Trial Outcomes & Findings for Phase 2 Study of ISIS 681257 (AKCEA-APO(a)-LRx) in Participants With Hyperlipoproteinemia(a) and Cardiovascular Disease (NCT NCT03070782)

Last Updated: 2020-10-30

Results Overview

An ANCOVA model was performed on the log ratio of Lp(a) value at the Primary Analysis Time Point to Lp(a) value at Baseline. The estimate of the log ratio was converted back to the original scale and percent change was calculated using formula: = (ratio of Lp(a) value at the Primary Analysis Time Point to Lp(a) value at Baseline - 1) × 100.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

286 participants

Primary outcome timeframe

Baseline and Month 6 (Week 25 for Cohorts A, B and C and Week 27 for Cohorts D and E)

Results posted on

2020-10-30

Participant Flow

Participants with a clinical diagnosis of hyperlipoproteinemia(a) and established CVD were enrolled in 31 study centers in United States, Canada, Denmark, Germany and Netherlands between 7th March 2017 to 13th November 2018.

286 participants were randomized in a 1:1:1:1:1 ratio to Cohorts A, B, C, D or E. In each cohort, participants were randomized in a 5:1 ratio to receive ISIS 681257 or placebo.

Participant milestones

Participant milestones
Measure	Cohort A: ISIS 681257: 20 mg Q4W Cohort A participants received 20 milligrams (mg) ISIS 681257, subcutaneous (SC) injection, once every 4 weeks (Q4W), for up to 49 weeks and a maximum of 13 doses.	Cohort B: ISIS 681257: 40 mg Q4W Cohort B participants received 40 mg of ISIS 681257, SC injection, once Q4W, for up to 49 weeks and a maximum of 13 doses.	Cohort C: ISIS 681257: 60 mg Q4W Cohort C participants received 60 mg of ISIS 681257, SC injection, once Q4W, for up to 49 weeks and a maximum of 13 doses.	Cohort D: ISIS 681257: 20 mg Q2W Cohort D participants received 20 mg of ISIS 681257, SC injection, once every 2 weeks (Q2W), for up to 51 weeks and a maximum of 26 doses.	Cohort E: ISIS 681257: 20 mg QW Cohort E participants received 20 mg of ISIS 681257, SC injection, once weekly (QW), for up to 52 weeks and a maximum of 52 doses.	Placebo Participants in each cohort were randomized to receive placebo at a dose-matched volume of study drug (ISIS 681257).
Overall Study STARTED	48	48	47	48	48	47
Overall Study COMPLETED	41	47	43	43	36	40
Overall Study NOT COMPLETED	7	1	4	5	12	7

Reasons for withdrawal

Reasons for withdrawal
Measure	Cohort A: ISIS 681257: 20 mg Q4W Cohort A participants received 20 milligrams (mg) ISIS 681257, subcutaneous (SC) injection, once every 4 weeks (Q4W), for up to 49 weeks and a maximum of 13 doses.	Cohort B: ISIS 681257: 40 mg Q4W Cohort B participants received 40 mg of ISIS 681257, SC injection, once Q4W, for up to 49 weeks and a maximum of 13 doses.	Cohort C: ISIS 681257: 60 mg Q4W Cohort C participants received 60 mg of ISIS 681257, SC injection, once Q4W, for up to 49 weeks and a maximum of 13 doses.	Cohort D: ISIS 681257: 20 mg Q2W Cohort D participants received 20 mg of ISIS 681257, SC injection, once every 2 weeks (Q2W), for up to 51 weeks and a maximum of 26 doses.	Cohort E: ISIS 681257: 20 mg QW Cohort E participants received 20 mg of ISIS 681257, SC injection, once weekly (QW), for up to 52 weeks and a maximum of 52 doses.	Placebo Participants in each cohort were randomized to receive placebo at a dose-matched volume of study drug (ISIS 681257).
Overall Study Adverse Event	3	0	3	1	6	2
Overall Study Withdrawal by Subject	2	1	1	0	4	3
Overall Study Reason Not Specified	2	0	0	1	2	1
Overall Study Ineligibility	0	0	0	1	0	1
Overall Study Pregnancy	0	0	0	1	0	0
Overall Study Investigator Judgement	0	0	0	1	0	0

Baseline Characteristics

Phase 2 Study of ISIS 681257 (AKCEA-APO(a)-LRx) in Participants With Hyperlipoproteinemia(a) and Cardiovascular Disease

