Study to Evaluate Safety, Tolerability, Pharmacokinetics,... | NCT02392611

ID	Type	Description	Link
2016-001912-39	EudraCT Number

Label	Type	Description	Intervention Names
Monotherapy: Alobresib 0.6 mg	Experimental	Participants with advanced solid tumors and lymphomas who have failed or are intolerant to standard therapy or for whom no standard therapy exists, will receive alobresib at a dose of 0.6 mg to determine the MTD.	Drug: Alobresib
Monotherapy: Alobresib 1.4 mg	Experimental	Participants with advanced solid tumors and lymphomas who have failed or are intolerant to standard therapy or for whom no standard therapy exists, will receive alobresib at a dose of 1.4 mg to determine the MTD.	Drug: Alobresib
Monotherapy: Alobresib 2 mg	Experimental	Participants with advanced solid tumors and lymphomas who have failed or are intolerant to standard therapy or for whom no standard therapy exists, will receive alobresib at a dose of 2 mg to determine the MTD.	Drug: Alobresib
Monotherapy: Alobresib 3 mg	Experimental	Participants with advanced solid tumors and lymphomas who have failed or are intolerant to standard therapy or for whom no standard therapy exists, will receive alobresib at a dose of 3 mg to determine the MTD.	Drug: Alobresib
Monotherapy: Alobresib 4 mg	Experimental

Name	Type	Description	Arm Group Labels	Other Names
Alobresib	Drug	Tablet administered orally once daily on Study Day 1 through Cycle 1 Day 28 of 28 days cycle	Combination Therapy: Alobresib 2 mg + Exemestane Combination Therapy: Alobresib 2 mg + Fulvestrant

Measure	Description	Time Frame
Number of Participants Experiencing Dose Limiting Toxicities (DLTs)	A DLT was a toxicity, considered possibly related to alobresib, and which occurred during DLT assessment window (Day 1 through Cycle 1 Day 28) in each cohort: Grade ≥ 4 neutropenia (absolute neutrophil count [ANC] < 500/mm^3); Grade ≥3 neutropenia (ANC< 1000/mm^3) with fever (a single temperature of > 38.3°C or a sustained temperature of ≥ 38°C for more than 1 hour [hr]); Grade ≥ 3 thrombocytopenia; Grade ≥ 2 bleeding; Grade ≥ 3 non hematologic toxicity, except Grade 3 nausea or emesis with maximum duration of 48 hrs on adequate medical therapy and Grade 3 diarrhea which persists for < 72 hrs in absence of maximal medical therapy; Grade ≥ 2 non hematologic treatment-emergent adverse event (TEAE) of potential clinical significance; treatment interruption ≥ 7 days due to unresolved toxicity; and any Grade 3 or 4 elevation in aspartate aminotransferase (AST) or alanine aminotransferase (ALT) associated with a Grade 2 elevation in bilirubin that is at least possibly related to alobresib.	Baseline (Day 1) up to 28 days

Measure	Description	Time Frame
Pharmacokinetic (PK) Parameter: Cmax of Alobresib	Cmax is defined as the maximum concentration of the drug.	Cycle 1: Predose (0 hr), 0.5, 1, 2, 3, 4, 6, 8, 12 and 24 hrs postdose on Days 1 and 8 (1 Cycle = 28 days)
PK Parameter: Ctau of Alobresib

Eligibility Module

Eligibility Criteria

Key Inclusion Criteria:

Group 1: Histologically or cytologically confirmed advanced malignant solid tumor or lymphoma (any subtype) that is refractory to or intolerant of standard therapy or for which no standard therapy is available
Group 2: Post-menopausal women with advanced stage estrogen receptor positive breast cancer who are candidates for exemestane or fulvestrant
Group 3: Individuals with lymphoma are limited to diffuse large B-cell lymphoma and peripheral T-cell lymphoma that are refractory to or intolerant of standard therapy or for which no standard therapy is available
Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 1
Adequate organ function defined as follows:
- Hematologic: Platelets ≥ 100 x 10^9/L; Hemoglobin ≥ 9.0 g/ dL; Absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L (without platelet transfusion or any growth factors within previous 7 days of the hematologic laboratory values obtained at screening visit). Participants in the Group 3 lymphoma expansion may be enrolled with an ANC of ≥ 1.0 x 10^9 /L; Platelets ≥ 75 x 10^9 /L.
- Hepatic: Aspartate transaminase (AST) / Alanine transaminase (ALT) ≤ 2.5 x upper limit of normal (ULN) (if liver metastases are present, ≤ 5 x ULN); Total or conjugated bilirubin ≤ 1.5 x ULN
- Renal: Serum creatinine ≤ 1.5 x ULN or creatinine clearance (CrCl) ≥ 60 ml/min as calculated by the cockcroft-gault method
Coagulation: International Normalized Ratio (INR) ≤ 1.2

Key Exclusion Criteria:

