Hypertension
Conditions
Keywords
Hypertension, Hypertensive, AGT, Angiotensinogen, Blood Pressure
Brief summary
This study evaluated the effect of ISIS 757456 (IONIS-AGT-LRx) on plasma angiotensinogen (AGT) and systolic blood pressure (SBP) in uncontrolled hypertensive participants who were on two to three antihypertensive medications.
Detailed description
This study was a Phase 2, double-blind, randomized, placebo-controlled study in 26 participants. Participants were randomized in a 2:1 ratio and received a once-weekly subcutaneous (SC) treatment with either IONIS-AGT-LRx or placebo, with an additional loading dose administered on Study Day 3. The treatment lasted for 8 weeks and the post-treatment period lasted for 13 weeks.
Interventions
DRUGPlacebo
ISIS 757456-matching placebo solution administered as SC injection.
DRUGISIS 757456
ISIS 757456 administered as SC injection.
Sponsors
Ionis Pharmaceuticals, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Males or females aged 18-75 inclusive and weighing ≥ 50 kilograms (kg) at the time of informed consent * Females must be non-pregnant and non-lactating, and either surgically sterile or post-menopausal * Males must be surgically sterile or, abstinent or, if engaged in sexual relations with a woman of child-bearing potential (WOCBP), the participant or participant's non-pregnant female partner must be using a highly effective contraceptive method * Body mass index (BMI) ≤ 35.0 kg/square meter (m\^2) * Participant must have been diagnosed with essential hypertension for a minimum of 3 months prior to screening * At screening, the participant must have been on a stable regimen of 2 to 3 antihypertensive medications for at least 1 month prior to screening and will be required to maintain this regimen throughout the study, using either an angiotensin-converting enzyme inhibitor (ACEi) or an angiotensin II receptor blocker (ARB), as well as 1 or 2 additional antihypertensive medications in the following categories: beta blocker, acebutolol, atenolol, betaxolol, bisoprolol, carvedilol, labetalol, metoprolol, nadolol, nebivolol, propranolol, pindolol, calcium channel blocker or, non-potassium sparing diuretic
Exclusion criteria
* Clinically significant abnormalities in medical history, screening laboratory results, or physical examination that would render the participant unsuitable for inclusion * History of secondary hypertension (HTN) The use of the following at time of screening and during the course of the study: * Other medications for the treatment of HTN (e.g., clonidine, guanfacine, guanabenz, alpha-methyldopa, hydralazine, minoxidil, diazoxide, renin inhibitors) * Medications that may cause hyperkalemia (e.g., cyclosporine or tacrolimus, pentamidine, trimethoprim-sulfamethoxazole, all heparins) * Oral or SC anticoagulants (e.g., warfarin, rivaroxaban, apixaban, heparin, lovenox) * Organic nitrate preparations (e.g., nitroglycerin, isosorbide mononitrate, isosorbide dinitrate, or pentaerythritol) * Phosphodiesterase 5 inhibitors (e.g., sildenafil, tadalafil, vardenafil, avanafil) * Potassium-sparing diuretics (e.g., eplerenone, spironolactone, amiloride, triamterene) Unstable/underlying cardiovascular disease defined as: * Any history of congestive heart failure (New York Heart Association \[NYHA\] class II-IV) * Any history of previous stroke, transient ischemic attack, unstable or stable angina pectoris, or myocardial infarction prior to screening * 12-lead electrocardiogram (ECG) corrected using Fridericia's formula (QTcF) \> 450 milliseconds (msec) in males and \> 470 msec in females at screening, or a history or evidence of long QT syndrome * Any clinically significant active atrial or ventricular arrhythmias * Any history of coronary bypass or percutaneous coronary intervention
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline in Plasma Angiotensinogen (AGT) at Day 57 Compared to Placebo | Baseline up to Day 57 (start of Week 9) | The baseline for plasma AGT was defined as the average of all values prior to the first dose of study drug. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Systolic Blood Pressure (SBP) at Each Scheduled, Post-Baseline Visit | Baseline, Days 3, 8, 15, 22, 29, 36, 43, 50, 57, 64, 78, 92, 120, and 141 | — |
| Absolute Change From Baseline in Plasma AGT at Each Scheduled, Post-Baseline Visit | Baseline, Days 3, 8, 15, 22, 29, 36, 43, 50, 57, 64, 78, 92, 120, and 141 | The baseline for plasma AGT was defined as the average of all values prior to the first dose of study drug |
| Percent Change From Baseline in Plasma AGT at Each Scheduled, Post-Baseline Visit | Baseline, Days 3, 8, 15, 22, 29, 36, 43, 50, 64, 78, 92, 120, and 141 | The baseline for plasma AGT was defined as the average of all values prior to the first dose of study drug. |
Countries
United States
Participant flow
Recruitment details
Participants took part in the study at 9 investigative sites from 13 November 2019 to 20 July 2020.
