Safety, Tolerability, and Effect of Alirocumab in High Cardiovascular Risk Patients With Severe Hypercholesterolemia Not Adequately Controlled With Conventional Lipid-modifying Therapies (ODYSSEY APPRISE)

• ClinicalTrials.gov Identifier: NCT02476006
• Recruitment Status: Completed
• First Posted: June 19, 2015
• Results First Posted: March 30, 2020
• Last Update Posted: March 30, 2020
• 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: Hypercholesterolemia
• Interventions: Drug: ALIROCUMAB SAR236553 (REGN727); Drug: placebo (for injection training only); Drug: ezetimibe; Drug: atorvastatin; Drug: rosuvastatin; Drug: simvastatin
• Enrollment: 998

Participant Flow

Recruitment Details	The study was conducted at 156 sites in 17 countries. A total of 1305 participants were screened between 23-June-2015 to 27-December 2016, of whom 307 were screen failures. Screen failures were mainly due to exclusion criteria met.
Pre-assignment Details	A total of 998 participants were enrolled in the study.

Arm/Group Title	Alirocumab
Arm/Group Description	Participants received Alirocumab 150 milligram (mg) subcutaneously (SC) once every two weeks (Q2W) or 75 mg SC Q2W added to stable lipid modifying therapies (LMT) up to a maximum of 120 weeks. Alirocumab dose was either up-titrated from 75 to 150 mg Q2W or down-titrated from 150 to 75 mg Q2W, based on Investigator judgment and treatment response.
Period Title: Overall Study
Started	998
Treated	994
Completed	878
Not Completed	120
Reason Not Completed
Death	4
Lack of treatment efficacy	2
Pregnancy	1
Participant did not wish to continue	39
Adverse Event	41
Poor compliance to study protocol	3
Sponsor decision	6
Lost to Follow-up	5
Physician Decision	5
Study ended treatment not available	4
Switched to commercial drug	4
Excluded from study	1
Protocol Violation	1
Enrolled but not treated	4

Baseline Characteristics

Arm/Group Title		Alirocumab
Arm/Group Description		Participants received Alirocumab 150 mg SC Q2W or 75 mg SC Q2W added to stable LMT up to a maximum of 120 weeks. Alirocumab dose was either up-titrated from 75 to 150 mg Q2W or down-titrated from 150 to 75 mg Q2W, based on Investigator judgment and treatment response.
Overall Number of Baseline Participants		994
Baseline Analysis Population Description		Analysis was performed on safety population that included all participants who had signed the informed consent form (ICF) and who had received at least one dose or partial dose of alirocumab.
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	994 participants
		56.6 (11.7)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	994 participants
	Female	369 37.1%
	Male	625 62.9%
Race/Ethnicity, Customized; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	994 participants
	White/Caucasian	969 97.5%
	Black	10 1.0%
	Asian/Oriental	6 0.6%
	Multiracial	1 0.1%
	Other	8 0.8%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With Treatment Emergent Adverse Events (TEAEs)
Description	Adverse Event (AE) was defined as any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. Treatment-emergent AEs (TEAEs) were defined as AEs that that developed or worsened or became serious during the TEAE period (time from the first injection of study drug up to the day of the last injection of study drug + 14 days). A Serious Adverse Event (SAE) was any untoward medical occurrence that at any dose: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, was a medically important event.
Time Frame	From first injection of investigational medicinal product (IMP) up to 2 weeks after last dose of study drug (Week 120)

Outcome Measure Data

Analysis Population Description

Analysis was performed on safety population.

