Trial Outcomes & Findings for A Study to Assess the Safety, Tolerability and Efficacy of IONIS-AGT-LRx in Hypertensive Participants With Uncontrolled Blood Pressure (NCT NCT04714320)
NCT ID: NCT04714320
Last Updated: 2025-02-18
Results Overview
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
160 participants
Primary outcome timeframe
Baseline to Day 85
Results posted on
2025-02-18
Participant Flow
Participants took part in the study at investigative sites in the US and Canada from 28 April 2021 to 03 October 2022.
Participants with uncontrolled hypertension who were on ≥ 3 antihypertensive medications were enrolled and randomized to receive either ISIS 757456 80 mg, ISIS 757456 120 mg or ISIS 757456 matched placebo for a 12-week treatment period.
Participant milestones
| Measure |
Pooled Placebo
Participants received ISIS 757456 matching placebo, subcutaneous (SC) injection, once weekly for 12 weeks.
|
IONIS-AGT-LRx 80 mg
Participants received ISIS 757456 80mg, SC injection, once weekly for 12 weeks.
|
IONIS-AGT-LRx 120 mg
Participants received ISIS 757456 120 mg, SC injection, once weekly for 12 weeks.
|
|---|---|---|---|
|
Overall Study
STARTED
|
53
|
54
|
53
|
|
Overall Study
Per Protocol Set (PPS)
|
45
|
45
|
46
|
|
Overall Study
COMPLETED
|
48
|
50
|
47
|
|
Overall Study
NOT COMPLETED
|
5
|
4
|
6
|
Reasons for withdrawal
| Measure |
Pooled Placebo
Participants received ISIS 757456 matching placebo, subcutaneous (SC) injection, once weekly for 12 weeks.
|
IONIS-AGT-LRx 80 mg
Participants received ISIS 757456 80mg, SC injection, once weekly for 12 weeks.
|
IONIS-AGT-LRx 120 mg
Participants received ISIS 757456 120 mg, SC injection, once weekly for 12 weeks.
|
|---|---|---|---|
|
Overall Study
Voluntary Withdrawal
|
4
|
1
|
2
|
|
Overall Study
Adverse Event or Serious Adverse Event (SAE)
|
0
|
0
|
1
|
|
Overall Study
Reason Not Specified
|
1
|
3
|
3
|
Baseline Characteristics
PPS included all FAS participants who received at least 10 of the 12 doses of study drug, did not alter antihypertensive medications during the treatment period and prior to Day 85, and have no significant protocol deviations that would be expected to affect efficacy assessment.
Baseline characteristics by cohort
| Measure |
Pooled Placebo
n=53 Participants
Participants received ISIS 757456 matching placebo, SC injection, once weekly for 12 weeks.
|
IONIS-AGT-LRx 80 mg
n=54 Participants
Participants received ISIS 757456 80mg, SC injection, once weekly for 12 weeks.
|
IONIS-AGT-LRx 120 mg
n=53 Participants
Participants received ISIS 757456 120 mg, SC injection, once weekly for 12 weeks.
|
Total
n=160 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
63.1 years
STANDARD_DEVIATION 8.29 • n=53 Participants
|
64.0 years
STANDARD_DEVIATION 7.47 • n=54 Participants
|
61.3 years
STANDARD_DEVIATION 9.17 • n=53 Participants
|
62.8 years
STANDARD_DEVIATION 8.36 • n=160 Participants
|
|
Sex: Female, Male
Female
|
33 Participants
n=53 Participants
|
32 Participants
n=54 Participants
|
32 Participants
n=53 Participants
|
97 Participants
n=160 Participants
|
|
Sex: Female, Male
Male
|
20 Participants
n=53 Participants
|
22 Participants
n=54 Participants
|
21 Participants
n=53 Participants
|
63 Participants
n=160 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
20 Participants
n=53 Participants
|
15 Participants
n=54 Participants
|
14 Participants
n=53 Participants
|
49 Participants
n=160 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
33 Participants
n=53 Participants
|
39 Participants
n=54 Participants
|
39 Participants
n=53 Participants
|
111 Participants
n=160 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=53 Participants
|
0 Participants
n=54 Participants
|
0 Participants
n=53 Participants
|
0 Participants
n=160 Participants
|
|
Race/Ethnicity, Customized
Race · White
|
35 Participants
n=53 Participants
|
30 Participants
n=54 Participants
|
29 Participants
n=53 Participants
|
94 Participants
n=160 Participants
|
|
Race/Ethnicity, Customized
Race · Black
|
16 Participants
n=53 Participants
|
20 Participants
n=54 Participants
|
21 Participants
n=53 Participants
|
57 Participants
n=160 Participants
|
|
Race/Ethnicity, Customized
Race · Asian
|
0 Participants
n=53 Participants
|
1 Participants
n=54 Participants
|
2 Participants
n=53 Participants
|
3 Participants
n=160 Participants
|
|
Race/Ethnicity, Customized
Race · Native Hawaiian or Other Pacific Islander
|
1 Participants
n=53 Participants
|
0 Participants
n=54 Participants
|
1 Participants
n=53 Participants
|
2 Participants
n=160 Participants
|
|
Race/Ethnicity, Customized
Race · Other Race
|
1 Participants
n=53 Participants
|
0 Participants
n=54 Participants
|
0 Participants
n=53 Participants
|
1 Participants
n=160 Participants
|
|
Race/Ethnicity, Customized
Race · Multiple Races
|
0 Participants
n=53 Participants
|
3 Participants
n=54 Participants
|
0 Participants
n=53 Participants
|
3 Participants
n=160 Participants
|
|
Seated Automated Office Systolic Blood Pressure (SBP)- PPS
|
148.8 millimeters of mercury (mmHg)
STANDARD_DEVIATION 12.51 • n=45 Participants • PPS included all FAS participants who received at least 10 of the 12 doses of study drug, did not alter antihypertensive medications during the treatment period and prior to Day 85, and have no significant protocol deviations that would be expected to affect efficacy assessment.
|
143.3 millimeters of mercury (mmHg)
STANDARD_DEVIATION 10.29 • n=45 Participants • PPS included all FAS participants who received at least 10 of the 12 doses of study drug, did not alter antihypertensive medications during the treatment period and prior to Day 85, and have no significant protocol deviations that would be expected to affect efficacy assessment.
|
144.0 millimeters of mercury (mmHg)
STANDARD_DEVIATION 11.35 • n=46 Participants • PPS included all FAS participants who received at least 10 of the 12 doses of study drug, did not alter antihypertensive medications during the treatment period and prior to Day 85, and have no significant protocol deviations that would be expected to affect efficacy assessment.
|
145.3 millimeters of mercury (mmHg)
STANDARD_DEVIATION 11.59 • n=136 Participants • PPS included all FAS participants who received at least 10 of the 12 doses of study drug, did not alter antihypertensive medications during the treatment period and prior to Day 85, and have no significant protocol deviations that would be expected to affect efficacy assessment.
|
|
Seated Automated Office Diastolic Blood Pressure (DBP)- PPS
|
82.5 mmHg
STANDARD_DEVIATION 8.50 • n=45 Participants • PPS included all FAS participants who received at least 10 of the 12 doses of study drug, did not alter antihypertensive medications during the treatment period and prior to Day 85, and have no significant protocol deviations that would be expected to affect efficacy assessment.
|
80.6 mmHg
STANDARD_DEVIATION 10.18 • n=45 Participants • PPS included all FAS participants who received at least 10 of the 12 doses of study drug, did not alter antihypertensive medications during the treatment period and prior to Day 85, and have no significant protocol deviations that would be expected to affect efficacy assessment.
|
81.7 mmHg
STANDARD_DEVIATION 10.48 • n=46 Participants • PPS included all FAS participants who received at least 10 of the 12 doses of study drug, did not alter antihypertensive medications during the treatment period and prior to Day 85, and have no significant protocol deviations that would be expected to affect efficacy assessment.
|
81.6 mmHg
STANDARD_DEVIATION 9.72 • n=136 Participants • PPS included all FAS participants who received at least 10 of the 12 doses of study drug, did not alter antihypertensive medications during the treatment period and prior to Day 85, and have no significant protocol deviations that would be expected to affect efficacy assessment.
|
|
Seated Automated Office Systolic Blood Pressure (SBP) -FAS
|
147.6 mmHg
STANDARD_DEVIATION 13.92 • n=53 Participants • FAS included all randomized participants who received at least 1 injection of study drug (ISIS 757456 or placebo) and had at least 1 post-baseline efficacy measurements.
|
143.6 mmHg
STANDARD_DEVIATION 10.04 • n=54 Participants • FAS included all randomized participants who received at least 1 injection of study drug (ISIS 757456 or placebo) and had at least 1 post-baseline efficacy measurements.
|
144.1 mmHg
STANDARD_DEVIATION 11.42 • n=53 Participants • FAS included all randomized participants who received at least 1 injection of study drug (ISIS 757456 or placebo) and had at least 1 post-baseline efficacy measurements.
|
145.1 mmHg
STANDARD_DEVIATION 11.95 • n=160 Participants • FAS included all randomized participants who received at least 1 injection of study drug (ISIS 757456 or placebo) and had at least 1 post-baseline efficacy measurements.
|
|
Seated Automated Office Diastolic Blood Pressure (DBP) -FAS
|
82.1 mmHg
STANDARD_DEVIATION 8.91 • n=53 Participants • FAS included all randomized participants who received at least 1 injection of study drug (ISIS 757456 or placebo) and had at least 1 post-baseline efficacy measurements.
|
81.5 mmHg
STANDARD_DEVIATION 10.20 • n=54 Participants • FAS included all randomized participants who received at least 1 injection of study drug (ISIS 757456 or placebo) and had at least 1 post-baseline efficacy measurements.
|
82.8 mmHg
STANDARD_DEVIATION 10.32 • n=53 Participants • FAS included all randomized participants who received at least 1 injection of study drug (ISIS 757456 or placebo) and had at least 1 post-baseline efficacy measurements.
|
82.1 mmHg
STANDARD_DEVIATION 9.78 • n=160 Participants • FAS included all randomized participants who received at least 1 injection of study drug (ISIS 757456 or placebo) and had at least 1 post-baseline efficacy measurements.
|
PRIMARY outcome
Timeframe: Baseline to Day 85Population: PPS included all FAS participants who received at least 10 of the 12 doses of study drug, did not alter antihypertensive medications during the treatment period and prior to Day 85, and had no significant protocol deviations that would have been expected to affect efficacy assessment.