Pre-assignment details
A total of 64 participants were screened out of which 26 were enrolled and randomized in 2:1 ratio to receive either ISIS 757456 80 mg or placebo.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants received ISIS 757456-matching placebo, SC injection, once-weekly for 8 weeks and an additional loading dose on Day 3. | 8 |
| ISIS 757456 Participants received ISIS 757456 80 mg, SC injection, once-weekly for 8 weeks and an additional loading dose on Day 3. | 18 |
| Total | 26 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Reason not Specified | 0 | 1 |
| Overall Study | Voluntary Withdrawal | 0 | 1 |
Baseline characteristics
| Characteristic | Placebo | ISIS 757456 | Total |
|---|---|---|---|
| Age, Continuous | 61 years STANDARD_DEVIATION 10 | 60 years STANDARD_DEVIATION 8 | 60 years STANDARD_DEVIATION 9 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 8 Participants | 10 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 6 Participants | 10 Participants | 16 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Plasma Angiotensinogen (AGT) | 25.5 micrograms per milliliter (μg/mL) STANDARD_DEVIATION 4.4 | 25.2 micrograms per milliliter (μg/mL) STANDARD_DEVIATION 3.4 | 25.3 micrograms per milliliter (μg/mL) STANDARD_DEVIATION 3.7 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants | 3 Participants | 7 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 4 Participants | 15 Participants | 19 Participants |
| Sex: Female, Male Female | 6 Participants | 14 Participants | 20 Participants |
| Sex: Female, Male Male | 2 Participants | 4 Participants | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 8 | 0 / 18 |
| other Total, other adverse events | 3 / 8 | 6 / 18 |
| serious Total, serious adverse events | 0 / 8 | 0 / 18 |
Outcome results
Primary
Percent Change From Baseline in Plasma Angiotensinogen (AGT) at Day 57 Compared to Placebo
The baseline for plasma AGT was defined as the average of all values prior to the first dose of study drug.
Time frame: Baseline up to Day 57 (start of Week 9)
Population: PPS included all randomized participants who had at least 1 post-baseline efficacy or exploratory measurement, received at least 7 of the 9 doses of study drug, did not alter antihypertensive medications during the treatment period and prior to Day 57, and had no significant protocol deviations that would have been expected to affect efficacy or exploratory assessments.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change From Baseline in Plasma Angiotensinogen (AGT) at Day 57 Compared to Placebo | -3.4 percent change | Standard Deviation 17.8 |
| ISIS 757456 | Percent Change From Baseline in Plasma Angiotensinogen (AGT) at Day 57 Compared to Placebo | -67.4 percent change | Standard Deviation 14.1 |
p-value: <0.001ANOVA
Secondary
Absolute Change From Baseline in Plasma AGT at Each Scheduled, Post-Baseline Visit
The baseline for plasma AGT was defined as the average of all values prior to the first dose of study drug
Time frame: Baseline, Days 3, 8, 15, 22, 29, 36, 43, 50, 57, 64, 78, 92, 120, and 141
Population: PPS included all randomized participants who had at least 1 post-baseline efficacy or exploratory measurement, received at least 7 of the 9 doses of study drug, did not alter antihypertensive medications during the treatment period and prior to Day 57, and had no significant protocol deviations that would have been expected to affect efficacy or exploratory assessments. 'Number analyzed' indicates the number of participants with available data at the specific timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Absolute Change From Baseline in Plasma AGT at Each Scheduled, Post-Baseline Visit | Change From Baseline at Day 22 | -0.7 ug/mL | Standard Deviation 1.6 |
