Colorectal Cancer Metastatic (AFEQT)

• ClinicalTrials.gov Identifier: NCT01670721
• Recruitment Status: Completed
• First Posted: August 22, 2012
• Results First Posted: November 28, 2016
• Last Update Posted: November 28, 2016
• Sponsor: Sanofi
• Collaborator: Regeneron Pharmaceuticals
• Information provided by (Responsible Party): Sanofi

• Study Type: Interventional
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Colorectal Cancer Metastatic
• Interventions: Drug: AFLIBERCEPT; Drug: Irinotecan; Drug: Fluorouracil; Drug: Leucovorin
• Enrollment: 175

Participant Flow

Recruitment Details	The study was conducted at 38 sites in France. A total of 182 participants were screened between 08 August 2012 and 30 June 2014, out of which 175 participants were enrolled and treated.
Pre-assignment Details	Participants enrolled in the study to assess the safety of Aflibercept in participants treated with a combination of Aflibercept with FOLFIRI regimen (Irinotecan, Leucovorin and 5-Fluorouracil [5-FU]).

Arm/Group Title	Aflibercept + FOLFIRI (Irinotecan, 5-FU & Leucovorin)
Arm/Group Description	Aflibercept 4 mg/kg intravenous (IV) infusion over 60 minutes followed by Irinotecan 180 mg/m^2 IV infusion over 90 minutes and Leucovorin 400 mg/m^2 IV infusion over 120 minutes at the same time followed by 5-FU 400 mg/m^2 IV bolus over 2-4 minutes followed by 5-FU 2400 mg/m^2 continuous IV infusion over 46 hours on Day 1 of each cycle (1 Cycle = 2 weeks), until disease progression (DP), unacceptable toxicity, death, Investigator's decision or participant's refusal of further treatment.
Period Title: Overall Study
Started	175
Completed	122 [1]
Not Completed	53
Reason Not Completed
Participant's decision	15
Other than specified above	38
[1] 81 participants with DP and 41 with adverse events were considered as completed.

Baseline Characteristics

Arm/Group Title		Aflibercept + FOLFIRI (Irinotecan, 5-FU & Leucovorin)
Arm/Group Description		Aflibercept 4 mg/kg IV infusion over 60 minutes followed by Irinotecan 180 mg/m^2 IV infusion over 90 minutes and Leucovorin 400 mg/m^2 IV infusion over 120 minutes at the same time followed by 5-FU 400 mg/m^2 IV bolus over 2-4 minutes followed by 5-FU 2400 mg/m^2 continuous IV infusion over 46 hours on Day 1 of each cycle (1 Cycle = 2 weeks), until DP, unacceptable toxicity, death, Investigator's decision or participant's refusal of further treatment.
Overall Number of Baseline Participants		175
Baseline Analysis Population Description		[Not Specified]
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	175 participants
		64.5 (11.0)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	175 participants
	Female	77 44.0%
	Male	98 56.0%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With Adverse Events (AEs)
Description	Any untoward medical occurrence in a participant who received investigational medicinal product (IMP) was considered an AE without regard to possibility of causal relationship with this treatment. Treatment-emergent adverse events (TEAEs) were defined as AEs that developed or worsened or became serious during on-treatment period. On-treatment period was defined as the time from the first dose of treatment to 30 days after the last dose of treatment (either Aflibercept or FOLFIRI). A serious adverse event (SAE) was defined as any untoward medical occurrence that resulted in any of the following outcomes: death, life-threatening, required initial or prolonged in-patient hospitalization, persistent or significant disability/incapacity, congenital anomaly/birth defect, or considered as medically important event. Any TEAE included participants with both serious and non-serious AEs.
Time Frame	Baseline upto 30 days after the last treatment administration (either Aflibercept or FOLFIRI whichever comes last) (maximum exposure:723 days)

Outcome Measure Data

Analysis Population Description

Safety population defined as the participants who signed the informed consent form and received at least part of one dose of study treatment.

