An Open-label Extension Study to Assess the Long-term Safety and Efficacy of ISIS 301012 (Mipomersen) in Patients With Familial Hypercholesterolemia or Severe-Hypercholesterolemia

• Sponsor: Kastle Therapeutics, LLC (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00694109
• Collaborator: Ionis Pharmaceuticals, Inc. (Industry)
• Enrollment: 144
• Locations: 33
• Arm: 1
• Duration (Months): 77
• Patients Per Site: 4.4
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

To evaluate the safety and efficacy of extended dosing with mipomersen (ISIS 301012) in participants with familial hypercholesterolemia or severe hypercholesterolemia on lipid-lowering therapy who had completed either the 301012-CS5 (NCT00607373), 301012-CS7 (NCT00706849), 301012-CS17 (NCT00477594) or MIPO3500108 (NCT00794664) clinical drug trials.

Condition or Disease	Intervention/Treatment	Phase
Lipid Metabolism, Inborn Errors; Hypercholesterolemia, Autosomal Dominant; Hyperlipidemias; Metabolic Diseases; Hyperlipoproteinemia Type II; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Infant, Newborn, Diseases; Metabolic Disorder; Congenital Abnormalities; Hypercholesterolemia; Hyperlipoproteinemias; Dyslipidemias; Lipid Metabolism Disorders	Drug: Mipomersen Sodium	Phase 3

Detailed Description

All familial hypercholesterolemia (FH) or severe hypercholesterolemia participants who had tolerated the treatment regimen in Protocol 301012-CS5 (NCT00607373), 301012-CS7 (NCT00706849) or MIPO3500108 (NCT00794664) and satisfactorily completed the study through to Week 28 were eligible for participation in this open label treatment extension study for up to 4 years or until mipomersen was commercially available, whichever comes first. Consenting participants who had tolerated mipomersen and satisfactorily completed 301012-CS17 (NCT00477594) through Year 3 may also enroll for up to an additional 2 years of treatment in this study or until mipomersen was commercially available, whichever comes first. All participants, who entered the study, received 200 mg mipomersen (ISIS 301012) subcutaneously (s.c.) every week, including those who were randomized to placebo in their initial study. Participants who were originally enrolled in Protocol 301012-CS5 (NCT00607373) and weighed <50 kg received 160 mg every week. Dose adjustments (70 mg injections administered three times per week, on separate days) were allowed for participants who were not tolerating or who had previous issues with tolerating the once a week injections due to injection site reactions (ISRs) or flu-like symptoms. Study visits and clinical lab assessments including hematology with differential, chemistry, serum lipid panel (total cholesterol, LDL-C, very low density lipoprotein cholesterol (VLDL-C), high density lipoprotein cholesterol (HDL-C), apolipoprotein B (apoB), apoA-1, triglycerides (TG) and Lp(a), and urinalysis was to be performed every 4-10 weeks during the treatment period. Plasma trough mipomersen (ISIS 301012) levels was to be measured to estimate exposure. Participants who completed dosing or who discontinued prematurely from the study for any reason was followed for safety for 24 weeks (safety follow-up period) after their last dose of mipomersen (ISIS 301012) or longer in the case of a significant adverse events (AE) or abnormal biochemical or clinical finding. Participants were required to return to the study center for clinical evaluation and clinical laboratory tests every 8 weeks during the safety follow-up period.

Study Design

• Study Type: Interventional
• Actual Enrollment: 144 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open-label Extension Study to Assess the Long-term Safety and Efficacy of ISIS 301012 in Patients With Familial Hypercholesterolemia or Severe-Hypercholesterolemia
• Study Start Date: Apr 1, 2008
• Actual Primary Completion Date: Sep 1, 2014
• Actual Study Completion Date: Sep 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Mipomersen Mipomersen Sodium once a week for up to 4 years (depending on participant's consent). Participants were followed for additional 24 week post-treatment.	Drug: Mipomersen Sodium; Subcutaneous injection as a single injection directly into the abdomen, thigh, or outer area of the upper arm.; Other Names: ISIS 301012 Kynamro®

Outcome Measures

Primary Outcome Measures

1. Percent Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-C) [Baseline up to Week 234; 24 weeks post treatment (up to 4.5 years)]

   Baseline was defined as the last value prior to receiving the first dose of mipomersen in this study (for participants randomized to placebo in their index study and for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered >=6 months from their last dose of mipomersen in their index study), or the last value prior to receiving the first dose of mipomersen in their index study (for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered <6 months from their last dose of mipomersen in their index study).

2. Percent Change From Baseline in Apolipoprotein B (Apo B) [Baseline up to Week 234; 24 weeks post treatment (up to 4.5 years)]

   Baseline was defined as the last value prior to receiving the first dose of mipomersen in this study (for participants randomized to placebo in their index study and for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered >=6 months from their last dose of mipomersen in their index study), or the last value prior to receiving the first dose of mipomersen in their index study (for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered <6 months from their last dose of mipomersen in their index study).

3. Percent Change From Baseline in Total Cholesterol [Baseline up to Week 234; 24 weeks post treatment (up to 4.5 years)]

   Baseline was defined as the last value prior to receiving the first dose of mipomersen in this study (for participants randomized to placebo in their index study and for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered >=6 months from their last dose of mipomersen in their index study), or the last value prior to receiving the first dose of mipomersen in their index study (for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered <6 months from their last dose of mipomersen in their index study).

4. Percent Change From Baseline in Non High Density Lipoprotein Cholesterol (Non-HDL-C) [Baseline up to Week 234; 24 weeks post treatment (up to 4.5 years)]

   Baseline was defined as the last value prior to receiving the first dose of mipomersen in this study (for participants randomized to placebo in their index study and for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered >=6 months from their last dose of mipomersen in their index study), or the last value prior to receiving the first dose of mipomersen in their index study (for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered <6 months from their last dose of mipomersen in their index study).

Secondary Outcome Measures

1. Percent Change From Baseline in Triglycerides [Baseline up to Week 234; 24 weeks post treatment (up to 4.5 years)]

   Baseline was defined as the last value prior to receiving the first dose of mipomersen in this study (for participants randomized to placebo in their index study and for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered >=6 months from their last dose of mipomersen in their index study), or the last value prior to receiving the first dose of mipomersen in their index study (for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered <6 months from their last dose of mipomersen in their index study).

2. Percent Change From Baseline in Lipoprotein (a) [Baseline up to Week 234; 24 weeks post treatment (up to 4.5 years)]

   Baseline was defined as the last value prior to receiving the first dose of mipomersen in this study (for participants randomized to placebo in their index study and for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered >=6 months from their last dose of mipomersen in their index study), or the last value prior to receiving the first dose of mipomersen in their index study (for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered <6 months from their last dose of mipomersen in their index study).

3. Percent Change From Baseline in LDL Particles' Size (Total) [Baseline up to End of treatment; 24 weeks post treatment (up to 4.5 years)]

   Baseline was defined as the last value prior to receiving the first dose of mipomersen in this study (for participants randomized to placebo in their index study and for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered >=6 months from their last dose of mipomersen in their index study), or the last value prior to receiving the first dose of mipomersen in their index study (for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered <6 months from their last dose of mipomersen in their index study).

4. Percent Change From Baseline in LDL Particles' Size (Large) [Baseline up to End of treatment; 24 weeks post treatment (up to 4.5 years)]

   Baseline was defined as the last value prior to receiving the first dose of mipomersen in this study (for participants randomized to placebo in their index study and for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered >=6 months from their last dose of mipomersen in their index study), or the last value prior to receiving the first dose of mipomersen in their index study (for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered <6 months from their last dose of mipomersen in their index study).

5. Percent Change From Baseline in LDL Particles' Size (Medium) [Baseline up to End of treatment; 24 weeks post treatment (up to 4.5 years)]

   Baseline was defined as the last value prior to receiving the first dose of mipomersen in this study (for participants randomized to placebo in their index study and for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered >=6 months from their last dose of mipomersen in their index study), or the last value prior to receiving the first dose of mipomersen in their index study (for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered <6 months from their last dose of mipomersen in their index study).

6. Percent Change From Baseline in LDL Particles' Size (Small) [Baseline up to End of treatment; 24 weeks post treatment (up to 4.5 years)]

   Baseline was defined as the last value prior to receiving the first dose of mipomersen in this study (for participants randomized to placebo in their index study and for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered >=6 months from their last dose of mipomersen in their index study), or the last value prior to receiving the first dose of mipomersen in their index study (for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered <6 months from their last dose of mipomersen in their index study).

7. Percent Change From Baseline in LDL Particles' Size (Very Small) [Baseline up to End of treatment; 24 weeks post treatment (up to 4.5 years)]

   Baseline was defined as the last value prior to receiving the first dose of mipomersen in this study (for participants randomized to placebo in their index study and for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered >=6 months from their last dose of mipomersen in their index study), or the last value prior to receiving the first dose of mipomersen in their index study (for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered <6 months from their last dose of mipomersen in their index study).

8. Percent Change From Baseline in HDL Particles' Size (Large) [Baseline up to End of treatment; 24 weeks post treatment (up to 4.5 years)]

   Baseline was defined as the last value prior to receiving the first dose of mipomersen in this study (for participants randomized to placebo in their index study and for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered >=6 months from their last dose of mipomersen in their index study), or the last value prior to receiving the first dose of mipomersen in their index study (for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered <6 months from their last dose of mipomersen in their index study).

