Baclofen-Amitriptyline Hydrochloride-Ketamine Gel in Trea... | NCT00516503

NCT00516503

ID	Type	Description	Link
NCI-2011-01768	Registry Identifier	CTRP (Clinical Trials Reporting System)
CDR0000560732	Registry Identifier	PDQ (Physician Data Query)

Status Module

Name	Class
National Cancer Institute (NCI)	NIH

Description Module

Label	Type	Description	Intervention Names
Arm I	Experimental	Patients apply 1 spoonful of baclofen-amitriptyline hydrochloride-ketamine gel> topically to each> area of pain,> numbness,> and/or tingling> on the> feet and/or hands twice daily> for> 4 weeks.	Drug: baclofen/amitriptyline/ketamine gel
Arm II	Placebo Comparator	Patients apply 1 spoonful of placebo gel topically to each area of pain, numbness, and/or tingling on the feet and/or hands twice daily for 4 weeks.	Other: placebo

Name	Type	Description	Arm Group Labels	Other Names
baclofen/amitriptyline/ketamine gel	Drug	Applied topically	Arm I
placebo

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Total Sensory Neuropathy as Measured by the European Organization for Research and Treatment of Cancer [EORTC] Quality of Life [QLQ] - Chemo-induced Peripheral Neuropathy [CIPN20]	The scoring algorithm for the parent instrument, the EORTC QLQ-C30, was applied for linearly converting items and subscales of CIPN-20 to 0-100 scales so that a high score corresponds to better condition or less symptom. The primary analysis was the change in sensory neuropathy subscale of the CIPN-20 from baseline to week 4. The area under the curve (AUC) from baseline to week 4 was calculated for each patient's sensory neuropathy score. The average AUC for the placebo arm was compared to the average AUC for the topical amitriptyline HCl/ baclofen/ ketamine arm using a Wilcoxon rank sum test.	From baseline to 4 weeks

Secondary Outcomes

Measure	Description	Time Frame
Motor Neuropathy as Measured by the EORTC QLQ-CIPN20 at Baseline and Week 4	The scoring algorithm for the parent instrument, the EORTC QLQ-C30, was applied for linearly converting items and subscales of CIPN-20 to 0-100 scales so that a high score corresponds to better condition or less symptom. The secondary analysis was to compare changes from baseline at 4 weeks for the motor neuropathy subscale of the CIPN-20. To analyze this endpoint, the area under the curve (AUC) from baseline to week 4 was calculated for each patient's motor neuropathy score. The average AUC for the placebo arm was compared to the average AUC for the topical amitriptyline HCl/ baclofen/ ketamine arm using a Wilcoxon rank sum test.

Eligibility Module

Eligibility Criteria

DISEASE CHARACTERISTICS:>

Diagnosis of cancer>
Received or currently receiving neurotoxic chemotherapy including, but not limited to, taxanes (e.g., paclitaxel or docetaxel); platinum-based compounds (e.g., carboplatin, cisplatin, or oxaliplatin); vinca alkaloids (e.g., vincristine or vinblastine); or other neurotoxic chemotherapy agents (e.g., bortezomib, lenalidomide, or thalidomide)>
Must have pain or symptoms of peripheral neuropathy attributable to chemotherapy for ≥ 1 month>
- Neuropathy is limited to either hands and/or feet where gel can be applied>
- Neuropathic pain score of ≥ 4 out of 10 on the numbness/tingling/pain numeric analogue scale>
No pre-existing or history of peripheral neuropathy due to any cause other than chemotherapy (e.g., diabetes, alcohol, toxin, heredity)> PATIENT CHARACTERISTICS:>
ECOG performance status 0-2>
Life expectancy ≥ 4 months>
Creatinine ≤ 1.5 times upper limit of normal>
Not pregnant or nursing>
No ability to bear children defined by 1 of the criteria:>
- Menopausal (12 months and no menstrual period if natural menopause)>
- Underwent a hysterectomy and/or oophorectomy>
- Permanent surgical sterilization (tubal ligation)>
Fertile patients must use effective contraception>
Able to complete questionnaires independently or with assistance>
Able to sign informed consent and understand the nature of a placebo-controlled trial>
No history of an allergic reaction to baclofen, amitriptyline hydrochloride, and/or ketamine>
No diagnosis of any New York Heart Association class I-IV congestive heart failure>
No diagnosis of coronary artery disease including, but not limited to, myocardial infarction, within the past 5 years>
No other medical condition that, in the opinion of the treating physician or allied health professional, would make this clinical trial unreasonably hazardous for the patient>
No skin abnormalities at the intended application sites (hands and feet) of study gel (i.e., skin breakdown)> PRIOR CONCURRENT THERAPY:>
See Disease Characteristics>
More than 30 days since prior anticonvulsants, tricyclic antidepressants, monoamine oxidase inhibitor, or other neuropathic pain medication (e.g., carbamazepine, phenytoin, valproic acid, gabapentin, lamotrigine, topical lidocaine patch or gel, capsaicin cream, or amifostine)>