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Cohort A: ISIS 681257: 20 mg Q4W n=48 Participants Cohort A participants received 20 milligrams (mg) ISIS 681257, subcutaneous (SC) injection, once every 4 weeks (Q4W), for up to 49 weeks and a maximum of 13 doses.	Cohort B: ISIS 681257: 40 mg Q4W n=48 Participants Cohort B participants received 40 mg of ISIS 681257, SC injection, once Q4W, for up to 49 weeks and a maximum of 13 doses.	Cohort C: ISIS 681257: 60 mg Q4W n=47 Participants Cohort C participants received 60 mg of ISIS 681257, SC injection, once Q4W, for up to 49 weeks and a maximum of 13 doses.	Cohort D: ISIS 681257: 20 mg Q2W n=48 Participants Cohort D participants received 20 mg of ISIS 681257, SC injection, once every 2 weeks (Q2W), for up to 51 weeks and a maximum of 26 doses.	Cohort E: ISIS 681257: 20 mg QW n=48 Participants Cohort E participants received 20 mg of ISIS 681257, SC injection, once weekly (QW), for up to 52 weeks and a maximum of 52 doses.	Placebo n=47 Participants Participants in each cohort were randomized to receive placebo at a dose-matched volume of study drug (ISIS 681257).	Total n=286 Participants Total of all reporting groups
Age, Continuous	60.0 years n=5 Participants	61.3 years n=7 Participants	62.2 years n=5 Participants	57.9 years n=4 Participants	58.9 years n=21 Participants	59.9 years n=8 Participants	60.0 years n=8 Participants
Sex: Female, Male Female	19 Participants n=5 Participants	12 Participants n=7 Participants	14 Participants n=5 Participants	17 Participants n=4 Participants	20 Participants n=21 Participants	15 Participants n=8 Participants	97 Participants n=8 Participants
Sex: Female, Male Male	29 Participants n=5 Participants	36 Participants n=7 Participants	33 Participants n=5 Participants	31 Participants n=4 Participants	28 Participants n=21 Participants	32 Participants n=8 Participants	189 Participants n=8 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	2 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants	1 Participants n=8 Participants	5 Participants n=8 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	46 Participants n=5 Participants	47 Participants n=7 Participants	47 Participants n=5 Participants	48 Participants n=4 Participants	47 Participants n=21 Participants	46 Participants n=8 Participants	281 Participants n=8 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants	0 Participants n=8 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants	0 Participants n=8 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	1 Participants n=8 Participants	2 Participants n=8 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants	0 Participants n=8 Participants
Race (NIH/OMB) Black or African American	2 Participants n=5 Participants	3 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants	0 Participants n=8 Participants	6 Participants n=8 Participants
Race (NIH/OMB) White	44 Participants n=5 Participants	45 Participants n=7 Participants	47 Participants n=5 Participants	47 Participants n=4 Participants	47 Participants n=21 Participants	46 Participants n=8 Participants	276 Participants n=8 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants	0 Participants n=8 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants	2 Participants n=8 Participants

PRIMARY outcome

Timeframe: Baseline and Month 6 (Week 25 for Cohorts A, B and C and Week 27 for Cohorts D and E)

Population: Full Analysis Set (FAS) included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo). FAS represented the practically feasible intent-to-treat (ITT) population as delineated in ICH Guideline E9.

Outcome measures

Outcome measures
Measure	Cohort A: ISIS 681257: 20 mg Q4W n=48 Participants Cohort A participants received 20 milligrams (mg) ISIS 681257, subcutaneous (SC) injection, once every 4 weeks (Q4W), for up to 49 weeks and a maximum of 13 doses.	Cohort B: ISIS 681257: 40 mg Q4W n=48 Participants Cohort B participants received 40 mg of ISIS 681257, SC injection, once Q4W, for up to 49 weeks and a maximum of 13 doses.	Cohort C: ISIS 681257: 60 mg Q4W n=47 Participants Cohort C participants received 60 mg of ISIS 681257, SC injection, once Q4W, for up to 49 weeks and a maximum of 13 doses.	Cohort D: ISIS 681257: 20 mg Q2W n=48 Participants Cohort D participants received 20 mg of ISIS 681257, SC injection, once every 2 weeks (Q2W), for up to 51 weeks and a maximum of 26 doses.	Cohort E: ISIS 681257: 20 mg QW n=48 Participants Cohort E participants received 20 mg of ISIS 681257, SC injection, once weekly (QW), for up to 52 weeks and a maximum of 52 doses.	Placebo n=47 Participants Participants in each cohort were randomized to receive placebo at a dose-matched volume of study drug (ISIS 681257).
Percent Change From Baseline in Fasting Lipoprotein A [Lp(a)] at the Primary Analysis Time Point	-35 percent change Interval -45.0 to -22.0	-56 percent change Interval -63.0 to -48.0	-72 percent change Interval -76.0 to -67.0	-58 percent change Interval -65.0 to -50.0	-80 percent change Interval -83.0 to -76.0	-6 percent change Interval -21.0 to 12.0

PRIMARY outcome

Timeframe: Up to 16 weeks post treatment period (up to approximately 1.3 years)

Population: Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).

An adverse event (AE) was defined as any unfavorable and unintended sign (including a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the study or use of investigational drug product, whether or not the AE was considered related to the investigational drug product. TEAEs was defined as any AE with onset after the first administration of study medication through the end of the study, or any event that was present at baseline but worsened in intensity or was subsequently considered drug-related by the Investigator through the end of the study.

Outcome measures

Outcome measures
Measure	Cohort A: ISIS 681257: 20 mg Q4W n=48 Participants Cohort A participants received 20 milligrams (mg) ISIS 681257, subcutaneous (SC) injection, once every 4 weeks (Q4W), for up to 49 weeks and a maximum of 13 doses.	Cohort B: ISIS 681257: 40 mg Q4W n=48 Participants Cohort B participants received 40 mg of ISIS 681257, SC injection, once Q4W, for up to 49 weeks and a maximum of 13 doses.	Cohort C: ISIS 681257: 60 mg Q4W n=47 Participants Cohort C participants received 60 mg of ISIS 681257, SC injection, once Q4W, for up to 49 weeks and a maximum of 13 doses.	Cohort D: ISIS 681257: 20 mg Q2W n=48 Participants Cohort D participants received 20 mg of ISIS 681257, SC injection, once every 2 weeks (Q2W), for up to 51 weeks and a maximum of 26 doses.	Cohort E: ISIS 681257: 20 mg QW n=48 Participants Cohort E participants received 20 mg of ISIS 681257, SC injection, once weekly (QW), for up to 52 weeks and a maximum of 52 doses.	Placebo n=47 Participants Participants in each cohort were randomized to receive placebo at a dose-matched volume of study drug (ISIS 681257).
Number of Participants With Treatment Emergent Adverse Events (TEAEs)	46 Participants	43 Participants	43 Participants	41 Participants	44 Participants	41 Participants

PRIMARY outcome

Timeframe: Up to 16 weeks post treatment period (up to approximately 1.3 years)

Population: Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo). Only participants with at least one TEAE were analyzed for this outcome measure.