| Placebo | Absolute Change From Baseline in Plasma AGT at Each Scheduled, Post-Baseline Visit | Change From Baseline at Day 50 | -2.2 ug/mL | Standard Deviation 3.2 |
| Placebo | Absolute Change From Baseline in Plasma AGT at Each Scheduled, Post-Baseline Visit | Change From Baseline at Day 3 | -1.7 ug/mL | Standard Deviation 2.3 |
| Placebo | Absolute Change From Baseline in Plasma AGT at Each Scheduled, Post-Baseline Visit | Change From Baseline at Day 57 | -1.1 ug/mL | Standard Deviation 4.5 |
| Placebo | Absolute Change From Baseline in Plasma AGT at Each Scheduled, Post-Baseline Visit | Change From Baseline at Day 29 | -0.8 ug/mL | Standard Deviation 3.9 |
| Placebo | Absolute Change From Baseline in Plasma AGT at Each Scheduled, Post-Baseline Visit | Change From Baseline at Day 64 | -4.3 ug/mL | Standard Deviation 3.7 |
| Placebo | Absolute Change From Baseline in Plasma AGT at Each Scheduled, Post-Baseline Visit | Change From Baseline at Day 15 | -1.6 ug/mL | Standard Deviation 2.1 |
| Placebo | Absolute Change From Baseline in Plasma AGT at Each Scheduled, Post-Baseline Visit | Change From Baseline at Day 78 | -3.0 ug/mL | Standard Deviation 3.1 |
| Placebo | Absolute Change From Baseline in Plasma AGT at Each Scheduled, Post-Baseline Visit | Change From Baseline at Day 36 | -2.0 ug/mL | Standard Deviation 2.6 |
| Placebo | Absolute Change From Baseline in Plasma AGT at Each Scheduled, Post-Baseline Visit | Change From Baseline at Day 92 | -1.7 ug/mL | Standard Deviation 3.9 |
| Placebo | Absolute Change From Baseline in Plasma AGT at Each Scheduled, Post-Baseline Visit | Change From Baseline at Day 8 | -1.5 ug/mL | Standard Deviation 3.1 |
| Placebo | Absolute Change From Baseline in Plasma AGT at Each Scheduled, Post-Baseline Visit | Change From Baseline at Day 120 | -3.1 ug/mL | Standard Deviation 1.9 |
| Placebo | Absolute Change From Baseline in Plasma AGT at Each Scheduled, Post-Baseline Visit | Change From Baseline at Day 43 | -2.9 ug/mL | Standard Deviation 2.5 |
| Placebo | Absolute Change From Baseline in Plasma AGT at Each Scheduled, Post-Baseline Visit | Change From Baseline at Day 141 | -3.4 ug/mL | Standard Deviation 4.7 |
| Placebo | Absolute Change From Baseline in Plasma AGT at Each Scheduled, Post-Baseline Visit | Baseline | 25.5 ug/mL | Standard Deviation 4.4 |
| ISIS 757456 | Absolute Change From Baseline in Plasma AGT at Each Scheduled, Post-Baseline Visit | Change From Baseline at Day 141 | -5.8 ug/mL | Standard Deviation 5.3 |
| ISIS 757456 | Absolute Change From Baseline in Plasma AGT at Each Scheduled, Post-Baseline Visit | Baseline | 25.2 ug/mL | Standard Deviation 3.4 |
| ISIS 757456 | Absolute Change From Baseline in Plasma AGT at Each Scheduled, Post-Baseline Visit | Change From Baseline at Day 3 | -2.5 ug/mL | Standard Deviation 4.2 |
| ISIS 757456 | Absolute Change From Baseline in Plasma AGT at Each Scheduled, Post-Baseline Visit | Change From Baseline at Day 8 | -9.6 ug/mL | Standard Deviation 4.3 |
| ISIS 757456 | Absolute Change From Baseline in Plasma AGT at Each Scheduled, Post-Baseline Visit | Change From Baseline at Day 15 | -13.4 ug/mL | Standard Deviation 5.7 |
| ISIS 757456 | Absolute Change From Baseline in Plasma AGT at Each Scheduled, Post-Baseline Visit | Change From Baseline at Day 22 | -15.7 ug/mL | Standard Deviation 4.7 |
| ISIS 757456 | Absolute Change From Baseline in Plasma AGT at Each Scheduled, Post-Baseline Visit | Change From Baseline at Day 29 | -17.1 ug/mL | Standard Deviation 4 |