Arm/Group Title	Alirocumab
Arm/Group Description:	Participants received Alirocumab 150 mg SC Q2W or 75 mg SC Q2W added to stable LMT up to a maximum of 120 weeks. Alirocumab dose was either up-titrated from 75 to 150 mg Q2W or down-titrated from 150 to 75 mg Q2W, based on Investigator judgment and treatment response.
Overall Number of Participants Analyzed	994
Measure Type: Number; Unit of Measure: percentage of participants
Any TEAE	71.6
Any treatment emergent SAE	16.2
Any TEAE leading to death	0.2
Any TEAE leading to treatment discontinuation	4.5

2. Secondary Outcome

Title	Percent Change From Baseline in Calculated Low Density Lipoprotein Cholesterol (LDL-C) at Week 12
Description	Calculated LDL-C values were obtained using the Friedewald formula. Calculated LDL-C in mg/dL from Friedewald formula (LDL cholesterol = Total cholesterol - HDL cholesterol - [Triglyceride/5]). Baseline value was defined as the last observation before the first dose of the treatment.
Time Frame	Baseline, Week 12

Outcome Measure Data

Analysis Population Description

Analysis was performed on modified intent-to-treat population (mITT): all enrolled participants who received at least one dose or part of a dose of alirocumab and had an evaluable efficacy endpoint during the efficacy treatment period (defined as time period from the first injection of alirocumab up to the day of last injection +21 days).

Arm/Group Title	Alirocumab
Arm/Group Description:	Participants received Alirocumab 150 mg SC Q2W or 75 mg SC Q2W added to stable LMT up to a maximum of 120 weeks. Alirocumab dose was either up-titrated from 75 to 150 mg Q2W or down-titrated from 150 to 75 mg Q2W, based on Investigator judgment and treatment response.
Overall Number of Participants Analyzed	921
Mean (Standard Deviation); Unit of Measure: percent change
	-54.84 (20.06)

3. Secondary Outcome

Title	Percentage of Participants Reaching Calculated LDL-C <100 mg/dL (2.59 mmol/L) at Week 12
Description	LDL-Cholesterol was calculated using the Friedewald formula. Percentage of participants who reached calculated LDL-C <100 mg/dL (2.59 mmol/L) at week 12 were reported.
Time Frame	At Week 12

Outcome Measure Data

Analysis Population Description

Analysis was performed on mITT population.

Arm/Group Title	Alirocumab
Arm/Group Description:	Participants received Alirocumab 150 mg SC Q2W or 75 mg SC Q2W added to stable LMT up to a maximum of 120 weeks. Alirocumab dose was either up-titrated from 75 to 150 mg Q2W or down-titrated from 150 to 75 mg Q2W, based on Investigator judgment and treatment response.
Overall Number of Participants Analyzed	921
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	74.6; (71.7 to 77.4)

4. Secondary Outcome

Title	Percentage of Participants Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) at Week 12
Description	LDL-Cholesterol was calculated using the Friedewald formula. Percentage of participants who reached calculated LDL-C <70 mg/dL (1.81 mmol/L) at week 12 were reported.
Time Frame	At Week 12

Outcome Measure Data

Analysis Population Description

Analysis was performed on mITT population.

Arm/Group Title	Alirocumab
Arm/Group Description:	Participants received Alirocumab 150 mg SC Q2W or 75 mg SC Q2W added to stable LMT up to a maximum of 120 weeks. Alirocumab dose was either up-titrated from 75 to 150 mg Q2W or down-titrated from 150 to 75 mg Q2W, based on Investigator judgment and treatment response.
Overall Number of Participants Analyzed	921
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	50.2; (46.9 to 53.4)

5. Secondary Outcome

Title	Percentage of Participants Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) and/or >=50% Reduction From Baseline in LDL-C at Week 12
Description	LDL-Cholesterol was calculated using the Friedewald formula. Percentage of participants who reached LDL-C <70 mg/dL at Week 12 and/or >=50% reduction from baseline in LDL-C at Week 12 are reported.
Time Frame	At Week 12

Outcome Measure Data

Analysis Population Description

Analysis was performed on mITT population.