Known brain metastasis or leptomeningeal disease
Myocardial infarction, symptomatic congestive heart failure (New York Heart Association Classification > Class II), unstable angina, or serious uncontrolled cardiac arrhythmia within the last 6 months of study Day 1
Major surgery, defined as any surgical procedure that involves general anesthesia and a significant incision (ie, larger than what is required for placement of central venous access, percutaneous feeding tube, or biopsy) within 28 days of first dose of study drug
History of long QT syndrome or whose corrected QT interval (QTc) measured (Fridericia method) at screening is prolonged (> 450 ms for males and > 470 ms for females). Individuals who screen-fail due to this criterion are not eligible to be re-screened
Clinically significant bleeding within 28 days of study Day 1
Known human immunodeficiency virus (HIV) infection
Hepatitis B surface antigen positive
Hepatitis C virus (HCV) antibody positive
No active anticoagulation within 7 days of study Day 1; including acetylsalicylic acid, low molecular weight heparin, or warfarin.

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Name	Affiliation	Role
Gilead Study Director	Gilead Sciences	Study Director

ID	Title	Description
FG000	Monotherapy: Alobresib 0.6 mg	Participants with advanced solid tumors and lymphomas who had failed or were intolerant to standard therapy, or for whom no standard therapy existed received alobresib tablets at a dose of 0.6 mg orally once daily on Study Day 1 through Cycle 1 Day 28 (C1D28) of 28 days cycle to determine the maximum tolerated dose (MTD).

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Jun 20, 2016	Oct 13, 2020

Arm/Group Information

ID	Title	Description
BG000	Monotherapy: Alobresib 0.6 mg	Participants with advanced solid tumors and lymphomas who had failed or were intolerant to standard therapy, or for whom no standard therapy existed received alobresib tablets at a dose of 0.6 mg orally once daily on Study Day 1 through C1D28 of 28 days cycle to determine the MTD.
BG001	Monotherapy: Alobresib 1.4 mg	Participants with advanced solid tumors and lymphomas who had failed or were intolerant to standard therapy, or for whom no standard therapy existed received alobresib tablets at a dose of 1.4 mg orally once daily on Study Day 1 through C1D28 of 28 days cycle to determine the MTD.
BG002	Monotherapy: Alobresib 2 mg	Participants with advanced solid tumors and lymphomas who had failed or were intolerant to standard therapy, or for whom no standard therapy existed received alobresib tablets at a dose of 2 mg orally once daily on Study Day 1 through C1D28 of 28 days cycle to determine the MTD.
BG003	Monotherapy: Alobresib 3 mg	Participants with advanced solid tumors and lymphomas who had failed or were intolerant to standard therapy, or for whom no standard therapy existed received alobresib tablets at a dose of 3 mg orally once daily on Study Day 1 through C1D28 of 28 days cycle to determine the MTD.
BG004	Monotherapy: Alobresib 4 mg	Participants with advanced solid tumors and lymphomas who had failed or were intolerant to standard therapy, or for whom no standard therapy existed received alobresib tablets at a dose of 4 mg orally once daily on Study Day 1 through C1D28 of 28 days cycle to determine the MTD.
BG005	Monotherapy: Alobresib 6 mg	Participants with advanced solid tumors and lymphomas who had failed or were intolerant to standard therapy, or for whom no standard therapy existed received alobresib tablets at a dose of 6 mg orally once daily on Study Day 1 through C1D28 of 28 days cycle to determine the MTD.
BG006	Combination Therapy: Alobresib 2 mg + Exemestane	Participants with advanced stage estrogen receptor positive breast cancer for whom no standard curative therapy existed, received alobresib tablets at a dose of 2 mg orally once daily on Study Day 1 through C1D28 of 28 days cycle in combination with exemestane 25 mg tablets administered orally once daily on C1D1 of 28 days cycle.
BG007	Combination Therapy: Alobresib 2 mg + Fulvestrant	Participants with advanced stage estrogen receptor positive breast cancer for whom no standard curative therapy existed, received alobresib tablets at a dose of 2 mg orally once daily on Study Day 1 through C1D28 of 28 days cycle in combination with fulvestrant 500 mg administered intramuscularly on C1D1 of 28 days cycle and every 28 days (± 3 days).
BG008	Combination Therapy: Alobresib 3 mg + Fulvestrant	Participants with advanced stage estrogen receptor positive breast cancer for whom no standard curative therapy existed, received alobresib tablets at a dose of 3 mg orally once daily on Study Day 1 through C1D28 of 28 days cycle in combination with fulvestrant 500 mg administered intramuscularly on C1D1 of 28 days cycle and every 28 days (± 3 days).
BG009	Total	Total of all reporting groups

Units	Counts
Participants	BG0002 BG0011 BG0021 BG0037 BG0046 BG0054 BG0064 BG0073 BG0083 BG00931

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

Number of Participants Experiencing Dose Limiting Toxicities (DLTs)

