137 events8 affected76 at risk EG0020 events0 affected3 at risk EG003
Cataract	Eye disorders	MedDRA 12	Systematic Assessment	EG0002 events1 affected45 at risk EG00114 events5 affected76 at risk EG0020 events0 affected3 at risk EG003
Dry eye	Eye disorders	MedDRA 12	Systematic Assessment	EG0003 events1 affected45 at risk EG0018 events3 affected76 at risk EG0020 events0 affected3 at risk EG003
Eye disorders - Other, specify	Eye disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected45 at risk EG00135 events7 affected76 at risk EG0021 events1 affected3 at risk EG003
Watering eyes	Eye disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected45 at risk EG0019 events2 affected76 at risk EG0020 events0 affected3 at risk EG003
Abdominal distension	Gastrointestinal disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected45 at risk EG0014 events2 affected76 at risk EG0020 events0 affected3 at risk EG003
Abdominal pain	Gastrointestinal disorders	MedDRA 12	Systematic Assessment	EG0005 events3 affected45 at risk EG0014 events4 affected76 at risk EG0020 events0 affected3 at risk EG003
Anal hemorrhage	Gastrointestinal disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected45 at risk EG0011 events1 affected76 at risk EG0020 events0 affected3 at risk EG003
Anal pain	Gastrointestinal disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected45 at risk EG0011 events1 affected76 at risk EG0020 events0 affected3 at risk EG003
Bloating	Gastrointestinal disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected45 at risk EG0018 events3 affected76 at risk EG0020 events0 affected3 at risk EG003
Constipation	Gastrointestinal disorders	MedDRA 12	Systematic Assessment	EG00059 events12 affected45 at risk EG001129 events20 affected76 at risk EG0023 events1 affected3 at risk EG003
Diarrhea	Gastrointestinal disorders	MedDRA 12	Systematic Assessment	EG00085 events24 affected45 at risk EG001364 events44 affected76 at risk EG0026 events2 affected3 at risk EG003
Dry mouth	Gastrointestinal disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected45 at risk EG00121 events4 affected76 at risk EG0020 events0 affected3 at risk EG003
Dyspepsia	Gastrointestinal disorders	MedDRA 12	Systematic Assessment	EG0006 events3 affected45 at risk EG0014 events1 affected76 at risk EG0020 events0 affected3 at risk EG003
Dysphagia	Gastrointestinal disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected45 at risk EG0013 events1 affected76 at risk EG0020 events0 affected3 at risk EG003
Flatulence	Gastrointestinal disorders	MedDRA 12	Systematic Assessment	EG00012 events1 affected45 at risk EG0013 events1 affected76 at risk EG0020 events0 affected3 at risk EG003
Gastritis	Gastrointestinal disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected45 at risk EG0010 events0 affected76 at risk EG0020 events0 affected3 at risk EG003
Gastroesophageal reflux disease	Gastrointestinal disorders	MedDRA 12	Systematic Assessment	EG00014 events1 affected45 at risk EG00126 events8 affected76 at risk EG0020 events0 affected3 at risk EG003
Gastrointestinal disorders - Oth spec	Gastrointestinal disorders	MedDRA 12	Systematic Assessment	EG0002 events2 affected45 at risk EG0018 events5 affected76 at risk EG0020 events0 affected3 at risk EG003
Gastrointestinal pain	Gastrointestinal disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected45 at risk EG0012 events1 affected76 at risk EG0020 events0 affected3 at risk EG003
Gingival pain	Gastrointestinal disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected45 at risk EG00114 events1 affected76 at risk EG0020 events0 affected3 at risk EG003
Hemorrhoids	Gastrointestinal disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected45 at risk EG0010 events0 affected76 at risk EG0020 events0 affected3 at risk EG003
Mucositis oral	Gastrointestinal disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected45 at risk EG0012 events1 affected76 at risk EG0020 events0 affected3 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA 12	Systematic Assessment	EG00028 events12 affected45 at risk EG001173 events33 affected76 at risk EG0026 events2 affected3 at risk EG003
Oral pain	Gastrointestinal disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected45 at risk EG0010 events0 affected76 at risk EG0020 events0 affected3 at risk EG003