Arm/Group Title	Alirocumab
Arm/Group Description:	Participants received Alirocumab 150 mg SC Q2W or 75 mg SC Q2W added to stable LMT up to a maximum of 120 weeks. Alirocumab dose was either up-titrated from 75 to 150 mg Q2W or down-titrated from 150 to 75 mg Q2W, based on Investigator judgment and treatment response.
Overall Number of Participants Analyzed	921
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	69.1; (66.0 to 72.0)

6. Secondary Outcome

Title	Percent Change From Baseline in Non-High Density Lipoprotein Cholesterol (Non-HDL-C) at Week 12
Description	Baseline value was defined as the last observation before the first dose of the treatment.
Time Frame	Baseline, Week 12

Outcome Measure Data

Analysis Population Description

Analysis was performed on mITT population.

Arm/Group Title	Alirocumab
Arm/Group Description:	Participants received Alirocumab 150 mg SC Q2W or 75 mg SC Q2W added to stable LMT up to a maximum of 120 weeks. Alirocumab dose was either up-titrated from 75 to 150 mg Q2W or down-titrated from 150 to 75 mg Q2W, based on Investigator judgment and treatment response.
Overall Number of Participants Analyzed	921
Mean (Standard Deviation); Unit of Measure: percent change
	-45.89 (35.82)

7. Secondary Outcome

Title	Percent Change From Baseline in Total Cholesterol (Total-C) at Week 12
Description	Baseline value was defined as the last observation before the first dose of the treatment.
Time Frame	Baseline, Week 12

Outcome Measure Data

Analysis Population Description

Analysis was performed on mITT population.

Arm/Group Title	Alirocumab
Arm/Group Description:	Participants received Alirocumab 150 mg SC Q2W or 75 mg SC Q2W added to stable LMT up to a maximum of 120 weeks. Alirocumab dose was either up-titrated from 75 to 150 mg Q2W or down-titrated from 150 to 75 mg Q2W, based on Investigator judgment and treatment response.
Overall Number of Participants Analyzed	921
Mean (Standard Deviation); Unit of Measure: percent change
	-38.28 (15.20)

8. Secondary Outcome

Title	Percent Change From Baseline in High Density Lipoprotein Cholesterol at Week 12
Description	Baseline value was defined as the last observation before the first dose of the treatment.
Time Frame	Baseline, Week 12

Outcome Measure Data

Analysis Population Description

Analysis was performed on mITT population.

Arm/Group Title	Alirocumab
Arm/Group Description:	Participants received Alirocumab 150 mg SC Q2W or 75 mg SC Q2W added to stable LMT up to a maximum of 120 weeks. Alirocumab dose was either up-titrated from 75 to 150 mg Q2W or down-titrated from 150 to 75 mg Q2W, based on Investigator judgment and treatment response.
Overall Number of Participants Analyzed	921
Mean (Standard Deviation); Unit of Measure: percent change
	4.37 (17.29)

9. Secondary Outcome

Title	Percent Change From Baseline in Triglycerides at Week 12
Description	Baseline value was defined as the last observation before the first dose of the treatment.
Time Frame	Baseline, Week 12

Outcome Measure Data

Analysis Population Description

Analysis was performed on mITT population.

Arm/Group Title	Alirocumab
Arm/Group Description:	Participants received Alirocumab 150 mg SC Q2W or 75 mg SC Q2W added to stable LMT up to a maximum of 120 weeks. Alirocumab dose was either up-titrated from 75 to 150 mg Q2W or down-titrated from 150 to 75 mg Q2W, based on Investigator judgment and treatment response.
Overall Number of Participants Analyzed	921
Mean (Standard Deviation); Unit of Measure: percent change
	-8.28 (33.99)