Arm/Group Title	Aflibercept + FOLFIRI (Irinotecan, 5-FU & Leucovorin)
Arm/Group Description:	Aflibercept 4 mg/kg IV infusion over 60 minutes followed by Irinotecan 180 mg/m^2 IV infusion over 90 minutes and Leucovorin 400 mg/m^2 IV infusion over 120 minutes at the same time followed by 5-FU 400 mg/m^2 IV bolus over 2-4 minutes followed by 5-FU 2400 mg/m^2 continuous IV infusion over 46 hours on Day 1 of each cycle (1 Cycle = 2 weeks), until DP, unacceptable toxicity, death, Investigator's decision or participant's refusal of further treatment.
Overall Number of Participants Analyzed	175
Measure Type: Number; Unit of Measure: Percentage of participants
Any TEAE	100.00
Any serious TEAE	40.6
Any serious related TEAE	21.1
Any TEAE leading to death	9.1
Any TEAE (permanent treatment discontinuation)	23.4
Any TEAE (premature treatment discontinuation)	16.0

2. Secondary Outcome

Title	Change From Baseline in Health Related Quality of Life (HRQL) European Organization for Research and Treatment for Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30)
Description	EORTC-QLQ-C30 is a cancer-specific instrument with 30 questions for evaluation of new chemotherapy and provides an assessment of participant reported outcome dimensions. First 28 questions used 4-point scale (1=not at all,2=a little,3=quite a bit,4=very much) for evaluating 5 functional scales (physical,role,emotional,cognitive,social), 3 symptom scales (fatigue,nausea/vomiting,pain) & other single items. For each item,high score represented high level of symptomatology/problem. Last 2 questions represented participant's assessment of overall health & quality of life, coded on 7-point scale (1=very poor to 7=excellent). EORTC QLQ-C30 observed values and change from baseline for global health status (scoring of questions 29 & 30) and 5 functional scales, 3 symptom scales and other single items (scoring of questions 1 to 28). Answers were converted into grading scale, with values between 0 and 100. A high score represented a favorable outcome with a best quality of life for participant.
Time Frame	Pre-dose at Baseline, Day 1 of every odd cycle; and at end of treatment (30 days after last study treatment) (maximum exposure: 99 weeks)

Outcome Measure Data

Analysis Population Description

EORTC QLQ-C30 analysis population: participants who signed informed consent form; had an evaluable QLQ-C30 questionnaire at baseline and at least one evaluable assessment post baseline and received at least part of one dose of study treatment(either Aflibercept or FOLFIRI).Here, n=number of participants with available data at specified time-points.

Arm/Group Title	Aflibercept + FOLFIRI (Irinotecan, 5-FU & Leucovorin)
Arm/Group Description:	Aflibercept 4 mg/kg IV infusion over 60 minutes followed by Irinotecan 180 mg/m^2 IV infusion over 90 minutes and Leucovorin 400 mg/m^2 IV infusion over 120 minutes at the same time followed by 5-FU 400 mg/m^2 IV bolus over 2-4 minutes followed by 5-FU 2400 mg/m^2 continuous IV infusion over 46 hours on Day 1 of each cycle (1 Cycle = 2 weeks), until DP, unacceptable toxicity, death, Investigator's decision or participant's refusal of further treatment.
Overall Number of Participants Analyzed	152
Mean (Standard Deviation); Unit of Measure: units on a scale
Baseline (n=148)	69.54 (18.97)
At Cycle 3 (n=130)	-7.56 (19.78)
At Cycle 5 (n=99)	-10.86 (19.76)
At Cycle 7 (n=72)	-8.22 (20.00)
At Cycle 9 (n=51)	-9.31 (19.34)
At Cycle 11 (n=45)	-14.81 (21.24)
At Cycle 13 (n=25)	-12.67 (24.31)
At Cycle 15 (n=24)	-12.50 (18.22)
At Cycle 17 (n=14)	-14.29 (15.82)
At Cycle 19 (n=12)	-15.28 (11.70)
At Cycle 21 (n=10)	-15.83 (19.82)
At Cycle 23 (n=6)	-9.72 (20.01)
At Cycle 25 (n=4)	-8.33 (6.80)
At Cycle 27 (n=4)	-12.50 (15.96)
At Cycle 29 (n=2)	-8.33 (11.79)
At Cycle 31 (n=2)	-16.67 (0.00)
At Cycle 33 (n=1)	0.00 [1] (NA)
At Cycle 35 (n=1)	0.00 [2] (NA)
At Cycle 37 (n=2)	-8.33 (11.79)
At Cycle 39 (n=2)	-8.33 (11.79)
At Cycle 41 (n=2)	-8.33 (11.79)
At Cycle 43 (n=2)	-12.50 (5.89)
At Cycle 45 (n=2)	-4.17 (17.68)
At Cycle 47 (n=1)	0.00 [3] (NA)
At end of study treatment (n=73)	-11.19 (24.38)

[1]

As only one participant was analyzed at cycle 33, standard deviation could not be calculated.