Rectal fistula	Gastrointestinal disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected45 at risk EG0011 events1 affected76 at risk EG0020 events0 affected3 at risk EG003
Stomach pain	Gastrointestinal disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected45 at risk EG0010 events0 affected76 at risk EG0020 events0 affected3 at risk EG003
Toothache	Gastrointestinal disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected45 at risk EG0012 events2 affected76 at risk EG0020 events0 affected3 at risk EG003
Vomiting	Gastrointestinal disorders	MedDRA 12	Systematic Assessment	EG0009 events7 affected45 at risk EG00132 events19 affected76 at risk EG0020 events0 affected3 at risk EG003
Chills	General disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected45 at risk EG0012 events2 affected76 at risk EG0020 events0 affected3 at risk EG003
Edema face	General disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected45 at risk EG0012 events2 affected76 at risk EG0020 events0 affected3 at risk EG003
Edema limbs	General disorders	MedDRA 12	Systematic Assessment	EG00025 events8 affected45 at risk EG001185 events25 affected76 at risk EG0029 events2 affected3 at risk EG003
Edema trunk	General disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected45 at risk EG0017 events1 affected76 at risk EG0020 events0 affected3 at risk EG003
Fatigue	General disorders	MedDRA 12	Systematic Assessment	EG000241 events39 affected45 at risk EG001647 events66 affected76 at risk EG00235 events2 affected3 at risk EG003
Fever	General disorders	MedDRA 12	Systematic Assessment	EG0003 events3 affected45 at risk EG0014 events4 affected76 at risk EG0021 events1 affected3 at risk EG003
Flu like symptoms	General disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected45 at risk EG0013 events2 affected76 at risk EG0020 events0 affected3 at risk EG003
Gait disturbance	General disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected45 at risk EG0011 events1 affected76 at risk EG0020 events0 affected3 at risk EG003
Gen disord and admin site conds-Oth spec	General disorders	MedDRA 12	Systematic Assessment	EG00099 events18 affected45 at risk EG001106 events20 affected76 at risk EG00217 events2 affected3 at risk EG003
Localized edema	General disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected45 at risk EG0013 events2 affected76 at risk EG0021 events1 affected3 at risk EG003
Malaise	General disorders	MedDRA 12	Systematic Assessment	EG0002 events2 affected45 at risk EG0013 events3 affected76 at risk EG0020 events0 affected3 at risk EG003
Non-cardiac chest pain	General disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected45 at risk EG0017 events3 affected76 at risk EG0020 events0 affected3 at risk EG003
Pain	General disorders	MedDRA 12	Systematic Assessment	EG0008 events3 affected45 at risk EG00140 events15 affected76 at risk EG0020 events0 affected3 at risk EG003
Allergic reaction	Immune system disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected45 at risk EG0011 events1 affected76 at risk EG0020 events0 affected3 at risk EG003
Immune system disorders - Other, specify	Immune system disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected45 at risk EG0011 events1 affected76 at risk EG0020 events0 affected3 at risk EG003
Bladder infection	Infections and infestations	MedDRA 12	Systematic Assessment	EG0000 events0 affected45 at risk EG0011 events1 affected76 at risk EG0020 events0 affected3 at risk EG003
Breast infection	Infections and infestations	MedDRA 12	Systematic Assessment	EG0000 events0 affected45 at risk EG0011 events1 affected76 at risk EG0020 events0 affected3 at risk EG003
Conjunctivitis	Infections and infestations	MedDRA 12	Systematic Assessment	EG0001 events1 affected45 at risk EG0011 events1 affected76 at risk EG0020 events0 affected3 at risk EG003
Conjunctivitis infective	Infections and infestations	MedDRA 12	Systematic Assessment	EG0000 events0 affected45 at risk EG0011 events1 affected76 at risk EG0020 events0 affected3 at risk EG003
Eye infection	Infections and infestations	MedDRA 12	Systematic Assessment	EG0000 events0 affected45 at risk EG0011 events1 affected76 at risk EG0020 events0 affected3 at risk EG003
Gum infection	Infections and infestations	MedDRA 12	Systematic Assessment	EG0006 events2 affected45 at risk EG00110 events1 affected76 at risk EG0020 events0 affected3 at risk EG003