10. Secondary Outcome

Title	Assessment of Participant's Acceptability of Self-Injection Using Self Injection Assessment Questionnaire (SIAQ): Feeling About Injections, Self Confidence, Satisfaction With Self-Injections
Description	Pre-SIAQ: self-completed before first self-injection & Post-SIAQ: self-completed after self-injection. Pre-SIAQ consisted of 7 items grouped into 3 domains:feelings about injections,self-confidence & satisfaction with self-injection. Post-SIAQ consisted of 21 items grouped into 6 domains:feelings about injections,self-image,self-confidence,injection-site reactions,ease of use & satisfaction with self-injection. Participants rated each item on 5-point (or 6-point) semantic Likert-type scale, where lower numbers indicate a worse experience. Item scores were transformed to obtain a score ranging from 0 (worst experience) to 10 (best experience). Transformed scores for items contributing to a domain were then averaged into a domain score. Each domain score ranges from 0 (worst experience) to 10 (best experience), higher score=better acceptability. Domain scores common to the Pre & Post SIAQ were analyzed on participants belonging to Pre & Post-SIAQ population and are reported.
Time Frame	Baseline (Pre-SIAQ), Week 4, Week 8, Week 12, Week 24, Week 48, Week 72, Week 96

Outcome Measure Data

Analysis Population Description

Pre and Post-SIAQ population: participants from the safety population who self-injected the training injection & completed a Pre-SIAQ before first self-injection, who self-injected study drug at least once during the study and completed a Post-SIAQ. Here, number analyzed = participants with available data at specified time points.

Arm/Group Title		Alirocumab
Arm/Group Description:		Participants received Alirocumab 150 mg SC Q2W or 75 mg SC Q2W added to stable LMT up to a maximum of 120 weeks. Alirocumab dose was either up-titrated from 75 to 150 mg Q2W or down-titrated from 150 to 75 mg Q2W, based on Investigator judgment and treatment response.
Overall Number of Participants Analyzed		952
Mean (Standard Deviation); Unit of Measure: units on a scale
Feelings about injections: Baseline	Number Analyzed	952 participants
		8.6 (1.8)
Feeling about injections: Week 4	Number Analyzed	909 participants
		9.1 (1.4)
Feeling about injections: Week 8	Number Analyzed	894 participants
		9.1 (1.4)
Feeling about injections: Week 12	Number Analyzed	847 participants
		9.2 (1.4)
Feeling about injections: Week 24	Number Analyzed	668 participants
		9.2 (1.4)
Feeling about injections: Week 48	Number Analyzed	547 participants
		9.2 (1.4)
Feeling about injections: Week 72	Number Analyzed	423 participants
		9.2 (1.4)
Feeling about injections: Week 96	Number Analyzed	343 participants
		9.3 (1.3)
Self confidence: Baseline	Number Analyzed	943 participants
		6.9 (2.4)
Self Confidence: Week 4	Number Analyzed	905 participants
		8.0 (2.1)
Self Confidence: Week 8	Number Analyzed	889 participants
		8.1 (2.0)
Self Confidence: Week 12	Number Analyzed	844 participants
		8.1 (1.9)
Self Confidence: Week 24	Number Analyzed	666 participants
		8.0 (2.1)
Self Confidence: Week 48	Number Analyzed	548 participants
		8.1 (2.1)
Self Confidence: Week 72	Number Analyzed	420 participants
		8.3 (2.0)
Self Confidence: Week 96	Number Analyzed	340 participants
		8.4 (2.0)
Satisfaction with self injection: Baseline	Number Analyzed	918 participants
		7.2 (2.5)
Satisfaction with self-injections: Week 4	Number Analyzed	906 participants
		8.5 (1.6)
Satisfaction with self-injections: Week 8	Number Analyzed	889 participants
		8.7 (1.6)
Satisfaction with self-injections: Week 12	Number Analyzed	842 participants
		8.7 (1.6)
Satisfaction with self-injections: Week 24	Number Analyzed	667 participants
		8.6 (1.8)
Satisfaction with self-injections: Week 48	Number Analyzed	542 participants
		8.7 (1.5)
Satisfaction with self-injections: Week 72	Number Analyzed	418 participants
		8.8 (1.7)
Satisfaction with self-injections: Week 96	Number Analyzed	338 participants
		8.8 (1.4)