9. Percent Change From Baseline in HDL Particles' Size (Medium) [Baseline up to End of treatment; 24 weeks post treatment (up to 4.5 years)]

   Baseline was defined as the last value prior to receiving the first dose of mipomersen in this study (for participants randomized to placebo in their index study and for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered >=6 months from their last dose of mipomersen in their index study), or the last value prior to receiving the first dose of mipomersen in their index study (for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered <6 months from their last dose of mipomersen in their index study).

10. Percent Change From Baseline in HDL Particles' Size (Small) [Baseline up to End of treatment; 24 weeks post treatment (up to 4.5 years)]

    Baseline was defined as the last value prior to receiving the first dose of mipomersen in this study (for participants randomized to placebo in their index study and for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered >=6 months from their last dose of mipomersen in their index study), or the last value prior to receiving the first dose of mipomersen in their index study (for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered <6 months from their last dose of mipomersen in their index study).

11. Percent Change From Baseline in Intermediate Density Lipoprotein Particles' Size [Baseline up to End of treatment; 24 weeks post treatment (up to 4.5 years)]

    Baseline was defined as the last value prior to receiving the first dose of mipomersen in this study (for participants randomized to placebo in their index study and for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered >=6 months from their last dose of mipomersen in their index study), or the last value prior to receiving the first dose of mipomersen in their index study (for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered <6 months from their last dose of mipomersen in their index study).

12. Percent Change From Baseline in Very Low Density Lipoprotein (VLDL) Particles' Size (Large) and Chylomicron Particles' Size [Baseline up to End of treatment; 24 weeks post treatment (up to 4.5 years)]

    Baseline was defined as the last value prior to receiving the first dose of mipomersen in this study (for participants randomized to placebo in their index study and for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered >=6 months from their last dose of mipomersen in their index study), or the last value prior to receiving the first dose of mipomersen in their index study (for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered <6 months from their last dose of mipomersen in their index study).

13. Percent Change From Baseline in VLDL Particles' Size (Medium) [Baseline up to End of treatment; 24 weeks post treatment (up to 4.5 years)]

    Baseline was defined as the last value prior to receiving the first dose of mipomersen in this study (for participants randomized to placebo in their index study and for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered >=6 months from their last dose of mipomersen in their index study), or the last value prior to receiving the first dose of mipomersen in their index study (for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered <6 months from their last dose of mipomersen in their index study).

14. Percent Change From Baseline in VLDL Particles' Size (Small) [Baseline up to End of treatment; 24 weeks post treatment (up to 4.5 years)]

    Baseline was defined as the last value prior to receiving the first dose of mipomersen in this study (for participants randomized to placebo in their index study and for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered >=6 months from their last dose of mipomersen in their index study), or the last value prior to receiving the first dose of mipomersen in their index study (for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered <6 months from their last dose of mipomersen in their index study).

15. Percent Change From Baseline in Total VLDL Particles' Size and Chylomicron Particles' Size [Baseline up to End of treatment; 24 weeks post treatment (up to 4.5 years)]

    Baseline was defined as the last value prior to receiving the first dose of mipomersen in this study (for participants randomized to placebo in their index study and for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered >=6 months from their last dose of mipomersen in their index study), or the last value prior to receiving the first dose of mipomersen in their index study (for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered <6 months from their last dose of mipomersen in their index study).

16. Change From Baseline in C-Reactive Protein [Baseline up to End of treatment; 24 weeks post treatment (up to 4.5 years)]

    Baseline was defined as the last value prior to receiving the first dose of mipomersen in this study (for participants randomized to placebo in their index study and for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered >=6 months from their last dose of mipomersen in their index study), or the last value prior to receiving the first dose of mipomersen in their index study (for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered <6 months from their last dose of mipomersen in their index study).

17. Percent Change From Baseline in Apolipoprotein A-1 [Baseline up to Week 234; 24 weeks post treatment (up to 4.5 years)]

    Baseline was defined as the last value prior to receiving the first dose of mipomersen in this study (for participants randomized to placebo in their index study and for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered >=6 months from their last dose of mipomersen in their index study), or the last value prior to receiving the first dose of mipomersen in their index study (for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered <6 months from their last dose of mipomersen in their index study).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 12 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Satisfactory completion of dosing in their initial study (Protocol 301012-CS5 [NCT00607373], 301012-CS7 [NCT00706849], 301012-CS17 [NCT00477594], or MIPO3500108 [NCT00794664])

Exclusion Criteria:

• Had any new condition or worsening of existing condition which in the opinion of the Investigator would make the participant unsuitable for enrollment, or could interfere with the participant participating in or completing the study

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Mission Viejo	California	United States	92691
2		Newport Beach	California	United States	92660
3		Bridgeport	Connecticut	United States	06606
4		Melbourne	Florida	United States	32901
5		Winter Park	Florida	United States	32792
6		Chicago	Illinois	United States	60654
7		Kansas City	Kansas	United States	66160
8		Biddeford	Maine	United States	04005
9		Boston	Massachusetts	United States	02114
10		St Louis	Missouri	United States	63110
11		Concord	New Hampshire	United States	03301
12		New York	New York	United States	10032
13		Charlotte	North Carolina	United States	28204
14		Durham	North Carolina	United States	27710
15		Cincinnati	Ohio	United States	45212
16		Franklin	Ohio	United States	45005
17		Portland	Oregon	United States	97239
18		Nashville	Tennessee	United States	37232
19		Dallas	Texas	United States	75226
20		Seattle	Washington	United States	98104
21		Sao Paulo		Brazil
22		Winnipeg	Manitoba	Canada	R3A 1M5
23		London	Ontario	Canada	N6A 5K8
24		Chicoutimi	Quebec	Canada	G7H 5H6
25		Montreal	Quebec	Canada	H1T 1C8
26		Montreal	Quebec	Canada	H2W 1R7
27		Sherbrooke	Quebec	Canada	J1H 5N4
28		Quebec		Canada	G1V 4M6
29		Singapore		Singapore	168752
30		Observatory		South Africa	7925
31		Parktown		South Africa	2193
32		Taipei		Taiwan	11217
33		London		United Kingdom	WC1N 3BG

Sponsors and Collaborators

• Kastle Therapeutics, LLC
• Ionis Pharmaceuticals, Inc.

Investigators

• Study Director: Medical Monitor, Genzyme, a Sanofi Company

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Kastle Therapeutics, LLC
• ClinicalTrials.gov Identifier: NCT00694109
• Other Study ID Numbers: 301012-CS6; 2005-003450-10
• First Posted: Jun 10, 2008
• Last Update Posted: Sep 9, 2016
• Last Verified: Aug 1, 2016

• Keywords provided by Kastle Therapeutics, LLC: Familial Hypercholesterolemia; FH; Heterozygous Familial Hypercholesterolemia; HeFH; Homozygous Familial Hypercholesterolemia; HoFH
• Additional relevant MeSH terms: Congenital Abnormalities; Hyperlipoproteinemia Type II; Genetic Diseases, Inborn; Metabolism, Inborn Errors; Infant, Newborn, Diseases; Lipid Metabolism, Inborn Errors; Hypercholesterolemia; Dyslipidemias; Hyperlipidemias; Hyperlipoproteinemias; Metabolic Diseases; Lipid Metabolism Disorders; Disease; Mipomersen

Study Results

Participant Flow

Recruitment Details	The study was conducted at 33 centers in 7 countries. A total of 144 patients were enrolled in the study. 1 patient never received study drug. 2 of the enrolled patients came from a phase 2 study and its extension and consequently had very different treatment from the other treated patients, and thus were excluded from all summary tables.
Pre-assignment Detail	Participants who successfully completed ISIS 301012 CS5 (NCT00607373), ISIS 301012CS7 (NCT00706849), ISIS 301012CS17 (NCT00694109) or MIPO3500108 (NCT00794664) with an acceptable safety profile were eligible for study.

Arm/Group Title	Mipomersen
Arm/Group Description	Mipomersen Sodium 200 mg (for participants weighed ≥ 50 kg) or 160 mg (for participants weighed <50 kg) subcutaneous injection once a week for up to 4 years (depending on participant's consent). Participants were followed for additional 24 week post-treatment.
Period Title: Overall Study
STARTED	142
Treated	141
Consented 2 Years Additional Treatment	42
Completed Consented Length of Treatment	60
COMPLETED	25
NOT COMPLETED	117

Baseline Characteristics

Arm/Group Title	Mipomersen
Arm/Group Description	Mipomersen Sodium 200 mg (for participants weighed ≥ 50 kg) or 160 mg (for participants weighed <50 kg) subcutaneous injection once a week for up to 4 years (depending on participant's consent). Participants were followed for additional 24 week post-treatment.
Overall Participants	141
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	49.3 (15.3)
Sex: Female, Male (Count of Participants)
Female	57 40.4%
Male	84 59.6%

Outcome Measures

1. Primary Outcome

Title	Percent Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-C)
Description	Baseline was defined as the last value prior to receiving the first dose of mipomersen in this study (for participants randomized to placebo in their index study and for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered >=6 months from their last dose of mipomersen in their index study), or the last value prior to receiving the first dose of mipomersen in their index study (for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered <6 months from their last dose of mipomersen in their index study).
Time Frame	Baseline up to Week 234; 24 weeks post treatment (up to 4.5 years)

Outcome Measure Data

Analysis Population Description

Analysis was performed on Safety set. Here n=participants with lipid parameter assessment at specified time.