Infections and infestations - Oth spec	Infections and infestations	MedDRA 12	Systematic Assessment	EG0008 events5 affected45 at risk EG00130 events14 affected76 at risk EG0021 events1 affected3 at risk EG003
Laryngitis	Infections and infestations	MedDRA 12	Systematic Assessment	EG0000 events0 affected45 at risk EG0011 events1 affected76 at risk EG0020 events0 affected3 at risk EG003
Lung infection	Infections and infestations	MedDRA 12	Systematic Assessment	EG0001 events1 affected45 at risk EG0011 events1 affected76 at risk EG0020 events0 affected3 at risk EG003
Sinusitis	Infections and infestations	MedDRA 12	Systematic Assessment	EG0004 events2 affected45 at risk EG0012 events1 affected76 at risk EG0020 events0 affected3 at risk EG003
Skin infection	Infections and infestations	MedDRA 12	Systematic Assessment	EG0001 events1 affected45 at risk EG00113 events5 affected76 at risk EG0020 events0 affected3 at risk EG003
Tooth infection	Infections and infestations	MedDRA 12	Systematic Assessment	EG0002 events2 affected45 at risk EG0012 events2 affected76 at risk EG0020 events0 affected3 at risk EG003
Upper respiratory infection	Infections and infestations	MedDRA 12	Systematic Assessment	EG00010 events6 affected45 at risk EG00113 events10 affected76 at risk EG0026 events2 affected3 at risk EG003
Urinary tract infection	Infections and infestations	MedDRA 12	Systematic Assessment	EG0003 events3 affected45 at risk EG0015 events5 affected76 at risk EG0021 events1 affected3 at risk EG003
Vaginal infection	Infections and infestations	MedDRA 12	Systematic Assessment	EG0000 events0 affected45 at risk EG0011 events1 affected76 at risk EG0020 events0 affected3 at risk EG003
Bruising	Injury, poisoning and procedural complications	MedDRA 12	Systematic Assessment	EG0000 events0 affected45 at risk EG00154 events7 affected76 at risk EG00216 events1 affected3 at risk EG003
Fall	Injury, poisoning and procedural complications	MedDRA 12	Systematic Assessment	EG0006 events5 affected45 at risk EG0016 events4 affected76 at risk EG0020 events0 affected3 at risk EG003
Infusion related reaction	Injury, poisoning and procedural complications	MedDRA 12	Systematic Assessment	EG0000 events0 affected45 at risk EG0011 events1 affected76 at risk EG0020 events0 affected3 at risk EG003
Seroma	Injury, poisoning and procedural complications	MedDRA 12	Systematic Assessment	EG0000 events0 affected45 at risk EG0011 events1 affected76 at risk EG0020 events0 affected3 at risk EG003
Alanine aminotransferase increased	Investigations	MedDRA 12	Systematic Assessment	EG00029 events6 affected45 at risk EG00137 events12 affected76 at risk EG0021 events1 affected3 at risk EG003
Alkaline phosphatase increased	Investigations	MedDRA 12	Systematic Assessment	EG0004 events4 affected45 at risk EG00113 events6 affected76 at risk EG0020 events0 affected3 at risk EG003
Aspartate aminotransferase increased	Investigations	MedDRA 12	Systematic Assessment	EG00020 events4 affected45 at risk EG00132 events9 affected76 at risk EG0020 events0 affected3 at risk EG003
Blood bilirubin increased	Investigations	MedDRA 12	Systematic Assessment	EG0000 events0 affected45 at risk EG0016 events4 affected76 at risk EG0020 events0 affected3 at risk EG003
Creatinine increased	Investigations	MedDRA 12	Systematic Assessment	EG00016 events8 affected45 at risk EG00187 events17 affected76 at risk EG0021 events1 affected3 at risk EG003
INR increased	Investigations	MedDRA 12	Systematic Assessment	EG0000 events0 affected45 at risk EG0010 events0 affected76 at risk EG0020 events0 affected3 at risk EG003
Investigations - Other, specify	Investigations	MedDRA 12	Systematic Assessment	EG0004 events4 affected45 at risk EG0015 events4 affected76 at risk EG00222 events1 affected3 at risk EG003
Lymphocyte count decreased	Investigations	MedDRA 12	Systematic Assessment	EG000101 events24 affected45 at risk EG001279 events44 affected76 at risk EG00233 events2 affected3 at risk EG003
Neutrophil count decreased	Investigations	MedDRA 12	Systematic Assessment	EG000181 events31 affected45 at risk EG001404 events55 affected76 at risk EG00230 events1 affected3 at risk EG003
Platelet count decreased	Investigations	MedDRA 12	Systematic Assessment	EG00046 events18 affected45 at risk EG001211 events48 affected76 at risk EG00233 events1 affected3 at risk EG003