11. Secondary Outcome

Title	Assessment of Participant's Acceptability of Self-Injection Using Self Injection Assessment Questionnaire (SIAQ): Self Image, Injection-Site Reactions, Ease of Use
Description	SIAQ: contained 2 modules: Pre-SIAQ and Post-SIAQ. Post-SIAQ: self-completed after self-injection. Post-SIAQ consisted of 21 items grouped into 6 domains: feelings about injections, self-image, self-confidence, injection-site reactions, ease of use & satisfaction with self-injection. Participants rated each item on 5-point (or 6-point) semantic Likert-type scale, where lower numbers indicated a worse experience. Item scores were transformed to obtain a score ranging from 0 (worst experience) to 10 (best experience) for each item. Transformed scores for items contributing to a domain were then averaged into a domain score. Each domain score ranges from 0 (worst experience) to 10 (best experience), higher score=better acceptability. Domain scores which are not in common with Pre-SIAQ were analyzed on the Post-SIAQ population and are reported here.
Time Frame	Week 4, Week 8, Week 12, Week 24, Week 48, Week 72, Week 96

Outcome Measure Data

Analysis Population Description

POST-SIAQ population: participants from safety population who self-injected at least once during the study and completed a POST-SIAQ regardless of completion of PRE-SIAQ. Here, number analyzed = participants with available data at specified time points.

Arm/Group Title		Alirocumab
Arm/Group Description:		Participants received Alirocumab 150 mg SC Q2W or 75 mg SC Q2W added to stable LMT up to a maximum of 120 weeks. Alirocumab dose was either up-titrated from 75 to 150 mg Q2W or down-titrated from 150 to 75 mg Q2W, based on Investigator judgment and treatment response.
Overall Number of Participants Analyzed		979
Mean (Standard Deviation); Unit of Measure: units on a scale
Self Image: Week 4	Number Analyzed	929 participants
		9.4 (1.4)
Self Image: Week 8	Number Analyzed	915 participants
		9.4 (1.4)
Self Image: Week 12	Number Analyzed	866 participants
		9.4 (1.4)
Self Image: Week 24	Number Analyzed	682 participants
		9.3 (1.5)
Self Image: Week 48	Number Analyzed	560 participants
		9.4 (1.4)
Self Image: Week 72	Number Analyzed	433 participants
		9.3 (1.5)
Self Image: Week 96	Number Analyzed	349 participants
		9.4 (1.4)
Injection-site reactions: Week 4	Number Analyzed	925 participants
		9.6 (0.7)
Injection-site reactions: Week 8	Number Analyzed	907 participants
		9.6 (0.8)
Injection-site reactions: Week 12	Number Analyzed	862 participants
		9.6 (0.7)
Injection-site reactions: Week 24	Number Analyzed	679 participants
		9.5 (0.9)
Injection-site reactions: Week 48	Number Analyzed	549 participants
		9.5 (0.8)
Injection-site reactions: Week 72	Number Analyzed	431 participants
		9.5 (0.8)
Injection-site reactions: Week 96	Number Analyzed	353 participants
		9.5 (0.8)
Ease of use: Week 4	Number Analyzed	927 participants
		8.7 (1.5)
Ease of use: Week 8	Number Analyzed	914 participants
		8.7 (1.6)
Ease of use: Week 12	Number Analyzed	866 participants
		8.8 (1.6)
Ease of use: Week 24	Number Analyzed	676 participants
		8.8 (1.6)
Ease of use: Week 48	Number Analyzed	559 participants
		8.9 (1.4)
Ease of use: Week 72	Number Analyzed	432 participants
		9.0 (1.5)
Ease of use: Week 96	Number Analyzed	353 participants
		9.0 (1.4)