Outcome measures
| Measure |
Pooled Placebo
n=45 Participants
Participants received ISIS 757456 matching placebo, SC injection, once weekly for 12 weeks.
|
IONIS-AGT-LRx 80 mg
n=45 Participants
Participants received ISIS 757456 80mg, SC injection, once weekly for 12 weeks.
|
IONIS-AGT-LRx 120 mg
n=46 Participants
Participants received ISIS 757456 120 mg, SC injection, once weekly for 12 weeks.
|
|---|---|---|---|
|
Change From Baseline in Seated Automated Office SBP to Day 85
|
-9 mmHg
Interval -14.0 to -3.0
|
-13 mmHg
Interval -18.0 to -8.0
|
-9 mmHg
Interval -14.0 to -4.0
|
SECONDARY outcome
Timeframe: Days 15, 29, 43, 57, 71, 85, 92, 106, 120, 148, and 169Population: PPS included all FAS participants who received at least 10 of the 12 doses of study drug, did not alter antihypertensive medications during the Treatment Period and prior to Study Day 85, and have no significant protocol deviations that would be expected to affect efficacy assessment. 'Number analyzed' indicates the number of participants with data available for analysis at the specified time point.
Outcome measures
| Measure |
Pooled Placebo
n=45 Participants
Participants received ISIS 757456 matching placebo, SC injection, once weekly for 12 weeks.
|
IONIS-AGT-LRx 80 mg
n=45 Participants
Participants received ISIS 757456 80mg, SC injection, once weekly for 12 weeks.
|
IONIS-AGT-LRx 120 mg
n=46 Participants
Participants received ISIS 757456 120 mg, SC injection, once weekly for 12 weeks.
|
|---|---|---|---|
|
Absolute Concentration of Plasma AGT at Each Scheduled, Post-Baseline Visit
At Day 15
|
878.36 nmol/L
Standard Deviation 239.895
|
575.68 nmol/L
Standard Deviation 248.708
|
446.29 nmol/L
Standard Deviation 189.521
|
|
Absolute Concentration of Plasma AGT at Each Scheduled, Post-Baseline Visit
At Day 29
|
836.74 nmol/L
Standard Deviation 228.202
|
388.61 nmol/L
Standard Deviation 193.723
|
293.27 nmol/L
Standard Deviation 129.051
|
|
Absolute Concentration of Plasma AGT at Each Scheduled, Post-Baseline Visit
At Day 43
|
837.24 nmol/L
Standard Deviation 251.610
|
319.86 nmol/L
Standard Deviation 180.741
|
239.02 nmol/L
Standard Deviation 133.633
|
|
Absolute Concentration of Plasma AGT at Each Scheduled, Post-Baseline Visit
At Day 57
|
848.45 nmol/L
Standard Deviation 256.088
|
303.03 nmol/L
Standard Deviation 168.530
|
293.12 nmol/L
Standard Deviation 157.651
|
|
Absolute Concentration of Plasma AGT at Each Scheduled, Post-Baseline Visit
At Day 71
|
790.50 nmol/L
Standard Deviation 256.568
|
308.99 nmol/L
Standard Deviation 174.893
|
308.86 nmol/L
Standard Deviation 156.533
|
|
Absolute Concentration of Plasma AGT at Each Scheduled, Post-Baseline Visit
At Day 85
|
793.77 nmol/L
Standard Deviation 202.796
|
328.28 nmol/L
Standard Deviation 199.364
|
321.71 nmol/L
Standard Deviation 176.356
|
|
Absolute Concentration of Plasma AGT at Each Scheduled, Post-Baseline Visit
At Day 92
|
748.11 nmol/L
Standard Deviation 204.231
|
330.68 nmol/L
Standard Deviation 176.868
|
317.93 nmol/L
Standard Deviation 159.204
|
|
Absolute Concentration of Plasma AGT at Each Scheduled, Post-Baseline Visit
At Day 106
|
756.89 nmol/L
Standard Deviation 212.891
|
429.04 nmol/L
Standard Deviation 175.316
|
443.95 nmol/L
Standard Deviation 196.226
|
|
Absolute Concentration of Plasma AGT at Each Scheduled, Post-Baseline Visit
At Day 120
|
746.63 nmol/L
Standard Deviation 190.789
|
531.33 nmol/L
Standard Deviation 203.681
|
562.27 nmol/L
Standard Deviation 202.035
|
|
Absolute Concentration of Plasma AGT at Each Scheduled, Post-Baseline Visit
At Day 148
|
753.35 nmol/L
Standard Deviation 186.906
|
658.33 nmol/L
Standard Deviation 248.413
|
662.13 nmol/L
Standard Deviation 130.207
|
|
Absolute Concentration of Plasma AGT at Each Scheduled, Post-Baseline Visit
At Day 169
|
797.92 nmol/L
Standard Deviation 238.442
|
676.60 nmol/L
Standard Deviation 236.881
|
700.48 nmol/L
Standard Deviation 195.702
|
SECONDARY outcome
Timeframe: Baseline, Days 15, 29, 43, 57, 71, 85, 92, 106, 120, 148, and 169Population: PPS included all FAS participants who received at least 10 of the 12 doses of study drug, did not alter antihypertensive medications during the treatment period and prior to Day 85, and had no significant protocol deviations that would have been expected to affect efficacy assessment. 'Number analyzed' indicates the number of participants with data available for analysis at the specified time point.
Outcome measures
| Measure |
Pooled Placebo
n=45 Participants
Participants received ISIS 757456 matching placebo, SC injection, once weekly for 12 weeks.
|
IONIS-AGT-LRx 80 mg
n=45 Participants
Participants received ISIS 757456 80mg, SC injection, once weekly for 12 weeks.
|
IONIS-AGT-LRx 120 mg
n=46 Participants
Participants received ISIS 757456 120 mg, SC injection, once weekly for 12 weeks.
|
|---|---|---|---|
|
Change From Baseline in Plasma AGT to Each Scheduled, Post-Baseline Visit
Baseline
|
833.42 nmol/L
Standard Deviation 196.561
|
877.70 nmol/L
Standard Deviation 290.487
|
836.60 nmol/L
Standard Deviation 189.204
|
|
Change From Baseline in Plasma AGT to Each Scheduled, Post-Baseline Visit
Change From Baseline at Day 15
|
44.94 nmol/L
Standard Deviation 137.033
|
-303.67 nmol/L
Standard Deviation 187.426
|
-390.31 nmol/L
Standard Deviation 189.039
|
|
Change From Baseline in Plasma AGT to Each Scheduled, Post-Baseline Visit
Change From Baseline at Day 29
|
3.31 nmol/L
Standard Deviation 132.768
|
-489.09 nmol/L
Standard Deviation 260.294
|
-543.33 nmol/L
Standard Deviation 211.294
|
|
Change From Baseline in Plasma AGT to Each Scheduled, Post-Baseline Visit
Change From Baseline at Day 43
|
8.15 nmol/L
Standard Deviation 152.008
|
-557.84 nmol/L
Standard Deviation 267.373
|
-544.34 nmol/L
Standard Deviation 227.409
|
|
Change From Baseline in Plasma AGT to Each Scheduled, Post-Baseline Visit
Change From Baseline at Day 57
|
15.03 nmol/L
Standard Deviation 182.246
|
-577.72 nmol/L
Standard Deviation 282.528
|
-542.84 nmol/L
Standard Deviation 223.631
|
|
Change From Baseline in Plasma AGT to Each Scheduled, Post-Baseline Visit
Change From Baseline at Day 71
|
-47.31 nmol/L
Standard Deviation 239.488
|
-578.49 nmol/L
Standard Deviation 276.950
|
-522.65 nmol/L
Standard Deviation 216.465
|
|
Change From Baseline in Plasma AGT to Each Scheduled, Post-Baseline Visit
Change From Baseline at Day 85
|
-39.65 nmol/L
Standard Deviation 171.289
|
-544.60 nmol/L
Standard Deviation 314.195
|
-517.42 nmol/L
Standard Deviation 230.730
|
|
Change From Baseline in Plasma AGT to Each Scheduled, Post-Baseline Visit
Change From Baseline at Day 92
|
-73.33 nmol/L
Standard Deviation 153.744
|
-542.20 nmol/L
Standard Deviation 281.935
|
-523.31 nmol/L
Standard Deviation 219.037
|
|
Change From Baseline in Plasma AGT to Each Scheduled, Post-Baseline Visit
Change From Baseline at Day 106
|
-57.84 nmol/L
Standard Deviation 169.818
|
-449.05 nmol/L
Standard Deviation 288.731
|
-395.60 nmol/L
Standard Deviation 218.864
|
|
Change From Baseline in Plasma AGT to Each Scheduled, Post-Baseline Visit
Change From Baseline at Day 120
|
-64.61 nmol/L
Standard Deviation 131.455
|
-341.33 nmol/L
Standard Deviation 259.403
|
-282.34 nmol/L
Standard Deviation 182.477
|
|
Change From Baseline in Plasma AGT to Each Scheduled, Post-Baseline Visit
Change From Baseline at Day 148
|
-62.29 nmol/L
Standard Deviation 153.117
|
-225.14 nmol/L
Standard Deviation 233.595
|
-165.06 nmol/L
Standard Deviation 139.585
|
|
Change From Baseline in Plasma AGT to Each Scheduled, Post-Baseline Visit
Change From Baseline at Day 169
|
-18.31 nmol/L
Standard Deviation 170.377
|
-189.48 nmol/L
Standard Deviation 260.868
|
-129.72 nmol/L
Standard Deviation 146.013
|
SECONDARY outcome
Timeframe: Baseline, Days 15, 29, 43, 57, 71, 85, 92, 106, 120, 148, and 169Population: PPS included all FAS participants who received at least 10 of 12 doses of study drug did not alter antihypertensive medications during treatment period \& prior to Day 85 have no significant protocol deviations that would be expected to affect efficacy assessment. 'Number analyzed' indicates number of participants with data available for analysis at specified time point.
Outcome measures
| Measure |
Pooled Placebo
n=45 Participants
Participants received ISIS 757456 matching placebo, SC injection, once weekly for 12 weeks.
|
IONIS-AGT-LRx 80 mg
n=45 Participants
Participants received ISIS 757456 80mg, SC injection, once weekly for 12 weeks.
|
IONIS-AGT-LRx 120 mg
n=46 Participants
Participants received ISIS 757456 120 mg, SC injection, once weekly for 12 weeks.