Weight gain	Investigations	MedDRA 12	Systematic Assessment	EG0009 events7 affected45 at risk EG00159 events13 affected76 at risk EG0020 events0 affected3 at risk EG003
Weight loss	Investigations	MedDRA 12	Systematic Assessment	EG0003 events2 affected45 at risk EG0016 events2 affected76 at risk EG0020 events0 affected3 at risk EG003
White blood cell decreased	Investigations	MedDRA 12	Systematic Assessment	EG00065 events15 affected45 at risk EG001264 events40 affected76 at risk EG00221 events1 affected3 at risk EG003
Anorexia	Metabolism and nutrition disorders	MedDRA 12	Systematic Assessment	EG0003 events3 affected45 at risk EG00116 events7 affected76 at risk EG0023 events1 affected3 at risk EG003
Dehydration	Metabolism and nutrition disorders	MedDRA 12	Systematic Assessment	EG0002 events2 affected45 at risk EG0018 events7 affected76 at risk EG0020 events0 affected3 at risk EG003
Glucose intolerance	Metabolism and nutrition disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected45 at risk EG0013 events1 affected76 at risk EG0020 events0 affected3 at risk EG003
Hypercalcemia	Metabolism and nutrition disorders	MedDRA 12	Systematic Assessment	EG0003 events3 affected45 at risk EG0013 events2 affected76 at risk EG0020 events0 affected3 at risk EG003
Hyperglycemia	Metabolism and nutrition disorders	MedDRA 12	Systematic Assessment	EG00081 events19 affected45 at risk EG001235 events42 affected76 at risk EG0020 events0 affected3 at risk EG003
Hyperkalemia	Metabolism and nutrition disorders	MedDRA 12	Systematic Assessment	EG0002 events1 affected45 at risk EG0012 events2 affected76 at risk EG0020 events0 affected3 at risk EG003
Hypernatremia	Metabolism and nutrition disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected45 at risk EG0011 events1 affected76 at risk EG0020 events0 affected3 at risk EG003
Hypoalbuminemia	Metabolism and nutrition disorders	MedDRA 12	Systematic Assessment	EG0006 events4 affected45 at risk EG00116 events8 affected76 at risk EG0020 events0 affected3 at risk EG003
Hypocalcemia	Metabolism and nutrition disorders	MedDRA 12	Systematic Assessment	EG0005 events4 affected45 at risk EG00129 events13 affected76 at risk EG0020 events0 affected3 at risk EG003
Hypoglycemia	Metabolism and nutrition disorders	MedDRA 12	Systematic Assessment	EG0002 events2 affected45 at risk EG0017 events4 affected76 at risk EG0020 events0 affected3 at risk EG003
Hypokalemia	Metabolism and nutrition disorders	MedDRA 12	Systematic Assessment	EG00010 events7 affected45 at risk EG00129 events17 affected76 at risk EG0023 events1 affected3 at risk EG003
Hypomagnesemia	Metabolism and nutrition disorders	MedDRA 12	Systematic Assessment	EG00041 events10 affected45 at risk EG00156 events14 affected76 at risk EG0020 events0 affected3 at risk EG003
Hyponatremia	Metabolism and nutrition disorders	MedDRA 12	Systematic Assessment	EG0004 events4 affected45 at risk EG00115 events11 affected76 at risk EG0020 events0 affected3 at risk EG003
Hypophosphatemia	Metabolism and nutrition disorders	MedDRA 12	Systematic Assessment	EG00027 events9 affected45 at risk EG00152 events19 affected76 at risk EG0020 events0 affected3 at risk EG003
Metabolism, nutrition disord - Oth spec	Metabolism and nutrition disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected45 at risk EG0017 events1 affected76 at risk EG0020 events0 affected3 at risk EG003
Obesity	Metabolism and nutrition disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected45 at risk EG0014 events1 affected76 at risk EG0020 events0 affected3 at risk EG003
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 12	Systematic Assessment	EG0003 events2 affected45 at risk EG00186 events10 affected76 at risk EG0020 events0 affected3 at risk EG003
Arthritis	Musculoskeletal and connective tissue disorders	MedDRA 12	Systematic Assessment	EG0003 events2 affected45 at risk EG0010 events0 affected76 at risk EG0021 events1 affected3 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 12	Systematic Assessment	EG00031 events14 affected45 at risk EG00174 events17 affected76 at risk EG0020 events0 affected3 at risk EG003
Bone pain	Musculoskeletal and connective tissue disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected45 at risk EG00136 events8 affected76 at risk EG0020 events0 affected3 at risk EG003