Adverse Events

Time Frame	All AEs were collected from first injection of IMP up to 2 weeks after last dose of study drug (Week 120).
Adverse Event Reporting Description	Reported AEs and deaths were TEAEs that developed or worsened or became serious and deaths that occurred during the TEAE period (time from the first injection of study drug up to the day of the last injection of study drug + 14 days). Analysis was performed on safety population.
Arm/Group Title	Alirocumab
Arm/Group Description	Participants received Alirocumab 150 mg SC Q2W or 75 mg SC Q2W added to stable LMT up to a maximum of 120 weeks. Alirocumab dose was either up-titrated from 75 to 150 mg Q2W or down-titrated from 150 to 75 mg Q2W, based on Investigator judgment and treatment response.
All-Cause Mortality
	Alirocumab
	Affected / at Risk (%)
Total	2/994 (0.20%)
Serious Adverse Events
	Alirocumab
	Affected / at Risk (%)	# Events
Total	161/994 (16.20%)
Blood and lymphatic system disorders
Anaemia † 1	2/994 (0.20%)	2
Cardiac disorders
Acute Coronary Syndrome † 1	5/994 (0.50%)	5
Acute Myocardial Infarction † 1	5/994 (0.50%)	5
Angina Pectoris † 1	15/994 (1.51%)	15
Angina Unstable † 1	12/994 (1.21%)	14
Aortic Valve Stenosis † 1	1/994 (0.10%)	1
Arteriosclerosis Coronary Artery † 1	1/994 (0.10%)	1
Atrial Fibrillation † 1	5/994 (0.50%)	5
Atrial Flutter † 1	1/994 (0.10%)	1
Atrial Tachycardia † 1	1/994 (0.10%)	1
Atrioventricular Block Second Degree † 1	1/994 (0.10%)	1
Cardiac Failure † 1	3/994 (0.30%)	3
Cardiac Failure Congestive † 1	1/994 (0.10%)	1
Coronary Artery Disease † 1	6/994 (0.60%)	6
Coronary Artery Stenosis † 1	6/994 (0.60%)	7
Coronary Ostial Stenosis † 1	1/994 (0.10%)	1
Mitral Valve Stenosis † 1	1/994 (0.10%)	1
Myocardial Infarction † 1	3/994 (0.30%)	3
Myocardial Ischaemia † 1	5/994 (0.50%)	5
Subendocardial Ischaemia † 1	1/994 (0.10%)	1
Ventricular Fibrillation † 1	1/994 (0.10%)	1
Congenital, familial and genetic disorders
Accessory Navicular Syndrome † 1	1/994 (0.10%)	1
Eye disorders
Cataract † 1	2/994 (0.20%)	2
Gastrointestinal disorders
Colitis Ischaemic † 1	1/994 (0.10%)	1
Diverticular Perforation † 1	1/994 (0.10%)	1
Diverticulum Intestinal † 1	1/994 (0.10%)	1
Dyspepsia † 1	1/994 (0.10%)	1
Gastrooesophageal Reflux Disease † 1	1/994 (0.10%)	1
Haemorrhoidal Haemorrhage † 1	1/994 (0.10%)	1
Hypoaesthesia Oral † 1	1/994 (0.10%)	1
Lower Gastrointestinal Haemorrhage † 1	1/994 (0.10%)	1
Melaena † 1	1/994 (0.10%)	1
Perianal Erythema † 1	1/994 (0.10%)	1
Rectal Haemorrhage † 1	1/994 (0.10%)	1
Umbilical Hernia † 1	1/994 (0.10%)	1
General disorders
Chest Discomfort † 1	1/994 (0.10%)	1
Chest Pain † 1	2/994 (0.20%)	2
Non-Cardiac Chest Pain † 1	2/994 (0.20%)	2
Vascular Stent Stenosis † 1	4/994 (0.40%)	4
Hepatobiliary disorders