A DLT was a toxicity, considered possibly related to alobresib, and which occurred during DLT assessment window (Day 1 through Cycle 1 Day 28) in each cohort: Grade ≥ 4 neutropenia (absolute neutrophil count [ANC] < 500/mm^3); Grade ≥3 neutropenia (ANC< 1000/mm^3) with fever (a single temperature of > 38.3°C or a sustained temperature of ≥ 38°C for more than 1 hour [hr]); Grade ≥ 3 thrombocytopenia; Grade ≥ 2 bleeding; Grade ≥ 3 non hematologic toxicity, except Grade 3 nausea or emesis with maximum duration of 48 hrs on adequate medical therapy and Grade 3 diarrhea which persists for < 72 hrs in absence of maximal medical therapy; Grade ≥ 2 non hematologic treatment-emergent adverse event (TEAE) of potential clinical significance; treatment interruption ≥ 7 days due to unresolved toxicity; and any Grade 3 or 4 elevation in aspartate aminotransferase (AST) or alanine aminotransferase (ALT) associated with a Grade 2 elevation in bilirubin that is at least possibly related to alobresib.

The Full Analysis Set included all participants who received at least 1 dose of study drug.

Posted

Count of Participants

Participants

Baseline (Day 1) up to 28 days

ID	Title	Description
OG000	Monotherapy: Alobresib 0.6 mg	Participants with advanced solid tumors and lymphomas who had failed or were intolerant to standard therapy, or for whom no standard therapy existed received alobresib tablets at a dose of 0.6 mg orally once daily on Study Day 1 through C1D28 of 28 days cycle to determine the MTD.
OG001	Monotherapy: Alobresib 1.4 mg	Participants with advanced solid tumors and lymphomas who had failed or were intolerant to standard therapy, or for whom no standard therapy existed received alobresib tablets at a dose of 1.4 mg orally once daily on Study Day 1 through C1D28 of 28 days cycle to determine the MTD.
OG002	Monotherapy: Alobresib 2 mg	Participants with advanced solid tumors and lymphomas who had failed or were intolerant to standard therapy, or for whom no standard therapy existed received alobresib tablets at a dose of 2 mg orally once daily on Study Day 1 through C1D28 of 28 days cycle to determine the MTD.
OG003	Monotherapy: Alobresib 3 mg	Participants with advanced solid tumors and lymphomas who had failed or were intolerant to standard therapy, or for whom no standard therapy existed received alobresib tablets at a dose of 3 mg orally once daily on Study Day 1 through C1D28 of 28 days cycle to determine the MTD.
OG004	Monotherapy: Alobresib 4 mg	Participants with advanced solid tumors and lymphomas who had failed or were intolerant to standard therapy, or for whom no standard therapy existed received alobresib tablets at a dose of 4 mg orally once daily on Study Day 1 through C1D28 of 28 days cycle to determine the MTD.
OG005	Monotherapy: Alobresib 6 mg

Units	Counts
Participants	OG0002 OG0011 OG0021 OG003

Title

Denominators

Categories

Title	Measurements
	OG0000 OG0010 OG0020 OG003

Secondary

Pharmacokinetic (PK) Parameter: Cmax of Alobresib

Cmax is defined as the maximum concentration of the drug.

Participants in the PK Analysis Set (included all enrolled participants who took at least 1 dose of study drug and had at least 1 nonmissing postdose value reported by the PK laboratory) with available data were analyzed.

Posted

Mean

Standard Deviation

ng/mL

Cycle 1: Predose (0 hr), 0.5, 1, 2, 3, 4, 6, 8, 12 and 24 hrs postdose on Days 1 and 8 (1 Cycle = 28 days)

ID	Title	Description
OG000	Monotherapy: Alobresib 0.6 mg	Participants with advanced solid tumors and lymphomas who had failed or were intolerant to standard therapy, or for whom no standard therapy existed received alobresib tablets at a dose of 0.6 mg orally once daily on Study Day 1 through C1D28 of 28 days cycle to determine the MTD.
OG001	Monotherapy: Alobresib 1.4 mg	Participants with advanced solid tumors and lymphomas who had failed or were intolerant to standard therapy, or for whom no standard therapy existed received alobresib tablets at a dose of 1.4 mg orally once daily on Study Day 1 through C1D28 of 28 days cycle to determine the MTD.
OG002	Monotherapy: Alobresib 2 mg	Participants with advanced solid tumors and lymphomas who had failed or were intolerant to standard therapy, or for whom no standard therapy existed received alobresib tablets at a dose of 2 mg orally once daily on Study Day 1 through C1D28 of 28 days cycle to determine the MTD.

Secondary

PK Parameter: Ctau of Alobresib

Ctau is defined as the observed drug concentration at the end of the dosing interval.

Participants in the PK Analysis Set with available data were analyzed.