|
|---|---|---|---|
|
Percent Change From Baseline in Plasma AGT at Each Scheduled, Post-Baseline Visit
Percent Change from Baseline at Day 15
|
5.6 percent change
Standard Deviation 16.8
|
-34.3 percent change
Standard Deviation 17.2
|
-46.4 percent change
Standard Deviation 18.8
|
|
Percent Change From Baseline in Plasma AGT at Each Scheduled, Post-Baseline Visit
Percent Change from Baseline at Day 29
|
0.5 percent change
Standard Deviation 16.7
|
-54.4 percent change
Standard Deviation 18.3
|
-63.6 percent change
Standard Deviation 17.5
|
|
Percent Change From Baseline in Plasma AGT at Each Scheduled, Post-Baseline Visit
Percent Change from Baseline at Day 43
|
0.3 percent change
Standard Deviation 18.6
|
-62.4 percent change
Standard Deviation 16.5
|
-63.2 percent change
Standard Deviation 20.4
|
|
Percent Change From Baseline in Plasma AGT at Each Scheduled, Post-Baseline Visit
Percent Change from Baseline at Day 57
|
1.6 percent change
Standard Deviation 21.1
|
-63.7 percent change
Standard Deviation 17.9
|
-64.0 percent change
Standard Deviation 18.3
|
|
Percent Change From Baseline in Plasma AGT at Each Scheduled, Post-Baseline Visit
Percent Change from Baseline at Day 71
|
-4.8 percent change
Standard Deviation 25.5
|
-63.3 percent change
Standard Deviation 19.4
|
-62.0 percent change
Standard Deviation 19.0
|
|
Percent Change From Baseline in Plasma AGT at Each Scheduled, Post-Baseline Visit
Percent Change from Baseline at Day 85
|
-3.3 percent change
Standard Deviation 19.6
|
-59.2 percent change
Standard Deviation 27.4
|
-60.7 percent change
Standard Deviation 23.1
|
|
Percent Change From Baseline in Plasma AGT at Each Scheduled, Post-Baseline Visit
Percent Change from Baseline at Day 92
|
-8.3 percent change
Standard Deviation 19.5
|
-60.0 percent change
Standard Deviation 18.7
|
-61.4 percent change
Standard Deviation 19.0
|
|
Percent Change From Baseline in Plasma AGT at Each Scheduled, Post-Baseline Visit
Percent Change from Baseline at Day 106
|
-6.3 percent change
Standard Deviation 20.4
|
-47.6 percent change
Standard Deviation 22.8
|
-46.4 percent change
Standard Deviation 21.9
|
|
Percent Change From Baseline in Plasma AGT at Each Scheduled, Post-Baseline Visit
Percent Change from Baseline at Day 120
|
-7.3 percent change
Standard Deviation 14.9
|
-36.3 percent change
Standard Deviation 20.6
|
-33.2 percent change
Standard Deviation 20.0
|
|
Percent Change From Baseline in Plasma AGT at Each Scheduled, Post-Baseline Visit
Percent Change from Baseline at Day 148
|
-6.1 percent change
Standard Deviation 20.0
|
-22.8 percent change
Standard Deviation 25.4
|
-18.4 percent change
Standard Deviation 15.9
|
|
Percent Change From Baseline in Plasma AGT at Each Scheduled, Post-Baseline Visit
Percent Change from Baseline at Day 169
|
-2.0 percent change
Standard Deviation 19.8
|
-18.3 percent change
Standard Deviation 29.6
|
-15.2 percent change
Standard Deviation 17.3
|
SECONDARY outcome
Timeframe: Baseline, Day 85Population: PPS included all FAS participants who received at least 10 of the 12 doses of study drug, did not alter antihypertensive medications during the Treatment Period and prior to Study Day 85, and have no significant protocol deviations that would be expected to affect efficacy assessment. 'Overall number of participants analyzed' indicates the number of participants with data available for the analysis of this outcome measure.
Outcome measures
| Measure |
Pooled Placebo
n=34 Participants
Participants received ISIS 757456 matching placebo, SC injection, once weekly for 12 weeks.
|
IONIS-AGT-LRx 80 mg
n=35 Participants
Participants received ISIS 757456 80mg, SC injection, once weekly for 12 weeks.
|
IONIS-AGT-LRx 120 mg
n=36 Participants
Participants received ISIS 757456 120 mg, SC injection, once weekly for 12 weeks.
|
|---|---|---|---|
|
Change From Baseline to Study Day 85 in 24-hour Mean SBP and Diastolic Blood Pressure (DBP) Measured by Ambulatory Blood Pressure Monitoring (ABPM)
Change from Baseline in 24-hour Mean SBP at Day 85
|
-1.362 mmHg
Interval -5.696 to 2.973
|
-5.675 mmHg
Interval -9.631 to -1.718
|
-0.862 mmHg
Interval -5.035 to 3.311
|
|
Change From Baseline to Study Day 85 in 24-hour Mean SBP and Diastolic Blood Pressure (DBP) Measured by Ambulatory Blood Pressure Monitoring (ABPM)
Change from Baseline in 24-hour Mean DBP at Day 85
|
-1.667 mmHg
Interval -4.201 to 0.867
|
-4.406 mmHg
Interval -6.725 to -2.087
|
-2.792 mmHg
Interval -5.214 to -0.369
|
SECONDARY outcome
Timeframe: Days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, 78, 85, 92, 106, 120, 148, and 169Population: PPS analysis set was used. Participants with SBP ≤ 140 mmHg at baseline were excluded from this analysis. 'Overall number of participants analyzed' indicates the number of participants with data available for the analysis of this outcome measure. 'Number analyzed' indicates number of participants with data available for analysis at specified time point.
Outcome measures
| Measure |
Pooled Placebo
n=32 Participants
Participants received ISIS 757456 matching placebo, SC injection, once weekly for 12 weeks.
|
IONIS-AGT-LRx 80 mg
n=26 Participants
Participants received ISIS 757456 80mg, SC injection, once weekly for 12 weeks.
|
IONIS-AGT-LRx 120 mg
n=25 Participants
Participants received ISIS 757456 120 mg, SC injection, once weekly for 12 weeks.
|
|---|---|---|---|
|
Percentage of Participants Who Achieved Seated Automated Office SBP ≤ 140 mmHg, DBP ≤ 90 mmHg, and Both at Each Scheduled Post-Baseline Visit
Percentage of Participants With SBP ≤ 140 mmHg at Day 8
|
37.5 percentage of participants
|
38.5 percentage of participants
|
40.0 percentage of participants
|
|
Percentage of Participants Who Achieved Seated Automated Office SBP ≤ 140 mmHg, DBP ≤ 90 mmHg, and Both at Each Scheduled Post-Baseline Visit
Percentage of Participants With SBP ≤ 140 mmHg at Day 15
|
31.3 percentage of participants
|
53.8 percentage of participants
|
40.0 percentage of participants
|
|
Percentage of Participants Who Achieved Seated Automated Office SBP ≤ 140 mmHg, DBP ≤ 90 mmHg, and Both at Each Scheduled Post-Baseline Visit
Percentage of Participants With SBP ≤ 140 mmHg at Day 22
|
31.3 percentage of participants
|
65.4 percentage of participants
|
40.0 percentage of participants
|
|
Percentage of Participants Who Achieved Seated Automated Office SBP ≤ 140 mmHg, DBP ≤ 90 mmHg, and Both at Each Scheduled Post-Baseline Visit
Percentage of Participants With SBP ≤ 140 mmHg at Day 29
|
46.9 percentage of participants
|
53.8 percentage of participants
|
40.0 percentage of participants
|
|
Percentage of Participants Who Achieved Seated Automated Office SBP ≤ 140 mmHg, DBP ≤ 90 mmHg, and Both at Each Scheduled Post-Baseline Visit
Percentage of Participants With SBP ≤ 140 mmHg at Day 36
|
48.4 percentage of participants
|
60.0 percentage of participants
|
52.0 percentage of participants
|
|
Percentage of Participants Who Achieved Seated Automated Office SBP ≤ 140 mmHg, DBP ≤ 90 mmHg, and Both at Each Scheduled Post-Baseline Visit
Percentage of Participants With SBP ≤ 140 mmHg at Day 43
|
40.6 percentage of participants
|
69.2 percentage of participants
|
45.8 percentage of participants
|
|
Percentage of Participants Who Achieved Seated Automated Office SBP ≤ 140 mmHg, DBP ≤ 90 mmHg, and Both at Each Scheduled Post-Baseline Visit
Percentage of Participants With SBP ≤ 140 mmHg at Day 50
|
58.1 percentage of participants
|
57.7 percentage of participants
|
41.7 percentage of participants
|
|
Percentage of Participants Who Achieved Seated Automated Office SBP ≤ 140 mmHg, DBP ≤ 90 mmHg, and Both at Each Scheduled Post-Baseline Visit
Percentage of Participants With SBP ≤ 140 mmHg at Day 57
|
46.9 percentage of participants
|
53.8 percentage of participants
|
56.5 percentage of participants
|
|
Percentage of Participants Who Achieved Seated Automated Office SBP ≤ 140 mmHg, DBP ≤ 90 mmHg, and Both at Each Scheduled Post-Baseline Visit
Percentage of Participants With SBP ≤ 140 mmHg at Day 64
|
59.4 percentage of participants
|
36.0 percentage of participants
|
68.2 percentage of participants
|
|
Percentage of Participants Who Achieved Seated Automated Office SBP ≤ 140 mmHg, DBP ≤ 90 mmHg, and Both at Each Scheduled Post-Baseline Visit
Percentage of Participants With SBP ≤ 140 mmHg at Day 71
|
48.4 percentage of participants
|
48.0 percentage of participants
|
56.0 percentage of participants
|
|
Percentage of Participants Who Achieved Seated Automated Office SBP ≤ 140 mmHg, DBP ≤ 90 mmHg, and Both at Each Scheduled Post-Baseline Visit
Percentage of Participants With SBP ≤ 140 mmHg at Day 78
|
56.7 percentage of participants
|
50.0 percentage of participants
|
58.3 percentage of participants
|
|
Percentage of Participants Who Achieved Seated Automated Office SBP ≤ 140 mmHg, DBP ≤ 90 mmHg, and Both at Each Scheduled Post-Baseline Visit
Percentage of Participants With SBP ≤ 140 mmHg at Day 85
|
40.6 percentage of participants
|
64.0 percentage of participants
|
33.3 percentage of participants
|
|
Percentage of Participants Who Achieved Seated Automated Office SBP ≤ 140 mmHg, DBP ≤ 90 mmHg, and Both at Each Scheduled Post-Baseline Visit
Percentage of Participants With SBP ≤ 140 mmHg at Day 92
|
55.2 percentage of participants
|
52.0 percentage of participants
|
23.8 percentage of participants
|
|
Percentage of Participants Who Achieved Seated Automated Office SBP ≤ 140 mmHg, DBP ≤ 90 mmHg, and Both at Each Scheduled Post-Baseline Visit
Percentage of Participants With SBP ≤ 140 mmHg at Day 106
|
55.2 percentage of participants
|
60.9 percentage of participants
|
56.5 percentage of participants
|
|
Percentage of Participants Who Achieved Seated Automated Office SBP ≤ 140 mmHg, DBP ≤ 90 mmHg, and Both at Each Scheduled Post-Baseline Visit
Percentage of Participants With SBP ≤ 140 mmHg at Day 120
|
51.9 percentage of participants
|
48.0 percentage of participants
|
43.5 percentage of participants
|
|
Percentage of Participants Who Achieved Seated Automated Office SBP ≤ 140 mmHg, DBP ≤ 90 mmHg, and Both at Each Scheduled Post-Baseline Visit
Percentage of Participants With SBP ≤ 140 mmHg at Day 148
|
44.8 percentage of participants
|
48.0 percentage of participants
|
34.8 percentage of participants
|
|
Percentage of Participants Who Achieved Seated Automated Office SBP ≤ 140 mmHg, DBP ≤ 90 mmHg, and Both at Each Scheduled Post-Baseline Visit
Percentage of Participants With SBP ≤ 140 mmHg at Day 169
|
50.0 percentage of participants
|
58.3 percentage of participants
|
37.5 percentage of participants
|
|
Percentage of Participants Who Achieved Seated Automated Office SBP ≤ 140 mmHg, DBP ≤ 90 mmHg, and Both at Each Scheduled Post-Baseline Visit
Percentage of Participants With DBP ≤ 90 mmHg at Day 8
|
81.3 percentage of participants
|
73.1 percentage of participants
|
72.0 percentage of participants
|
|