Bile Duct Stone † 1	1/994 (0.10%)	1
Cholelithiasis † 1	1/994 (0.10%)	1
Chronic Hepatitis † 1	1/994 (0.10%)	1
Hepatocellular Injury † 1	1/994 (0.10%)	1
Hypertransaminasaemia † 1	1/994 (0.10%)	1
Infections and infestations
Bronchitis † 1	1/994 (0.10%)	1
Campylobacter Colitis † 1	1/994 (0.10%)	1
Diabetic Foot Infection † 1	1/994 (0.10%)	1
Diverticulitis † 1	3/994 (0.30%)	3
Escherichia Sepsis † 1	1/994 (0.10%)	1
Gastroenteritis Viral † 1	2/994 (0.20%)	2
Liver Abscess † 1	1/994 (0.10%)	1
Pneumonia † 1	3/994 (0.30%)	3
Urinary Tract Infection † 1	1/994 (0.10%)	1
Urosepsis † 1	1/994 (0.10%)	1
Viral Infection † 1	1/994 (0.10%)	1
Wound Infection † 1	1/994 (0.10%)	1
Injury, poisoning and procedural complications
Fall † 1	2/994 (0.20%)	2
Hip Fracture † 1	1/994 (0.10%)	1
Injury † 1	1/994 (0.10%)	1
Joint Injury † 1	1/994 (0.10%)	1
Lower Limb Fracture † 1	1/994 (0.10%)	1
Meniscus Injury † 1	2/994 (0.20%)	3
Peripheral Artery Restenosis † 1	1/994 (0.10%)	1
Post Procedural Complication † 1	1/994 (0.10%)	1
Post Procedural Haematoma † 1	1/994 (0.10%)	1
Rib Fracture † 1	2/994 (0.20%)	2
Scapula Fracture † 1	1/994 (0.10%)	1
Spinal Column Injury † 1	1/994 (0.10%)	1
Tendon Rupture † 1	3/994 (0.30%)	3
Tibia Fracture † 1	1/994 (0.10%)	1
Upper Limb Fracture † 1	2/994 (0.20%)	2
Vascular Graft Occlusion † 1	1/994 (0.10%)	1
Investigations
Transaminases Increased † 1	1/994 (0.10%)	1
Metabolism and nutrition disorders
Dehydration † 1	1/994 (0.10%)	1
Diabetes Mellitus † 1	3/994 (0.30%)	3
Diabetes Mellitus Inadequate Control † 1	1/994 (0.10%)	1
Musculoskeletal and connective tissue disorders
Fibromyalgia † 1	1/994 (0.10%)	1
Intervertebral Disc Protrusion † 1	1/994 (0.10%)	1
Myopathy † 1	1/994 (0.10%)	1
Osteoarthritis † 1	3/994 (0.30%)	3
Polymyalgia Rheumatica † 1	1/994 (0.10%)	1
Spondylolisthesis † 1	1/994 (0.10%)	1
Tendonitis † 1	1/994 (0.10%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Benign Neoplasm Of Prostate † 1	1/994 (0.10%)	1
Bladder Cancer Stage 0, With Cancer In Situ † 1	1/994 (0.10%)	1
Breast Cancer † 1	1/994 (0.10%)	1
Clear Cell Renal Cell Carcinoma † 1	1/994 (0.10%)	1
Colon Adenoma † 1	1/994 (0.10%)	1
Gastrointestinal Tract Adenoma † 1	1/994 (0.10%)	1
Lung Adenocarcinoma † 1	2/994 (0.20%)	2
Myelodysplastic Syndrome † 1	1/994 (0.10%)	1
Prostate Cancer † 1	3/994 (0.30%)	3
Rectal Adenocarcinoma † 1	1/994 (0.10%)	1
Transitional Cell Carcinoma † 1	1/994 (0.10%)	1
Uterine Cancer † 1	1/994 (0.10%)	1
Nervous system disorders
Amnesia † 1	1/994 (0.10%)	1
Ataxia † 1	1/994 (0.10%)	1
Carotid Artery Stenosis † 1	3/994 (0.30%)	3
Carpal Tunnel Syndrome † 1	1/994 (0.10%)	1
Cerebrovascular Accident † 1	1/994 (0.10%)	1
Facial Paralysis † 1	1/994 (0.10%)	1
Headache † 1	1/994 (0.10%)	1
Ischaemic Stroke † 1	1/994 (0.10%)	1