[2]

As only one participant was analyzed at cycle 35, standard deviation could not be calculated.

[3]

As only one participant was analyzed at cycle 47, standard deviation could not be calculated.

3. Secondary Outcome

Title	Change From Baseline in HRQL European-Quality of Life-5 Dimension Instrument-3 Levels (EQ-5D-3L) Index Score
Description	EQ-5D was a standardized HRQL questionnaire consisting of EQ-5D descriptive system and Visual Analogue Scale (VAS). EQ-5D descriptive system comprised of 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression measured on 3 levels (no problem, some problems & severe problems) within a particular EQ-5D dimension. 5 dimensional 3-level system was converted into single index utility score. Possible values for single index utility score ranged from -0.594 (severe problems in all dimensions) to 1.0 (no problem in all dimensions) on scale where 1 represented best possible health state.
Time Frame	Pre-dose at Baseline, Day 1 of every odd cycle; and at end of treatment (30 days after last study treatment) (maximum exposure: 99 weeks)

Outcome Measure Data

Analysis Population Description

EQ-5D analysis population: participants who signed informed consent form, had an evaluable EQ-5D questionnaire at baseline and at least one evaluable assessment post baseline and received at least part of one dose of study treatment (either Aflibercept or FOLFIRI).Here, n = number of participants with available data at specified time-points.

Arm/Group Title	Aflibercept + FOLFIRI (Irinotecan, 5-FU & Leucovorin)
Arm/Group Description:	Aflibercept 4 mg/kg IV infusion over 60 minutes followed by Irinotecan 180 mg/m^2 IV infusion over 90 minutes and Leucovorin 400 mg/m^2 IV infusion over 120 minutes at the same time followed by 5-FU 400 mg/m^2 IV bolus over 2-4 minutes followed by 5-FU 2400 mg/m^2 continuous IV infusion over 46 hours on Day 1 of each cycle (1 Cycle = 2 weeks), until DP, unacceptable toxicity, death, Investigator's decision or participant's refusal of further treatment.
Overall Number of Participants Analyzed	148
Mean (Standard Deviation); Unit of Measure: units on a scale
Baseline (n=148)	0.78 (0.21)
At Cycle 3 (n=127)	-0.04 (0.23)
At Cycle 5 (n=96)	-0.08 (0.25)
At Cycle 7 (n=72)	-0.05 (0.20)
At Cycle 9 (n=49)	-0.09 (0.23)
At Cycle 11 (n=43)	-0.06 (0.20)
At Cycle 13 (n=24)	-0.09 (0.14)
At Cycle 15 (n=25)	-0.10 (0.16)
At Cycle 17 (n=14)	-0.03 (0.10)
At Cycle 19 (n=12)	-0.10 (0.12)
At Cycle 21 (n=10)	-0.03 (0.18)
At Cycle 23 (n=6)	-0.08 (0.15)
At Cycle 25 (n=3)	0.04 (0.22)
At Cycle 27 (n=3)	-0.09 (0.20)
At Cycle 29 (n=2)	-0.18 (0.04)
At Cycle 31 (n=1)	0.00 [1] (NA)
At Cycle 37 (n=1)	-0.15 [2] (NA)
At Cycle 39 (n=1)	0.00 [3] (NA)
At Cycle 41 (n=1)	0.00 [4] (NA)
At Cycle 43 (n=1)	0.00 [5] (NA)
At Cycle 45 (n=1)	0.00 [6] (NA)
At end of study treatment (n=71)	-0.20 (0.31)

[1]

As only one participant was analyzed at cycle 31, standard deviation could not be calculated.

[2]

As only one participant was analyzed at cycle 37, standard deviation could not be calculated.

[3]

As only one participant was analyzed at cycle 39, standard deviation could not be calculated.

[4]

As only one participant was analyzed at cycle 41, standard deviation could not be calculated.

[5]

As only one participant was analyzed at cycle 43, standard deviation could not be calculated.

[6]

As only one participant was analyzed at cycle 45, standard deviation could not be calculated.