Percentage of Participants Who Achieved Seated Automated Office SBP ≤ 140 mmHg, DBP ≤ 90 mmHg, and Both at Each Scheduled Post-Baseline Visit
Percentage of Participants With DBP ≤ 90 mmHg at Day 15
|
78.1 percentage of participants
|
80.8 percentage of participants
|
88.0 percentage of participants
|
|
Percentage of Participants Who Achieved Seated Automated Office SBP ≤ 140 mmHg, DBP ≤ 90 mmHg, and Both at Each Scheduled Post-Baseline Visit
Percentage of Participants With DBP ≤ 90 mmHg at Day 22
|
87.5 percentage of participants
|
88.5 percentage of participants
|
72.0 percentage of participants
|
|
Percentage of Participants Who Achieved Seated Automated Office SBP ≤ 140 mmHg, DBP ≤ 90 mmHg, and Both at Each Scheduled Post-Baseline Visit
Percentage of Participants With DBP ≤ 90 mmHg at Day 29
|
81.3 percentage of participants
|
88.5 percentage of participants
|
80.0 percentage of participants
|
|
Percentage of Participants Who Achieved Seated Automated Office SBP ≤ 140 mmHg, DBP ≤ 90 mmHg, and Both at Each Scheduled Post-Baseline Visit
Percentage of Participants With DBP ≤ 90 mmHg at Day 36
|
83.9 percentage of participants
|
92.0 percentage of participants
|
92.0 percentage of participants
|
|
Percentage of Participants Who Achieved Seated Automated Office SBP ≤ 140 mmHg, DBP ≤ 90 mmHg, and Both at Each Scheduled Post-Baseline Visit
Percentage of Participants With DBP ≤ 90 mmHg at Day 43
|
90.6 percentage of participants
|
84.6 percentage of participants
|
79.2 percentage of participants
|
|
Percentage of Participants Who Achieved Seated Automated Office SBP ≤ 140 mmHg, DBP ≤ 90 mmHg, and Both at Each Scheduled Post-Baseline Visit
Percentage of Participants With DBP ≤ 90 mmHg at Day 50
|
87.1 percentage of participants
|
96.2 percentage of participants
|
83.3 percentage of participants
|
|
Percentage of Participants Who Achieved Seated Automated Office SBP ≤ 140 mmHg, DBP ≤ 90 mmHg, and Both at Each Scheduled Post-Baseline Visit
Percentage of Participants With DBP ≤ 90 mmHg at Day 57
|
90.6 percentage of participants
|
80.8 percentage of participants
|
82.6 percentage of participants
|
|
Percentage of Participants Who Achieved Seated Automated Office SBP ≤ 140 mmHg, DBP ≤ 90 mmHg, and Both at Each Scheduled Post-Baseline Visit
Percentage of Participants With DBP ≤ 90 mmHg at Day 64
|
96.9 percentage of participants
|
80.0 percentage of participants
|
86.4 percentage of participants
|
|
Percentage of Participants Who Achieved Seated Automated Office SBP ≤ 140 mmHg, DBP ≤ 90 mmHg, and Both at Each Scheduled Post-Baseline Visit
Percentage of Participants With DBP ≤ 90 mmHg at Day 71
|
93.5 percentage of participants
|
84.0 percentage of participants
|
92.0 percentage of participants
|
|
Percentage of Participants Who Achieved Seated Automated Office SBP ≤ 140 mmHg, DBP ≤ 90 mmHg, and Both at Each Scheduled Post-Baseline Visit
Percentage of Participants With DBP ≤ 90 mmHg at Day 78
|
93.3 percentage of participants
|
84.6 percentage of participants
|
79.2 percentage of participants
|
|
Percentage of Participants Who Achieved Seated Automated Office SBP ≤ 140 mmHg, DBP ≤ 90 mmHg, and Both at Each Scheduled Post-Baseline Visit
Percentage of Participants With DBP ≤ 90 mmHg at Day 85
|
81.3 percentage of participants
|
88.0 percentage of participants
|
83.3 percentage of participants
|
|
Percentage of Participants Who Achieved Seated Automated Office SBP ≤ 140 mmHg, DBP ≤ 90 mmHg, and Both at Each Scheduled Post-Baseline Visit
Percentage of Participants With DBP ≤ 90 mmHg at Day 92
|
82.8 percentage of participants
|
88.0 percentage of participants
|
85.7 percentage of participants
|
|
Percentage of Participants Who Achieved Seated Automated Office SBP ≤ 140 mmHg, DBP ≤ 90 mmHg, and Both at Each Scheduled Post-Baseline Visit
Percentage of Participants With DBP ≤ 90 mmHg at Day 106
|
86.2 percentage of participants
|
95.7 percentage of participants
|
82.6 percentage of participants
|
|
Percentage of Participants Who Achieved Seated Automated Office SBP ≤ 140 mmHg, DBP ≤ 90 mmHg, and Both at Each Scheduled Post-Baseline Visit
Percentage of Participants With DBP ≤ 90 mmHg at Day 120
|
81.5 percentage of participants
|
72.0 percentage of participants
|
95.7 percentage of participants
|
|
Percentage of Participants Who Achieved Seated Automated Office SBP ≤ 140 mmHg, DBP ≤ 90 mmHg, and Both at Each Scheduled Post-Baseline Visit
Percentage of Participants With DBP ≤ 90 mmHg at Day 148
|
82.8 percentage of participants
|
80.0 percentage of participants
|
95.7 percentage of participants
|
|
Percentage of Participants Who Achieved Seated Automated Office SBP ≤ 140 mmHg, DBP ≤ 90 mmHg, and Both at Each Scheduled Post-Baseline Visit
Percentage of Participants With DBP ≤ 90 mmHg at Day 169
|
86.7 percentage of participants
|
83.3 percentage of participants
|
87.5 percentage of participants
|
|
Percentage of Participants Who Achieved Seated Automated Office SBP ≤ 140 mmHg, DBP ≤ 90 mmHg, and Both at Each Scheduled Post-Baseline Visit
Percentage of Participants With SBP ≤ 140 mmHg and DBP ≤ 90 mmHg at Day 8
|
37.5 percentage of participants
|
34.6 percentage of participants
|
36.0 percentage of participants
|
|
Percentage of Participants Who Achieved Seated Automated Office SBP ≤ 140 mmHg, DBP ≤ 90 mmHg, and Both at Each Scheduled Post-Baseline Visit
Percentage of Participants With SBP ≤ 140 mmHg and DBP ≤ 90 mmHg at Day 15
|
28.1 percentage of participants
|
50.0 percentage of participants
|
36.0 percentage of participants
|
|
Percentage of Participants Who Achieved Seated Automated Office SBP ≤ 140 mmHg, DBP ≤ 90 mmHg, and Both at Each Scheduled Post-Baseline Visit
Percentage of Participants With SBP ≤ 140 mmHg and DBP ≤ 90 mmHg at Day 22
|
28.1 percentage of participants
|
65.4 percentage of participants
|
36.0 percentage of participants
|
|
Percentage of Participants Who Achieved Seated Automated Office SBP ≤ 140 mmHg, DBP ≤ 90 mmHg, and Both at Each Scheduled Post-Baseline Visit
Percentage of Participants With SBP ≤ 140 mmHg and DBP ≤ 90 mmHg at Day 29
|
46.9 percentage of participants
|
50.0 percentage of participants
|
40.0 percentage of participants
|
|
Percentage of Participants Who Achieved Seated Automated Office SBP ≤ 140 mmHg, DBP ≤ 90 mmHg, and Both at Each Scheduled Post-Baseline Visit
Percentage of Participants With SBP ≤ 140 mmHg and DBP ≤ 90 mmHg at Day 36
|
45.2 percentage of participants
|
57.7 percentage of participants
|
52.0 percentage of participants
|
|
Percentage of Participants Who Achieved Seated Automated Office SBP ≤ 140 mmHg, DBP ≤ 90 mmHg, and Both at Each Scheduled Post-Baseline Visit
Percentage of Participants With SBP ≤ 140 mmHg and DBP ≤ 90 mmHg at Day 43
|
40.6 percentage of participants
|
65.4 percentage of participants
|
41.7 percentage of participants
|
|
Percentage of Participants Who Achieved Seated Automated Office SBP ≤ 140 mmHg, DBP ≤ 90 mmHg, and Both at Each Scheduled Post-Baseline Visit
Percentage of Participants With SBP ≤ 140 mmHg and DBP ≤ 90 mmHg at Day 50
|
58.1 percentage of participants
|
57.7 percentage of participants
|
37.5 percentage of participants
|
|
Percentage of Participants Who Achieved Seated Automated Office SBP ≤ 140 mmHg, DBP ≤ 90 mmHg, and Both at Each Scheduled Post-Baseline Visit
Percentage of Participants With SBP ≤ 140 mmHg and DBP ≤ 90 mmHg at Day 57
|
46.9 percentage of participants
|
50.0 percentage of participants
|
52.2 percentage of participants
|
|
Percentage of Participants Who Achieved Seated Automated Office SBP ≤ 140 mmHg, DBP ≤ 90 mmHg, and Both at Each Scheduled Post-Baseline Visit
Percentage of Participants With SBP ≤ 140 mmHg and DBP ≤ 90 mmHg at Day 64
|
59.4 percentage of participants
|
36.0 percentage of participants
|
63.6 percentage of participants
|
|
Percentage of Participants Who Achieved Seated Automated Office SBP ≤ 140 mmHg, DBP ≤ 90 mmHg, and Both at Each Scheduled Post-Baseline Visit
Percentage of Participants With SBP ≤ 140 mmHg and DBP ≤ 90 mmHg at Day 71
|
48.4 percentage of participants
|
44.0 percentage of participants
|
52.0 percentage of participants
|
|
Percentage of Participants Who Achieved Seated Automated Office SBP ≤ 140 mmHg, DBP ≤ 90 mmHg, and Both at Each Scheduled Post-Baseline Visit
Percentage of Participants With SBP ≤ 140 mmHg and DBP ≤ 90 mmHg at Day 78
|
56.7 percentage of participants
|
46.2 percentage of participants
|
54.2 percentage of participants
|
|
Percentage of Participants Who Achieved Seated Automated Office SBP ≤ 140 mmHg, DBP ≤ 90 mmHg, and Both at Each Scheduled Post-Baseline Visit
Percentage of Participants With SBP ≤ 140 mmHg and DBP ≤ 90 mmHg at Day 85
|
40.6 percentage of participants
|
60.0 percentage of participants
|
33.3 percentage of participants
|
|
Percentage of Participants Who Achieved Seated Automated Office SBP ≤ 140 mmHg, DBP ≤ 90 mmHg, and Both at Each Scheduled Post-Baseline Visit
Percentage of Participants With SBP ≤ 140 mmHg and DBP ≤ 90 mmHg at Day 92
|
51.7 percentage of participants
|
48.0 percentage of participants
|
23.8 percentage of participants
|
|
Percentage of Participants Who Achieved Seated Automated Office SBP ≤ 140 mmHg, DBP ≤ 90 mmHg, and Both at Each Scheduled Post-Baseline Visit
Percentage of Participants With SBP ≤ 140 mmHg and DBP ≤ 90 mmHg at Day 106
|
55.2 percentage of participants
|
60.9 percentage of participants
|
52.2 percentage of participants
|
|
Percentage of Participants Who Achieved Seated Automated Office SBP ≤ 140 mmHg, DBP ≤ 90 mmHg, and Both at Each Scheduled Post-Baseline Visit
Percentage of Participants With SBP ≤ 140 mmHg and DBP ≤ 90 mmHg at Day 120
|
51.9 percentage of participants
|
44.0 percentage of participants
|
39.1 percentage of participants
|
|
Percentage of Participants Who Achieved Seated Automated Office SBP ≤ 140 mmHg, DBP ≤ 90 mmHg, and Both at Each Scheduled Post-Baseline Visit
Percentage of Participants With SBP ≤ 140 mmHg and DBP ≤ 90 mmHg at Day 148
|
37.9 percentage of participants
|
44.0 percentage of participants
|
34.8 percentage of participants
|
|
Percentage of Participants Who Achieved Seated Automated Office SBP ≤ 140 mmHg, DBP ≤ 90 mmHg, and Both at Each Scheduled Post-Baseline Visit
Percentage of Participants With SBP ≤ 140 mmHg and DBP ≤ 90 mmHg at Day 169
|
50.0 percentage of participants
|
54.2 percentage of participants
|
37.5 percentage of participants
|
SECONDARY outcome
Timeframe: Days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, 78, 85, 92, 106, 120, 148, and 169Population: PPS included all FAS participants who received at least 10 of the 12 doses of study drug, did not alter antihypertensive medications during the Treatment Period and prior to study day 85, and have no significant protocol deviations that would be expected to affect efficacy assessment. 'Number analyzed' indicates the number of participants with data available for analysis at the specified time point.