Posted

Mean

Standard Deviation

ng/mL

Cycle 1: Predose (0 hr), 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hrs postdose on Day 8 (1 Cycle = 28 days)

ID	Title	Description
OG000	Monotherapy: Alobresib 0.6 mg	Participants with advanced solid tumors and lymphomas who had failed or were intolerant to standard therapy, or for whom no standard therapy existed received alobresib tablets at a dose of 0.6 mg orally once daily on Study Day 1 through C1D28 of 28 days cycle to determine the MTD.
OG001	Monotherapy: Alobresib 1.4 mg	Participants with advanced solid tumors and lymphomas who had failed or were intolerant to standard therapy, or for whom no standard therapy existed received alobresib tablets at a dose of 1.4 mg orally once daily on Study Day 1 through C1D28 of 28 days cycle to determine the MTD.
OG002	Monotherapy: Alobresib 2 mg	Participants with advanced solid tumors and lymphomas who had failed or were intolerant to standard therapy, or for whom no standard therapy existed received alobresib tablets at a dose of 2 mg orally once daily on Study Day 1 through C1D28 of 28 days cycle to determine the MTD.

Secondary

PK Parameter: AUC0-24 of Alobresib

AUC0-24 is defined as the concentration of drug over time from time zero to time 24 hrs.

Participants in the PK Analysis Set with available data were analyzed.

Posted

Mean

Standard Deviation

h*ng/mL

Cycle 1: Predose (0 hr), 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hrs postdose on Days 1 and 8 (1 Cycle = 28 days)

ID	Title	Description
OG000	Monotherapy: Alobresib 0.6 mg	Participants with advanced solid tumors and lymphomas who had failed or were intolerant to standard therapy, or for whom no standard therapy existed received alobresib tablets at a dose of 0.6 mg orally once daily on Study Day 1 through C1D28 of 28 days cycle to determine the MTD.
OG001	Monotherapy: Alobresib 1.4 mg	Participants with advanced solid tumors and lymphomas who had failed or were intolerant to standard therapy, or for whom no standard therapy existed received alobresib tablets at a dose of 1.4 mg orally once daily on Study Day 1 through C1D28 of 28 days cycle to determine the MTD.
OG002	Monotherapy: Alobresib 2 mg	Participants with advanced solid tumors and lymphomas who had failed or were intolerant to standard therapy, or for whom no standard therapy existed received alobresib tablets at a dose of 2 mg orally once daily on Study Day 1 through C1D28 of 28 days cycle to determine the MTD.

Secondary

PK Parameter: AUCtau of Alobresib

AUCtau is defined as the concentration of drug over time (the area under the concentration verses time curve over the dosing interval).

Participants in the PK Analysis Set with available data were analyzed.

Posted

Mean

Standard Deviation

h*ng/mL

Cycle 1: Predose (0 hr), 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hrs postdose on Day 8 (1 Cycle = 28 days)

ID	Title	Description
OG000	Monotherapy: Alobresib 0.6 mg	Participants with advanced solid tumors and lymphomas who had failed or were intolerant to standard therapy, or for whom no standard therapy existed received alobresib tablets at a dose of 0.6 mg orally once daily on Study Day 1 through C1D28 of 28 days cycle to determine the MTD.
OG001	Monotherapy: Alobresib 1.4 mg	Participants with advanced solid tumors and lymphomas who had failed or were intolerant to standard therapy, or for whom no standard therapy existed received alobresib tablets at a dose of 1.4 mg orally once daily on Study Day 1 through C1D28 of 28 days cycle to determine the MTD.
OG002	Monotherapy: Alobresib 2 mg	Participants with advanced solid tumors and lymphomas who had failed or were intolerant to standard therapy, or for whom no standard therapy existed received alobresib tablets at a dose of 2 mg orally once daily on Study Day 1 through C1D28 of 28 days cycle to determine the MTD.

Secondary

PK Parameter: Tmax of Alobresib

Tmax is defined as the time (observed time point) of Cmax.

Participants in the PK Analysis Set with available data were analyzed.

Posted

Median

Full Range

hour

Cycle 1: Predose (0 hr), 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hrs postdose on Days 1 and 8 (1 Cycle = 28 days)

ID	Title	Description
OG000	Monotherapy: Alobresib 0.6 mg	Participants with advanced solid tumors and lymphomas who had failed or were intolerant to standard therapy, or for whom no standard therapy existed received alobresib tablets at a dose of 0.6 mg orally once daily on Study Day 1 through C1D28 of 28 days cycle to determine the MTD.
OG001	Monotherapy: Alobresib 1.4 mg	Participants with advanced solid tumors and lymphomas who had failed or were intolerant to standard therapy, or for whom no standard therapy existed received alobresib tablets at a dose of 1.4 mg orally once daily on Study Day 1 through C1D28 of 28 days cycle to determine the MTD.
OG002	Monotherapy: Alobresib 2 mg	Participants with advanced solid tumors and lymphomas who had failed or were intolerant to standard therapy, or for whom no standard therapy existed received alobresib tablets at a dose of 2 mg orally once daily on Study Day 1 through C1D28 of 28 days cycle to determine the MTD.