Arm/Group Title	Mipomersen
Arm/Group Description	Mipomersen Sodium 200 mg (for participants weighed ≥ 50 kg) or 160 mg (for participants weighed <50 kg) subcutaneous injection once a week for up to 4 years (depending on participant's consent). Participants were followed for additional 24 week post-treatment.
Measure Participants	141
week 26 (n = 130)	-28.5
week 52 (n = 111)	-27
week 76 (n = 66)	-27.3
week 104 (n = 57)	-27.9
week 130 (n = 42)	-21.9
week 156 (n = 30)	-21.4
week 182 (n = 26)	-23.6
week 208 (n = 27)	-26.3
week 234 (n = 17)	-22.5
24 weeks post last dose (n=117)	1.6

2. Primary Outcome

Title	Percent Change From Baseline in Apolipoprotein B (Apo B)
Description	Baseline was defined as the last value prior to receiving the first dose of mipomersen in this study (for participants randomized to placebo in their index study and for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered >=6 months from their last dose of mipomersen in their index study), or the last value prior to receiving the first dose of mipomersen in their index study (for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered <6 months from their last dose of mipomersen in their index study).
Time Frame	Baseline up to Week 234; 24 weeks post treatment (up to 4.5 years)

Outcome Measure Data

Analysis Population Description

Analysis was performed on Safety set. Here n=participants with lipid parameter assessment at specified time.

Arm/Group Title	Mipomersen
Arm/Group Description	Mipomersen Sodium 200 mg (for participants weighed ≥ 50 kg) or 160 mg (for participants weighed <50 kg) subcutaneous injection once a week for up to 4 years (depending on participant's consent). Participants were followed for additional 24 week post-treatment.
Measure Participants	141
week 26 (n = 130)	-28.9
week 52 (n = 111)	-28.1
week 76 (n = 66)	-30.3
week 104 (n = 57)	-31.2
week 130 (n = 43)	-29.1
week 156 (n = 30)	-30.2
week 182 (n = 26)	-31.1
week 208 (n = 27)	-33.3
week 234 (n = 17)	-31.4
24 weeks post last dose (n=117)	-3.46

3. Primary Outcome

Title	Percent Change From Baseline in Total Cholesterol
Description	Baseline was defined as the last value prior to receiving the first dose of mipomersen in this study (for participants randomized to placebo in their index study and for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered >=6 months from their last dose of mipomersen in their index study), or the last value prior to receiving the first dose of mipomersen in their index study (for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered <6 months from their last dose of mipomersen in their index study).
Time Frame	Baseline up to Week 234; 24 weeks post treatment (up to 4.5 years)

Outcome Measure Data

Analysis Population Description

Analysis was performed on Safety set. Here n=participants with lipid parameter assessment at specified time.

Arm/Group Title	Mipomersen
Arm/Group Description	Mipomersen Sodium 200 mg (for participants weighed ≥ 50 kg) or 160 mg (for participants weighed <50 kg) subcutaneous injection once a week for up to 4 years (depending on participant's consent). Participants were followed for additional 24 week post-treatment.
Measure Participants	141
week 26 (n = 130)	-21.7
week 52 (n = 111)	-20.4
week 76 (n = 66)	-20.1
week 104 (n = 57)	-19.8
week 130 (n = 43)	-14.9
week 156 (n = 30)	-14.4
week 182 (n = 26)	-14.3
week 208 (n = 27)	-16.5
week 234 (n = 17)	-12.5
24 weeks post last dose (n=117)	1.94

4. Primary Outcome

Title	Percent Change From Baseline in Non High Density Lipoprotein Cholesterol (Non-HDL-C)
Description	Baseline was defined as the last value prior to receiving the first dose of mipomersen in this study (for participants randomized to placebo in their index study and for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered >=6 months from their last dose of mipomersen in their index study), or the last value prior to receiving the first dose of mipomersen in their index study (for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered <6 months from their last dose of mipomersen in their index study).
Time Frame	Baseline up to Week 234; 24 weeks post treatment (up to 4.5 years)

Outcome Measure Data

Analysis Population Description

Analysis was performed on Safety set. Here n=participants with lipid parameter assessment at specified time.

Arm/Group Title	Mipomersen
Arm/Group Description	Mipomersen Sodium 200 mg (for participants weighed ≥ 50 kg) or 160 mg (for participants weighed <50 kg) subcutaneous injection once a week for up to 4 years (depending on participant's consent). Participants were followed for additional 24 week post-treatment.
Measure Participants	141
week 26 (n = 130)	-27.2
week 52 (n = 111)	-25.4
week 76 (n = 66)	-25
week 104 (n = 57)	-26.2
week 130 (n = 43)	-20.7
week 156 (n = 30)	-20
week 182 (n = 26)	-21.7
week 208 (n = 27)	-23.9
week 234 (n = 17)	-19.9
24 weeks post last dose (n=117)	2.5

5. Secondary Outcome

Title	Percent Change From Baseline in Triglycerides
Description	Baseline was defined as the last value prior to receiving the first dose of mipomersen in this study (for participants randomized to placebo in their index study and for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered >=6 months from their last dose of mipomersen in their index study), or the last value prior to receiving the first dose of mipomersen in their index study (for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered <6 months from their last dose of mipomersen in their index study).
Time Frame	Baseline up to Week 234; 24 weeks post treatment (up to 4.5 years)

Outcome Measure Data

Analysis Population Description

Analysis was performed on Safety set. Here n=participants with lipid parameter assessment at specified time.

Arm/Group Title	Mipomersen
Arm/Group Description	Mipomersen Sodium 200 mg (for participants weighed ≥ 50 kg) or 160 mg (for participants weighed <50 kg) subcutaneous injection once a week for up to 4 years (depending on participant's consent). Participants were followed for additional 24 week post-treatment.
Measure Participants	141
week 26 (n = 130)	-20.1
week 52 (n = 111)	-7.9
week 76 (n = 66)	-10.2
week 104 (n = 57)	-12.5
week 130 (n = 43)	-10.9
week 156 (n = 30)	-10.4
week 182 (n = 26)	-12.9
week 208 (n = 27)	-13.9
week 234 (n = 17)	1.3
24 weeks post last dose (n=117)	2.1

6. Secondary Outcome

Title	Percent Change From Baseline in Lipoprotein (a)
Description	Baseline was defined as the last value prior to receiving the first dose of mipomersen in this study (for participants randomized to placebo in their index study and for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered >=6 months from their last dose of mipomersen in their index study), or the last value prior to receiving the first dose of mipomersen in their index study (for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered <6 months from their last dose of mipomersen in their index study).
Time Frame	Baseline up to Week 234; 24 weeks post treatment (up to 4.5 years)

Outcome Measure Data

Analysis Population Description

Analysis was performed on Safety set. Here n=participants with lipid parameter assessment at specified time.

Arm/Group Title	Mipomersen
Arm/Group Description	Mipomersen Sodium 200 mg (for participants weighed ≥ 50 kg) or 160 mg (for participants weighed <50 kg) subcutaneous injection once a week for up to 4 years (depending on participant's consent). Participants were followed for additional 24 week post-treatment.
Measure Participants	141
week 26 (n = 130)	-20.5
week 52 (n = 111)	-19
week 76 (n = 66)	-17.9
week 104 (n = 57)	-16.6
week 130 (n = 43)	-15.8
week 156 (n = 30)	-9.1
week 182 (n = 26)	-9
week 208 (n = 27)	-9.9
week 234 (n = 17)	-18.3
24 weeks post last dose (n=117)	0

7. Secondary Outcome

Title	Percent Change From Baseline in LDL Particles' Size (Total)
Description	Baseline was defined as the last value prior to receiving the first dose of mipomersen in this study (for participants randomized to placebo in their index study and for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered >=6 months from their last dose of mipomersen in their index study), or the last value prior to receiving the first dose of mipomersen in their index study (for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered <6 months from their last dose of mipomersen in their index study).
Time Frame	Baseline up to End of treatment; 24 weeks post treatment (up to 4.5 years)

Outcome Measure Data

Analysis Population Description

Analysis was performed on Safety set. Here n=participants with lipid parameter assessment at specified time. Number of participants analyzed = participants with available data for LDL Particles' Size (Total).

Arm/Group Title	Mipomersen
Arm/Group Description	Mipomersen Sodium 200 mg (for participants weighed ≥ 50 kg) or 160 mg (for participants weighed <50 kg) subcutaneous injection once a week for up to 4 years (depending on participant's consent). Participants were followed for additional 24 week post-treatment.
Measure Participants	140
week 52 (n = 91)	-26.77
week 104 (n = 47)	-27.77
week 156 (n = 20)	-25.1
week 208 (n = 19)	-32.65
End of treatment (n=139)	-22.63
24 weeks post last dose (n=115)	6.11

8. Secondary Outcome

Title	Percent Change From Baseline in LDL Particles' Size (Large)
Description	Baseline was defined as the last value prior to receiving the first dose of mipomersen in this study (for participants randomized to placebo in their index study and for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered >=6 months from their last dose of mipomersen in their index study), or the last value prior to receiving the first dose of mipomersen in their index study (for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered <6 months from their last dose of mipomersen in their index study).
Time Frame	Baseline up to End of treatment; 24 weeks post treatment (up to 4.5 years)

Outcome Measure Data

Analysis Population Description

Analysis was performed on Safety set. Here n=participants with lipid parameter assessment at specified time. Number of participants analyzed = participants with available data for LDL Particles' Size (Large).