- Patients treated with any of these agents for peripheral neuropathy for ≤ 1 week during the past 30 days are eligible provided they are no longer taking the agent>
More than 5 years since prior percutaneous transluminal coronary angioplasty or coronary artery bypass graft>

- Prior heart valve replacement surgery allowed provided patient has fully recovered from the surgery>
No concurrent use of study agents other than as specified in the trial>

Name	Affiliation	Role
Debra Barton, RN, PhD, AOCN, FAAN	Mayo Clinic	Study Chair

Facility	Status	City	State	ZIP	Country	Contacts
Mayo Clinic Scottsdale		Scottsdale	Arizona	85259-5499	United States
Mayo Clinic - Jacksonville

PubMed Identifier	Type	Citation	Retractions
21479990	Result	Wolf SL, Barton DL, Qin R, Wos EJ, Sloan JA, Liu H, Aaronson NK, Satele DV, Mattar BI, Green NB, Loprinzi CL. The relationship between numbness, tingling, and shooting/burning pain in patients with chemotherapy-induced peripheral neuropathy (CIPN) as measured by the EORTC QLQ-CIPN20 instrument, N06CA. Support Care Cancer. 2012 Mar;20(3):625-32. doi: 10.1007/s00520-011-1141-9. Epub 2011 Apr 12.
20496177

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Baclofen-amitriptyline Hydrochloride-ketamine	Patients apply 1 spoonful of baclofen-amitriptyline hydrochloride-ketamine gel topically to each area of pain, numbness, and/or tingling on the feet and/or hands twice daily for 4 weeks. Baclofen/amitriptyline/ketamine gel: Applied topically.
FG001

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

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

Total Sensory Neuropathy as Measured by the European Organization for Research and Treatment of Cancer [EORTC] Quality of Life [QLQ] - Chemo-induced Peripheral Neuropathy [CIPN20]

The scoring algorithm for the parent instrument, the EORTC QLQ-C30, was applied for linearly converting items and subscales of CIPN-20 to 0-100 scales so that a high score corresponds to better condition or less symptom. The primary analysis was the change in sensory neuropathy subscale of the CIPN-20 from baseline to week 4. The area under the curve (AUC) from baseline to week 4 was calculated for each patient's sensory neuropathy score. The average AUC for the placebo arm was compared to the average AUC for the topical amitriptyline HCl/ baclofen/ ketamine arm using a Wilcoxon rank sum test.

There were 26 participants in the BAK arm and 27 in the placebo arm who did not provide primary endpoint data. In the BAK arm, 11 refused due to experiencing an adverse event and 15 refused for non-specified reasons. In the placebo arm, eight refused due to an adverse event, one patient died, and 18 refused for non-specified reasons.