An AE was defined as any unfavorable and unintended sign (including a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the study or use of investigational drug product, whether or not the AE was considered related to the investigational drug product. TEAEs was defined as any AE with onset after the first administration of study medication through the end of the study, or any event that was present at baseline but worsened in intensity or was subsequently considered drug-related by the Investigator through the end of the study. The severity of TEAEs was assessed based on the National Cancer Institute's (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03. TEAEs were graded on a 5-point scale where 1 = Mild, 2 = Moderate, 3 = Severe, 4 = Potentially life-threatening and 5 = Death.

Outcome measures

Outcome measures
Measure	Cohort A: ISIS 681257: 20 mg Q4W n=46 Participants Cohort A participants received 20 milligrams (mg) ISIS 681257, subcutaneous (SC) injection, once every 4 weeks (Q4W), for up to 49 weeks and a maximum of 13 doses.	Cohort B: ISIS 681257: 40 mg Q4W n=43 Participants Cohort B participants received 40 mg of ISIS 681257, SC injection, once Q4W, for up to 49 weeks and a maximum of 13 doses.	Cohort C: ISIS 681257: 60 mg Q4W n=43 Participants Cohort C participants received 60 mg of ISIS 681257, SC injection, once Q4W, for up to 49 weeks and a maximum of 13 doses.	Cohort D: ISIS 681257: 20 mg Q2W n=41 Participants Cohort D participants received 20 mg of ISIS 681257, SC injection, once every 2 weeks (Q2W), for up to 51 weeks and a maximum of 26 doses.	Cohort E: ISIS 681257: 20 mg QW n=44 Participants Cohort E participants received 20 mg of ISIS 681257, SC injection, once weekly (QW), for up to 52 weeks and a maximum of 52 doses.	Placebo n=41 Participants Participants in each cohort were randomized to receive placebo at a dose-matched volume of study drug (ISIS 681257).
Number of Participants With TEAEs by Maximum Severity Mild	20 Participants	21 Participants	16 Participants	24 Participants	21 Participants	22 Participants
Number of Participants With TEAEs by Maximum Severity Moderate	20 Participants	19 Participants	21 Participants	15 Participants	20 Participants	16 Participants
Number of Participants With TEAEs by Maximum Severity Severe	6 Participants	3 Participants	6 Participants	2 Participants	3 Participants	3 Participants

PRIMARY outcome

Timeframe: Up to 16 weeks post treatment period (up to approximately 1.3 years)

Population: Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).

Outcome measures

Outcome measures
Measure	Cohort A: ISIS 681257: 20 mg Q4W n=48 Participants Cohort A participants received 20 milligrams (mg) ISIS 681257, subcutaneous (SC) injection, once every 4 weeks (Q4W), for up to 49 weeks and a maximum of 13 doses.	Cohort B: ISIS 681257: 40 mg Q4W n=48 Participants Cohort B participants received 40 mg of ISIS 681257, SC injection, once Q4W, for up to 49 weeks and a maximum of 13 doses.	Cohort C: ISIS 681257: 60 mg Q4W n=47 Participants Cohort C participants received 60 mg of ISIS 681257, SC injection, once Q4W, for up to 49 weeks and a maximum of 13 doses.	Cohort D: ISIS 681257: 20 mg Q2W n=48 Participants Cohort D participants received 20 mg of ISIS 681257, SC injection, once every 2 weeks (Q2W), for up to 51 weeks and a maximum of 26 doses.	Cohort E: ISIS 681257: 20 mg QW n=48 Participants Cohort E participants received 20 mg of ISIS 681257, SC injection, once weekly (QW), for up to 52 weeks and a maximum of 52 doses.	Placebo n=47 Participants Participants in each cohort were randomized to receive placebo at a dose-matched volume of study drug (ISIS 681257).
Number of Participants With TEAEs Leading to Study Discontinuation	3 Participants	0 Participants	3 Participants	1 Participants	6 Participants	2 Participants

SECONDARY outcome

Timeframe: Baseline and Month 6 (Week 25 for Cohorts A, B and C and Week 27 for Cohorts D and E)

Population: FAS included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo). FAS represented the practically feasible ITT population as delineated in ICH Guideline E9.

An ANCOVA model was performed on the log ratio of LDL-C value at the Primary Analysis Time Point to LDL-C value at Baseline. The estimate of the log ratio was converted back to the original scale and percent change was calculated using formula: = (ratio of LDL-C value at the Primary Analysis Time Point to LDL-C value at Baseline - 1) × 100.

Outcome measures

Outcome measures
Measure	Cohort A: ISIS 681257: 20 mg Q4W n=48 Participants Cohort A participants received 20 milligrams (mg) ISIS 681257, subcutaneous (SC) injection, once every 4 weeks (Q4W), for up to 49 weeks and a maximum of 13 doses.	Cohort B: ISIS 681257: 40 mg Q4W n=48 Participants Cohort B participants received 40 mg of ISIS 681257, SC injection, once Q4W, for up to 49 weeks and a maximum of 13 doses.	Cohort C: ISIS 681257: 60 mg Q4W n=47 Participants Cohort C participants received 60 mg of ISIS 681257, SC injection, once Q4W, for up to 49 weeks and a maximum of 13 doses.	Cohort D: ISIS 681257: 20 mg Q2W n=48 Participants Cohort D participants received 20 mg of ISIS 681257, SC injection, once every 2 weeks (Q2W), for up to 51 weeks and a maximum of 26 doses.	Cohort E: ISIS 681257: 20 mg QW n=48 Participants Cohort E participants received 20 mg of ISIS 681257, SC injection, once weekly (QW), for up to 52 weeks and a maximum of 52 doses.	Placebo n=47 Participants Participants in each cohort were randomized to receive placebo at a dose-matched volume of study drug (ISIS 681257).
Percent Change From Baseline in Fasting Low-Density Lipoprotein Cholesterol (LDL-C)	-7 percent change Interval -16.0 to 3.0	-26 percent change Interval -33.0 to -18.0	-16 percent change Interval -24.0 to -7.0	-17 percent change Interval -25.0 to -8.0	-23 percent change Interval -31.0 to -14.0	-1 percent change Interval -11.0 to 9.0

SECONDARY outcome

Timeframe: Baseline and Month 6 (Week 25 for Cohorts A, B and C and Week 27 for Cohorts D and E)

The percentage of participants who achieved ≤ 125 nmol/L or ≤ 50 mg/dL in fasting Lp(a) at the primary analysis time point were compared between each ISIS 681257 treatment group and pooled placebo group using a logistic regression model with log-transformed baseline Lp(a) as a covariate.