Secondary

PK Parameter: t1/2 of Alobresib

t1/2 is defined as the estimate of the terminal elimination half-life of the drug. Due to short sampling period of the terminal elimination phase in these cohorts t1/2 values should be interpreted with caution.

Participants in the PK Analysis Set with available data were analyzed.

Posted

Median

Full Range

hour

Cycle 1: Predose (0 hr), 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hrs postdose on Days 1 and 8 (1 Cycle = 28 days)

ID	Title	Description
OG000	Monotherapy: Alobresib 0.6 mg	Participants with advanced solid tumors and lymphomas who had failed or were intolerant to standard therapy, or for whom no standard therapy existed received alobresib tablets at a dose of 0.6 mg orally once daily on Study Day 1 through C1D28 of 28 days cycle to determine the MTD.
OG001	Monotherapy: Alobresib 1.4 mg	Participants with advanced solid tumors and lymphomas who had failed or were intolerant to standard therapy, or for whom no standard therapy existed received alobresib tablets at a dose of 1.4 mg orally once daily on Study Day 1 through C1D28 of 28 days cycle to determine the MTD.
OG002	Monotherapy: Alobresib 2 mg	Participants with advanced solid tumors and lymphomas who had failed or were intolerant to standard therapy, or for whom no standard therapy existed received alobresib tablets at a dose of 2 mg orally once daily on Study Day 1 through C1D28 of 28 days cycle to determine the MTD.

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	Monotherapy: Alobresib 0.6 mg	Participants with advanced solid tumors and lymphomas who had failed or were intolerant to standard therapy, or for whom no standard therapy existed received alobresib tablets at a dose of 0.6 mg orally once daily on Study Day 1 through C1D28 of 28 days cycle to determine the MTD.	1	2	1	2	2	2
EG001	Monotherapy: Alobresib 1.4 mg	Participants with advanced solid tumors and lymphomas who had failed or were intolerant to standard therapy, or for whom no standard therapy existed received alobresib tablets at a dose of 1.4 mg orally once daily on Study Day 1 through C1D28 of 28 days cycle to determine the MTD.	0	1	1	1	1	1
EG002	Monotherapy: Alobresib 2 mg	Participants with advanced solid tumors and lymphomas who had failed or were intolerant to standard therapy, or for whom no standard therapy existed received alobresib tablets at a dose of 2 mg orally once daily on Study Day 1 through C1D28 of 28 days cycle to determine the MTD.	0	1	0	1	1	1
EG003	Monotherapy: Alobresib 3 mg	Participants with advanced solid tumors and lymphomas who had failed or were intolerant to standard therapy, or for whom no standard therapy existed received alobresib tablets at a dose of 3 mg orally once daily on Study Day 1 through C1D28 of 28 days cycle to determine the MTD.	1	7	3	7	7	7
EG004	Monotherapy: Alobresib 4 mg	Participants with advanced solid tumors and lymphomas who had failed or were intolerant to standard therapy, or for whom no standard therapy existed received alobresib tablets at a dose of 4 mg orally once daily on Study Day 1 through C1D28 of 28 days cycle to determine the MTD.	0	6	2	6	5	6
EG005	Monotherapy: Alobresib 6 mg	Participants with advanced solid tumors and lymphomas who had failed or were intolerant to standard therapy, or for whom no standard therapy existed received alobresib tablets at a dose of 6 mg orally once daily on Study Day 1 through C1D28 of 28 days cycle to determine the MTD.	1	4	1	4	4	4
EG006	Combination Therapy: Alobresib 2 mg + Exemestane	Participants with advanced stage estrogen receptor positive breast cancer for whom no standard curative therapy existed, received alobresib tablets at a dose of 2 mg orally once daily on Study Day 1 through C1D28 of 28 days cycle in combination with exemestane 25 mg tablets administered orally once daily on C1D1 of 28 days cycle.	1	4	0	4	3	4
EG007	Combination Therapy: Alobresib 2 mg + Fulvestrant	Participants with advanced stage estrogen receptor positive breast cancer for whom no standard curative therapy existed, received alobresib tablets at a dose of 2 mg orally once daily on Study Day 1 through C1D28 of 28 days cycle in combination with fulvestrant 500 mg administered intramuscularly on C1D1 of 28 days cycle and every 28 days (± 3 days).	0	3	0	3	3	3
EG008	Combination Therapy: Alobresib 3 mg + Fulvestrant	Participants with advanced stage estrogen receptor positive breast cancer for whom no standard curative therapy existed, received alobresib tablets at a dose of 3 mg orally once daily on Study Day 1 through C1D28 of 28 days cycle in combination with fulvestrant 500 mg administered intramuscularly on C1D1 of 28 days cycle and every 28 days (± 3 days).	0	3	0	3	3	3