Outcome measures
| Measure |
Pooled Placebo
n=45 Participants
Participants received ISIS 757456 matching placebo, SC injection, once weekly for 12 weeks.
|
IONIS-AGT-LRx 80 mg
n=45 Participants
Participants received ISIS 757456 80mg, SC injection, once weekly for 12 weeks.
|
IONIS-AGT-LRx 120 mg
n=46 Participants
Participants received ISIS 757456 120 mg, SC injection, once weekly for 12 weeks.
|
|---|---|---|---|
|
Percentage of Participants Who Achieved Seated Automated SBP ≤ 130 mmHg, DBP ≤ 80 mmHg, and Both at Each Scheduled Post-Baseline Visit
Percentage of Participants With SBP ≤ 130 mmHg at Day 8
|
20.0 percentage of participants
|
37.8 percentage of participants
|
30.4 percentage of participants
|
|
Percentage of Participants Who Achieved Seated Automated SBP ≤ 130 mmHg, DBP ≤ 80 mmHg, and Both at Each Scheduled Post-Baseline Visit
Percentage of Participants With SBP ≤ 130 mmHg at Day 15
|
20.0 percentage of participants
|
35.6 percentage of participants
|
26.1 percentage of participants
|
|
Percentage of Participants Who Achieved Seated Automated SBP ≤ 130 mmHg, DBP ≤ 80 mmHg, and Both at Each Scheduled Post-Baseline Visit
Percentage of Participants With SBP ≤ 130 mmHg at Day 22
|
27.3 percentage of participants
|
31.1 percentage of participants
|
34.8 percentage of participants
|
|
Percentage of Participants Who Achieved Seated Automated SBP ≤ 130 mmHg, DBP ≤ 80 mmHg, and Both at Each Scheduled Post-Baseline Visit
Percentage of Participants With SBP ≤ 130 mmHg at Day 29
|
28.9 percentage of participants
|
44.4 percentage of participants
|
43.5 percentage of participants
|
|
Percentage of Participants Who Achieved Seated Automated SBP ≤ 130 mmHg, DBP ≤ 80 mmHg, and Both at Each Scheduled Post-Baseline Visit
Percentage of Participants With SBP ≤ 130 mmHg at Day 36
|
36.4 percentage of participants
|
43.2 percentage of participants
|
48.9 percentage of participants
|
|
Percentage of Participants Who Achieved Seated Automated SBP ≤ 130 mmHg, DBP ≤ 80 mmHg, and Both at Each Scheduled Post-Baseline Visit
Percentage of Participants With SBP ≤ 130 mmHg at Day 43
|
28.9 percentage of participants
|
46.7 percentage of participants
|
44.4 percentage of participants
|
|
Percentage of Participants Who Achieved Seated Automated SBP ≤ 130 mmHg, DBP ≤ 80 mmHg, and Both at Each Scheduled Post-Baseline Visit
Percentage of Participants With SBP ≤ 130 mmHg at Day 50
|
27.3 percentage of participants
|
44.4 percentage of participants
|
40.0 percentage of participants
|
|
Percentage of Participants Who Achieved Seated Automated SBP ≤ 130 mmHg, DBP ≤ 80 mmHg, and Both at Each Scheduled Post-Baseline Visit
Percentage of Participants With SBP ≤ 130 mmHg at Day 57
|
24.4 percentage of participants
|
43.2 percentage of participants
|
39.5 percentage of participants
|
|
Percentage of Participants Who Achieved Seated Automated SBP ≤ 130 mmHg, DBP ≤ 80 mmHg, and Both at Each Scheduled Post-Baseline Visit
Percentage of Participants With SBP ≤ 130 mmHg at Day 64
|
40.0 percentage of participants
|
31.8 percentage of participants
|
34.9 percentage of participants
|
|
Percentage of Participants Who Achieved Seated Automated SBP ≤ 130 mmHg, DBP ≤ 80 mmHg, and Both at Each Scheduled Post-Baseline Visit
Percentage of Participants With SBP ≤ 130 mmHg at Day 71
|
30.2 percentage of participants
|
44.2 percentage of participants
|
40.0 percentage of participants
|
|
Percentage of Participants Who Achieved Seated Automated SBP ≤ 130 mmHg, DBP ≤ 80 mmHg, and Both at Each Scheduled Post-Baseline Visit
Percentage of Participants With SBP ≤ 130 mmHg at Day 78
|
41.9 percentage of participants
|
44.2 percentage of participants
|
37.8 percentage of participants
|
|
Percentage of Participants Who Achieved Seated Automated SBP ≤ 130 mmHg, DBP ≤ 80 mmHg, and Both at Each Scheduled Post-Baseline Visit
Percentage of Participants With SBP ≤ 130 mmHg at Day 85
|
26.7 percentage of participants
|
50.0 percentage of participants
|
37.8 percentage of participants
|
|
Percentage of Participants Who Achieved Seated Automated SBP ≤ 130 mmHg, DBP ≤ 80 mmHg, and Both at Each Scheduled Post-Baseline Visit
Percentage of Participants With SBP ≤ 130 mmHg at Day 92
|
40.5 percentage of participants
|
34.1 percentage of participants
|
33.3 percentage of participants
|
|
Percentage of Participants Who Achieved Seated Automated SBP ≤ 130 mmHg, DBP ≤ 80 mmHg, and Both at Each Scheduled Post-Baseline Visit
Percentage of Participants With SBP ≤ 130 mmHg at Day 106
|
35.7 percentage of participants
|
52.4 percentage of participants
|
40.9 percentage of participants
|
|
Percentage of Participants Who Achieved Seated Automated SBP ≤ 130 mmHg, DBP ≤ 80 mmHg, and Both at Each Scheduled Post-Baseline Visit
Percentage of Participants With SBP ≤ 130 mmHg at Day 120
|
28.2 percentage of participants
|
34.1 percentage of participants
|
30.2 percentage of participants
|
|
Percentage of Participants Who Achieved Seated Automated SBP ≤ 130 mmHg, DBP ≤ 80 mmHg, and Both at Each Scheduled Post-Baseline Visit
Percentage of Participants With SBP ≤ 130 mmHg at Day 148
|
31.7 percentage of participants
|
33.3 percentage of participants
|
27.9 percentage of participants
|
|
Percentage of Participants Who Achieved Seated Automated SBP ≤ 130 mmHg, DBP ≤ 80 mmHg, and Both at Each Scheduled Post-Baseline Visit
Percentage of Participants With SBP ≤ 130 mmHg at Day 169
|
30.2 percentage of participants
|
42.9 percentage of participants
|
34.9 percentage of participants
|
|
Percentage of Participants Who Achieved Seated Automated SBP ≤ 130 mmHg, DBP ≤ 80 mmHg, and Both at Each Scheduled Post-Baseline Visit
Percentage of Participants With DBP ≤ 80 mmHg at Day 8
|
53.3 percentage of participants
|
64.4 percentage of participants
|
60.9 percentage of participants
|
|
Percentage of Participants Who Achieved Seated Automated SBP ≤ 130 mmHg, DBP ≤ 80 mmHg, and Both at Each Scheduled Post-Baseline Visit
Percentage of Participants With DBP ≤ 80 mmHg at Day 15
|
48.9 percentage of participants
|
66.7 percentage of participants
|
56.5 percentage of participants
|
|
Percentage of Participants Who Achieved Seated Automated SBP ≤ 130 mmHg, DBP ≤ 80 mmHg, and Both at Each Scheduled Post-Baseline Visit
Percentage of Participants With DBP ≤ 80 mmHg at Day 22
|
59.1 percentage of participants
|
64.4 percentage of participants
|
58.7 percentage of participants
|
|
Percentage of Participants Who Achieved Seated Automated SBP ≤ 130 mmHg, DBP ≤ 80 mmHg, and Both at Each Scheduled Post-Baseline Visit
Percentage of Participants With DBP ≤ 80 mmHg at Day 29
|
60.0 percentage of participants
|
68.9 percentage of participants
|
65.2 percentage of participants
|
|
Percentage of Participants Who Achieved Seated Automated SBP ≤ 130 mmHg, DBP ≤ 80 mmHg, and Both at Each Scheduled Post-Baseline Visit
Percentage of Participants With DBP ≤ 80 mmHg at Day 36
|
56.8 percentage of participants
|
75.0 percentage of participants
|
55.6 percentage of participants
|
|
Percentage of Participants Who Achieved Seated Automated SBP ≤ 130 mmHg, DBP ≤ 80 mmHg, and Both at Each Scheduled Post-Baseline Visit
Percentage of Participants With DBP ≤ 80 mmHg at Day 43
|
57.8 percentage of participants
|
71.1 percentage of participants
|
60.0 percentage of participants
|
|
Percentage of Participants Who Achieved Seated Automated SBP ≤ 130 mmHg, DBP ≤ 80 mmHg, and Both at Each Scheduled Post-Baseline Visit
Percentage of Participants With DBP ≤ 80 mmHg at Day 50
|
63.6 percentage of participants
|
66.7 percentage of participants
|
53.3 percentage of participants
|
|
Percentage of Participants Who Achieved Seated Automated SBP ≤ 130 mmHg, DBP ≤ 80 mmHg, and Both at Each Scheduled Post-Baseline Visit
Percentage of Participants With DBP ≤ 80 mmHg at Day 57
|
66.7 percentage of participants
|
68.2 percentage of participants
|
65.1 percentage of participants
|
|
Percentage of Participants Who Achieved Seated Automated SBP ≤ 130 mmHg, DBP ≤ 80 mmHg, and Both at Each Scheduled Post-Baseline Visit
Percentage of Participants With DBP ≤ 80 mmHg at Day 64
|
60.0 percentage of participants
|
68.2 percentage of participants
|
62.8 percentage of participants
|
|