Outcome measures

Outcome measures
Measure	Cohort A: ISIS 681257: 20 mg Q4W n=48 Participants Cohort A participants received 20 milligrams (mg) ISIS 681257, subcutaneous (SC) injection, once every 4 weeks (Q4W), for up to 49 weeks and a maximum of 13 doses.	Cohort B: ISIS 681257: 40 mg Q4W n=48 Participants Cohort B participants received 40 mg of ISIS 681257, SC injection, once Q4W, for up to 49 weeks and a maximum of 13 doses.	Cohort C: ISIS 681257: 60 mg Q4W n=47 Participants Cohort C participants received 60 mg of ISIS 681257, SC injection, once Q4W, for up to 49 weeks and a maximum of 13 doses.	Cohort D: ISIS 681257: 20 mg Q2W n=48 Participants Cohort D participants received 20 mg of ISIS 681257, SC injection, once every 2 weeks (Q2W), for up to 51 weeks and a maximum of 26 doses.	Cohort E: ISIS 681257: 20 mg QW n=48 Participants Cohort E participants received 20 mg of ISIS 681257, SC injection, once weekly (QW), for up to 52 weeks and a maximum of 52 doses.	Placebo n=47 Participants Participants in each cohort were randomized to receive placebo at a dose-matched volume of study drug (ISIS 681257).
Percentage of Participants Who Achieved Plasma Lp(a) ≤ 125 Nanomoles Per Liter (Nmol/L) or ≤ 50 Milligrams Per Deciliter (mg/dL)	22.9 percentage of participants	62.5 percentage of participants	80.9 percentage of participants	64.6 percentage of participants	97.9 percentage of participants	6.4 percentage of participants

SECONDARY outcome

Timeframe: Baseline and Month 6 (Week 25 for Cohorts A, B and C and Week 27 for Cohorts D and E)

The percentage of participants who achieved ≤ 75 nmol/L or ≤ 30 mg/dL in fasting Lp(a) at the primary analysis time point were compared between each ISIS 681257 treatment group and pooled placebo group using a logistic regression model with log-transformed baseline Lp(a) as a covariate.

Outcome measures

Outcome measures
Measure	Cohort A: ISIS 681257: 20 mg Q4W n=48 Participants Cohort A participants received 20 milligrams (mg) ISIS 681257, subcutaneous (SC) injection, once every 4 weeks (Q4W), for up to 49 weeks and a maximum of 13 doses.	Cohort B: ISIS 681257: 40 mg Q4W n=48 Participants Cohort B participants received 40 mg of ISIS 681257, SC injection, once Q4W, for up to 49 weeks and a maximum of 13 doses.	Cohort C: ISIS 681257: 60 mg Q4W n=47 Participants Cohort C participants received 60 mg of ISIS 681257, SC injection, once Q4W, for up to 49 weeks and a maximum of 13 doses.	Cohort D: ISIS 681257: 20 mg Q2W n=48 Participants Cohort D participants received 20 mg of ISIS 681257, SC injection, once every 2 weeks (Q2W), for up to 51 weeks and a maximum of 26 doses.	Cohort E: ISIS 681257: 20 mg QW n=48 Participants Cohort E participants received 20 mg of ISIS 681257, SC injection, once weekly (QW), for up to 52 weeks and a maximum of 52 doses.	Placebo n=47 Participants Participants in each cohort were randomized to receive placebo at a dose-matched volume of study drug (ISIS 681257).
Percentage of Participants Who Achieved Plasma Lp(a) ≤ 75 Nmol/L or ≤ 30 mg/dL	6.3 percentage of participants	25.0 percentage of participants	53.2 percentage of participants	33.3 percentage of participants	70.8 percentage of participants	0 percentage of participants

SECONDARY outcome

Timeframe: Baseline and Month 6 (Week 25 for Cohorts A, B and C and Week 27 for Cohorts D and E)

An ANCOVA model was performed on the log ratio of apoB value at the Primary Analysis Time Point to apoB value at Baseline. The estimate of the log ratio was converted back to the original scale and percent change was calculated using formula: = (ratio of apoB value at the Primary Analysis Time Point to apoB value at Baseline - 1) × 100.

Outcome measures

Outcome measures
Measure	Cohort A: ISIS 681257: 20 mg Q4W n=48 Participants Cohort A participants received 20 milligrams (mg) ISIS 681257, subcutaneous (SC) injection, once every 4 weeks (Q4W), for up to 49 weeks and a maximum of 13 doses.	Cohort B: ISIS 681257: 40 mg Q4W n=48 Participants Cohort B participants received 40 mg of ISIS 681257, SC injection, once Q4W, for up to 49 weeks and a maximum of 13 doses.	Cohort C: ISIS 681257: 60 mg Q4W n=47 Participants Cohort C participants received 60 mg of ISIS 681257, SC injection, once Q4W, for up to 49 weeks and a maximum of 13 doses.	Cohort D: ISIS 681257: 20 mg Q2W n=48 Participants Cohort D participants received 20 mg of ISIS 681257, SC injection, once every 2 weeks (Q2W), for up to 51 weeks and a maximum of 26 doses.	Cohort E: ISIS 681257: 20 mg QW n=48 Participants Cohort E participants received 20 mg of ISIS 681257, SC injection, once weekly (QW), for up to 52 weeks and a maximum of 52 doses.	Placebo n=47 Participants Participants in each cohort were randomized to receive placebo at a dose-matched volume of study drug (ISIS 681257).
Percent Change From Baseline in the Plasma Levels of Apolipoprotein B (apoB)	-3 percent change Interval -9.0 to 4.0	-15 percent change Interval -20.0 to -10.0	-8 percent change Interval -14.0 to -2.0	-9 percent change Interval -15.0 to -3.0	-16 percent change Interval -21.0 to -10.0	1 percent change Interval -5.0 to 8.0