4. Secondary Outcome

Title	Change From Baseline in HRQL EQ-5D-3L VAS Score
Description	EQ-5D VAS was used to record a participant's rating for his/her current health-related quality of life state and captured on a vertical VAS (0-100), where 0 = worst imaginable health state and 100 = best imaginable health state. Baseline corresponded to last evaluable assessment before treatment administration.
Time Frame	Pre-dose at Baseline, Day 1 of every odd cycle; and at end of treatment (30 days after last study treatment) (maximum exposure: 99 weeks)

Outcome Measure Data

Analysis Population Description

EQ-5D analysis population: participants who signed informed consent form, had an evaluable EQ-5D questionnaire at baseline and at least one evaluable assessment post baseline and received at least part of one dose of study treatment (either Aflibercept or FOLFIRI).Here, n = number of participants with available data at specified time-points.

Arm/Group Title	Aflibercept + FOLFIRI (Irinotecan, 5-FU & Leucovorin)
Arm/Group Description:	Aflibercept 4 mg/kg IV infusion over 60 minutes followed by Irinotecan 180 mg/m^2 IV infusion over 90 minutes and Leucovorin 400 mg/m^2 IV infusion over 120 minutes at the same time followed by 5-FU 400 mg/m^2 IV bolus over 2-4 minutes followed by 5-FU 2400 mg/m^2 continuous IV infusion over 46 hours on Day 1 of each cycle (1 Cycle = 2 weeks), until DP, unacceptable toxicity, death, Investigator's decision or participant's refusal of further treatment.
Overall Number of Participants Analyzed	148
Mean (Standard Deviation); Unit of Measure: units on a scale
Baseline (n=125)	69.48 (19.10)
At cycle 3 (n=94)	-6.23 (17.82)
At cycle 5 (n=76)	-7.62 (17.23)
At cycle 7 (n=57)	-7.79 (14.14)
At cycle 9 (n=38)	-7.55 (16.12)
At cycle 11 (n=36)	-8.67 (16.09)
At cycle 13 (n=22)	-8.95 (17.56)
At cycle 15 (n=22)	-12.41 (19.57)
At cycle 17 (n=13)	-10.31 (17.44)
At cycle 19 (n=10)	-15.70 (18.19)
At cycle 21 (n=8)	-15.13 (19.87)
At cycle 23 (n=5)	-8.80 (10.71)
At cycle 25 (n=2)	-13.00 (4.24)
At cycle 27 (n=3)	-15.67 (9.81)
At cycle 29 (n=2)	-17.50 (3.54)
At cycle 31 (n=1)	-15.00 [1] (NA)
At cycle 37 (n=1)	-15.00 [2] (NA)
At cycle 39 (n=1)	-15.00 [3] (NA)
At cycle 41 (n=1)	-15.00 [4] (NA)
At cycle 43 (n=1)	-15.00 [5] (NA)
At cycle 45 (n=1)	-15.00 [6] (NA)
At end of study treatment (n=55)	-13.05 (20.82)

[1]

As only one participant was analyzed at cycle 31, standard deviation could not be calculated.

[2]

As only one participant was analyzed at cycle 37, standard deviation could not be calculated.

[3]

As only one participant was analyzed at cycle 39, standard deviation could not be calculated.

[4]

As only one participant was analyzed at cycle 41, standard deviation could not be calculated.

[5]

As only one participant was analyzed at cycle 43, standard deviation could not be calculated.

[6]

As only one participant was analyzed at cycle 45, standard deviation could not be calculated.