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 20.1	Systematic Assessment	EG0001 affected2 at risk EG0010 affected1 at risk EG0020 affected1 at risk EG0031 affected7 at risk EG0040 affected6 at risk EG0051 affected4 at risk EG0060 affected4 at risk EG0070 affected3 at risk EG0081 affected3 at risk
Neutropenia	Blood and lymphatic system disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected2 at risk EG0010 affected1 at risk EG0020 affected1 at risk EG003
Splenomegaly	Blood and lymphatic system disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected2 at risk EG0011 affected1 at risk EG0020 affected1 at risk EG003
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected2 at risk EG0011 affected1 at risk EG0020 affected1 at risk EG003
Palpitations	Cardiac disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected2 at risk EG0010 affected1 at risk EG0020 affected1 at risk EG003
Tachycardia	Cardiac disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected2 at risk EG0010 affected1 at risk EG0020 affected1 at risk EG003
Cataract	Eye disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected2 at risk EG0010 affected1 at risk EG0020 affected1 at risk EG003
Abdominal distension	Gastrointestinal disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected2 at risk EG0010 affected1 at risk EG0020 affected1 at risk EG003
Abdominal pain	Gastrointestinal disorders	MedDRA 20.1	Systematic Assessment	EG0001 affected2 at risk EG0010 affected1 at risk EG0020 affected1 at risk EG003
Ascites	Gastrointestinal disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected2 at risk EG0010 affected1 at risk EG0020 affected1 at risk EG003
Constipation	Gastrointestinal disorders	MedDRA 20.1	Systematic Assessment	EG0001 affected2 at risk EG0010 affected1 at risk EG0020 affected1 at risk EG003
Diarrhoea	Gastrointestinal disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected2 at risk EG0010 affected1 at risk EG0020 affected1 at risk EG003
Dry mouth	Gastrointestinal disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected2 at risk EG0010 affected1 at risk EG0020 affected1 at risk EG003
Dyspepsia	Gastrointestinal disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected2 at risk EG0010 affected1 at risk EG0020 affected1 at risk EG003
Flatulence	Gastrointestinal disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected2 at risk EG0010 affected1 at risk EG0020 affected1 at risk EG003
Gastrointestinal sounds abnormal	Gastrointestinal disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected2 at risk EG0010 affected1 at risk EG0020 affected1 at risk EG003
Gastrooesophageal reflux disease	Gastrointestinal disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected2 at risk EG0010 affected1 at risk EG0020 affected1 at risk EG003
Gingival pain	Gastrointestinal disorders	MedDRA 20.1	Systematic Assessment	EG0001 affected2 at risk EG0010 affected1 at risk EG0020 affected1 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA 20.1	Systematic Assessment	EG0001 affected2 at risk EG0011 affected1 at risk EG0020 affected1 at risk EG003
Vomiting	Gastrointestinal disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected2 at risk EG0010 affected1 at risk EG0020 affected1 at risk EG003
Catheter site pain	General disorders	MedDRA 20.1	Systematic Assessment	EG0001 affected2 at risk EG0010 affected1 at risk EG0020 affected1 at risk EG003
Chest pain	General disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected2 at risk EG0010 affected1 at risk EG0020 affected1 at risk EG003
Fatigue	General disorders	MedDRA 20.1	Systematic Assessment	EG0001 affected2 at risk EG0011 affected1 at risk EG0020 affected1 at risk EG003
Generalised oedema	General disorders	MedDRA 20.1	Systematic Assessment	EG0001 affected2 at risk EG0010 affected1 at risk EG0020 affected1 at risk EG003
Ill-defined disorder	General disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected2 at risk EG0010 affected1 at risk EG0020 affected1 at risk EG003
Injection site reaction	General disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected2 at risk EG0010 affected1 at risk EG0020 affected1 at risk EG003
Oedema peripheral	General disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected2 at risk EG0010 affected1 at risk EG0020 affected1 at risk EG003
Pyrexia	General disorders	MedDRA 20.1	Systematic Assessment	EG0001 affected2 at risk EG0010 affected1 at risk EG0020 affected1 at risk EG003
Hyperbilirubinaemia	Hepatobiliary disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected2 at risk EG0011 affected1 at risk EG0020 affected1 at risk EG003
Bronchitis	Infections and infestations	MedDRA 20.1	Systematic Assessment	EG0000 affected2 at risk EG0010 affected1 at risk EG0020 affected1 at risk EG003
Cellulitis	Infections and infestations	MedDRA 20.1	Systematic Assessment	EG0000 affected2 at risk EG0010 affected1 at risk EG0020 affected1 at risk EG003
Localised infection	Infections and infestations	MedDRA 20.1	Systematic Assessment	EG0000 affected2 at risk EG0010 affected1 at risk EG0020 affected1 at risk EG003
Oral candidiasis	Infections and infestations	MedDRA 20.1	Systematic Assessment	EG0000 affected2 at risk EG0010 affected1 at risk EG0020 affected1 at risk EG003