SECONDARY outcome

Timeframe: Baseline and Month 6 (Week 25 for Cohorts A, B and C and Week 27 for Cohorts D and E)

An ANCOVA model was performed on the log ratio of OxPL-apo(a) value at the Primary Analysis Time Point to OxPL-apo(a) value at Baseline. The estimate of the log ratio was converted back to the original scale and percent change was calculated using formula: = (ratio of OxPL-apo(a) value at the Primary Analysis Time Point to OxPL-apo(a) value at Baseline - 1) × 100.

Outcome measures

Outcome measures
Measure	Cohort A: ISIS 681257: 20 mg Q4W n=48 Participants Cohort A participants received 20 milligrams (mg) ISIS 681257, subcutaneous (SC) injection, once every 4 weeks (Q4W), for up to 49 weeks and a maximum of 13 doses.	Cohort B: ISIS 681257: 40 mg Q4W n=48 Participants Cohort B participants received 40 mg of ISIS 681257, SC injection, once Q4W, for up to 49 weeks and a maximum of 13 doses.	Cohort C: ISIS 681257: 60 mg Q4W n=47 Participants Cohort C participants received 60 mg of ISIS 681257, SC injection, once Q4W, for up to 49 weeks and a maximum of 13 doses.	Cohort D: ISIS 681257: 20 mg Q2W n=48 Participants Cohort D participants received 20 mg of ISIS 681257, SC injection, once every 2 weeks (Q2W), for up to 51 weeks and a maximum of 26 doses.	Cohort E: ISIS 681257: 20 mg QW n=48 Participants Cohort E participants received 20 mg of ISIS 681257, SC injection, once weekly (QW), for up to 52 weeks and a maximum of 52 doses.	Placebo n=47 Participants Participants in each cohort were randomized to receive placebo at a dose-matched volume of study drug (ISIS 681257).
Percent Change From Baseline in the Plasma Levels of Oxidized Phospholipids (OxPL) on Apolipoprotein(a) [OxPL-apo(a)]	-28 percent change Interval -41.0 to -12.0	-49 percent change Interval -58.0 to -38.0	-63 percent change Interval -70.0 to -55.0	-45 percent change Interval -55.0 to -33.0	-70 percent change Interval -75.0 to -62.0	-20 percent change Interval -35.0 to -2.0

SECONDARY outcome

Timeframe: Baseline and Month 6 (Week 25 for Cohorts A, B and C and Week 27 for Cohorts D and E)

An ANCOVA model was performed on the log ratio of OxPL-apoB value at the Primary Analysis Time Point to OxPL-apoB value at Baseline. The estimate of the log ratio was converted back to the original scale and percent change was calculated using formula: = (ratio of OxPL-apoB value at the Primary Analysis Time Point to OxPL-apoB value at Baseline - 1) × 100.

Outcome measures

Outcome measures
Measure	Cohort A: ISIS 681257: 20 mg Q4W n=48 Participants Cohort A participants received 20 milligrams (mg) ISIS 681257, subcutaneous (SC) injection, once every 4 weeks (Q4W), for up to 49 weeks and a maximum of 13 doses.	Cohort B: ISIS 681257: 40 mg Q4W n=48 Participants Cohort B participants received 40 mg of ISIS 681257, SC injection, once Q4W, for up to 49 weeks and a maximum of 13 doses.	Cohort C: ISIS 681257: 60 mg Q4W n=47 Participants Cohort C participants received 60 mg of ISIS 681257, SC injection, once Q4W, for up to 49 weeks and a maximum of 13 doses.	Cohort D: ISIS 681257: 20 mg Q2W n=48 Participants Cohort D participants received 20 mg of ISIS 681257, SC injection, once every 2 weeks (Q2W), for up to 51 weeks and a maximum of 26 doses.	Cohort E: ISIS 681257: 20 mg QW n=48 Participants Cohort E participants received 20 mg of ISIS 681257, SC injection, once weekly (QW), for up to 52 weeks and a maximum of 52 doses.	Placebo n=47 Participants Participants in each cohort were randomized to receive placebo at a dose-matched volume of study drug (ISIS 681257).
Percent Change From Baseline in the Plasma Levels of Oxidized Phospholipids (OxPL) on Apolipoprotein B (OxPL-apoB)	-37 percent change Interval -52.0 to -17.0	-57 percent change Interval -67.0 to -45.0	-79 percent change Interval -84.0 to -73.0	-64 percent change Interval -72.0 to -53.0	-88 percent change Interval -91.0 to -84.0	14 percent change Interval -12.0 to 49.0

OTHER_PRE_SPECIFIED outcome

Timeframe: 6 months

Cmax will be calculated for the treatment groups.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: 6 months

Tmax will be calculated for the treatment groups.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: 6 months

AUC values will be calculated for the treatment groups.