Adverse Events

Time Frame	All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Day 723) regardless of seriousness or relationship to investigational product.
Adverse Event Reporting Description	Reported AEs and deaths are treatment-emergent that is AEs that developed/worsened and deaths that occurred during 'on-treatment period' (from the first dose of treatment to 30 days after the last dose of treatment [either aflibercept or FOLFIRI]).
Arm/Group Title	Aflibercept + FOLFIRI(Irinotecan, 5-Fluorouracil & Leucovorin)
Arm/Group Description	Aflibercept 4 mg/kg IV infusion over 60 minutes followed by Irinotecan 180 mg/m^2 IV infusion over 90 minutes and Leucovorin 400 mg/m^2 IV infusion over 120 minutes at the same time followed by 5-FU 400 mg/m^2 IV bolus over 2-4 minutes followed by 5-FU 2400 mg/m^2 continuous IV infusion over 46 hours on Day 1 of each cycle (1 Cycle = 2 weeks), until DP, unacceptable toxicity, death, Investigator's decision or participant's refusal of further treatment (maximum exposure: Week 99).
All-Cause Mortality
	Aflibercept + FOLFIRI(Irinotecan, 5-Fluorouracil & Leucovorin)
	Affected / at Risk (%)
Total	--/--
Serious Adverse Events
	Aflibercept + FOLFIRI(Irinotecan, 5-Fluorouracil & Leucovorin)
	Affected / at Risk (%)
Total	71/175 (40.57%)
Blood and lymphatic system disorders
ANAEMIA † 1	1/175 (0.57%)
FEBRILE NEUTROPENIA † 1	2/175 (1.14%)
PANCYTOPENIA † 1	1/175 (0.57%)
Eye disorders
VITREOUS HAEMORRHAGE † 1	1/175 (0.57%)
Gastrointestinal disorders
ABDOMINAL PAIN † 1	3/175 (1.71%)
ANAL FISTULA † 1	1/175 (0.57%)
DIARRHOEA † 1	8/175 (4.57%)
GASTROINTESTINAL FISTULA † 1	1/175 (0.57%)
GASTROINTESTINAL HAEMORRHAGE † 1	1/175 (0.57%)
INTESTINAL OBSTRUCTION † 1	3/175 (1.71%)
NAUSEA † 1	2/175 (1.14%)
PANCREATITIS † 1	1/175 (0.57%)
RECTAL HAEMORRHAGE † 1	1/175 (0.57%)
RECTOURETHRAL FISTULA † 1	1/175 (0.57%)
SMALL INTESTINAL PERFORATION † 1	1/175 (0.57%)
STOMATITIS † 1	1/175 (0.57%)
SUBILEUS † 1	2/175 (1.14%)
TOOTH LOSS † 1	1/175 (0.57%)
VOMITING † 1	1/175 (0.57%)
General disorders
ASTHENIA † 1	1/175 (0.57%)
DISEASE PROGRESSION † 1	9/175 (5.14%)
FATIGUE † 1	1/175 (0.57%)
GENERAL PHYSICAL HEALTH DETERIORATION † 1	8/175 (4.57%)
INFLUENZA LIKE ILLNESS † 1	1/175 (0.57%)
PYREXIA † 1	3/175 (1.71%)
Hepatobiliary disorders
HEPATIC FAILURE † 1	2/175 (1.14%)
Infections and infestations
ABDOMINAL WALL ABSCESS † 1	1/175 (0.57%)
DEVICE RELATED INFECTION † 1	1/175 (0.57%)
DEVICE RELATED SEPSIS † 1	1/175 (0.57%)
ESCHERICHIA INFECTION † 1	1/175 (0.57%)
INFECTION † 1	2/175 (1.14%)
LUNG INFECTION † 1	2/175 (1.14%)
PELVIC ABSCESS † 1	1/175 (0.57%)
SEPSIS † 1	1/175 (0.57%)
SEPTIC SHOCK † 1	1/175 (0.57%)
TOOTH INFECTION † 1	1/175 (0.57%)
Injury, poisoning and procedural complications
HEAD INJURY † 1	1/175 (0.57%)
Investigations
BLOOD ALKALINE PHOSPHATASE INCREASED † 1	1/175 (0.57%)
LAPAROSCOPY † 1	1/175 (0.57%)
Metabolism and nutrition disorders
DECREASED APPETITE † 1	2/175 (1.14%)
DEHYDRATION † 1	1/175 (0.57%)
HYPERGLYCAEMIA † 1	1/175 (0.57%)
HYPOKALAEMIA † 1	1/175 (0.57%)
Musculoskeletal and connective tissue disorders
BONE PAIN † 1	1/175 (0.57%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
INFECTED NEOPLASM † 1	1/175 (0.57%)
METASTASES TO CENTRAL NERVOUS SYSTEM † 1	2/175 (1.14%)
METASTATIC PAIN † 1	1/175 (0.57%)
Nervous system disorders
CEREBELLAR ISCHAEMIA † 1	1/175 (0.57%)
CEREBROVASCULAR ACCIDENT † 1	1/175 (0.57%)
DIZZINESS † 1	1/175 (0.57%)
HEADACHE † 1	1/175 (0.57%)