Chest wall pain	Musculoskeletal and connective tissue disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected45 at risk EG0010 events0 affected76 at risk EG0021 events1 affected3 at risk EG003
Flank pain	Musculoskeletal and connective tissue disorders	MedDRA 12	Systematic Assessment	EG0004 events1 affected45 at risk EG0011 events1 affected76 at risk EG0020 events0 affected3 at risk EG003
Generalized muscle weakness	Musculoskeletal and connective tissue disorders	MedDRA 12	Systematic Assessment	EG00011 events8 affected45 at risk EG00133 events8 affected76 at risk EG0020 events0 affected3 at risk EG003
Muscle weakness lower limb	Musculoskeletal and connective tissue disorders	MedDRA 12	Systematic Assessment	EG0006 events2 affected45 at risk EG00124 events4 affected76 at risk EG0020 events0 affected3 at risk EG003
Muscle weakness upper limb	Musculoskeletal and connective tissue disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected45 at risk EG0013 events2 affected76 at risk EG0020 events0 affected3 at risk EG003
Musculoskeletal, conn tissue - Oth spec	Musculoskeletal and connective tissue disorders	MedDRA 12	Systematic Assessment	EG00018 events5 affected45 at risk EG00124 events5 affected76 at risk EG0020 events0 affected3 at risk EG003
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA 12	Systematic Assessment	EG00029 events7 affected45 at risk EG00179 events14 affected76 at risk EG0020 events0 affected3 at risk EG003
Neck pain	Musculoskeletal and connective tissue disorders	MedDRA 12	Systematic Assessment	EG0004 events1 affected45 at risk EG0011 events1 affected76 at risk EG0020 events0 affected3 at risk EG003
Osteonecrosis of jaw	Musculoskeletal and connective tissue disorders	MedDRA 12	Systematic Assessment	EG0007 events3 affected45 at risk EG0018 events3 affected76 at risk EG0020 events0 affected3 at risk EG003
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA 12	Systematic Assessment	EG00012 events7 affected45 at risk EG00150 events8 affected76 at risk EG00215 events1 affected3 at risk EG003
Neoplasms benign, mal, uncpec - Oth spec	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 12	Systematic Assessment	EG0001 events1 affected45 at risk EG0010 events0 affected76 at risk EG0020 events0 affected3 at risk EG003
Treatment related secondary malignancy	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 12	Systematic Assessment	EG0000 events0 affected45 at risk EG0011 events1 affected76 at risk EG0020 events0 affected3 at risk EG003
Cognitive disturbance	Nervous system disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected45 at risk EG0012 events1 affected76 at risk EG0020 events0 affected3 at risk EG003
Concentration impairment	Nervous system disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected45 at risk EG0013 events3 affected76 at risk EG0020 events0 affected3 at risk EG003
Dizziness	Nervous system disorders	MedDRA 12	Systematic Assessment	EG00018 events8 affected45 at risk EG00190 events14 affected76 at risk EG0021 events1 affected3 at risk EG003
Dysgeusia	Nervous system disorders	MedDRA 12	Systematic Assessment	EG0004 events2 affected45 at risk EG00117 events4 affected76 at risk EG00220 events2 affected3 at risk EG003
Dysphasia	Nervous system disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected45 at risk EG0010 events0 affected76 at risk EG0020 events0 affected3 at risk EG003
Headache	Nervous system disorders	MedDRA 12	Systematic Assessment	EG00018 events7 affected45 at risk EG00142 events12 affected76 at risk EG00230 events2 affected3 at risk EG003
Lethargy	Nervous system disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected45 at risk EG00111 events3 affected76 at risk EG0020 events0 affected3 at risk EG003
Memory impairment	Nervous system disorders	MedDRA 12	Systematic Assessment	EG0005 events2 affected45 at risk EG0012 events2 affected76 at risk EG0021 events1 affected3 at risk EG003
Muscle weakness left-sided	Nervous system disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected45 at risk EG0011 events1 affected76 at risk EG0020 events0 affected3 at risk EG003
Nervous system disorders - Oth spec	Nervous system disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected45 at risk EG0012 events2 affected76 at risk EG0020 events0 affected3 at risk EG003