Percentage of Participants Who Achieved Seated Automated SBP ≤ 130 mmHg, DBP ≤ 80 mmHg, and Both at Each Scheduled Post-Baseline Visit
Percentage of Participants With DBP ≤ 80 mmHg at Day 71
|
58.1 percentage of participants
|
58.1 percentage of participants
|
62.2 percentage of participants
|
|
Percentage of Participants Who Achieved Seated Automated SBP ≤ 130 mmHg, DBP ≤ 80 mmHg, and Both at Each Scheduled Post-Baseline Visit
Percentage of Participants With DBP ≤ 80 mmHg at Day 78
|
67.4 percentage of participants
|
69.8 percentage of participants
|
66.7 percentage of participants
|
|
Percentage of Participants Who Achieved Seated Automated SBP ≤ 130 mmHg, DBP ≤ 80 mmHg, and Both at Each Scheduled Post-Baseline Visit
Percentage of Participants With DBP ≤ 80 mmHg at Day 85
|
60.0 percentage of participants
|
75.0 percentage of participants
|
66.7 percentage of participants
|
|
Percentage of Participants Who Achieved Seated Automated SBP ≤ 130 mmHg, DBP ≤ 80 mmHg, and Both at Each Scheduled Post-Baseline Visit
Percentage of Participants With DBP ≤ 80 mmHg at Day 92
|
66.7 percentage of participants
|
70.5 percentage of participants
|
64.3 percentage of participants
|
|
Percentage of Participants Who Achieved Seated Automated SBP ≤ 130 mmHg, DBP ≤ 80 mmHg, and Both at Each Scheduled Post-Baseline Visit
Percentage of Participants With DBP ≤ 80 mmHg at Day 106
|
61.9 percentage of participants
|
66.7 percentage of participants
|
59.1 percentage of participants
|
|
Percentage of Participants Who Achieved Seated Automated SBP ≤ 130 mmHg, DBP ≤ 80 mmHg, and Both at Each Scheduled Post-Baseline Visit
Percentage of Participants With DBP ≤ 80 mmHg at Day 120
|
64.1 percentage of participants
|
63.6 percentage of participants
|
60.5 percentage of participants
|
|
Percentage of Participants Who Achieved Seated Automated SBP ≤ 130 mmHg, DBP ≤ 80 mmHg, and Both at Each Scheduled Post-Baseline Visit
Percentage of Participants With DBP ≤ 80 mmHg at Day 148
|
53.7 percentage of participants
|
61.9 percentage of participants
|
60.5 percentage of participants
|
|
Percentage of Participants Who Achieved Seated Automated SBP ≤ 130 mmHg, DBP ≤ 80 mmHg, and Both at Each Scheduled Post-Baseline Visit
Percentage of Participants With DBP ≤ 80 mmHg at Day 169
|
55.8 percentage of participants
|
66.7 percentage of participants
|
48.8 percentage of participants
|
|
Percentage of Participants Who Achieved Seated Automated SBP ≤ 130 mmHg, DBP ≤ 80 mmHg, and Both at Each Scheduled Post-Baseline Visit
Percentage of Participants With SBP ≤ 130 mmHg and DBP ≤ 80 mmHg at Day 8
|
17.8 percentage of participants
|
33.3 percentage of participants
|
26.1 percentage of participants
|
|
Percentage of Participants Who Achieved Seated Automated SBP ≤ 130 mmHg, DBP ≤ 80 mmHg, and Both at Each Scheduled Post-Baseline Visit
Percentage of Participants With SBP ≤ 130 mmHg and DBP ≤ 80 mmHg at Day 15
|
20.0 percentage of participants
|
33.3 percentage of participants
|
17.4 percentage of participants
|
|
Percentage of Participants Who Achieved Seated Automated SBP ≤ 130 mmHg, DBP ≤ 80 mmHg, and Both at Each Scheduled Post-Baseline Visit
Percentage of Participants With SBP ≤ 130 mmHg and DBP ≤ 80 mmHg at Day 22
|
27.3 percentage of participants
|
24.4 percentage of participants
|
30.4 percentage of participants
|
|
Percentage of Participants Who Achieved Seated Automated SBP ≤ 130 mmHg, DBP ≤ 80 mmHg, and Both at Each Scheduled Post-Baseline Visit
Percentage of Participants With SBP ≤ 130 mmHg and DBP ≤ 80 mmHg at Day 29
|
24.4 percentage of participants
|
40.0 percentage of participants
|
34.8 percentage of participants
|
|
Percentage of Participants Who Achieved Seated Automated SBP ≤ 130 mmHg, DBP ≤ 80 mmHg, and Both at Each Scheduled Post-Baseline Visit
Percentage of Participants With SBP ≤ 130 mmHg and DBP ≤ 80 mmHg at Day 36
|
27.3 percentage of participants
|
37.8 percentage of participants
|
35.6 percentage of participants
|
|
Percentage of Participants Who Achieved Seated Automated SBP ≤ 130 mmHg, DBP ≤ 80 mmHg, and Both at Each Scheduled Post-Baseline Visit
Percentage of Participants With SBP ≤ 130 mmHg and DBP ≤ 80 mmHg at Day 43
|
24.4 percentage of participants
|
37.8 percentage of participants
|
35.6 percentage of participants
|
|
Percentage of Participants Who Achieved Seated Automated SBP ≤ 130 mmHg, DBP ≤ 80 mmHg, and Both at Each Scheduled Post-Baseline Visit
Percentage of Participants With SBP ≤ 130 mmHg and DBP ≤ 80 mmHg at Day 50
|
25.0 percentage of participants
|
37.8 percentage of participants
|
28.9 percentage of participants
|
|
Percentage of Participants Who Achieved Seated Automated SBP ≤ 130 mmHg, DBP ≤ 80 mmHg, and Both at Each Scheduled Post-Baseline Visit
Percentage of Participants With SBP ≤ 130 mmHg and DBP ≤ 80 mmHg at Day 57
|
22.2 percentage of participants
|
40.9 percentage of participants
|
30.2 percentage of participants
|
|
Percentage of Participants Who Achieved Seated Automated SBP ≤ 130 mmHg, DBP ≤ 80 mmHg, and Both at Each Scheduled Post-Baseline Visit
Percentage of Participants With SBP ≤ 130 mmHg and DBP ≤ 80 mmHg at Day 64
|
33.3 percentage of participants
|
25.0 percentage of participants
|
25.6 percentage of participants
|
|
Percentage of Participants Who Achieved Seated Automated SBP ≤ 130 mmHg, DBP ≤ 80 mmHg, and Both at Each Scheduled Post-Baseline Visit
Percentage of Participants With SBP ≤ 130 mmHg and DBP ≤ 80 mmHg at Day 71
|
30.2 percentage of participants
|
34.9 percentage of participants
|
31.1 percentage of participants
|
|
Percentage of Participants Who Achieved Seated Automated SBP ≤ 130 mmHg, DBP ≤ 80 mmHg, and Both at Each Scheduled Post-Baseline Visit
Percentage of Participants With SBP ≤ 130 mmHg and DBP ≤ 80 mmHg at Day 78
|
37.2 percentage of participants
|
37.2 percentage of participants
|
37.8 percentage of participants
|
|
Percentage of Participants Who Achieved Seated Automated SBP ≤ 130 mmHg, DBP ≤ 80 mmHg, and Both at Each Scheduled Post-Baseline Visit
Percentage of Participants With SBP ≤ 130 mmHg and DBP ≤ 80 mmHg at Day 85
|
26.7 percentage of participants
|
40.9 percentage of participants
|
31.1 percentage of participants
|
|
Percentage of Participants Who Achieved Seated Automated SBP ≤ 130 mmHg, DBP ≤ 80 mmHg, and Both at Each Scheduled Post-Baseline Visit
Percentage of Participants With SBP ≤ 130 mmHg and DBP ≤ 80 mmHg at Day 92
|
38.1 percentage of participants
|
27.3 percentage of participants
|
28.6 percentage of participants
|
|
Percentage of Participants Who Achieved Seated Automated SBP ≤ 130 mmHg, DBP ≤ 80 mmHg, and Both at Each Scheduled Post-Baseline Visit
Percentage of Participants With SBP ≤ 130 mmHg and DBP ≤ 80 mmHg at Day 106
|
31.0 percentage of participants
|
40.5 percentage of participants
|
29.5 percentage of participants
|
|
Percentage of Participants Who Achieved Seated Automated SBP ≤ 130 mmHg, DBP ≤ 80 mmHg, and Both at Each Scheduled Post-Baseline Visit
Percentage of Participants With SBP ≤ 130 mmHg and DBP ≤ 80 mmHg at Day 120
|
25.6 percentage of participants
|
31.8 percentage of participants
|
23.3 percentage of participants
|
|
Percentage of Participants Who Achieved Seated Automated SBP ≤ 130 mmHg, DBP ≤ 80 mmHg, and Both at Each Scheduled Post-Baseline Visit
Percentage of Participants With SBP ≤ 130 mmHg and DBP ≤ 80 mmHg at Day 148
|
26.8 percentage of participants
|
31.0 percentage of participants
|
23.3 percentage of participants
|
|
Percentage of Participants Who Achieved Seated Automated SBP ≤ 130 mmHg, DBP ≤ 80 mmHg, and Both at Each Scheduled Post-Baseline Visit
Percentage of Participants With SBP ≤ 130 mmHg and DBP ≤ 80 mmHg at Day 169
|
27.9 percentage of participants
|
38.1 percentage of participants
|
27.9 percentage of participants
|
SECONDARY outcome
Timeframe: Baseline, Days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, 78, 85, 92, 106, 120, 148, and 169Population: PPS included all FAS participants who received at least 10 of 12 doses of study drug did not alter antihypertensive medications during treatment period \& prior to Day 85 have no significant protocol deviations that would be expected to affect efficacy assessment. 'Number analyzed' indicates number of participants with data available for analysis at specified time point.