| ISIS 757456 | Absolute Change From Baseline in Plasma AGT at Each Scheduled, Post-Baseline Visit | Change From Baseline at Day 36 | -17.2 ug/mL | Standard Deviation 4 |
| ISIS 757456 | Absolute Change From Baseline in Plasma AGT at Each Scheduled, Post-Baseline Visit | Change From Baseline at Day 43 | -17.5 ug/mL | Standard Deviation 3.7 |
| ISIS 757456 | Absolute Change From Baseline in Plasma AGT at Each Scheduled, Post-Baseline Visit | Change From Baseline at Day 50 | -17.7 ug/mL | Standard Deviation 3.8 |
| ISIS 757456 | Absolute Change From Baseline in Plasma AGT at Each Scheduled, Post-Baseline Visit | Change From Baseline at Day 57 | -17.0 ug/mL | Standard Deviation 4.1 |
| ISIS 757456 | Absolute Change From Baseline in Plasma AGT at Each Scheduled, Post-Baseline Visit | Change From Baseline at Day 64 | -15.9 ug/mL | Standard Deviation 3.7 |
| ISIS 757456 | Absolute Change From Baseline in Plasma AGT at Each Scheduled, Post-Baseline Visit | Change From Baseline at Day 78 | -12.9 ug/mL | Standard Deviation 3.9 |
| ISIS 757456 | Absolute Change From Baseline in Plasma AGT at Each Scheduled, Post-Baseline Visit | Change From Baseline at Day 92 | -9.8 ug/mL | Standard Deviation 4.2 |
| ISIS 757456 | Absolute Change From Baseline in Plasma AGT at Each Scheduled, Post-Baseline Visit | Change From Baseline at Day 120 | -5.7 ug/mL | Standard Deviation 4 |
Comparison: Day 3p-value: 0.661ANOVA
Comparison: Day 8p-value: <0.001ANOVA
Comparison: Day 15p-value: <0.001ANOVA
Comparison: Day 22p-value: <0.001ANOVA
Comparison: Day 29p-value: <0.001ANOVA
Comparison: Day 36p-value: <0.001ANOVA
Comparison: Day 43p-value: <0.001ANOVA
Comparison: Day 50p-value: <0.001ANOVA
Comparison: Day 57p-value: <0.001ANOVA
Comparison: Day 64p-value: <0.001ANOVA
Comparison: Day 78p-value: <0.001ANOVA
Comparison: Day 92p-value: <0.001ANOVA
Comparison: Day 120p-value: 0.106ANOVA
Comparison: Day 141p-value: 0.318ANOVA
Secondary
Change From Baseline in Systolic Blood Pressure (SBP) at Each Scheduled, Post-Baseline Visit
Time frame: Baseline, Days 3, 8, 15, 22, 29, 36, 43, 50, 57, 64, 78, 92, 120, and 141
Population: PPS included all randomized participants who had at least 1 post-baseline efficacy or exploratory measurement, received at least 7 of the 9 doses of study drug, did not alter antihypertensive medications during the treatment period and prior to Day 57, and had no significant protocol deviations that would have been expected to affect efficacy or exploratory assessments. 'Number analyzed' indicates the number of participants with available data at the specific timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Systolic Blood Pressure (SBP) at Each Scheduled, Post-Baseline Visit | Change From Baseline at Day 92 | -5 mmHg | Standard Deviation 13 |
| Placebo | Change From Baseline in Systolic Blood Pressure (SBP) at Each Scheduled, Post-Baseline Visit | Baseline | 152 mmHg | Standard Deviation 8 |
| Placebo | Change From Baseline in Systolic Blood Pressure (SBP) at Each Scheduled, Post-Baseline Visit | Change From Baseline at Day 3 | -6 mmHg | Standard Deviation 15 |
| Placebo | Change From Baseline in Systolic Blood Pressure (SBP) at Each Scheduled, Post-Baseline Visit | Change From Baseline at Day 8 | -8 mmHg | Standard Deviation 9 |
| Placebo | Change From Baseline in Systolic Blood Pressure (SBP) at Each Scheduled, Post-Baseline Visit | Change From Baseline at Day 15 | -0 mmHg | Standard Deviation 16 |
| Placebo | Change From Baseline in Systolic Blood Pressure (SBP) at Each Scheduled, Post-Baseline Visit | Change From Baseline at Day 22 | -8 mmHg | Standard Deviation 15 |