Sepsis	Infections and infestations	MedDRA 20.1	Systematic Assessment	EG0001 affected2 at risk EG0010 affected1 at risk EG0020 affected1 at risk EG003
Sinusitis	Infections and infestations	MedDRA 20.1	Systematic Assessment	EG0000 affected2 at risk EG0010 affected1 at risk EG0020 affected1 at risk EG003
Tinea cruris	Infections and infestations	MedDRA 20.1	Systematic Assessment	EG0000 affected2 at risk EG0010 affected1 at risk EG0020 affected1 at risk EG003
Upper respiratory tract infection	Infections and infestations	MedDRA 20.1	Systematic Assessment	EG0000 affected2 at risk EG0010 affected1 at risk EG0020 affected1 at risk EG003
Urinary tract infection	Infections and infestations	MedDRA 20.1	Systematic Assessment	EG0000 affected2 at risk EG0010 affected1 at risk EG0020 affected1 at risk EG003
Contusion	Injury, poisoning and procedural complications	MedDRA 20.1	Systematic Assessment	EG0000 affected2 at risk EG0010 affected1 at risk EG0020 affected1 at risk EG003
Face injury	Injury, poisoning and procedural complications	MedDRA 20.1	Systematic Assessment	EG0000 affected2 at risk EG0010 affected1 at risk EG0020 affected1 at risk EG003
Incision site pain	Injury, poisoning and procedural complications	MedDRA 20.1	Systematic Assessment	EG0000 affected2 at risk EG0010 affected1 at risk EG0020 affected1 at risk EG003
Stoma site haemorrhage	Injury, poisoning and procedural complications	MedDRA 20.1	Systematic Assessment	EG0001 affected2 at risk EG0010 affected1 at risk EG0020 affected1 at risk EG003
Wound	Injury, poisoning and procedural complications	MedDRA 20.1	Systematic Assessment	EG0000 affected2 at risk EG0010 affected1 at risk EG0020 affected1 at risk EG003
Wrist fracture	Injury, poisoning and procedural complications	MedDRA 20.1	Systematic Assessment	EG0000 affected2 at risk EG0010 affected1 at risk EG0020 affected1 at risk EG003
Aspartate aminotransferase increased	Investigations	MedDRA 20.1	Systematic Assessment	EG0000 affected2 at risk EG0011 affected1 at risk EG0020 affected1 at risk EG003
Blood bilirubin increased	Investigations	MedDRA 20.1	Systematic Assessment	EG0001 affected2 at risk EG0010 affected1 at risk EG0020 affected1 at risk EG003
Platelet count decreased	Investigations	MedDRA 20.1	Systematic Assessment	EG0000 affected2 at risk EG0010 affected1 at risk EG0020 affected1 at risk EG003
Decreased appetite	Metabolism and nutrition disorders	MedDRA 20.1	Systematic Assessment	EG0002 affected2 at risk EG0010 affected1 at risk EG0020 affected1 at risk EG003
Dehydration	Metabolism and nutrition disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected2 at risk EG0011 affected1 at risk EG0020 affected1 at risk EG003
Hypokalaemia	Metabolism and nutrition disorders	MedDRA 20.1	Systematic Assessment	EG0001 affected2 at risk EG0011 affected1 at risk EG0020 affected1 at risk EG003
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected2 at risk EG0010 affected1 at risk EG0020 affected1 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected2 at risk EG0010 affected1 at risk EG0020 affected1 at risk EG003
Bone pain	Musculoskeletal and connective tissue disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected2 at risk EG0011 affected1 at risk EG0020 affected1 at risk EG003
Flank pain	Musculoskeletal and connective tissue disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected2 at risk EG0010 affected1 at risk EG0020 affected1 at risk EG003
Muscle spasms	Musculoskeletal and connective tissue disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected2 at risk EG0010 affected1 at risk EG0020 affected1 at risk EG003
Muscular weakness	Musculoskeletal and connective tissue disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected2 at risk EG0010 affected1 at risk EG0020 affected1 at risk EG003
Musculoskeletal pain	Musculoskeletal and connective tissue disorders	MedDRA 20.1	Systematic Assessment	EG0001 affected2 at risk EG0010 affected1 at risk EG0020 affected1 at risk EG003
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected2 at risk EG0010 affected1 at risk EG0020 affected1 at risk EG003
Neck pain	Musculoskeletal and connective tissue disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected2 at risk EG0010 affected1 at risk EG0020 affected1 at risk EG003
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected2 at risk EG0010 affected1 at risk EG0020 affected1 at risk EG003
Tumour pain	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 20.1	Systematic Assessment	EG0000 affected2 at risk EG0011 affected1 at risk EG0020 affected1 at risk EG003
Dizziness	Nervous system disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected2 at risk EG0011 affected1 at risk EG0020 affected1 at risk EG003
Dysgeusia	Nervous system disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected2 at risk EG0010 affected1 at risk EG0020 affected1 at risk EG003
Hypoaesthesia	Nervous system disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected2 at risk EG0010 affected1 at risk EG0020 affected1 at risk EG003
Presyncope	Nervous system disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected2 at risk EG0010 affected1 at risk EG0020 affected1 at risk EG003