Posted

Mean

Standard Deviation

(units on a scale) * week

From baseline to 4 weeks

ID	Title	Description
OG000	Baclofen-amitriptyline Hydrochloride-ketamine	Patients apply 1 spoonful of baclofen-amitriptyline hydrochloride-ketamine gel topically to each area of pain, numbness, and/or tingling on the feet and/or hands twice daily for 4 weeks. Baclofen/amitriptyline/ketamine gel: Applied topically.
OG001	Placebo	Patients apply 1 spoonful of placebo gel topically to each area of pain, numbness, and/or tingling on the feet and/or hands twice daily for 4 weeks. Placebo: Applied topically

Units	Counts
Participants	OG00075 OG00175

Title

Denominators

Categories

Title	Measurements
	OG00061.0± 16.22 OG00160.9± 17.9

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001		Wilcoxon (Mann-Whitney)		0.90														Superiority or Other

Secondary

Motor Neuropathy as Measured by the EORTC QLQ-CIPN20 at Baseline and Week 4

The scoring algorithm for the parent instrument, the EORTC QLQ-C30, was applied for linearly converting items and subscales of CIPN-20 to 0-100 scales so that a high score corresponds to better condition or less symptom. The secondary analysis was to compare changes from baseline at 4 weeks for the motor neuropathy subscale of the CIPN-20. To analyze this endpoint, the area under the curve (AUC) from baseline to week 4 was calculated for each patient's motor neuropathy score. The average AUC for the placebo arm was compared to the average AUC for the topical amitriptyline HCl/ baclofen/ ketamine arm using a Wilcoxon rank sum test.

There were 26 participants in the BAK arm and 27 in the placebo arm who did not provide primary endpoint data. In the BAK arm, 11 refused due to experiencing an adverse> event and 15 refused for non-specified reasons. In the placebo arm, eight refused due to an> adverse event, one patient died, and 18 refused for non-specified reasons.

Posted

Mean

Standard Deviation

(units on a scale)* week

From Baseline to week 4

ID	Title	Description
OG000	Baclofen-amitriptyline Hydrochloride-ketamine	Patients apply 1 spoonful of baclofen-amitriptyline hydrochloride-ketamine gel topically to each area of pain, numbness, and/or tingling on the feet and/or hands twice daily for 4 weeks. Baclofen/amitriptyline/ketamine gel: Applied topically.
OG001	Placebo

Secondary

Autonomic Symptoms and Functioning as Measured by the EORTC QLQ-CIPN20 at Baseline and Week 4

The scoring algorithm for the parent instrument, the EORTC QLQ-C30, was applied for linearly converting items and subscales of CIPN-20 to 0-100 scales so that a high score corresponds to better condition or less symptom. The secondary analysis was to compare changes from baseline at 4 weeks for the autonomic neuropathy subscale of the CIPN-20. To analyze this endpoint, the area under the curve (AUC) from baseline to week 4 was calculated for each patient's motor neuropathy score. The average AUC for the placebo arm was compared to the average AUC for the topical amitriptyline HCl/ baclofen/ ketamine arm using a Wilcoxon rank sum test.

Posted

Mean

Standard Deviation

(units on a scale)*week

Up to 4 weeks

ID	Title	Description
OG000	Baclofen-amitriptyline Hydrochloride-ketamine	Patients apply 1 spoonful of baclofen-amitriptyline hydrochloride-ketamine gel topically to each area of pain, numbness, and/or tingling on the feet and/or hands twice daily for 4 weeks. Baclofen/amitriptyline/ketamine gel: Applied topically.
OG001	Placebo

Secondary

Mood States and Total Mood Disturbance as Measured by the Profile of Mood States (POMS)

Each mood scale (0 - 100, higher is better mood) will be analyzed as an endpoint along with the total mood disturbance score.

Posted

Mean

Standard Deviation

units on a scale

At 4 weeks

ID	Title	Description
OG000	Baclofen-amitriptyline Hydrochloride-ketamine	Patients apply 1 spoonful of baclofen-amitriptyline hydrochloride-ketamine gel topically to each area of pain, numbness, and/or tingling on the feet and/or hands twice daily for 4 weeks. Baclofen/amitriptyline/ketamine gel: Applied topically.
OG001	Placebo	Patients apply 1 spoonful of placebo gel topically to each area of pain, numbness, and/or tingling on the feet and/or hands twice daily for 4 weeks. Placebo: Applied topically

Units	Counts
Participants	OG000

Secondary

Pain Severity and Interference as Measured by the Brief Pain Inventory (BPI) at Baseline and Week 4

Pain severity, defined by the four items addressing worst, least, and average pain and pain right now as measured by the BPI will be analyzed identical to the primary endpoint. Additionally, total pain interference as measured by the BPI will be transformed onto a 0-100 ( higher is less pain) point scale. The area under the curve (AUC) from baseline to week 4 was calculated for each patient's score. The average AUC for the placebo arm and the topical amitriptyline HCl/ baclofen/ ketamine arm are reported.