| Placebo | Change From Baseline in Systolic Blood Pressure (SBP) at Each Scheduled, Post-Baseline Visit | Change From Baseline at Day 29 | 3 mmHg | Standard Deviation 14 |
| Placebo | Change From Baseline in Systolic Blood Pressure (SBP) at Each Scheduled, Post-Baseline Visit | Change From Baseline at Day 36 | 0 mmHg | Standard Deviation 15 |
| Placebo | Change From Baseline in Systolic Blood Pressure (SBP) at Each Scheduled, Post-Baseline Visit | Change From Baseline at Day 43 | -2 mmHg | Standard Deviation 9 |
| Placebo | Change From Baseline in Systolic Blood Pressure (SBP) at Each Scheduled, Post-Baseline Visit | Change From Baseline at Day 50 | -3 mmHg | Standard Deviation 12 |
| Placebo | Change From Baseline in Systolic Blood Pressure (SBP) at Each Scheduled, Post-Baseline Visit | Change From Baseline at Day 57 | -5 mmHg | Standard Deviation 10 |
| Placebo | Change From Baseline in Systolic Blood Pressure (SBP) at Each Scheduled, Post-Baseline Visit | Change From Baseline at Day 64 | -8 mmHg | Standard Deviation 16 |
| Placebo | Change From Baseline in Systolic Blood Pressure (SBP) at Each Scheduled, Post-Baseline Visit | Change From Baseline at Day 78 | -8 mmHg | Standard Deviation 14 |
| Placebo | Change From Baseline in Systolic Blood Pressure (SBP) at Each Scheduled, Post-Baseline Visit | Change From Baseline at Day 120 | -3 mmHg | Standard Deviation 10 |
| Placebo | Change From Baseline in Systolic Blood Pressure (SBP) at Each Scheduled, Post-Baseline Visit | Change From Baseline at Day 141 | 0 mmHg | Standard Deviation 13 |
| ISIS 757456 | Change From Baseline in Systolic Blood Pressure (SBP) at Each Scheduled, Post-Baseline Visit | Change From Baseline at Day 120 | -10 mmHg | Standard Deviation 14 |
| ISIS 757456 | Change From Baseline in Systolic Blood Pressure (SBP) at Each Scheduled, Post-Baseline Visit | Change From Baseline at Day 43 | -11 mmHg | Standard Deviation 12 |
| ISIS 757456 | Change From Baseline in Systolic Blood Pressure (SBP) at Each Scheduled, Post-Baseline Visit | Baseline | 153 mmHg | Standard Deviation 10 |
| ISIS 757456 | Change From Baseline in Systolic Blood Pressure (SBP) at Each Scheduled, Post-Baseline Visit | Change From Baseline at Day 78 | -12 mmHg | Standard Deviation 13 |
| ISIS 757456 | Change From Baseline in Systolic Blood Pressure (SBP) at Each Scheduled, Post-Baseline Visit | Change From Baseline at Day 3 | -12 mmHg | Standard Deviation 14 |
| ISIS 757456 | Change From Baseline in Systolic Blood Pressure (SBP) at Each Scheduled, Post-Baseline Visit | Change From Baseline at Day 50 | -17 mmHg | Standard Deviation 16 |
| ISIS 757456 | Change From Baseline in Systolic Blood Pressure (SBP) at Each Scheduled, Post-Baseline Visit | Change From Baseline at Day 8 | -14 mmHg | Standard Deviation 15 |
| ISIS 757456 | Change From Baseline in Systolic Blood Pressure (SBP) at Each Scheduled, Post-Baseline Visit | Change From Baseline at Day 92 | -15 mmHg | Standard Deviation 15 |
| ISIS 757456 | Change From Baseline in Systolic Blood Pressure (SBP) at Each Scheduled, Post-Baseline Visit | Change From Baseline at Day 15 | -9 mmHg | Standard Deviation 13 |
| ISIS 757456 | Change From Baseline in Systolic Blood Pressure (SBP) at Each Scheduled, Post-Baseline Visit | Change From Baseline at Day 57 | -12 mmHg | Standard Deviation 16 |
| ISIS 757456 | Change From Baseline in Systolic Blood Pressure (SBP) at Each Scheduled, Post-Baseline Visit | Change From Baseline at Day 22 | -8 mmHg | Standard Deviation 16 |
| ISIS 757456 | Change From Baseline in Systolic Blood Pressure (SBP) at Each Scheduled, Post-Baseline Visit | Change From Baseline at Day 141 | -11 mmHg | Standard Deviation 13 |