Paresthesia	Nervous system disorders	MedDRA 12	Systematic Assessment	EG0004 events2 affected45 at risk EG00118 events2 affected76 at risk EG0022 events1 affected3 at risk EG003
Peripheral motor neuropathy	Nervous system disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected45 at risk EG0010 events0 affected76 at risk EG0020 events0 affected3 at risk EG003
Peripheral sensory neuropathy	Nervous system disorders	MedDRA 12	Systematic Assessment	EG000298 events31 affected45 at risk EG001559 events57 affected76 at risk EG0023 events1 affected3 at risk EG003
Presyncope	Nervous system disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected45 at risk EG0010 events0 affected76 at risk EG0021 events1 affected3 at risk EG003
Somnolence	Nervous system disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected45 at risk EG0011 events1 affected76 at risk EG0020 events0 affected3 at risk EG003
Syncope	Nervous system disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected45 at risk EG0011 events1 affected76 at risk EG0020 events0 affected3 at risk EG003
Tremor	Nervous system disorders	MedDRA 12	Systematic Assessment	EG00031 events6 affected45 at risk EG00133 events9 affected76 at risk EG00232 events2 affected3 at risk EG003
Vasovagal reaction	Nervous system disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected45 at risk EG0011 events1 affected76 at risk EG0020 events0 affected3 at risk EG003
Agitation	Psychiatric disorders	MedDRA 12	Systematic Assessment	EG0008 events5 affected45 at risk EG00144 events7 affected76 at risk EG0020 events0 affected3 at risk EG003
Anxiety	Psychiatric disorders	MedDRA 12	Systematic Assessment	EG00030 events10 affected45 at risk EG00138 events10 affected76 at risk EG0023 events2 affected3 at risk EG003
Confusion	Psychiatric disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected45 at risk EG0013 events3 affected76 at risk EG0020 events0 affected3 at risk EG003
Depression	Psychiatric disorders	MedDRA 12	Systematic Assessment	EG0007 events4 affected45 at risk EG00144 events11 affected76 at risk EG0022 events1 affected3 at risk EG003
Insomnia	Psychiatric disorders	MedDRA 12	Systematic Assessment	EG00085 events18 affected45 at risk EG001204 events25 affected76 at risk EG00219 events2 affected3 at risk EG003
Irritability	Psychiatric disorders	MedDRA 12	Systematic Assessment	EG0005 events4 affected45 at risk EG00145 events5 affected76 at risk EG0020 events0 affected3 at risk EG003
Mania	Psychiatric disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected45 at risk EG0010 events0 affected76 at risk EG0020 events0 affected3 at risk EG003
Personality change	Psychiatric disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected45 at risk EG0011 events1 affected76 at risk EG0020 events0 affected3 at risk EG003
Psychiatric disorders - Other, specify	Psychiatric disorders	MedDRA 12	Systematic Assessment	EG0009 events4 affected45 at risk EG0019 events4 affected76 at risk EG0020 events0 affected3 at risk EG003
Restlessness	Psychiatric disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected45 at risk EG0012 events2 affected76 at risk EG0020 events0 affected3 at risk EG003
Suicidal ideation	Psychiatric disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected45 at risk EG0011 events1 affected76 at risk EG0020 events0 affected3 at risk EG003
Chronic kidney disease	Renal and urinary disorders	MedDRA 12	Systematic Assessment	EG0007 events4 affected45 at risk EG00120 events3 affected76 at risk EG0020 events0 affected3 at risk EG003
Hematuria	Renal and urinary disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected45 at risk EG0010 events0 affected76 at risk EG0020 events0 affected3 at risk EG003
Proteinuria	Renal and urinary disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected45 at risk EG0011 events1 affected76 at risk EG0020 events0 affected3 at risk EG003
Renal and urinary disorders - Oth spec	Renal and urinary disorders	MedDRA 12	Systematic Assessment	EG0005 events4 affected45 at risk EG0017 events3 affected76 at risk EG0020 events0 affected3 at risk EG003
Urinary frequency	Renal and urinary disorders	MedDRA 12	Systematic Assessment	EG0002 events1 affected45 at risk EG0010 events0 affected76 at risk EG0020 events0 affected3 at risk EG003