Outcome measures

Outcome data not reported

Adverse Events

Cohort A: ISIS 681257: 20 mg Q4W

Serious events: 7 serious events

Other events: 38 other events

Deaths: 0 deaths

Cohort B: ISIS 681257: 40 mg Q4W

Serious events: 7 serious events

Other events: 42 other events

Deaths: 0 deaths

Cohort C: ISIS 681257: 60 mg Q4W

Serious events: 7 serious events

Other events: 40 other events

Deaths: 1 deaths

Cohort D: ISIS 681257: 20 mg Q2W

Serious events: 3 serious events

Other events: 36 other events

Deaths: 0 deaths

Cohort E: ISIS 681257: 20 mg QW

Serious events: 4 serious events

Other events: 42 other events

Deaths: 1 deaths

Placebo

Serious events: 3 serious events

Other events: 36 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Cohort A: ISIS 681257: 20 mg Q4W n=48 participants at risk Cohort A participants received 20 milligrams (mg) ISIS 681257, subcutaneous (SC) injection, once every 4 weeks (Q4W), for up to 49 weeks and a maximum of 13 doses.	Cohort B: ISIS 681257: 40 mg Q4W n=48 participants at risk Cohort B participants received 40 mg of ISIS 681257, SC injection, once Q4W, for up to 49 weeks and a maximum of 13 doses.	Cohort C: ISIS 681257: 60 mg Q4W n=47 participants at risk Cohort C participants received 60 mg of ISIS 681257, SC injection, once Q4W, for up to 49 weeks and a maximum of 13 doses.	Cohort D: ISIS 681257: 20 mg Q2W n=48 participants at risk Cohort D participants received 20 mg of ISIS 681257, SC injection, once every 2 weeks (Q2W), for up to 51 weeks and a maximum of 26 doses.	Cohort E: ISIS 681257: 20 mg QW n=48 participants at risk Cohort E participants received 20 mg of ISIS 681257, SC injection, once weekly (QW), for up to 52 weeks and a maximum of 52 doses.	Placebo n=47 participants at risk Participants in each cohort were randomized to receive placebo at a dose-matched volume of study drug (ISIS 681257).
Cardiac disorders Acute myocardial infarction	4.2% 2/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	0.00% 0/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	2.1% 1/47 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	2.1% 1/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	0.00% 0/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	0.00% 0/47 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).
Cardiac disorders Angina unstable	2.1% 1/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	0.00% 0/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	2.1% 1/47 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	2.1% 1/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	0.00% 0/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	0.00% 0/47 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).
Cardiac disorders Angina pectoris	2.1% 1/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	2.1% 1/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	0.00% 0/47 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	0.00% 0/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	0.00% 0/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	2.1% 1/47 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).
Cardiac disorders Coronary artery disease	0.00% 0/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	2.1% 1/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	0.00% 0/47 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	0.00% 0/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	0.00% 0/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	0.00% 0/47 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).
Cardiac disorders Ventricular tachycardia	0.00% 0/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	0.00% 0/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	2.1% 1/47 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	0.00% 0/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	0.00% 0/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	0.00% 0/47 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).
Injury, poisoning and procedural complications Ankle fracture	0.00% 0/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	0.00% 0/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	0.00% 0/47 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	0.00% 0/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	2.1% 1/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	0.00% 0/47 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).
Injury, poisoning and procedural complications Joint dislocation	0.00% 0/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	0.00% 0/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	0.00% 0/47 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	0.00% 0/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	2.1% 1/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	0.00% 0/47 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).
Injury, poisoning and procedural complications Lower limb fracture	0.00% 0/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	2.1% 1/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	0.00% 0/47 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	0.00% 0/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	0.00% 0/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	0.00% 0/47 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).
Injury, poisoning and procedural complications Radius fracture	0.00% 0/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	0.00% 0/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	2.1% 1/47 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	0.00% 0/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	0.00% 0/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	0.00% 0/47 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).
Injury, poisoning and procedural complications Road traffic accident	0.00% 0/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	0.00% 0/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	2.1% 1/47 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	0.00% 0/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	0.00% 0/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	0.00% 0/47 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).
Injury, poisoning and procedural complications Gastrointestinal anastomotic stenosis	0.00% 0/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	0.00% 0/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	0.00% 0/47 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	0.00% 0/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	0.00% 0/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	2.1% 1/47 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).
Gastrointestinal disorders Oesophagitis haemorrhagic	2.1% 1/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	0.00% 0/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	0.00% 0/47 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	0.00% 0/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	0.00% 0/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	0.00% 0/47 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).
Gastrointestinal disorders Pancreatitis acute	0.00% 0/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	0.00% 0/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	0.00% 0/47 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	2.1% 1/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	0.00% 0/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	0.00% 0/47 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).
General disorders Malaise	2.1% 1/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	0.00% 0/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	0.00% 0/47 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	0.00% 0/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	0.00% 0/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	0.00% 0/47 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).
General disorders Non-cardiac chest pain	0.00% 0/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	2.1% 1/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	0.00% 0/47 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	0.00% 0/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	0.00% 0/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	0.00% 0/47 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).
General disorders Cyst	0.00% 0/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	0.00% 0/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	0.00% 0/47 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	0.00% 0/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	0.00% 0/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	2.1% 1/47 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).
Infections and infestations Pneumonia	0.00% 0/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	0.00% 0/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	0.00% 0/47 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	0.00% 0/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	2.1% 1/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	0.00% 0/47 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).
Infections and infestations Upper respiratory tract infection	0.00% 0/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	2.1% 1/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	0.00% 0/47 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	0.00% 0/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	0.00% 0/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	0.00% 0/47 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung neoplasm	2.1% 1/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	0.00% 0/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	0.00% 0/47 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	0.00% 0/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	0.00% 0/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	0.00% 0/47 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung neoplasm malignant	0.00% 0/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	0.00% 0/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	2.1% 1/47 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	0.00% 0/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	0.00% 0/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	0.00% 0/47 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).
Nervous system disorders Syncope	2.1% 1/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	0.00% 0/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	0.00% 0/47 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	0.00% 0/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	2.1% 1/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	0.00% 0/47 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).
Nervous system disorders Ischaemic stroke	0.00% 0/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	0.00% 0/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	0.00% 0/47 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	0.00% 0/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	0.00% 0/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	2.1% 1/47 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).
Psychiatric disorders Acute psychosis	0.00% 0/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	2.1% 1/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	0.00% 0/47 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	0.00% 0/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	0.00% 0/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	0.00% 0/47 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).
Psychiatric disorders Depression	0.00% 0/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	0.00% 0/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	0.00% 0/47 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	0.00% 0/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	2.1% 1/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	0.00% 0/47 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).
Metabolism and nutrition disorders Gout	0.00% 0/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	0.00% 0/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	0.00% 0/47 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	2.1% 1/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	0.00% 0/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	0.00% 0/47 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).
Musculoskeletal and connective tissue disorders Myalgia	0.00% 0/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	2.1% 1/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	0.00% 0/47 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	0.00% 0/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	0.00% 0/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	0.00% 0/47 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).
Reproductive system and breast disorders Vaginal haemorrhage	0.00% 0/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	2.1% 1/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	0.00% 0/47 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	0.00% 0/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	0.00% 0/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	0.00% 0/47 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).
Surgical and medical procedures Open reduction of fracture	0.00% 0/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	0.00% 0/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	0.00% 0/47 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	0.00% 0/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	2.1% 1/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	0.00% 0/47 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).
Vascular disorders Hypertensive crisis	0.00% 0/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	0.00% 0/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	2.1% 1/47 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	0.00% 0/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	0.00% 0/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	0.00% 0/47 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).