Posted

Mean

Standard Deviation

units on a scale * week

Up to 4 weeks

ID	Title	Description
OG000	Baclofen-amitriptyline Hydrochloride-ketamine	Patients apply 1 spoonful of baclofen-amitriptyline hydrochloride-ketamine gel topically to each area of pain, numbness, and/or tingling on the feet and/or hands twice daily for 4 weeks. Baclofen/amitriptyline/ketamine gel: Applied topically.
OG001	Placebo	Patients apply 1 spoonful of placebo gel topically to each area of pain, numbness, and/or tingling on the feet and/or hands twice daily for 4 weeks. Placebo: Applied topically

Units	Counts

Secondary

Numbness, Tingling, and Pain as Measured by the Peripheral Neuropathy Questionnaire at Baseline and Weekly for 4 Weeks

The Peripheral Neuropathy Questionnaire was used to analyze this endpoint. Patient neuropathy symptoms were scored on a 0 - 100 scale (higher score represents less symptomatic). The area under the curve (AUC) from baseline to week 4 was calculated for each patient's score. The average AUC for the placebo arm and the topical amitriptyline HCl/ baclofen/ ketamine arm are reported.

Posted

Mean

Standard Deviation

units on a scale * week

Up to 4 weeks

ID	Title	Description
OG000	Baclofen-amitriptyline Hydrochloride-ketamine	Patients apply 1 spoonful of baclofen-amitriptyline hydrochloride-ketamine gel topically to each area of pain, numbness, and/or tingling on the feet and/or hands twice daily for 4 weeks. Baclofen/amitriptyline/ketamine gel: Applied topically.
OG001	Placebo	Patients apply 1 spoonful of placebo gel topically to each area of pain, numbness, and/or tingling on the feet and/or hands twice daily for 4 weeks. Placebo: Applied topically

Units	Counts
Participants

Secondary

Adverse Event Profile of Topical Amitriptyline HCl/ Baclofen/Ketamine > Frequency and Severity of Adverse Events Reported by the Patient in the > Symptom Experience Diary and Evaluated Through Clinical Assessment by NCI CTCAE v3.0

Frequency and severity of adverse events reported by patients in weekly diary and evaluated through clinical assessment by NCI CTCAE v3.0. The number of patients reporting grade 3 or higher events are reported in this outcome measure. For a full list of all events, please refer to the Adverse Events section of this report.

All patients that were assessed for adverse events are used in this analysis.

Posted

Count of Participants

Participants

Up to 4 weeks

ID	Title	Description
OG000	Baclofen-amitriptyline Hydrochloride-ketamine	Patients apply 1 spoonful of baclofen-amitriptyline hydrochloride-ketamine gel topically to each area of pain, numbness, and/or tingling on the feet and/or hands twice daily for 4 weeks. Baclofen/amitriptyline/ketamine gel: Applied topically.
OG001	Placebo	Patients apply 1 spoonful of placebo gel topically to each area of pain, numbness, and/or tingling on the feet and/or hands twice daily for 4 weeks. Placebo: Applied topically