| ISIS 757456 | Change From Baseline in Systolic Blood Pressure (SBP) at Each Scheduled, Post-Baseline Visit | Change From Baseline at Day 29 | -8 mmHg | Standard Deviation 16 |
| ISIS 757456 | Change From Baseline in Systolic Blood Pressure (SBP) at Each Scheduled, Post-Baseline Visit | Change From Baseline at Day 64 | -16 mmHg | Standard Deviation 11 |
| ISIS 757456 | Change From Baseline in Systolic Blood Pressure (SBP) at Each Scheduled, Post-Baseline Visit | Change From Baseline at Day 36 | -13 mmHg | Standard Deviation 15 |
Comparison: Day 3p-value: 0.399ANOVA
Comparison: Day 8p-value: 0.338ANOVA
Comparison: Day 15p-value: 0.207ANOVA
Comparison: Day 22p-value: 0.927ANOVA
Comparison: Day 29p-value: 0.146ANOVA
Comparison: Day 36p-value: 0.055ANOVA
Comparison: Day 43p-value: 0.095ANOVA
Comparison: Day 50p-value: 0.046ANOVA
Comparison: Day 57p-value: 0.246ANOVA
Comparison: Day 64p-value: 0.17ANOVA
Comparison: Day 78p-value: 0.527ANOVA
Comparison: Day 92p-value: 0.167ANOVA
Comparison: Day 120p-value: 0.266ANOVA
Comparison: Day 141p-value: 0.078ANOVA
Secondary
Percent Change From Baseline in Plasma AGT at Each Scheduled, Post-Baseline Visit
The baseline for plasma AGT was defined as the average of all values prior to the first dose of study drug.
Time frame: Baseline, Days 3, 8, 15, 22, 29, 36, 43, 50, 64, 78, 92, 120, and 141
Population: PPS included all randomized participants who had at least 1 post-baseline efficacy or exploratory measurement, received at least 7 of the 9 doses of study drug, did not alter antihypertensive medications during the treatment period and prior to Day 57, and had no significant protocol deviations that would have been expected to affect efficacy or exploratory assessments. 'Number analyzed' indicates the number of participants with available data at the specific timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Percent Change From Baseline in Plasma AGT at Each Scheduled, Post-Baseline Visit | Percent Change From Baseline at Day 15 | -6.6 percent change | Standard Deviation 8.1 |
| Placebo | Percent Change From Baseline in Plasma AGT at Each Scheduled, Post-Baseline Visit | Percent Change From Baseline at Day 43 | -10.6 percent change | Standard Deviation 8.2 |
| Placebo | Percent Change From Baseline in Plasma AGT at Each Scheduled, Post-Baseline Visit | Percent Change From Baseline at Day 50 | -7.9 percent change | Standard Deviation 11.4 |
| Placebo | Percent Change From Baseline in Plasma AGT at Each Scheduled, Post-Baseline Visit | Percent Change From Baseline at Day 64 | -18.0 percent change | Standard Deviation 15.5 |
| Placebo | Percent Change From Baseline in Plasma AGT at Each Scheduled, Post-Baseline Visit | Percent Change From Baseline at Day 22 | -2.4 percent change | Standard Deviation 6.3 |
| Placebo | Percent Change From Baseline in Plasma AGT at Each Scheduled, Post-Baseline Visit | Percent Change From Baseline at Day 78 | -12.3 percent change | Standard Deviation 12.2 |
| Placebo | Percent Change From Baseline in Plasma AGT at Each Scheduled, Post-Baseline Visit | Percent Change From Baseline at Day 8 | -4.8 percent change | Standard Deviation 12.9 |
| Placebo | Percent Change From Baseline in Plasma AGT at Each Scheduled, Post-Baseline Visit | Percent Change From Baseline at Day 92 | -6.6 percent change | Standard Deviation 14.5 |
| Placebo | Percent Change From Baseline in Plasma AGT at Each Scheduled, Post-Baseline Visit | Percent Change From Baseline at Day 29 | -2.8 percent change | Standard Deviation 15.5 |