Other adverse events

Other adverse events
Measure	Cohort A: ISIS 681257: 20 mg Q4W n=48 participants at risk Cohort A participants received 20 milligrams (mg) ISIS 681257, subcutaneous (SC) injection, once every 4 weeks (Q4W), for up to 49 weeks and a maximum of 13 doses.	Cohort B: ISIS 681257: 40 mg Q4W n=48 participants at risk Cohort B participants received 40 mg of ISIS 681257, SC injection, once Q4W, for up to 49 weeks and a maximum of 13 doses.	Cohort C: ISIS 681257: 60 mg Q4W n=47 participants at risk Cohort C participants received 60 mg of ISIS 681257, SC injection, once Q4W, for up to 49 weeks and a maximum of 13 doses.	Cohort D: ISIS 681257: 20 mg Q2W n=48 participants at risk Cohort D participants received 20 mg of ISIS 681257, SC injection, once every 2 weeks (Q2W), for up to 51 weeks and a maximum of 26 doses.	Cohort E: ISIS 681257: 20 mg QW n=48 participants at risk Cohort E participants received 20 mg of ISIS 681257, SC injection, once weekly (QW), for up to 52 weeks and a maximum of 52 doses.	Placebo n=47 participants at risk Participants in each cohort were randomized to receive placebo at a dose-matched volume of study drug (ISIS 681257).
Infections and infestations Viral upper respiratory tract infection	16.7% 8/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	20.8% 10/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	17.0% 8/47 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	16.7% 8/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	31.2% 15/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	23.4% 11/47 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).
Infections and infestations Urinary tract infection	14.6% 7/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	14.6% 7/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	21.3% 10/47 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	12.5% 6/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	18.8% 9/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	6.4% 3/47 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).
Infections and infestations Sinusitis	4.2% 2/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	4.2% 2/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	8.5% 4/47 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	8.3% 4/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	6.2% 3/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	6.4% 3/47 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).
Infections and infestations Upper respiratory tract infection	8.3% 4/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	6.2% 3/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	0.00% 0/47 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	6.2% 3/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	8.3% 4/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	10.6% 5/47 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).
Infections and infestations Influenza	10.4% 5/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	0.00% 0/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	4.3% 2/47 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	4.2% 2/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	10.4% 5/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	2.1% 1/47 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).
Infections and infestations Gastroenteritis	4.2% 2/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	2.1% 1/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	2.1% 1/47 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	4.2% 2/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	8.3% 4/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	6.4% 3/47 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).
Infections and infestations Bronchitis	2.1% 1/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	0.00% 0/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	4.3% 2/47 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	4.2% 2/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	0.00% 0/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	6.4% 3/47 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).
Infections and infestations Conjunctivitis	0.00% 0/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	0.00% 0/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	0.00% 0/47 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	6.2% 3/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	2.1% 1/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	0.00% 0/47 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).
General disorders Injection site erythema	6.2% 3/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	27.1% 13/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	27.7% 13/47 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	22.9% 11/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	45.8% 22/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	0.00% 0/47 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).
General disorders Fatigue	16.7% 8/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	14.6% 7/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	4.3% 2/47 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	2.1% 1/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	6.2% 3/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	2.1% 1/47 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).
General disorders Injection site pain	4.2% 2/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	4.2% 2/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	6.4% 3/47 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	2.1% 1/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	6.2% 3/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	0.00% 0/47 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).
General disorders Influenza like illness	6.2% 3/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	4.2% 2/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	8.5% 4/47 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	2.1% 1/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	0.00% 0/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	4.3% 2/47 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).
General disorders Injection site pruritus	2.1% 1/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	8.3% 4/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	2.1% 1/47 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	4.2% 2/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	4.2% 2/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	0.00% 0/47 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).
General disorders Oedema peripheral	2.1% 1/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	4.2% 2/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	4.3% 2/47 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	4.2% 2/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	0.00% 0/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	8.5% 4/47 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).
General disorders Pyrexia	0.00% 0/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	6.2% 3/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	2.1% 1/47 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	0.00% 0/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	4.2% 2/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	6.4% 3/47 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).
General disorders Injection site bruising	0.00% 0/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	0.00% 0/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	0.00% 0/47 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	0.00% 0/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	8.3% 4/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	0.00% 0/47 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).
Musculoskeletal and connective tissue disorders Myalgia	8.3% 4/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	10.4% 5/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	21.3% 10/47 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	12.5% 6/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	6.2% 3/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	10.6% 5/47 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).
Musculoskeletal and connective tissue disorders Arthralgia	2.1% 1/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	10.4% 5/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	8.5% 4/47 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	4.2% 2/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	8.3% 4/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	4.3% 2/47 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).
Musculoskeletal and connective tissue disorders Back pain	4.2% 2/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	14.6% 7/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	4.3% 2/47 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	2.1% 1/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	8.3% 4/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	6.4% 3/47 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).
Musculoskeletal and connective tissue disorders Pain in extremity	8.3% 4/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	4.2% 2/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	6.4% 3/47 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	2.1% 1/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	6.2% 3/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	2.1% 1/47 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).
Musculoskeletal and connective tissue disorders Neck pain	2.1% 1/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	2.1% 1/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	8.5% 4/47 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	6.2% 3/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	2.1% 1/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	2.1% 1/47 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).
Musculoskeletal and connective tissue disorders Muscle spasms	6.2% 3/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	2.1% 1/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	0.00% 0/47 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	4.2% 2/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	6.2% 3/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	4.3% 2/47 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).