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Tinnitus	Ear and labyrinth disorders	MedDRA 10	Systematic Assessment	EG0000 events0 affected101 at risk EG0011 events1 affected102 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA 10	Systematic Assessment	EG0000 events0 affected101 at risk EG0015 events2 affected102 at risk
Constipation	Gastrointestinal disorders	MedDRA 10	Systematic Assessment	EG00062 events24 affected101 at risk EG00171 events28 affected102 at risk
Diarrhea	Gastrointestinal disorders	MedDRA 10	Systematic Assessment	EG0001 events1 affected101 at risk EG0011 events1 affected102 at risk
Dry mouth	Gastrointestinal disorders	MedDRA 10	Systematic Assessment	EG00055 events18 affected101 at risk EG00155 events23 affected102 at risk
Ileal obstruction	Gastrointestinal disorders	MedDRA 10	Systematic Assessment	EG0000 events0 affected101 at risk EG0011 events1 affected102 at risk
Nausea	Gastrointestinal disorders	MedDRA 10	Systematic Assessment	EG0001 events1 affected101 at risk EG0010 events0 affected102 at risk
Small intestinal obstruction	Gastrointestinal disorders	MedDRA 10	Systematic Assessment	EG0000 events0 affected101 at risk EG0014 events2 affected102 at risk
Stomach pain	Gastrointestinal disorders	MedDRA 10	Systematic Assessment	EG0000 events0 affected101 at risk EG0010 events0 affected102 at risk
Vomiting	Gastrointestinal disorders	MedDRA 10	Systematic Assessment	EG0001 events1 affected101 at risk EG0010 events0 affected102 at risk
Edema limbs	General disorders	MedDRA 10	Systematic Assessment	EG0001 events1 affected101 at risk EG0011 events1 affected102 at risk
Fatigue	General disorders	MedDRA 10	Systematic Assessment	EG0001 events1 affected101 at risk EG0011 events1 affected102 at risk
Pain	General disorders	MedDRA 10	Systematic Assessment	EG0000 events0 affected101 at risk EG0010 events0 affected102 at risk
Hypersensitivity	Immune system disorders	MedDRA 10	Systematic Assessment	EG0000 events0 affected101 at risk EG0011 events1 affected102 at risk
Bladder infection	Infections and infestations	MedDRA 10	Systematic Assessment	EG0000 events0 affected101 at risk EG0010 events0 affected102 at risk
Skin infection	Infections and infestations	MedDRA 10	Systematic Assessment	EG0002 events1 affected101 at risk EG0010 events0 affected102 at risk
Fracture	Injury, poisoning and procedural complications	MedDRA 10	Systematic Assessment	EG0000 events0 affected101 at risk EG0010 events0 affected102 at risk
Alkaline phosphatase increased	Investigations	MedDRA 10	Systematic Assessment	EG0000 events0 affected101 at risk EG0011 events1 affected102 at risk
Aspartate aminotransferase increased	Investigations	MedDRA 10	Systematic Assessment	EG0000 events0 affected101 at risk EG0011 events1 affected102 at risk
Platelet count decreased	Investigations	MedDRA 10	Systematic Assessment	EG0000 events0 affected101 at risk EG0011 events1 affected102 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 10	Systematic Assessment	EG0000 events0 affected101 at risk EG0010 events0 affected102 at risk
Chest wall pain	Musculoskeletal and connective tissue disorders	MedDRA 10	Systematic Assessment	EG0000 events0 affected101 at risk EG0010 events0 affected102 at risk
Joint pain	Musculoskeletal and connective tissue disorders	MedDRA 10	Systematic Assessment	EG0001 events1 affected101 at risk EG0010 events0 affected102 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA 10	Systematic Assessment	EG0001 events1 affected101 at risk EG0010 events0 affected102 at risk
Ataxia	Nervous system disorders	MedDRA 10	Systematic Assessment	EG0000 events0 affected101 at risk EG0011 events1 affected102 at risk
Depressed level of consciousness	Nervous system disorders	MedDRA 10	Systematic Assessment	EG0002 events2 affected101 at risk EG0012 events2 affected102 at risk
Dizziness	Nervous system disorders	MedDRA 10	Systematic Assessment	EG0000 events0 affected101 at risk EG0010 events0 affected102 at risk
Neuralgia	Nervous system disorders	MedDRA 10	Systematic Assessment	EG0001 events1 affected101 at risk EG0010 events0 affected102 at risk
Peripheral sensory neuropathy	Nervous system disorders	MedDRA 10	Systematic Assessment	EG0000 events0 affected101 at risk EG0012 events2 affected102 at risk
Syncope vasovagal	Nervous system disorders	MedDRA 10	Systematic Assessment	EG0000 events0 affected101 at risk EG0010 events0 affected102 at risk
Anxiety	Psychiatric disorders	MedDRA 10	Systematic Assessment	EG0000 events0 affected101 at risk EG0010 events0 affected102 at risk
Confusion	Psychiatric disorders	MedDRA 10	Systematic Assessment	EG0005 events5 affected101 at risk EG0014 events4 affected102 at risk
Dry skin	Skin and subcutaneous tissue disorders	MedDRA 10	Systematic Assessment	EG0001 events1 affected101 at risk EG0010 events0 affected102 at risk
Hand-and-foot syndrome	Skin and subcutaneous tissue disorders	MedDRA 10	Systematic Assessment	EG00026 events16 affected101 at risk EG00125 events12 affected102 at risk
Pruritus	Skin and subcutaneous tissue disorders	MedDRA 10	Systematic Assessment	EG0000 events0 affected101 at risk EG0010 events0 affected102 at risk
Thrombosis	Vascular disorders	MedDRA 10	Systematic Assessment	EG0000 events0 affected101 at risk EG0012 events1 affected102 at risk