NEUROPATHY PERIPHERAL † 1	1/175 (0.57%)
Psychiatric disorders
CONFUSIONAL STATE † 1	1/175 (0.57%)
DEPRESSION † 1	1/175 (0.57%)
Renal and urinary disorders
RENAL COLIC † 1	1/175 (0.57%)
RENAL FAILURE † 1	2/175 (1.14%)
URINARY RETENTION † 1	1/175 (0.57%)
Reproductive system and breast disorders
PRIAPISM † 1	1/175 (0.57%)
Respiratory, thoracic and mediastinal disorders
DYSPNOEA † 1	1/175 (0.57%)
EPISTAXIS † 1	1/175 (0.57%)
PLEURAL EFFUSION † 1	1/175 (0.57%)
PNEUMOTHORAX † 1	2/175 (1.14%)
PULMONARY EMBOLISM † 1	4/175 (2.29%)
PULMONARY OEDEMA † 1	1/175 (0.57%)
Surgical and medical procedures
HEPATECTOMY † 1	1/175 (0.57%)
INTRAPERITONEAL HYPERTHERMIC CHEMOTHERAPY † 1	1/175 (0.57%)
Vascular disorders
PHLEBITIS † 1	1/175 (0.57%)
THROMBOSIS † 1	1/175 (0.57%)
VARICOSE ULCERATION † 1	1/175 (0.57%)
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, MedDRA 18.1
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Aflibercept + FOLFIRI(Irinotecan, 5-Fluorouracil & Leucovorin)
	Affected / at Risk (%)
Total	172/175 (98.29%)
Blood and lymphatic system disorders
NEUTROPENIA † 1	39/175 (22.29%)
Gastrointestinal disorders
ABDOMINAL PAIN † 1	36/175 (20.57%)
ABDOMINAL PAIN UPPER † 1	14/175 (8.00%)
CONSTIPATION † 1	39/175 (22.29%)
DIARRHOEA † 1	121/175 (69.14%)
GASTROOESOPHAGEAL REFLUX DISEASE † 1	10/175 (5.71%)
NAUSEA † 1	86/175 (49.14%)
PROCTALGIA † 1	10/175 (5.71%)
RECTAL HAEMORRHAGE † 1	11/175 (6.29%)
STOMATITIS † 1	83/175 (47.43%)
VOMITING † 1	47/175 (26.86%)
General disorders
ASTHENIA † 1	98/175 (56.00%)
FATIGUE † 1	33/175 (18.86%)
PYREXIA † 1	14/175 (8.00%)
Investigations
WEIGHT DECREASED † 1	68/175 (38.86%)
Metabolism and nutrition disorders
DECREASED APPETITE † 1	59/175 (33.71%)
Musculoskeletal and connective tissue disorders
ARTHRALGIA † 1	10/175 (5.71%)
BACK PAIN † 1	18/175 (10.29%)
MYALGIA † 1	11/175 (6.29%)
Nervous system disorders
DYSGEUSIA † 1	13/175 (7.43%)
HEADACHE † 1	32/175 (18.29%)
NEUROPATHY PERIPHERAL † 1	19/175 (10.86%)
PARAESTHESIA † 1	9/175 (5.14%)
Renal and urinary disorders
PROTEINURIA † 1	25/175 (14.29%)
Respiratory, thoracic and mediastinal disorders
DYSPHONIA † 1	22/175 (12.57%)
DYSPNOEA † 1	17/175 (9.71%)
EPISTAXIS † 1	43/175 (24.57%)
Skin and subcutaneous tissue disorders
ALOPECIA † 1	36/175 (20.57%)
PALMAR-PLANTAR ERYTHRODYSAESTHESIA SYNDROME † 1	23/175 (13.14%)
Vascular disorders
HYPERTENSION † 1	74/175 (42.29%)
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, MedDRA 18.1

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

If no publication has occurred within 12 months of the completion of the study, the Investigator shall have the right to publish/present independently the results of the study. The Investigator shall provide the Sponsor with a copy of any such presentation/publication for comment at least 30 days before any presentation/submission for publication. If requested by the Sponsor, any presentation/submission shall be delayed up to 90 days, to allow the Sponsor to preserve its proprietary rights.

Results Point of Contact

• Name/Title: Trial Transparency Team
• Organization: Sanofi
• EMail: Contact-US@sanofi.com

• Responsible Party: Sanofi
• ClinicalTrials.gov Identifier: NCT01670721
• Other Study ID Numbers: AFLIBL06266; 2012-000048-89; U1111-1128-9325 ( Other Identifier: UTN )
• First Submitted: July 13, 2012
• First Posted: August 22, 2012
• Results First Submitted: June 8, 2016
• Results First Posted: November 28, 2016
• Last Update Posted: November 28, 2016