Arm/Group Title	Mipomersen
Arm/Group Description	Mipomersen Sodium 200 mg (for participants weighed ≥ 50 kg) or 160 mg (for participants weighed <50 kg) subcutaneous injection once a week for up to 4 years (depending on participant's consent). Participants were followed for additional 24 week post-treatment.
Measure Participants	140
week 52 (n = 91)	-5.01
week 104 (n = 47)	-14.32
week 156 (n = 20)	-27.04
week 208 (n = 19)	-22.67
End of treatment (n=139)	-2.94
24 weeks post last dose (n=115)	6.19

9. Secondary Outcome

Title	Percent Change From Baseline in LDL Particles' Size (Medium)
Description	Baseline was defined as the last value prior to receiving the first dose of mipomersen in this study (for participants randomized to placebo in their index study and for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered >=6 months from their last dose of mipomersen in their index study), or the last value prior to receiving the first dose of mipomersen in their index study (for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered <6 months from their last dose of mipomersen in their index study).
Time Frame	Baseline up to End of treatment; 24 weeks post treatment (up to 4.5 years)

Outcome Measure Data

Analysis Population Description

Analysis was performed on Safety set. Here n=participants with lipid parameter assessment at specified time. Number of participants analyzed = participants with available data for LDL Particles' Size (Medium).

Arm/Group Title	Mipomersen
Arm/Group Description	Mipomersen Sodium 200 mg (for participants weighed ≥ 50 kg) or 160 mg (for participants weighed <50 kg) subcutaneous injection once a week for up to 4 years (depending on participant's consent). Participants were followed for additional 24 week post-treatment.
Measure Participants	140
week 52 (n = 91)	-9.50
week 104 (n = 47)	11.09
week 156 (n = 20)	-19.62
week 208 (n = 19)	-15.82
End of treatment (n=139)	-5.65
24 weeks post last dose (n=115)	46.92

10. Secondary Outcome

Title	Percent Change From Baseline in LDL Particles' Size (Small)
Description	Baseline was defined as the last value prior to receiving the first dose of mipomersen in this study (for participants randomized to placebo in their index study and for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered >=6 months from their last dose of mipomersen in their index study), or the last value prior to receiving the first dose of mipomersen in their index study (for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered <6 months from their last dose of mipomersen in their index study).
Time Frame	Baseline up to End of treatment; 24 weeks post treatment (up to 4.5 years)

Outcome Measure Data

Analysis Population Description

Analysis was performed on Safety set. Here n=participants with lipid parameter assessment at specified time. Number of participants analyzed = participants with available data for LDL Particles' Size (Small).

Arm/Group Title	Mipomersen
Arm/Group Description	Mipomersen Sodium 200 mg (for participants weighed ≥ 50 kg) or 160 mg (for participants weighed <50 kg) subcutaneous injection once a week for up to 4 years (depending on participant's consent). Participants were followed for additional 24 week post-treatment.
Measure Participants	140
week 52 (n = 91)	-8.79
week 104 (n = 47)	1.72
week 156 (n = 20)	-18.95
week 208 (n = 19)	-27.95
End of treatment (n=139)	-5.17
24 weeks post last dose (n=115)	51.94

11. Secondary Outcome

Title	Percent Change From Baseline in LDL Particles' Size (Very Small)
Description	Baseline was defined as the last value prior to receiving the first dose of mipomersen in this study (for participants randomized to placebo in their index study and for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered >=6 months from their last dose of mipomersen in their index study), or the last value prior to receiving the first dose of mipomersen in their index study (for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered <6 months from their last dose of mipomersen in their index study).
Time Frame	Baseline up to End of treatment; 24 weeks post treatment (up to 4.5 years)

Outcome Measure Data

Analysis Population Description

Analysis was performed on Safety set. Here n=participants with lipid parameter assessment at specified time. Number of participants analyzed = participants with available data for LDL Particles' Size (Very Small).

Arm/Group Title	Mipomersen
Arm/Group Description	Mipomersen Sodium 200 mg (for participants weighed ≥ 50 kg) or 160 mg (for participants weighed <50 kg) subcutaneous injection once a week for up to 4 years (depending on participant's consent). Participants were followed for additional 24 week post-treatment.
Measure Participants	140
week 52 (n = 91)	-5.05
week 104 (n = 47)	-0.11
week 156 (n = 20)	-18.7
week 208 (n = 19)	-30.77
End of treatment (n=139)	0.75
24 weeks post last dose (n=115)	60.22

12. Secondary Outcome

Title	Percent Change From Baseline in HDL Particles' Size (Large)
Description	Baseline was defined as the last value prior to receiving the first dose of mipomersen in this study (for participants randomized to placebo in their index study and for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered >=6 months from their last dose of mipomersen in their index study), or the last value prior to receiving the first dose of mipomersen in their index study (for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered <6 months from their last dose of mipomersen in their index study).
Time Frame	Baseline up to End of treatment; 24 weeks post treatment (up to 4.5 years)

Outcome Measure Data

Analysis Population Description

Analysis was performed on Safety set. Here n=participants with lipid parameter assessment at specified time. Number of participants analyzed = participants with available data for LDL Particles' Size (Large).

Arm/Group Title	Mipomersen
Arm/Group Description	Mipomersen Sodium 200 mg (for participants weighed ≥ 50 kg) or 160 mg (for participants weighed <50 kg) subcutaneous injection once a week for up to 4 years (depending on participant's consent). Participants were followed for additional 24 week post-treatment.
Measure Participants	140
week 52 (n = 89)	160.8
week 104 (n = 47)	43.23
week 156 (n = 20)	58.26
week 208 (n = 19)	61.76
End of treatment (n=134)	121.16
24 weeks post last dose (n=110)	85.93

13. Secondary Outcome

Title	Percent Change From Baseline in HDL Particles' Size (Medium)
Description	Baseline was defined as the last value prior to receiving the first dose of mipomersen in this study (for participants randomized to placebo in their index study and for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered >=6 months from their last dose of mipomersen in their index study), or the last value prior to receiving the first dose of mipomersen in their index study (for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered <6 months from their last dose of mipomersen in their index study).
Time Frame	Baseline up to End of treatment; 24 weeks post treatment (up to 4.5 years)

Outcome Measure Data

Analysis Population Description

Analysis was performed on Safety set. Here n=participants with lipid parameter assessment at specified time. Number of participants analyzed = participants with available data for HDL Particles' Size (Medium).

Arm/Group Title	Mipomersen
Arm/Group Description	Mipomersen Sodium 200 mg (for participants weighed ≥ 50 kg) or 160 mg (for participants weighed <50 kg) subcutaneous injection once a week for up to 4 years (depending on participant's consent). Participants were followed for additional 24 week post-treatment.
Measure Participants	140
week 52 (n = 44)	154.77
week 104 (n = 28)	176.14
week 156 (n = 9)	21.24
week 208 (n = 8)	838.32
End of treatment (n= 68)	388.16
24 weeks post last dose (n=56)	233.78

14. Secondary Outcome

Title	Percent Change From Baseline in HDL Particles' Size (Small)
Description	Baseline was defined as the last value prior to receiving the first dose of mipomersen in this study (for participants randomized to placebo in their index study and for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered >=6 months from their last dose of mipomersen in their index study), or the last value prior to receiving the first dose of mipomersen in their index study (for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered <6 months from their last dose of mipomersen in their index study).
Time Frame	Baseline up to End of treatment; 24 weeks post treatment (up to 4.5 years)

Outcome Measure Data

Analysis Population Description

Analysis was performed on Safety set. Here n=participants with lipid parameter assessment at specified time. Number of participants analyzed = participants with available data for HDL Particles' Size (Small).

Arm/Group Title	Mipomersen
Arm/Group Description	Mipomersen Sodium 200 mg (for participants weighed ≥ 50 kg) or 160 mg (for participants weighed <50 kg) subcutaneous injection once a week for up to 4 years (depending on participant's consent). Participants were followed for additional 24 week post-treatment.
Measure Participants	140
week 52 (n = 91)	1.83
week 104 (n = 47)	-9.81
week 156 (n = 20)	-14.18
week 208 (n = 19)	-11.47
End of treatment (n= 139)	0.44
24 weeks post last dose (n=115)	8.31

15. Secondary Outcome

Title	Percent Change From Baseline in Intermediate Density Lipoprotein Particles' Size
Description	Baseline was defined as the last value prior to receiving the first dose of mipomersen in this study (for participants randomized to placebo in their index study and for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered >=6 months from their last dose of mipomersen in their index study), or the last value prior to receiving the first dose of mipomersen in their index study (for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered <6 months from their last dose of mipomersen in their index study).
Time Frame	Baseline up to End of treatment; 24 weeks post treatment (up to 4.5 years)

Outcome Measure Data

Analysis Population Description

Analysis was performed on Safety set. Here n=participants with lipid parameter assessment at specified time. Number of participants analyzed = participants with available data for Intermediate Density Lipoprotein Particles' Size.