| Placebo | Percent Change From Baseline in Plasma AGT at Each Scheduled, Post-Baseline Visit | Percent Change From Baseline at Day 120 | -12.4 percent change | Standard Deviation 7.7 |
| Placebo | Percent Change From Baseline in Plasma AGT at Each Scheduled, Post-Baseline Visit | Percent Change From Baseline at Day 3 | -6.6 percent change | Standard Deviation 9.5 |
| Placebo | Percent Change From Baseline in Plasma AGT at Each Scheduled, Post-Baseline Visit | Percent Change From Baseline at Day 141 | -14.3 percent change | Standard Deviation 17.4 |
| Placebo | Percent Change From Baseline in Plasma AGT at Each Scheduled, Post-Baseline Visit | Percent Change From Baseline at Day 36 | -8.1 percent change | Standard Deviation 10.2 |
| ISIS 757456 | Percent Change From Baseline in Plasma AGT at Each Scheduled, Post-Baseline Visit | Percent Change From Baseline at Day 141 | -22.3 percent change | Standard Deviation 19.8 |
| ISIS 757456 | Percent Change From Baseline in Plasma AGT at Each Scheduled, Post-Baseline Visit | Percent Change From Baseline at Day 3 | -10.3 percent change | Standard Deviation 16.6 |
| ISIS 757456 | Percent Change From Baseline in Plasma AGT at Each Scheduled, Post-Baseline Visit | Percent Change From Baseline at Day 8 | -38.5 percent change | Standard Deviation 16.6 |
| ISIS 757456 | Percent Change From Baseline in Plasma AGT at Each Scheduled, Post-Baseline Visit | Percent Change From Baseline at Day 15 | -53.3 percent change | Standard Deviation 22.1 |
| ISIS 757456 | Percent Change From Baseline in Plasma AGT at Each Scheduled, Post-Baseline Visit | Percent Change From Baseline at Day 22 | -62.4 percent change | Standard Deviation 17.9 |
| ISIS 757456 | Percent Change From Baseline in Plasma AGT at Each Scheduled, Post-Baseline Visit | Percent Change From Baseline at Day 29 | -67.9 percent change | Standard Deviation 13.5 |
| ISIS 757456 | Percent Change From Baseline in Plasma AGT at Each Scheduled, Post-Baseline Visit | Percent Change From Baseline at Day 36 | -68.4 percent change | Standard Deviation 13.9 |
| ISIS 757456 | Percent Change From Baseline in Plasma AGT at Each Scheduled, Post-Baseline Visit | Percent Change From Baseline at Day 50 | -70.3 percent change | Standard Deviation 11.1 |
| ISIS 757456 | Percent Change From Baseline in Plasma AGT at Each Scheduled, Post-Baseline Visit | Percent Change From Baseline at Day 64 | -63.5 percent change | Standard Deviation 14 |
| ISIS 757456 | Percent Change From Baseline in Plasma AGT at Each Scheduled, Post-Baseline Visit | Percent Change From Baseline at Day 78 | -51.1 percent change | Standard Deviation 14.5 |
| ISIS 757456 | Percent Change From Baseline in Plasma AGT at Each Scheduled, Post-Baseline Visit | Percent Change From Baseline at Day 92 | -38.9 percent change | Standard Deviation 15.7 |
| ISIS 757456 | Percent Change From Baseline in Plasma AGT at Each Scheduled, Post-Baseline Visit | Percent Change From Baseline at Day 120 | -22.1 percent change | Standard Deviation 14.9 |
| ISIS 757456 | Percent Change From Baseline in Plasma AGT at Each Scheduled, Post-Baseline Visit | Percent Change From Baseline at Day 43 | -69.5 percent change | Standard Deviation 11.3 |
Comparison: Day 3p-value: 0.609ANOVA
Comparison: Day 8p-value: <0.001ANOVA
Comparison: Day 15p-value: <0.001ANOVA
Comparison: Day 22p-value: <0.001ANOVA
Comparison: Day 29p-value: <0.001ANOVA
Comparison: Day 36p-value: <0.001ANOVA
Comparison: Day 43p-value: <0.001ANOVA
Comparison: Day 50p-value: <0.001ANOVA
Comparison: Day 64p-value: <0.001ANOVA
Comparison: Day 78p-value: <0.001ANOVA
Comparison: Day 92p-value: <0.001ANOVA
Comparison: Day 120p-value: 0.112ANOVA
Comparison: Day 141p-value: 0.371ANOVA