Somnolence	Nervous system disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected2 at risk EG0010 affected1 at risk EG0020 affected1 at risk EG003
Transient ischaemic attack	Nervous system disorders	MedDRA 20.1	Systematic Assessment	EG0001 affected2 at risk EG0010 affected1 at risk EG0020 affected1 at risk EG003
Anxiety	Psychiatric disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected2 at risk EG0010 affected1 at risk EG0020 affected1 at risk EG003
Depression	Psychiatric disorders	MedDRA 20.1	Systematic Assessment	EG0001 affected2 at risk EG0010 affected1 at risk EG0020 affected1 at risk EG003
Insomnia	Psychiatric disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected2 at risk EG0010 affected1 at risk EG0020 affected1 at risk EG003
Acute kidney injury	Renal and urinary disorders	MedDRA 20.1	Systematic Assessment	EG0001 affected2 at risk EG0010 affected1 at risk EG0020 affected1 at risk EG003
Haematuria	Renal and urinary disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected2 at risk EG0010 affected1 at risk EG0020 affected1 at risk EG003
Hydronephrosis	Renal and urinary disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected2 at risk EG0010 affected1 at risk EG0020 affected1 at risk EG003
Urinary retention	Renal and urinary disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected2 at risk EG0010 affected1 at risk EG0020 affected1 at risk EG003
Breast tenderness	Reproductive system and breast disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected2 at risk EG0010 affected1 at risk EG0020 affected1 at risk EG003
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected2 at risk EG0010 affected1 at risk EG0020 affected1 at risk EG003
Dysphonia	Respiratory, thoracic and mediastinal disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected2 at risk EG0010 affected1 at risk EG0020 affected1 at risk EG003
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected2 at risk EG0010 affected1 at risk EG0020 affected1 at risk EG003
Dyspnoea exertional	Respiratory, thoracic and mediastinal disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected2 at risk EG0010 affected1 at risk EG0020 affected1 at risk EG003
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected2 at risk EG0010 affected1 at risk EG0020 affected1 at risk EG003
Lower respiratory tract congestion	Respiratory, thoracic and mediastinal disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected2 at risk EG0010 affected1 at risk EG0020 affected1 at risk EG003
Pleural effusion	Respiratory, thoracic and mediastinal disorders	MedDRA 20.1	Systematic Assessment	EG0001 affected2 at risk EG0010 affected1 at risk EG0020 affected1 at risk EG003
Productive cough	Respiratory, thoracic and mediastinal disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected2 at risk EG0010 affected1 at risk EG0020 affected1 at risk EG003
Rhinorrhoea	Respiratory, thoracic and mediastinal disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected2 at risk EG0010 affected1 at risk EG0020 affected1 at risk EG003
Dry skin	Skin and subcutaneous tissue disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected2 at risk EG0010 affected1 at risk EG0020 affected1 at risk EG003
Ecchymosis	Skin and subcutaneous tissue disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected2 at risk EG0010 affected1 at risk EG0020 affected1 at risk EG003
Nail ridging	Skin and subcutaneous tissue disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected2 at risk EG0010 affected1 at risk EG0020 affected1 at risk EG003
Pruritus	Skin and subcutaneous tissue disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected2 at risk EG0010 affected1 at risk EG0020 affected1 at risk EG003
Rash maculo-papular	Skin and subcutaneous tissue disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected2 at risk EG0010 affected1 at risk EG0020 affected1 at risk EG003
Swelling face	Skin and subcutaneous tissue disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected2 at risk EG0010 affected1 at risk EG0021 affected1 at risk EG003
Embolism	Vascular disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected2 at risk EG0010 affected1 at risk EG0020 affected1 at risk EG003
Hot flush	Vascular disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected2 at risk EG0010 affected1 at risk EG0020 affected1 at risk EG003
Hypotension	Vascular disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected2 at risk EG0010 affected1 at risk EG0020 affected1 at risk EG003

Facility	Status	City	State	ZIP	Country	Contacts
		Scottsdale	Arizona		United States

ID	Term
D009370	Neoplasms by Histologic Type
D009369	Neoplasms
D008232	Lymphoproliferative Disorders
D008206	Lymphatic Diseases
D006425	Hemic and Lymphatic Diseases
D007160	Immunoproliferative Disorders
D007154	Immune System Diseases

ID	Term
D004958	Estradiol
D004963	Estrenes
D004962	Estranes
D013256	Steroids
D000072473	Fused-Ring Compounds
D011083	Polycyclic Compounds
D045166	Estradiol Congeners
D012739	Gonadal Steroid Hormones
D042341	Gonadal Hormones
D006728	Hormones
D006730	Hormones, Hormone Substitutes, and Hormone Antagonists