Arm/Group Title	Mipomersen
Arm/Group Description	Mipomersen Sodium 200 mg (for participants weighed ≥ 50 kg) or 160 mg (for participants weighed <50 kg) subcutaneous injection once a week for up to 4 years (depending on participant's consent). Participants were followed for additional 24 week post-treatment.
Measure Participants	140
week 52 (n = 79)	-9.9
week 104 (n = 40)	-27.35
week 156 (n = 16)	155.42
week 208 (n = 15)	32.88
End of treatment (n= 122)	24.66
24 weeks post last dose (n=101)	57.46

16. Secondary Outcome

Title	Percent Change From Baseline in Very Low Density Lipoprotein (VLDL) Particles' Size (Large) and Chylomicron Particles' Size
Description	Baseline was defined as the last value prior to receiving the first dose of mipomersen in this study (for participants randomized to placebo in their index study and for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered >=6 months from their last dose of mipomersen in their index study), or the last value prior to receiving the first dose of mipomersen in their index study (for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered <6 months from their last dose of mipomersen in their index study).
Time Frame	Baseline up to End of treatment; 24 weeks post treatment (up to 4.5 years)

Outcome Measure Data

Analysis Population Description

Analysis was performed on Safety set. Here n=participants with lipid parameter assessment at specified time. Number of participants analyzed = participants with available data for Very Low Density Lipoprotein (VLDL) Particles' Size (Large) and Chylomicron Particles' Size.

Arm/Group Title	Mipomersen
Arm/Group Description	Mipomersen Sodium 200 mg (for participants weighed ≥ 50 kg) or 160 mg (for participants weighed <50 kg) subcutaneous injection once a week for up to 4 years (depending on participant's consent). Participants were followed for additional 24 week post-treatment.
Measure Participants	140
week 52 (n = 86)	109.23
week 104 (n = 46)	107.5
week 156 (n = 19)	123.42
week 208 (n = 18)	241.76
End of treatment (n= 132)	86.75
24 weeks post last dose (n=110)	90.82

17. Secondary Outcome

Title	Percent Change From Baseline in VLDL Particles' Size (Medium)
Description	Baseline was defined as the last value prior to receiving the first dose of mipomersen in this study (for participants randomized to placebo in their index study and for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered >=6 months from their last dose of mipomersen in their index study), or the last value prior to receiving the first dose of mipomersen in their index study (for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered <6 months from their last dose of mipomersen in their index study).
Time Frame	Baseline up to End of treatment; 24 weeks post treatment (up to 4.5 years)

Outcome Measure Data

Analysis Population Description

Analysis was performed on Safety set. Here n=participants with lipid parameter assessment at specified time. Number of participants analyzed = participants with available data for VLDL Particles' Size (Medium).

Arm/Group Title	Mipomersen
Arm/Group Description	Mipomersen Sodium 200 mg (for participants weighed ≥ 50 kg) or 160 mg (for participants weighed <50 kg) once a week subcutaneously for up to 4 years (depending on participant's consent). Participants were followed for additional 24 week post-treatment.
Measure Participants	140
week 52 (n = 88)	70.81
week 104 (n = 47)	97.74
week 156 (n = 20)	172.46
week 208 (n = 19)	98.7
End of treatment (n= 136)	63.25
24 weeks post last dose (n=113)	99.57

18. Secondary Outcome

Title	Percent Change From Baseline in VLDL Particles' Size (Small)
Description	Baseline was defined as the last value prior to receiving the first dose of mipomersen in this study (for participants randomized to placebo in their index study and for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered >=6 months from their last dose of mipomersen in their index study), or the last value prior to receiving the first dose of mipomersen in their index study (for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered <6 months from their last dose of mipomersen in their index study).
Time Frame	Baseline up to End of treatment; 24 weeks post treatment (up to 4.5 years)

Outcome Measure Data

Analysis Population Description

Analysis was performed on Safety set. Here n=participants with lipid parameter assessment at specified time. Number of participants analyzed = participants with available data for VLDL Particles' Size (Small).

Arm/Group Title	Mipomersen
Arm/Group Description	Mipomersen Sodium 200 mg (for participants weighed ≥ 50 kg) or 160 mg (for participants weighed <50 kg) subcutaneous injection once a week for up to 4 years (depending on participant's consent). Participants were followed for additional 24 week post-treatment.
Measure Participants	140
week 52 (n = 91)	49.51
week 104 (n = 47)	30.48
week 156 (n = 20)	9.34
week 208 (n = 19)	-30.36
End of treatment (n= 139)	31.27
24 weeks post last dose (n=115)	32.14

19. Secondary Outcome

Title	Percent Change From Baseline in Total VLDL Particles' Size and Chylomicron Particles' Size
Description	Baseline was defined as the last value prior to receiving the first dose of mipomersen in this study (for participants randomized to placebo in their index study and for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered >=6 months from their last dose of mipomersen in their index study), or the last value prior to receiving the first dose of mipomersen in their index study (for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered <6 months from their last dose of mipomersen in their index study).
Time Frame	Baseline up to End of treatment; 24 weeks post treatment (up to 4.5 years)

Outcome Measure Data

Analysis Population Description

Analysis was performed on Safety set. Here n=participants with lipid parameter assessment at specified time. Number of participants analyzed = participants with available data for Total VLDL Particles' Size and Chylomicron Particles' Size.

Arm/Group Title	Mipomersen
Arm/Group Description	Mipomersen Sodium 200 mg (for participants weighed ≥ 50 kg) or 160 mg (for participants weighed <50 kg) subcutaneous injection once a week for up to 4 years (depending on participant's consent). Participants were followed for additional 24 week post-treatment.
Measure Participants	140
week 52 (n = 91)	19.94
week 104 (n = 47)	-14.25
week 156 (n = 20)	3.48
week 208 (n = 19)	-18.66
End of treatment (n= 139)	12.82
24 weeks post last dose (n=115)	19.69

20. Secondary Outcome

Title	Change From Baseline in C-Reactive Protein
Description	Baseline was defined as the last value prior to receiving the first dose of mipomersen in this study (for participants randomized to placebo in their index study and for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered >=6 months from their last dose of mipomersen in their index study), or the last value prior to receiving the first dose of mipomersen in their index study (for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered <6 months from their last dose of mipomersen in their index study).
Time Frame	Baseline up to End of treatment; 24 weeks post treatment (up to 4.5 years)

Outcome Measure Data

Analysis Population Description

Analysis was performed on Safety set. Here n=participants with lipid parameter assessment at specified time.

Arm/Group Title	Mipomersen
Arm/Group Description	Mipomersen Sodium 200 mg (for participants weighed ≥ 50 kg) or 160 mg (for participants weighed <50 kg) subcutaneous injection once a week for up to 4 years (depending on participant's consent). Participants were followed for additional 24 week post-treatment.
Measure Participants	141
week 26 (n=130)	0.67
week 52 (n=111)	-0.37
week 76 (n=84)	-1.05
week 104 (n=58)	0.12
week 130 (n=42)	-0.18
week 156 (n=30)	0.02
week 182 (n=31)	0.73
week 208 (n=27)	0.2
week 234 (n=18)	0.53
End of treatment (n=140)	0.41
24 weeks post last dose (n=116)	0.09

21. Secondary Outcome

Title	Percent Change From Baseline in Apolipoprotein A-1
Description	Baseline was defined as the last value prior to receiving the first dose of mipomersen in this study (for participants randomized to placebo in their index study and for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered >=6 months from their last dose of mipomersen in their index study), or the last value prior to receiving the first dose of mipomersen in their index study (for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered <6 months from their last dose of mipomersen in their index study).
Time Frame	Baseline up to Week 234; 24 weeks post treatment (up to 4.5 years)

Outcome Measure Data

Analysis Population Description

Analysis was performed on Safety set. Here n=participants with lipid parameter assessment at specified time.