ID	Term
D009196	Myeloproliferative Disorders
D007938	Leukemia
D008223	Lymphoma
D008232	Lymphoproliferative Disorders
D009101	Multiple Myeloma
D054219	Neoplasms, Plasma Cell
D009190	Myelodysplastic Syndromes
D054437	Myelodysplastic-Myeloproliferative Diseases
D020258	Neurotoxicity Syndromes
D010146	Pain

ID	Term
D001855	Bone Marrow Diseases
D006402	Hematologic Diseases
D006425	Hemic and Lymphatic Diseases
D009370	Neoplasms by Histologic Type
D009369	Neoplasms
D008206	Lymphatic Diseases
D007160	Immunoproliferative Disorders
D007154	Immune System Diseases
D020141	Hemostatic Disorders
D014652	Vascular Diseases
D002318	Cardiovascular Diseases
D010265	Paraproteinemias
D001796	Blood Protein Disorders
D006474	Hemorrhagic Disorders
D009422	Nervous System Diseases
D011041	Poisoning
D064419	Chemically-Induced Disorders
D009461	Neurologic Manifestations
D012816	Signs and Symptoms
D013568	Pathological Conditions, Signs and Symptoms

ID	Term
D005680	gamma-Aminobutyric Acid
D000613	Aminobutyrates
D002087	Butyrates
D000144	Acids, Acyclic
D002264	Carboxylic Acids
D009930	Organic Chemicals

ID	Title	Description
BG000	Baclofen-amitriptyline Hydrochloride-ketamine	Patients apply 1 spoonful of baclofen-amitriptyline hydrochloride-ketamine gel topically to each area of pain, numbness, and/or tingling on the feet and/or hands twice daily for 4 weeks. Baclofen/amitriptyline/ketamine gel: Applied topically.
BG001	Placebo	Patients apply 1 spoonful of placebo gel topically to each area of pain, numbness, and/or tingling on the feet and/or hands twice daily for 4 weeks. Placebo: Applied topically
BG002	Total	Total of all reporting groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Baclofen-amitriptyline Hydrochloride-ketamine	Patients apply 1 spoonful of baclofen-amitriptyline hydrochloride-ketamine gel topically to each area of pain, numbness, and/or tingling on the feet and/or hands twice daily for 4 weeks. Baclofen/amitriptyline/ketamine gel: Applied topically.			1	101	48	101
EG001	Placebo	Patients apply 1 spoonful of placebo gel topically to each area of pain, numbness, and/or tingling on the feet and/or hands twice daily for 4 weeks. Placebo: Applied topically			1	102	45	102

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Disease progression	General disorders	MedDRA 10	Systematic Assessment		EG0000 events0 affected101 at risk EG0011 events1 affected102 at risk
Thrombosis	Vascular disorders	MedDRA 10	Systematic Assessment		EG0001 events1 affected101 at risk EG0010 events0 affected102 at risk