Urinary incontinence	Renal and urinary disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected45 at risk EG0018 events4 affected76 at risk EG0020 events0 affected3 at risk EG003
Urinary retention	Renal and urinary disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected45 at risk EG0010 events0 affected76 at risk EG0020 events0 affected3 at risk EG003
Urinary tract pain	Renal and urinary disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected45 at risk EG0010 events0 affected76 at risk EG0020 events0 affected3 at risk EG003
Urinary urgency	Renal and urinary disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected45 at risk EG0010 events0 affected76 at risk EG0020 events0 affected3 at risk EG003
Dysmenorrhea	Reproductive system and breast disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected45 at risk EG0010 events0 affected76 at risk EG0020 events0 affected3 at risk EG003
Erectile dysfunction	Reproductive system and breast disorders	MedDRA 12	Systematic Assessment	EG0004 events1 affected45 at risk EG0010 events0 affected76 at risk EG0020 events0 affected3 at risk EG003
Genital edema	Reproductive system and breast disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected45 at risk EG0010 events0 affected76 at risk EG0020 events0 affected3 at risk EG003
Pelvic pain	Reproductive system and breast disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected45 at risk EG0010 events0 affected76 at risk EG0021 events1 affected3 at risk EG003
Allergic rhinitis	Respiratory, thoracic and mediastinal disorders	MedDRA 12	Systematic Assessment	EG0002 events2 affected45 at risk EG0016 events2 affected76 at risk EG0020 events0 affected3 at risk EG003
Bronchopulmonary hemorrhage	Respiratory, thoracic and mediastinal disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected45 at risk EG0011 events1 affected76 at risk EG0020 events0 affected3 at risk EG003
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 12	Systematic Assessment	EG0004 events4 affected45 at risk EG00114 events9 affected76 at risk EG0023 events1 affected3 at risk EG003
Dyspnea	Respiratory, thoracic and mediastinal disorders	MedDRA 12	Systematic Assessment	EG00022 events8 affected45 at risk EG00192 events16 affected76 at risk EG0020 events0 affected3 at risk EG003
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected45 at risk EG0010 events0 affected76 at risk EG0020 events0 affected3 at risk EG003
Hiccups	Respiratory, thoracic and mediastinal disorders	MedDRA 12	Systematic Assessment	EG00017 events3 affected45 at risk EG0014 events1 affected76 at risk EG0022 events1 affected3 at risk EG003
Hoarseness	Respiratory, thoracic and mediastinal disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected45 at risk EG0015 events2 affected76 at risk EG0020 events0 affected3 at risk EG003
Hypoxia	Respiratory, thoracic and mediastinal disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected45 at risk EG0011 events1 affected76 at risk EG0020 events0 affected3 at risk EG003
Nasal congestion	Respiratory, thoracic and mediastinal disorders	MedDRA 12	Systematic Assessment	EG0002 events2 affected45 at risk EG0017 events6 affected76 at risk EG0020 events0 affected3 at risk EG003
Pleural effusion	Respiratory, thoracic and mediastinal disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected45 at risk EG0011 events1 affected76 at risk EG0020 events0 affected3 at risk EG003
Postnasal drip	Respiratory, thoracic and mediastinal disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected45 at risk EG0011 events1 affected76 at risk EG0020 events0 affected3 at risk EG003
Productive cough	Respiratory, thoracic and mediastinal disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected45 at risk EG00122 events3 affected76 at risk EG0020 events0 affected3 at risk EG003
Resp, thoracic, mediastinal - Oth spec	Respiratory, thoracic and mediastinal disorders	MedDRA 12	Systematic Assessment	EG0005 events4 affected45 at risk EG0011 events1 affected76 at risk EG0020 events0 affected3 at risk EG003
Sinus pain	Respiratory, thoracic and mediastinal disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected45 at risk EG0010 events0 affected76 at risk EG0020 events0 affected3 at risk EG003
Sleep apnea	Respiratory, thoracic and mediastinal disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected45 at risk EG0016 events1 affected76 at risk EG0020 events0 affected3 at risk EG003