Arm/Group Title	Mipomersen
Arm/Group Description	Mipomersen Sodium 200 mg (for participants weighed ≥ 50 kg) or 160 mg (for participants weighed <50 kg) subcutaneous injection once a week for up to 4 years (depending on participant's consent). Participants were followed for additional 24 week post-treatment.
Measure Participants	141
week 26 (n=130)	-1.01
week 52 (n=111)	-1.59
week 76 (n=66)	-3.73
week 104 (n=57)	-4.33
week 130 (n=43)	-1.37
week 156 (n=30)	-5.55
week 182 (n=26)	-3.17
week 208 (n=27)	-2.19
week 234 (n=17)	3.68
24 weeks post last dose (n = 117)	-0.67

Adverse Events

Time Frame	All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (59.7 months) regardless of seriousness or relationship to investigational product.
Adverse Event Reporting Description	Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (from the start of study drug in this study up to 24 weeks post-treatment).
Arm/Group Title	Mipomersen
Arm/Group Description	Mipomersen Sodium 200 mg (for participants weighed ≥ 50 kg) or 160 mg (for participants weighed <50 kg) subcutaneous injection once a week for up to 4 years (depending on participant's consent). Participants were followed for additional 24 week post-treatment.
All Cause Mortality
	Mipomersen
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Mipomersen
	Affected / at Risk (%)	# Events
Total	36/141 (25.5%)
Blood and lymphatic system disorders
Splenic haemorrhage	1/141 (0.7%)
Cardiac disorders
Acute coronary syndrome	1/141 (0.7%)
Acute myocardial infarction	2/141 (1.4%)
Angina pectoris	3/141 (2.1%)
Angina unstable	1/141 (0.7%)
Aortic valve stenosis	2/141 (1.4%)
Atrial fibrillation	3/141 (2.1%)
Cardiac failure congestive	1/141 (0.7%)
Coronary artery disease	3/141 (2.1%)
Myocardial infarction	1/141 (0.7%)
Supraventricular tachycardia	1/141 (0.7%)
Gastrointestinal disorders
Diverticulum intestinal	1/141 (0.7%)
General disorders
Chest pain	1/141 (0.7%)
Device malfunction	1/141 (0.7%)
Non-cardiac chest pain	4/141 (2.8%)
Pyrexia	1/141 (0.7%)
Hepatobiliary disorders
Biliary colic	1/141 (0.7%)
Immune system disorders
Contrast media allergy	1/141 (0.7%)
Infections and infestations
Appendicitis	1/141 (0.7%)
Influenza	1/141 (0.7%)
Injury, poisoning and procedural complications
Ankle fracture	2/141 (1.4%)
Coronary artery restenosis	1/141 (0.7%)
Extradural haematoma	1/141 (0.7%)
Gastrointestinal anastomotic leak	1/141 (0.7%)
Metabolism and nutrition disorders
Dehydration	1/141 (0.7%)
Musculoskeletal and connective tissue disorders
Neck pain	1/141 (0.7%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma	1/141 (0.7%)
Breast cancer	1/141 (0.7%)
Rectal cancer	1/141 (0.7%)
Squamous cell carcinoma	1/141 (0.7%)
Nervous system disorders
Amnesia	1/141 (0.7%)
Arachnoid cyst	1/141 (0.7%)
Dementia Alzheimer's type	1/141 (0.7%)
Partial seizures	1/141 (0.7%)
Syncope	2/141 (1.4%)
Psychiatric disorders
Alcoholism	1/141 (0.7%)
Renal and urinary disorders
Glomerulonephritis membranous	1/141 (0.7%)
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease	1/141 (0.7%)
Dyspnoea	1/141 (0.7%)
Pulmonary hypertension	1/141 (0.7%)
Surgical and medical procedures
Ileostomy	1/141 (0.7%)
Vascular disorders
Aortic aneurysm	1/141 (0.7%)
Aortic stenosis	1/141 (0.7%)
Femoral artery occlusion	1/141 (0.7%)
Peripheral artery dissection	1/141 (0.7%)
Other (Not Including Serious) Adverse Events
	Mipomersen
	Affected / at Risk (%)	# Events
Total	141/141 (100%)
Blood and lymphatic system disorders
Anaemia	9/141 (6.4%)
Leukopenia	1/141 (0.7%)
Lymphadenopathy	3/141 (2.1%)
Thrombocytopenia	5/141 (3.5%)
Cardiac disorders
Angina pectoris	14/141 (9.9%)
Aortic valve disease	1/141 (0.7%)
Aortic valve incompetence	1/141 (0.7%)
Atrial fibrillation	4/141 (2.8%)
Atrioventricular block second degree	1/141 (0.7%)
Bradycardia	1/141 (0.7%)
Coronary artery disease	2/141 (1.4%)
Extrasystoles	1/141 (0.7%)
Myocardial ischaemia	1/141 (0.7%)
Palpitations	4/141 (2.8%)
Supraventricular extrasystoles	2/141 (1.4%)
Tachycardia	3/141 (2.1%)
Ventricular dysfunction	1/141 (0.7%)
Ventricular extrasystoles	2/141 (1.4%)
Ear and labyrinth disorders
Ear discomfort	1/141 (0.7%)
Ear pain	2/141 (1.4%)
Eustachian tube dysfunction	1/141 (0.7%)
Hypoacusis	1/141 (0.7%)
Tinnitus	2/141 (1.4%)
Vertigo	3/141 (2.1%)
Endocrine disorders
Hypothyroidism	1/141 (0.7%)
Eye disorders
Arcus lipoides	2/141 (1.4%)
Cataract	4/141 (2.8%)
Diplopia	1/141 (0.7%)
Dry eye	2/141 (1.4%)
Eye irritation	1/141 (0.7%)
Eye pain	1/141 (0.7%)
Eye swelling	1/141 (0.7%)
Eyelid cyst	1/141 (0.7%)
Halo vision	1/141 (0.7%)
Ocular hyperaemia	1/141 (0.7%)
Presbyopia	1/141 (0.7%)
Vision blurred	3/141 (2.1%)
Vitreous floaters	1/141 (0.7%)
Gastrointestinal disorders
Abdominal discomfort	2/141 (1.4%)
Abdominal distension	3/141 (2.1%)
Abdominal hernia	1/141 (0.7%)
Abdominal pain	14/141 (9.9%)
Abdominal pain lower	5/141 (3.5%)
Abdominal pain upper	7/141 (5%)
Anal haemorrhage	1/141 (0.7%)
Bezoar	1/141 (0.7%)
Colitis	1/141 (0.7%)
Constipation	6/141 (4.3%)
Dental caries	2/141 (1.4%)
Diarrhoea	21/141 (14.9%)
Diverticulum	1/141 (0.7%)
Diverticulum intestinal	2/141 (1.4%)
Dyspepsia	5/141 (3.5%)
Dysphagia	2/141 (1.4%)
Faecal incontinence	1/141 (0.7%)
Faeces soft	1/141 (0.7%)
Flatulence	1/141 (0.7%)
Food poisoning	3/141 (2.1%)
Gastric ulcer	2/141 (1.4%)
Gastritis	4/141 (2.8%)
Gastritis erosive	1/141 (0.7%)
Gastrooesophageal reflux disease	4/141 (2.8%)
Gingival recession	1/141 (0.7%)
Haematochezia	1/141 (0.7%)
Haemorrhoids	2/141 (1.4%)
Hiatus hernia	3/141 (2.1%)
Hypoaesthesia oral	1/141 (0.7%)
Inguinal hernia	1/141 (0.7%)
Intestinal obstruction	1/141 (0.7%)
Lip blister	1/141 (0.7%)
Lip swelling	2/141 (1.4%)
Mouth ulceration	1/141 (0.7%)
Nausea	37/141 (26.2%)
Odynophagia	1/141 (0.7%)
Oesophageal dilatation	1/141 (0.7%)
Oesophageal spasm	1/141 (0.7%)
Oesophagitis	1/141 (0.7%)
Pancreatic duct dilatation	1/141 (0.7%)
Periodontal disease	1/141 (0.7%)
Proctitis ulcerative	1/141 (0.7%)
Rectal haemorrhage	1/141 (0.7%)
Retching	1/141 (0.7%)
Tooth impacted	1/141 (0.7%)
Toothache	5/141 (3.5%)
Umbilical hernia	1/141 (0.7%)
Vomiting	13/141 (9.2%)
Vomiting projectile	1/141 (0.7%)
General disorders
Asthenia	6/141 (4.3%)
Chest discomfort	2/141 (1.4%)
Chest pain	9/141 (6.4%)
Chills	27/141 (19.1%)
Cyst	2/141 (1.4%)
Device breakage	1/141 (0.7%)
Device failure	1/141 (0.7%)
Discomfort	1/141 (0.7%)
Exercise tolerance decreased	1/141 (0.7%)
Facial pain	1/141 (0.7%)
Fatigue	38/141 (27%)
Feeling cold	3/141 (2.1%)
Gait disturbance	2/141 (1.4%)
Influenza like illness	70/141 (49.6%)
Injection site atrophy	1/141 (0.7%)
Injection site bruising	72/141 (51.1%)
Injection site discolouration	55/141 (39%)
Injection site discomfort	14/141 (9.9%)