Paraesthesia † 1	1/994 (0.10%)	1
Seizure † 1	1/994 (0.10%)	2
Syncope † 1	3/994 (0.30%)	3
Transient Ischaemic Attack † 1	1/994 (0.10%)	1
Product Issues
Device Dislocation † 1	1/994 (0.10%)	1
Psychiatric disorders
Completed Suicide † 1	1/994 (0.10%)	1
Depression † 1	2/994 (0.20%)	2
Schizophrenia † 1	1/994 (0.10%)	1
Renal and urinary disorders
Bladder Trabeculation † 1	1/994 (0.10%)	1
Nephrolithiasis † 1	1/994 (0.10%)	1
Renal Impairment † 1	1/994 (0.10%)	1
Reproductive system and breast disorders
Metrorrhagia † 1	1/994 (0.10%)	1
Prostatitis † 1	2/994 (0.20%)	2
Respiratory, thoracic and mediastinal disorders
Epistaxis † 1	1/994 (0.10%)	1
Lung Disorder † 1	2/994 (0.20%)	2
Pulmonary Embolism † 1	1/994 (0.10%)	1
Skin and subcutaneous tissue disorders
Actinic Keratosis † 1	1/994 (0.10%)	1
Parapsoriasis † 1	1/994 (0.10%)	1
Rash † 1	1/994 (0.10%)	1
Social circumstances
Pregnancy Of Partner † 1	1/994 (0.10%)	1
Vascular disorders
Aortic Aneurysm † 1	1/994 (0.10%)	1
Aortic Dissection † 1	1/994 (0.10%)	1
Deep Vein Thrombosis † 1	2/994 (0.20%)	2
Hypertension † 1	1/994 (0.10%)	1
Intermittent Claudication † 1	2/994 (0.20%)	2
Peripheral Arterial Occlusive Disease † 1	2/994 (0.20%)	2
Peripheral Artery Aneurysm † 1	1/994 (0.10%)	1
Peripheral Artery Stenosis † 1	2/994 (0.20%)	2
Peripheral Artery Thrombosis † 1	1/994 (0.10%)	1
1 Term from vocabulary, MedDRA 21.1; † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Alirocumab
	Affected / at Risk (%)	# Events
Total	221/994 (22.23%)
Infections and infestations
Influenza † 1	53/994 (5.33%)	61
Nasopharyngitis † 1	78/994 (7.85%)	86
Musculoskeletal and connective tissue disorders
Myalgia † 1	71/994 (7.14%)	93
Nervous system disorders
Headache † 1	61/994 (6.14%)	94
1 Term from vocabulary, MedDRA 21.1; † Indicates events were collected by systematic assessment

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.

The Sponsor supports publication of clinical trial results but may request that investigators temporarily delay or alter publications in order to protect proprietary information. The Sponsor may also require that the results of multicenter studies be published only in their entirety and not as individual site data.

Results Point of Contact

• Name/Title: Trial Transparency Team
• Organization: Sanofi aventis recherche & développement
• Phone: 800-633-1610 ext 1#
• EMail: Contact-US@sanofi.com

• Responsible Party: Sanofi
• ClinicalTrials.gov Identifier: NCT02476006
• Other Study ID Numbers: LPS14245; 2015-000620-28 ( EudraCT Number ); U1111-1163-0984 ( Other Identifier: UTN )
• First Submitted: June 16, 2015
• First Posted: June 19, 2015
• Results First Submitted: March 13, 2020
• Results First Posted: March 30, 2020
• Last Update Posted: March 30, 2020