Musculoskeletal and connective tissue disorders Musculoskeletal pain	2.1% 1/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	6.2% 3/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	0.00% 0/47 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	2.1% 1/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	2.1% 1/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	4.3% 2/47 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).
Musculoskeletal and connective tissue disorders Musculoskeletal stiffness	0.00% 0/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	0.00% 0/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	2.1% 1/47 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	0.00% 0/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	6.2% 3/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	0.00% 0/47 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).
Musculoskeletal and connective tissue disorders Flank pain	0.00% 0/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	2.1% 1/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	0.00% 0/47 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	0.00% 0/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	0.00% 0/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	6.4% 3/47 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).
Investigations Blood creatine phosphokinase increased	10.4% 5/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	2.1% 1/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	2.1% 1/47 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	6.2% 3/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	6.2% 3/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	4.3% 2/47 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).
Investigations Blood bilirubin increased	2.1% 1/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	0.00% 0/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	4.3% 2/47 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	4.2% 2/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	10.4% 5/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	6.4% 3/47 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).
Investigations Laboratory test abnormal	6.2% 3/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	2.1% 1/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	2.1% 1/47 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	6.2% 3/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	2.1% 1/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	2.1% 1/47 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).
Investigations Alanine aminotransferase increased	4.2% 2/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	2.1% 1/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	0.00% 0/47 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	2.1% 1/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	6.2% 3/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	0.00% 0/47 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).
Gastrointestinal disorders Diarrhoea	10.4% 5/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	6.2% 3/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	4.3% 2/47 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	6.2% 3/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	10.4% 5/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	6.4% 3/47 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).
Gastrointestinal disorders Nausea	6.2% 3/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	6.2% 3/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	6.4% 3/47 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	0.00% 0/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	4.2% 2/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	2.1% 1/47 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).
Gastrointestinal disorders Vomiting	2.1% 1/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	6.2% 3/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	4.3% 2/47 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	6.2% 3/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	2.1% 1/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	0.00% 0/47 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).
Respiratory, thoracic and mediastinal disorders Cough	4.2% 2/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	6.2% 3/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	6.4% 3/47 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	4.2% 2/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	12.5% 6/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	10.6% 5/47 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	6.2% 3/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	6.2% 3/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	8.5% 4/47 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	2.1% 1/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	10.4% 5/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	2.1% 1/47 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).
Respiratory, thoracic and mediastinal disorders Dyspnoea	4.2% 2/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	10.4% 5/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	0.00% 0/47 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	2.1% 1/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	6.2% 3/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	4.3% 2/47 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	6.2% 3/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	0.00% 0/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	2.1% 1/47 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	2.1% 1/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	4.2% 2/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	2.1% 1/47 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).
Respiratory, thoracic and mediastinal disorders Nasal congestion	2.1% 1/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	6.2% 3/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	0.00% 0/47 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	0.00% 0/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	2.1% 1/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	4.3% 2/47 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).
Respiratory, thoracic and mediastinal disorders Epistaxis	0.00% 0/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	2.1% 1/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	0.00% 0/47 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	4.2% 2/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	2.1% 1/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	8.5% 4/47 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).
Nervous system disorders Headache	12.5% 6/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	14.6% 7/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	8.5% 4/47 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	8.3% 4/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	12.5% 6/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	10.6% 5/47 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).
Nervous system disorders Dizziness	8.3% 4/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	6.2% 3/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	8.5% 4/47 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	4.2% 2/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	8.3% 4/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	4.3% 2/47 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).
Injury, poisoning and procedural complications Contusion	4.2% 2/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	0.00% 0/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	2.1% 1/47 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	6.2% 3/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	6.2% 3/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	0.00% 0/47 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).
Injury, poisoning and procedural complications Fall	4.2% 2/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	6.2% 3/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	0.00% 0/47 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	2.1% 1/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	4.2% 2/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	0.00% 0/47 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).
Skin and subcutaneous tissue disorders Dermatitis	0.00% 0/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	2.1% 1/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	0.00% 0/47 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	0.00% 0/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	6.2% 3/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	2.1% 1/47 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).
Cardiac disorders Angina pectoris	16.7% 8/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	6.2% 3/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	4.3% 2/47 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	2.1% 1/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	4.2% 2/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	2.1% 1/47 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).
Vascular disorders Hypertension	6.2% 3/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	2.1% 1/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	6.4% 3/47 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	8.3% 4/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	8.3% 4/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	4.3% 2/47 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).
Immune system disorders Seasonal allergy	0.00% 0/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	2.1% 1/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	4.3% 2/47 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	2.1% 1/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	4.2% 2/48 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).	6.4% 3/47 • Up to 16 weeks post-treatment period (up to approximately 1.3 years) Safety Set included all participants who were randomized and received at least 1 dose of study drug (ISIS 681257 or placebo).

Additional Information

Study Director

Akcea Therapeutics

Phone: 617-207-0289

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60