Injection site eczema	1/141 (0.7%)
Injection site erythema	117/141 (83%)
Injection site exfoliation	1/141 (0.7%)
Injection site extravasation	1/141 (0.7%)
Injection site haematoma	2/141 (1.4%)
Injection site haemorrhage	17/141 (12.1%)
Injection site hypersensitivity	2/141 (1.4%)
Injection site hypertrophy	3/141 (2.1%)
Injection site hypoaesthesia	2/141 (1.4%)
Injection site induration	31/141 (22%)
Injection site inflammation	12/141 (8.5%)
Injection site lymphadenopathy	1/141 (0.7%)
Injection site macule	4/141 (2.8%)
Injection site mass	14/141 (9.9%)
Injection site nodule	9/141 (6.4%)
Injection site oedema	19/141 (13.5%)
Injection site pain	102/141 (72.3%)
Injection site pallor	3/141 (2.1%)
Injection site papule	7/141 (5%)
Injection site paraesthesia	3/141 (2.1%)
Injection site pruritus	46/141 (32.6%)
Injection site rash	16/141 (11.3%)
Injection site reaction	12/141 (8.5%)
Injection site recall reaction	10/141 (7.1%)
Injection site swelling	31/141 (22%)
Injection site urticaria	10/141 (7.1%)
Injection site vesicles	3/141 (2.1%)
Injection site warmth	19/141 (13.5%)
Local swelling	2/141 (1.4%)
Localised oedema	2/141 (1.4%)
Malaise	3/141 (2.1%)
Non-cardiac chest pain	5/141 (3.5%)
Oedema peripheral	10/141 (7.1%)
Pain	13/141 (9.2%)
Pyrexia	25/141 (17.7%)
Swelling	1/141 (0.7%)
Temperature intolerance	1/141 (0.7%)
Tenderness	1/141 (0.7%)
Vaccination site pain	1/141 (0.7%)
Vessel puncture site bruise	1/141 (0.7%)
Xerosis	2/141 (1.4%)
Hepatobiliary disorders
Biliary cyst	1/141 (0.7%)
Cholecystitis acute	1/141 (0.7%)
Cholecystitis chronic	1/141 (0.7%)
Cholelithiasis	1/141 (0.7%)
Hepatic cyst	1/141 (0.7%)
Hepatic fibrosis	1/141 (0.7%)
Hepatic steatosis	17/141 (12.1%)
Hepatomegaly	9/141 (6.4%)
Immune system disorders
Hypersensitivity	1/141 (0.7%)
Seasonal allergy	3/141 (2.1%)
Serum sickness	1/141 (0.7%)
Infections and infestations
Abscess limb	1/141 (0.7%)
Acarodermatitis	1/141 (0.7%)
Acute sinusitis	2/141 (1.4%)
Anal abscess	1/141 (0.7%)
Asymptomatic bacteriuria	1/141 (0.7%)
Bronchitis	10/141 (7.1%)
Bronchopneumonia	1/141 (0.7%)
Cellulitis	2/141 (1.4%)
Conjunctivitis	1/141 (0.7%)
Cystitis	1/141 (0.7%)
Diverticulitis	1/141 (0.7%)
Ear infection	4/141 (2.8%)
Eye infection	2/141 (1.4%)
Folliculitis	1/141 (0.7%)
Furuncle	1/141 (0.7%)
Gastroenteritis	4/141 (2.8%)
Gastroenteritis viral	5/141 (3.5%)
Gastrointestinal infection	1/141 (0.7%)
Gastrointestinal viral infection	5/141 (3.5%)
Genital herpes simplex	1/141 (0.7%)
Giardiasis	1/141 (0.7%)
H1N1 influenza	1/141 (0.7%)
Helicobacter gastritis	1/141 (0.7%)
Herpes zoster	4/141 (2.8%)
Influenza	17/141 (12.1%)
Kidney infection	2/141 (1.4%)
Laryngitis	1/141 (0.7%)
Localised infection	1/141 (0.7%)
Lower respiratory tract infection	3/141 (2.1%)
Nasopharyngitis	28/141 (19.9%)
Onychomycosis	1/141 (0.7%)
Oral herpes	1/141 (0.7%)
Otitis externa	2/141 (1.4%)
Otitis media acute	1/141 (0.7%)
Paronychia	1/141 (0.7%)
Pharyngitis	4/141 (2.8%)
Pharyngitis streptococcal	2/141 (1.4%)
Pneumonia	2/141 (1.4%)
Post procedural infection	1/141 (0.7%)
Respiratory tract infection	2/141 (1.4%)
Rhinitis	4/141 (2.8%)
Sinobronchitis	1/141 (0.7%)
Sinusitis	20/141 (14.2%)
Skin bacterial infection	1/141 (0.7%)
Tinea cruris	1/141 (0.7%)
Tinea versicolour	1/141 (0.7%)
Tooth abscess	2/141 (1.4%)
Tooth infection	2/141 (1.4%)
Upper respiratory tract infection	27/141 (19.1%)
Urinary tract infection	23/141 (16.3%)
Vaginal infection	1/141 (0.7%)
Viral infection	2/141 (1.4%)
Viral upper respiratory tract infection	2/141 (1.4%)
Wound infection	1/141 (0.7%)
Wound sepsis	2/141 (1.4%)
Injury, poisoning and procedural complications
Animal scratch	1/141 (0.7%)
Ankle fracture	1/141 (0.7%)
Arthropod bite	4/141 (2.8%)
Arthropod sting	1/141 (0.7%)
Back injury	1/141 (0.7%)
Brain contusion	1/141 (0.7%)
Concussion	1/141 (0.7%)
Contusion	9/141 (6.4%)
Epicondylitis	3/141 (2.1%)
Excoriation	2/141 (1.4%)
Fall	2/141 (1.4%)
Fractured coccyx	1/141 (0.7%)
Gastrointestinal anastomotic leak	1/141 (0.7%)
Incisional hernia	1/141 (0.7%)
Injury	3/141 (2.1%)
Jaw fracture	1/141 (0.7%)
Kidney contusion	1/141 (0.7%)
Laceration	7/141 (5%)
Ligament sprain	8/141 (5.7%)
Limb injury	2/141 (1.4%)
Meniscus injury	1/141 (0.7%)
Muscle strain	3/141 (2.1%)
Post procedural contusion	1/141 (0.7%)
Post-traumatic pain	3/141 (2.1%)
Procedural pain	9/141 (6.4%)
Procedural vomiting	1/141 (0.7%)
Radius fracture	1/141 (0.7%)
Repetitive strain injury	1/141 (0.7%)
Road traffic accident	2/141 (1.4%)
Scratch	1/141 (0.7%)
Spinal compression fracture	1/141 (0.7%)
Splenic haematoma	1/141 (0.7%)
Sunburn	1/141 (0.7%)
Suture related complication	1/141 (0.7%)
Thermal burn	5/141 (3.5%)
Tibia fracture	1/141 (0.7%)
Tooth fracture	3/141 (2.1%)
Vaccination complication	1/141 (0.7%)
Wound	2/141 (1.4%)
Investigations
Alanine aminotransferase increased	26/141 (18.4%)
Albumin urine present	1/141 (0.7%)
Aspartate aminotransferase increased	21/141 (14.9%)
Beta 2 microglobulin urine increased	2/141 (1.4%)
Blood alkaline phosphatase increased	2/141 (1.4%)
Blood bicarbonate decreased	1/141 (0.7%)
Blood creatine phosphokinase increased	2/141 (1.4%)
Blood creatinine increased	5/141 (3.5%)
Blood phosphorus decreased	1/141 (0.7%)
Blood potassium increased	2/141 (1.4%)
Blood pressure increased	1/141 (0.7%)
Blood testosterone decreased	1/141 (0.7%)
Blood uric acid increased	2/141 (1.4%)
Body temperature increased	2/141 (1.4%)
C-reactive protein increased	1/141 (0.7%)
Cardiac murmur	3/141 (2.1%)
Carotid bruit	4/141 (2.8%)
Electrocardiogram ST segment depression	1/141 (0.7%)
Electrocardiogram T wave abnormal	1/141 (0.7%)
Electrocardiogram T wave inversion	2/141 (1.4%)
Electrocardiogram abnormal	1/141 (0.7%)
Gamma-glutamyltransferase increased	1/141 (0.7%)
Haematocrit decreased	2/141 (1.4%)
Haemoglobin decreased	2/141 (1.4%)
Heart rate increased	1/141 (0.7%)
Hepatic enzyme increased	6/141 (4.3%)
International normalised ratio increased	2/141 (1.4%)
Liver function test abnormal	3/141 (2.1%)
Liver scan abnormal	1/141 (0.7%)
Lymph node palpable	1/141 (0.7%)
Lymphocyte count decreased	1/141 (0.7%)
Multiple gated acquisition scan abnormal	1/141 (0.7%)
Mycobacterium tuberculosis complex test positive	1/141 (0.7%)
Nuclear magnetic resonance imaging abnormal	1/141 (0.7%)
Peripheral pulse decreased	1/141 (0.7%)
Platelet count decreased	5/141 (3.5%)
Protein urine present	1/141 (0.7%)
Prothrombin time prolonged	1/141 (0.7%)
Red blood cell acanthocytes present	1/141 (0.7%)
Red blood cell count decreased	1/141 (0.7%)
Red blood cell schistocytes present	1/141 (0.7%)
Red blood cells urine positive	2/141 (1.4%)
Scan myocardial perfusion abnormal	2/141 (1.4%)
Transaminases increased	1/141 (0.7%)
Urine analysis abnormal	1/141 (0.7%)