Outcome measures
| Measure |
Pooled Placebo
n=45 Participants
Participants received ISIS 757456 matching placebo, SC injection, once weekly for 12 weeks.
|
IONIS-AGT-LRx 80 mg
n=45 Participants
Participants received ISIS 757456 80mg, SC injection, once weekly for 12 weeks.
|
IONIS-AGT-LRx 120 mg
n=46 Participants
Participants received ISIS 757456 120 mg, SC injection, once weekly for 12 weeks.
|
|---|---|---|---|
|
Change From Baseline in Seated Automated Office SBP to Each Scheduled, Post-Baseline Visit
Change from Baseline at Day 8
|
-7.98 mmHg
Standard Deviation 13.973
|
-5.87 mmHg
Standard Deviation 12.427
|
-4.78 mmHg
Standard Deviation 13.306
|
|
Change From Baseline in Seated Automated Office SBP to Each Scheduled, Post-Baseline Visit
Change from Baseline at Day 15
|
-7.38 mmHg
Standard Deviation 14.967
|
-7.73 mmHg
Standard Deviation 13.768
|
-4.11 mmHg
Standard Deviation 11.443
|
|
Change From Baseline in Seated Automated Office SBP to Each Scheduled, Post-Baseline Visit
Change from Baseline at Day 22
|
-9.50 mmHg
Standard Deviation 15.725
|
-7.84 mmHg
Standard Deviation 16.100
|
-6.80 mmHg
Standard Deviation 13.881
|
|
Change From Baseline in Seated Automated Office SBP to Each Scheduled, Post-Baseline Visit
Change from Baseline at Day 29
|
-9.49 mmHg
Standard Deviation 16.385
|
-9.13 mmHg
Standard Deviation 14.258
|
-6.91 mmHg
Standard Deviation 12.096
|
|
Change From Baseline in Seated Automated Office SBP to Each Scheduled, Post-Baseline Visit
Change from Baseline at Day 36
|
-11.48 mmHg
Standard Deviation 15.953
|
-11.57 mmHg
Standard Deviation 13.971
|
-6.40 mmHg
Standard Deviation 14.318
|
|
Change From Baseline in Seated Automated Office SBP to Each Scheduled, Post-Baseline Visit
Change from Baseline at Day 43
|
-9.31 mmHg
Standard Deviation 11.853
|
-11.73 mmHg
Standard Deviation 15.193
|
-7.24 mmHg
Standard Deviation 16.563
|
|
Change From Baseline in Seated Automated Office SBP to Each Scheduled, Post-Baseline Visit
Change from Baseline at Day 50
|
-10.93 mmHg
Standard Deviation 12.250
|
-9.64 mmHg
Standard Deviation 17.112
|
-6.13 mmHg
Standard Deviation 16.453
|
|
Change From Baseline in Seated Automated Office SBP to Each Scheduled, Post-Baseline Visit
Change from Baseline at Day 57
|
-10.13 mmHg
Standard Deviation 13.844
|
-9.89 mmHg
Standard Deviation 14.257
|
-7.47 mmHg
Standard Deviation 18.194
|
|
Change From Baseline in Seated Automated Office SBP to Each Scheduled, Post-Baseline Visit
Change from Baseline at Day 64
|
-13.31 mmHg
Standard Deviation 13.019
|
-7.70 mmHg
Standard Deviation 14.305
|
-8.19 mmHg
Standard Deviation 15.241
|
|
Change From Baseline in Seated Automated Office SBP to Each Scheduled, Post-Baseline Visit
Change from Baseline at Day 71
|
-12.26 mmHg
Standard Deviation 14.671
|
-8.35 mmHg
Standard Deviation 15.426
|
-5.71 mmHg
Standard Deviation 16.045
|
|
Change From Baseline in Seated Automated Office SBP to Each Scheduled, Post-Baseline Visit
Change from Baseline at Day 78
|
-14.19 mmHg
Standard Deviation 11.827
|
-9.37 mmHg
Standard Deviation 16.435
|
-8.22 mmHg
Standard Deviation 14.734
|
|
Change From Baseline in Seated Automated Office SBP to Each Scheduled, Post-Baseline Visit
Change from Baseline at Day 85
|
-9.64 mmHg
Standard Deviation 16.346
|
-10.93 mmHg
Standard Deviation 15.319
|
-6.98 mmHg
Standard Deviation 15.995
|
|
Change From Baseline in Seated Automated Office SBP to Each Scheduled, Post-Baseline Visit
Change from Baseline at Day 92
|
-11.76 mmHg
Standard Deviation 18.127
|
-7.57 mmHg
Standard Deviation 15.855
|
-6.57 mmHg
Standard Deviation 13.110
|
|
Change From Baseline in Seated Automated Office SBP to Each Scheduled, Post-Baseline Visit
Change from Baseline at Day 106
|
-12.14 mmHg
Standard Deviation 13.258
|
-8.57 mmHg
Standard Deviation 16.476
|
-6.61 mmHg
Standard Deviation 16.158
|
|
Change From Baseline in Seated Automated Office SBP to Each Scheduled, Post-Baseline Visit
Change from Baseline at Day 120
|
-9.36 mmHg
Standard Deviation 13.240
|
-5.14 mmHg
Standard Deviation 15.514
|
-5.14 mmHg
Standard Deviation 15.020
|
|
Change From Baseline in Seated Automated Office SBP to Each Scheduled, Post-Baseline Visit
Change from Baseline at Day 148
|
-9.07 mmHg
Standard Deviation 13.650
|
-6.76 mmHg
Standard Deviation 15.637
|
-4.30 mmHg
Standard Deviation 14.393
|
|
Change From Baseline in Seated Automated Office SBP to Each Scheduled, Post-Baseline Visit
Change from Baseline at Day 169
|
-9.23 mmHg
Standard Deviation 13.336
|
-8.76 mmHg
Standard Deviation 16.798
|
-2.02 mmHg
Standard Deviation 17.468
|
SECONDARY outcome
Timeframe: Baseline, Days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, 78, 85, 92, 106, 120, 148, and 169Population: PPS included all FAS participants who received at least 10 of 12 doses of study drug, did not alter antihypertensive medications during treatment period and prior to Day 85,and had no significant protocol deviations that would have been expected to affect efficacy assessment. 'Number analyzed' is the number of participants with data available for analysis at the specified timepoint
Outcome measures
| Measure |
Pooled Placebo
n=45 Participants
Participants received ISIS 757456 matching placebo, SC injection, once weekly for 12 weeks.
|
IONIS-AGT-LRx 80 mg
n=45 Participants
Participants received ISIS 757456 80mg, SC injection, once weekly for 12 weeks.
|
IONIS-AGT-LRx 120 mg
n=46 Participants
Participants received ISIS 757456 120 mg, SC injection, once weekly for 12 weeks.
|
|---|---|---|---|
|
Change From Baseline in Seated Automated Office DBP to Each Scheduled, Post-Baseline Visit
Change from Baseline at Day 8
|
-5.07 mmHg
Interval -8.2 to 1.94
|
-3.47 mmHg
Interval -6.44 to -0.49
|
-4.25 mmHg
Interval -7.31 to -1.19
|
|
Change From Baseline in Seated Automated Office DBP to Each Scheduled, Post-Baseline Visit
Change from Baseline at Day 15
|
-4.78 mmHg
Interval -7.84 to -1.73
|
-4.70 mmHg
Interval -7.59 to -1.8
|
-4.38 mmHg
Interval -7.36 to -1.4
|
|
Change From Baseline in Seated Automated Office DBP to Each Scheduled, Post-Baseline Visit
Change from Baseline at Day 22
|
-6.05 mmHg
Interval -9.48 to -2.62
|
-5.62 mmHg
Interval -8.78 to -2.45
|
-4.31 mmHg
Interval -7.57 to -1.04
|
|
Change From Baseline in Seated Automated Office DBP to Each Scheduled, Post-Baseline Visit
Change from Baseline at Day 29
|
-5.93 mmHg
Interval -9.02 to -2.85
|
-6.72 mmHg
Interval -9.65 to -3.79
|
-4.84 mmHg
Interval -7.86 to -1.83
|
|
Change From Baseline in Seated Automated Office DBP to Each Scheduled, Post-Baseline Visit
Change from Baseline at Day 36
|
-4.87 mmHg
Interval -8.03 to -1.72
|
-6.32 mmHg
Interval -9.32 to -3.33
|
-3.90 mmHg
Interval -6.98 to -0.82
|
|
Change From Baseline in Seated Automated Office DBP to Each Scheduled, Post-Baseline Visit
Change from Baseline at Day 43
|
-6.37 mmHg
Interval -9.52 to -3.23
|
-6.87 mmHg
Interval -9.86 to -3.89
|
-5.42 mmHg
Interval -8.5 to -2.33
|
|
Change From Baseline in Seated Automated Office DBP to Each Scheduled, Post-Baseline Visit
Change from Baseline at Day 50
|
-4.72 mmHg
Interval -7.64 to -1.81
|
-5.99 mmHg
Interval -8.74 to -3.24
|
-3.29 mmHg
Interval -6.13 to -0.45
|
|
Change From Baseline in Seated Automated Office DBP to Each Scheduled, Post-Baseline Visit
Change from Baseline at Day 57
|
-8.06 mmHg
Interval -11.14 to -4.97
|
-7.90 mmHg
Interval -10.84 to -4.97
|
-6.26 mmHg
Interval -9.38 to -3.14
|
|
Change From Baseline in Seated Automated Office DBP to Each Scheduled, Post-Baseline Visit
Change from Baseline at Day 64
|
-7.52 mmHg
Interval -10.31 to -4.72
|
-5.73 mmHg
Interval -8.4 to -3.06
|
-5.26 mmHg
Interval -8.03 to -2.48
|
|
Change From Baseline in Seated Automated Office DBP to Each Scheduled, Post-Baseline Visit
Change from Baseline at Day 71
|
-7.59 mmHg
Interval -10.54 to -4.64
|
-5.36 mmHg
Interval -8.16 to -2.56
|
-6.46 mmHg
Interval -9.32 to -3.59
|
|
Change From Baseline in Seated Automated Office DBP to Each Scheduled, Post-Baseline Visit
Change from Baseline at Day 78
|
-7.83 mmHg
Interval -10.79 to -4.87
|
-6.11 mmHg
Interval -8.91 to -3.31
|
-5.87 mmHg
Interval -8.74 to -2.99
|
|
Change From Baseline in Seated Automated Office DBP to Each Scheduled, Post-Baseline Visit
Change from Baseline at Day 85
|
-5.20 mmHg
Interval -8.24 to -2.16
|
-6.78 mmHg
Interval -9.68 to -3.88
|
-6.13 mmHg
Interval -9.11 to -3.14
|
|
Change From Baseline in Seated Automated Office DBP to Each Scheduled, Post-Baseline Visit
Change from Baseline at Day 92
|
-6.13 mmHg
Interval -9.37 to -2.9
|
-5.82 mmHg
Interval -8.85 to -2.79
|
-4.87 mmHg
Interval -8.11 to -1.62
|
|
Change From Baseline in Seated Automated Office DBP to Each Scheduled, Post-Baseline Visit
Change from Baseline at Day 106
|
-5.61 mmHg
Interval -8.95 to -2.27
|
-5.94 mmHg
Interval -9.08 to -2.79
|
-4.85 mmHg
Interval -8.01 to -1.68
|
|
Change From Baseline in Seated Automated Office DBP to Each Scheduled, Post-Baseline Visit
Change from Baseline at Day 120
|
-5.50 mmHg
Interval -8.77 to -2.24
|
-3.50 mmHg
Interval -6.36 to -0.63
|
-4.68 mmHg
Interval -7.67 to -1.7
|
|
Change From Baseline in Seated Automated Office DBP to Each Scheduled, Post-Baseline Visit
Change from Baseline at Day 148
|
-4.67 mmHg
Interval -8.18 to -1.71
|
-4.80 mmHg
Interval -7.93 to -1.67
|
-3.86 mmHg
Interval -7.17 to -0.55
|
|
Change From Baseline in Seated Automated Office DBP to Each Scheduled, Post-Baseline Visit
Change from Baseline at Day 169
|
-4.07 mmHg
Interval -7.39 to -0.75
|
-5.34 mmHg
Interval -8.43 to -2.26
|
-1.54 mmHg
Interval -4.79 to 1.72
|
Adverse Events
Pooled Placebo
Serious events: 1 serious events
Other events: 9 other events
Deaths: 0 deaths
IONIS-AGT-LRx 80 mg
Serious events: 2 serious events
Other events: 18 other events
Deaths: 0 deaths
IONIS-AGT-LRx 120 mg
Serious events: 1 serious events
Other events: 14 other events
Deaths: 1 deaths
Serious adverse events
| Measure |
Pooled Placebo
n=53 participants at risk
Participants received ISIS 757456 matching placebo, SC injection, once weekly for 12 weeks.