Sore throat	Respiratory, thoracic and mediastinal disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected45 at risk EG0012 events2 affected76 at risk EG0020 events0 affected3 at risk EG003
Voice alteration	Respiratory, thoracic and mediastinal disorders	MedDRA 12	Systematic Assessment	EG00016 events1 affected45 at risk EG0014 events1 affected76 at risk EG0020 events0 affected3 at risk EG003
Wheezing	Respiratory, thoracic and mediastinal disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected45 at risk EG0014 events1 affected76 at risk EG0020 events0 affected3 at risk EG003
Alopecia	Skin and subcutaneous tissue disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected45 at risk EG0018 events3 affected76 at risk EG0020 events0 affected3 at risk EG003
Dry skin	Skin and subcutaneous tissue disorders	MedDRA 12	Systematic Assessment	EG0002 events1 affected45 at risk EG00110 events1 affected76 at risk EG0020 events0 affected3 at risk EG003
Erythema multiforme	Skin and subcutaneous tissue disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected45 at risk EG0011 events1 affected76 at risk EG0020 events0 affected3 at risk EG003
Hyperhidrosis	Skin and subcutaneous tissue disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected45 at risk EG0011 events1 affected76 at risk EG00216 events1 affected3 at risk EG003
Nail ridging	Skin and subcutaneous tissue disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected45 at risk EG0013 events1 affected76 at risk EG0020 events0 affected3 at risk EG003
Pain of skin	Skin and subcutaneous tissue disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected45 at risk EG0011 events1 affected76 at risk EG0020 events0 affected3 at risk EG003
Pruritus	Skin and subcutaneous tissue disorders	MedDRA 12	Systematic Assessment	EG0004 events4 affected45 at risk EG00123 events4 affected76 at risk EG0021 events1 affected3 at risk EG003
Rash acneiform	Skin and subcutaneous tissue disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected45 at risk EG0011 events1 affected76 at risk EG0020 events0 affected3 at risk EG003
Rash maculo-papular	Skin and subcutaneous tissue disorders	MedDRA 12	Systematic Assessment	EG00022 events13 affected45 at risk EG00131 events13 affected76 at risk EG0021 events1 affected3 at risk EG003
Skin and subcut tissue disord - Oth spec	Skin and subcutaneous tissue disorders	MedDRA 12	Systematic Assessment	EG0004 events2 affected45 at risk EG00110 events5 affected76 at risk EG0020 events0 affected3 at risk EG003
Urticaria	Skin and subcutaneous tissue disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected45 at risk EG0010 events0 affected76 at risk EG0020 events0 affected3 at risk EG003
Surgical and medical proced - Oth spec	Surgical and medical procedures	MedDRA 12	Systematic Assessment	EG0002 events2 affected45 at risk EG0014 events1 affected76 at risk EG0020 events0 affected3 at risk EG003
Flushing	Vascular disorders	MedDRA 12	Systematic Assessment	EG00026 events3 affected45 at risk EG00113 events3 affected76 at risk EG0020 events0 affected3 at risk EG003
Hematoma	Vascular disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected45 at risk EG0011 events1 affected76 at risk EG0020 events0 affected3 at risk EG003
Hot flashes	Vascular disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected45 at risk EG00132 events4 affected76 at risk EG0020 events0 affected3 at risk EG003
Hypertension	Vascular disorders	MedDRA 12	Systematic Assessment	EG00036 events9 affected45 at risk EG001103 events16 affected76 at risk EG0020 events0 affected3 at risk EG003
Hypotension	Vascular disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected45 at risk EG00117 events5 affected76 at risk EG0020 events0 affected3 at risk EG003
Phlebitis	Vascular disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected45 at risk EG0011 events1 affected76 at risk EG0020 events0 affected3 at risk EG003
Thromboembolic event	Vascular disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected45 at risk EG0016 events3 affected76 at risk EG0020 events0 affected3 at risk EG003

ID	Term
D011246	Pregnadienetriols
D011245	Pregnadienes
D011278	Pregnanes
D013256	Steroids
D000072473	Fused-Ring Compounds
D011083	Polycyclic Compounds
D013259	Steroids, Fluorinated