Weight decreased	1/141 (0.7%)
Weight increased	1/141 (0.7%)
White blood cell count decreased	1/141 (0.7%)
Metabolism and nutrition disorders
Decreased appetite	3/141 (2.1%)
Dehydration	2/141 (1.4%)
Fluid retention	1/141 (0.7%)
Glucose tolerance impaired	2/141 (1.4%)
Gout	1/141 (0.7%)
Hyperkalaemia	1/141 (0.7%)
Hypocalcaemia	1/141 (0.7%)
Iron deficiency	2/141 (1.4%)
Type 2 diabetes mellitus	1/141 (0.7%)
Vitamin B12 deficiency	1/141 (0.7%)
Vitamin D deficiency	1/141 (0.7%)
Musculoskeletal and connective tissue disorders
Arthralgia	19/141 (13.5%)
Arthritis	4/141 (2.8%)
Back pain	24/141 (17%)
Bone pain	1/141 (0.7%)
Bunion	1/141 (0.7%)
Bursitis	2/141 (1.4%)
Cervical spinal stenosis	1/141 (0.7%)
Chondrocalcinosis pyrophosphate	1/141 (0.7%)
Coccydynia	1/141 (0.7%)
Costochondritis	1/141 (0.7%)
Dupuytren's contracture	2/141 (1.4%)
Exostosis	1/141 (0.7%)
Fibromyalgia	1/141 (0.7%)
Flank pain	2/141 (1.4%)
Fracture pain	1/141 (0.7%)
Haemarthrosis	1/141 (0.7%)
Intervertebral disc degeneration	1/141 (0.7%)
Joint effusion	1/141 (0.7%)
Joint swelling	1/141 (0.7%)
Muscle atrophy	1/141 (0.7%)
Muscle spasms	8/141 (5.7%)
Muscle tightness	1/141 (0.7%)
Muscle twitching	1/141 (0.7%)
Muscular weakness	4/141 (2.8%)
Musculoskeletal chest pain	3/141 (2.1%)
Musculoskeletal discomfort	1/141 (0.7%)
Musculoskeletal pain	7/141 (5%)
Musculoskeletal stiffness	5/141 (3.5%)
Myalgia	33/141 (23.4%)
Neck pain	6/141 (4.3%)
Osteoarthritis	4/141 (2.8%)
Osteopenia	1/141 (0.7%)
Pain in extremity	14/141 (9.9%)
Pain in jaw	1/141 (0.7%)
Plantar fasciitis	1/141 (0.7%)
Rotator cuff syndrome	3/141 (2.1%)
Soft tissue atrophy	1/141 (0.7%)
Spinal osteoarthritis	5/141 (3.5%)
Temporomandibular joint syndrome	1/141 (0.7%)
Tendon pain	1/141 (0.7%)
Tendonitis	2/141 (1.4%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma	4/141 (2.8%)
Benign breast neoplasm	1/141 (0.7%)
Lipoma	1/141 (0.7%)
Melanocytic naevus	1/141 (0.7%)
Seborrhoeic keratosis	3/141 (2.1%)
Skin papilloma	1/141 (0.7%)
Thyroid neoplasm	1/141 (0.7%)
Nervous system disorders
Burning sensation	2/141 (1.4%)
Carotid artery stenosis	1/141 (0.7%)
Carpal tunnel syndrome	2/141 (1.4%)
Cluster headache	1/141 (0.7%)
Cognitive disorder	1/141 (0.7%)
Dizziness	10/141 (7.1%)
Dizziness postural	2/141 (1.4%)
Dysgeusia	1/141 (0.7%)
Headache	35/141 (24.8%)
Hypoaesthesia	7/141 (5%)
Lethargy	2/141 (1.4%)
Loss of consciousness	1/141 (0.7%)
Migraine	2/141 (1.4%)
Migraine with aura	1/141 (0.7%)
Morton's neuralgia	1/141 (0.7%)
Nerve compression	1/141 (0.7%)
Neuralgia	1/141 (0.7%)
Neuropathy peripheral	1/141 (0.7%)
Orthostatic intolerance	1/141 (0.7%)
Paraesthesia	4/141 (2.8%)
Post herpetic neuralgia	1/141 (0.7%)
Presyncope	2/141 (1.4%)
Restless legs syndrome	1/141 (0.7%)
Sciatica	3/141 (2.1%)
Sinus headache	4/141 (2.8%)
Somnolence	1/141 (0.7%)
Syncope	4/141 (2.8%)
Transient ischaemic attack	1/141 (0.7%)
Tremor	8/141 (5.7%)
VIIth nerve paralysis	1/141 (0.7%)
Psychiatric disorders
Abnormal sleep-related event	1/141 (0.7%)
Anxiety	6/141 (4.3%)
Attention deficit/hyperactivity disorder	1/141 (0.7%)
Confusional state	1/141 (0.7%)
Depression	8/141 (5.7%)
Insomnia	9/141 (6.4%)
Libido decreased	2/141 (1.4%)
Panic attack	1/141 (0.7%)
Stress	2/141 (1.4%)
Renal and urinary disorders
Albuminuria	1/141 (0.7%)
Bladder discomfort	1/141 (0.7%)
Dysuria	4/141 (2.8%)
Haematuria	6/141 (4.3%)
Micturition urgency	1/141 (0.7%)
Nephrolithiasis	2/141 (1.4%)
Nephropathy	1/141 (0.7%)
Pollakiuria	4/141 (2.8%)
Proteinuria	6/141 (4.3%)
Pyelocaliectasis	1/141 (0.7%)
Pyuria	1/141 (0.7%)
Renal cyst	4/141 (2.8%)
Renal failure	1/141 (0.7%)
Stress urinary incontinence	1/141 (0.7%)
Urge incontinence	1/141 (0.7%)
Urinary tract disorder	1/141 (0.7%)
Reproductive system and breast disorders
Amenorrhoea	1/141 (0.7%)
Breast mass	2/141 (1.4%)
Dyspareunia	1/141 (0.7%)
Erectile dysfunction	1/141 (0.7%)
Menopausal symptoms	1/141 (0.7%)
Menorrhagia	1/141 (0.7%)
Menstruation delayed	1/141 (0.7%)
Ovarian cyst	1/141 (0.7%)
Pelvic pain	1/141 (0.7%)
Prostatitis	1/141 (0.7%)
Pruritus genital	1/141 (0.7%)
Testicular cyst	1/141 (0.7%)
Uterine haemorrhage	1/141 (0.7%)
Uterine prolapse	1/141 (0.7%)
Vaginal discharge	1/141 (0.7%)
Vaginal haemorrhage	2/141 (1.4%)
Vulvovaginal burning sensation	1/141 (0.7%)
Vulvovaginal dryness	1/141 (0.7%)
Respiratory, thoracic and mediastinal disorders
Bronchial hyperreactivity	1/141 (0.7%)
Cough	15/141 (10.6%)
Dysphonia	1/141 (0.7%)
Dyspnoea	12/141 (8.5%)
Dyspnoea exertional	4/141 (2.8%)
Epistaxis	4/141 (2.8%)
Hiccups	1/141 (0.7%)
Hypoxia	1/141 (0.7%)
Nasal congestion	3/141 (2.1%)
Oropharyngeal pain	13/141 (9.2%)
Painful respiration	1/141 (0.7%)
Paranasal sinus hypersecretion	1/141 (0.7%)
Pneumonia aspiration	1/141 (0.7%)
Productive cough	2/141 (1.4%)
Respiratory tract congestion	2/141 (1.4%)
Rhinitis allergic	2/141 (1.4%)
Rhinorrhoea	8/141 (5.7%)
Sinus congestion	6/141 (4.3%)
Sinus disorder	1/141 (0.7%)
Sleep apnoea syndrome	2/141 (1.4%)
Upper respiratory tract congestion	4/141 (2.8%)
Wheezing	2/141 (1.4%)
Skin and subcutaneous tissue disorders
Alopecia	2/141 (1.4%)
Blister	1/141 (0.7%)
Cold sweat	1/141 (0.7%)
Dermatitis	2/141 (1.4%)
Dermatitis acneiform	1/141 (0.7%)
Dermatitis allergic	1/141 (0.7%)
Dermatitis contact	2/141 (1.4%)
Dry skin	1/141 (0.7%)
Ecchymosis	3/141 (2.1%)
Eczema	1/141 (0.7%)
Erythema	1/141 (0.7%)
Hair growth abnormal	3/141 (2.1%)
Ingrowing nail	1/141 (0.7%)
Ingrown hair	1/141 (0.7%)
Intertrigo	1/141 (0.7%)
Lipodystrophy acquired	1/141 (0.7%)
Macule	2/141 (1.4%)
Onychoclasis	1/141 (0.7%)
Pain of skin	1/141 (0.7%)
Petechiae	1/141 (0.7%)
Pigmentation disorder	1/141 (0.7%)
Pruritus	6/141 (4.3%)
Pruritus generalised	2/141 (1.4%)
Rash	6/141 (4.3%)
Rash erythematous	1/141 (0.7%)
Rash maculo-papular	1/141 (0.7%)
Rash papular	1/141 (0.7%)
Rash pruritic	1/141 (0.7%)
Rash vesicular	1/141 (0.7%)
Scab	1/141 (0.7%)
Skin hyperpigmentation	1/141 (0.7%)
Skin lesion	2/141 (1.4%)
Skin plaque	2/141 (1.4%)
Urticaria	6/141 (4.3%)
Xanthelasma	2/141 (1.4%)
Xanthoma	1/141 (0.7%)
Vascular disorders
Aortic aneurysm	3/141 (2.1%)
Aortic arteriosclerosis	1/141 (0.7%)
Aortic calcification	1/141 (0.7%)
Aortic dilatation	3/141 (2.1%)
Aortic stenosis	1/141 (0.7%)
Flushing	3/141 (2.1%)
Haematoma	2/141 (1.4%)
Hot flush	4/141 (2.8%)
Hypertension	8/141 (5.7%)
Hypertensive crisis	1/141 (0.7%)
Hypotension	2/141 (1.4%)
Infarction	1/141 (0.7%)
Intermittent claudication	1/141 (0.7%)
Orthostatic hypotension	1/141 (0.7%)
Pallor	1/141 (0.7%)
Peripheral coldness	1/141 (0.7%)
Peripheral vascular disorder	1/141 (0.7%)
Phlebitis	1/141 (0.7%)
Subclavian artery stenosis	1/141 (0.7%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

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.