|
IONIS-AGT-LRx 80 mg
n=54 participants at risk
Participants received ISIS 757456 80mg, SC injection, once weekly for 12 weeks.
|
IONIS-AGT-LRx 120 mg
n=53 participants at risk
Participants received ISIS 757456 120 mg, SC injection, once weekly for 12 weeks.
|
|---|---|---|---|
|
Cardiac disorders
Atrial fibrillation
|
0.00%
0/53 • From signing of informed consent up to end of post-treatment period (up to 25 weeks)
Safety set included all randomized participants that received at least 1 dose of study drug.
|
1.9%
1/54 • From signing of informed consent up to end of post-treatment period (up to 25 weeks)
Safety set included all randomized participants that received at least 1 dose of study drug.
|
0.00%
0/53 • From signing of informed consent up to end of post-treatment period (up to 25 weeks)
Safety set included all randomized participants that received at least 1 dose of study drug.
|
|
Cardiac disorders
Cardiac arrest
|
0.00%
0/53 • From signing of informed consent up to end of post-treatment period (up to 25 weeks)
Safety set included all randomized participants that received at least 1 dose of study drug.
|
0.00%
0/54 • From signing of informed consent up to end of post-treatment period (up to 25 weeks)
Safety set included all randomized participants that received at least 1 dose of study drug.
|
1.9%
1/53 • From signing of informed consent up to end of post-treatment period (up to 25 weeks)
Safety set included all randomized participants that received at least 1 dose of study drug.
|
|
Nervous system disorders
Cerebral infarction
|
0.00%
0/53 • From signing of informed consent up to end of post-treatment period (up to 25 weeks)
Safety set included all randomized participants that received at least 1 dose of study drug.
|
1.9%
1/54 • From signing of informed consent up to end of post-treatment period (up to 25 weeks)
Safety set included all randomized participants that received at least 1 dose of study drug.
|
0.00%
0/53 • From signing of informed consent up to end of post-treatment period (up to 25 weeks)
Safety set included all randomized participants that received at least 1 dose of study drug.
|
|
Nervous system disorders
Transient ischaemic attack
|
1.9%
1/53 • From signing of informed consent up to end of post-treatment period (up to 25 weeks)
Safety set included all randomized participants that received at least 1 dose of study drug.
|
0.00%
0/54 • From signing of informed consent up to end of post-treatment period (up to 25 weeks)
Safety set included all randomized participants that received at least 1 dose of study drug.
|
0.00%
0/53 • From signing of informed consent up to end of post-treatment period (up to 25 weeks)
Safety set included all randomized participants that received at least 1 dose of study drug.
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory failure
|
0.00%
0/53 • From signing of informed consent up to end of post-treatment period (up to 25 weeks)
Safety set included all randomized participants that received at least 1 dose of study drug.
|
0.00%
0/54 • From signing of informed consent up to end of post-treatment period (up to 25 weeks)
Safety set included all randomized participants that received at least 1 dose of study drug.
|
1.9%
1/53 • From signing of informed consent up to end of post-treatment period (up to 25 weeks)
Safety set included all randomized participants that received at least 1 dose of study drug.
|
|
Vascular disorders
Aortic dissection
|
0.00%
0/53 • From signing of informed consent up to end of post-treatment period (up to 25 weeks)
Safety set included all randomized participants that received at least 1 dose of study drug.
|
0.00%
0/54 • From signing of informed consent up to end of post-treatment period (up to 25 weeks)
Safety set included all randomized participants that received at least 1 dose of study drug.
|
1.9%
1/53 • From signing of informed consent up to end of post-treatment period (up to 25 weeks)
Safety set included all randomized participants that received at least 1 dose of study drug.
|
Other adverse events
| Measure |
Pooled Placebo
n=53 participants at risk
Participants received ISIS 757456 matching placebo, SC injection, once weekly for 12 weeks.
|
IONIS-AGT-LRx 80 mg
n=54 participants at risk
Participants received ISIS 757456 80mg, SC injection, once weekly for 12 weeks.
|
IONIS-AGT-LRx 120 mg
n=53 participants at risk
Participants received ISIS 757456 120 mg, SC injection, once weekly for 12 weeks.
|
|---|---|---|---|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/53 • From signing of informed consent up to end of post-treatment period (up to 25 weeks)
Safety set included all randomized participants that received at least 1 dose of study drug.
|
5.6%
3/54 • From signing of informed consent up to end of post-treatment period (up to 25 weeks)
Safety set included all randomized participants that received at least 1 dose of study drug.
|
1.9%
1/53 • From signing of informed consent up to end of post-treatment period (up to 25 weeks)
Safety set included all randomized participants that received at least 1 dose of study drug.
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/53 • From signing of informed consent up to end of post-treatment period (up to 25 weeks)
Safety set included all randomized participants that received at least 1 dose of study drug.
|
5.6%
3/54 • From signing of informed consent up to end of post-treatment period (up to 25 weeks)
Safety set included all randomized participants that received at least 1 dose of study drug.
|
3.8%
2/53 • From signing of informed consent up to end of post-treatment period (up to 25 weeks)
Safety set included all randomized participants that received at least 1 dose of study drug.
|
|
General disorders
Injection site erythema
|
0.00%
0/53 • From signing of informed consent up to end of post-treatment period (up to 25 weeks)
Safety set included all randomized participants that received at least 1 dose of study drug.
|
3.7%
2/54 • From signing of informed consent up to end of post-treatment period (up to 25 weeks)
Safety set included all randomized participants that received at least 1 dose of study drug.
|
5.7%
3/53 • From signing of informed consent up to end of post-treatment period (up to 25 weeks)
Safety set included all randomized participants that received at least 1 dose of study drug.
|
|
Infections and infestations
COVID-19
|
1.9%
1/53 • From signing of informed consent up to end of post-treatment period (up to 25 weeks)
Safety set included all randomized participants that received at least 1 dose of study drug.
|
3.7%
2/54 • From signing of informed consent up to end of post-treatment period (up to 25 weeks)
Safety set included all randomized participants that received at least 1 dose of study drug.
|
5.7%
3/53 • From signing of informed consent up to end of post-treatment period (up to 25 weeks)
Safety set included all randomized participants that received at least 1 dose of study drug.
|
|
Infections and infestations
Urinary tract infection
|
3.8%
2/53 • From signing of informed consent up to end of post-treatment period (up to 25 weeks)
Safety set included all randomized participants that received at least 1 dose of study drug.
|
9.3%
5/54 • From signing of informed consent up to end of post-treatment period (up to 25 weeks)
Safety set included all randomized participants that received at least 1 dose of study drug.
|
5.7%
3/53 • From signing of informed consent up to end of post-treatment period (up to 25 weeks)
Safety set included all randomized participants that received at least 1 dose of study drug.
|
|
Investigations
Alanine aminotransferase increased
|
0.00%
0/53 • From signing of informed consent up to end of post-treatment period (up to 25 weeks)
Safety set included all randomized participants that received at least 1 dose of study drug.
|
5.6%
3/54 • From signing of informed consent up to end of post-treatment period (up to 25 weeks)
Safety set included all randomized participants that received at least 1 dose of study drug.
|
1.9%
1/53 • From signing of informed consent up to end of post-treatment period (up to 25 weeks)
Safety set included all randomized participants that received at least 1 dose of study drug.
|
|
Metabolism and nutrition disorders
Hyperkalaemia
|
0.00%
0/53 • From signing of informed consent up to end of post-treatment period (up to 25 weeks)
Safety set included all randomized participants that received at least 1 dose of study drug.
|
7.4%
4/54 • From signing of informed consent up to end of post-treatment period (up to 25 weeks)
Safety set included all randomized participants that received at least 1 dose of study drug.
|
0.00%
0/53 • From signing of informed consent up to end of post-treatment period (up to 25 weeks)
Safety set included all randomized participants that received at least 1 dose of study drug.
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
0.00%
0/53 • From signing of informed consent up to end of post-treatment period (up to 25 weeks)
Safety set included all randomized participants that received at least 1 dose of study drug.
|
5.6%
3/54 • From signing of informed consent up to end of post-treatment period (up to 25 weeks)
Safety set included all randomized participants that received at least 1 dose of study drug.
|
1.9%
1/53 • From signing of informed consent up to end of post-treatment period (up to 25 weeks)
Safety set included all randomized participants that received at least 1 dose of study drug.
|
|
Nervous system disorders
Headache
|
7.5%
4/53 • From signing of informed consent up to end of post-treatment period (up to 25 weeks)
Safety set included all randomized participants that received at least 1 dose of study drug.
|
1.9%
1/54 • From signing of informed consent up to end of post-treatment period (up to 25 weeks)
Safety set included all randomized participants that received at least 1 dose of study drug.
|
3.8%
2/53 • From signing of informed consent up to end of post-treatment period (up to 25 weeks)
Safety set included all randomized participants that received at least 1 dose of study drug.
|
|
Vascular disorders
Hypertension
|
5.7%
3/53 • From signing of informed consent up to end of post-treatment period (up to 25 weeks)
Safety set included all randomized participants that received at least 1 dose of study drug.
|
0.00%
0/54 • From signing of informed consent up to end of post-treatment period (up to 25 weeks)
Safety set included all randomized participants that received at least 1 dose of study drug.
|
3.8%
2/53 • From signing of informed consent up to end of post-treatment period (up to 25 weeks)
Safety set included all randomized participants that received at least 1 dose of study drug.
|
Additional Information
Ionis Pharmaceuticals, Inc.
Ionis Pharmaceuticals, Inc.
Phone: 760-603-2346
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place