Diabetes Mellitus, Type 2, Hypertension
Conditions
Brief summary
To compare the safety, tolerability, pharmacokinetic (PK) profile, and pharmacodynamic (PD) effects of 2 treatment regimens of IW-1973 tablet (40 mg per day) administered orally for 2 weeks to patients with stable type 2 diabetes mellitus and hypertension.
Interventions
DRUGIW-1973
Oral Tablet
DRUGPlacebo
Oral Tablet
Sponsors
Cyclerion Therapeutics
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Masking description
Double-Blind
Eligibility
Sex/Gender
ALL
Age
30 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Patient is ambulatory male or female * Patient's body mass index score is \> 20 and \< 40 kg/m\^2 at the Screening Visit * Women of childbearing potential must have a negative pregnancy test at the time of screening and check-in and must agree to use protocol-specified contraception throughout the duration of the study * Patient's health is stable with no clinically significant findings on physical examination * Patient has type 2 (ie, adult onset) diabetes mellitus diagnosed by a physician or nurse practitioner \> 6 months before the Screening Visit, is on a stable glycemic control medication, and protocol specified hemoglobin (Hb)A1c values at the Screening Visit * Patient has hypertension diagnosed by a physician or nurse practitioner \> 6 months before the Screening Visit, and blood pressure (BP) within the protocol's acceptable range * Patients must be on a stable regimen for hypertension control that includes an angiotensin converting enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB), stable for 28 days * Other inclusion criteria per protocol
Exclusion criteria
* Patient has a clinically significant active or unstable medical condition that, in the opinion of the Investigator, would preclude trial participation * Patient is on medication(s) that, when co-administered with a sGC stimulator, could increase the risk of hypotension * Patient has evidence of severe or active end-organ damage * Patient is an active smoker or has used any nicotine-containing products (cigarettes, e-cigarettes, vape pens, cigars, chewing tobacco, gum, patches) during the 6 months before Check-in. Use of nicotine is excluded during the study until after the End of Trial Visit. * Other
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Study Baseline Over Time in Supine Systolic Blood Pressure | Study Baseline (Day 1 predose AM); Days 2-14: predose AM; Days 1, 2, 7, 8, 13: postdose AM 1 hour and 4 hour; Day 1: postdose AM 8 hour; Days 1, 2, 8, 13: predose PM; Days 1, 2: postdose PM 1 hour; Days 2, 3: postdose PM 4 hour; Days 15, 21, 42 | — |
| Change From Study Baseline Over Time in Supine Diastolic Blood Pressure | Study Baseline (Day 1 predose AM); Days 2-14: predose AM; Days 1, 2, 7, 8, 13: postdose AM 1 hour and 4 hour; Day 1: postdose AM 8 hour; Days 1, 2, 8, 13: predose PM; Days 1, 2: postdose PM 1 hour; Days 2, 3: postdose PM 4 hour; Days 15, 21, 42 | — |
| Change From Study Baseline Over Time in Supine Pulse | Study Baseline (Day 1 predose AM); Days 2-14: predose AM; Days 1, 2, 7, 8, 13: postdose AM 1 hour and 4 hour; Day 1: postdose AM 8 hour; Days 1, 2, 8, 13: predose PM; Days 1, 2: postdose PM 1 hour; Days 2, 3: postdose PM 4 hour; Days 15, 21, 42 | — |
| Percentage of Participants With Postdose Supine Blood Pressure Less Than 130/80 mmHg Over Time | Baseline, Days 1-14, Day 15, 21, 42 | — |
| Orthostatic Systolic Blood Pressure Over Time | Days -1, 1, 2, 7, 8, 13: 1 and 4 hour AM; Days -1, 1, 2, 8, 13: 0 hour PM; Days -1, 1, 2: 1 hour PM; Days 1, 2, 7, 8, 13: 0 hour AM; Day 1: 8 hour AM; Days 1, 2: 4 hour PM | An orthostatic measurement is obtained by subtracting the supine measurement from the standing measurement. |
| Orthostatic Diastolic Blood Pressure Over Time | Days -1, 1, 2, 7, 8, 13: 1 and 4 hour AM; Days -1, 1, 2, 8, 13: 0 hour PM; Days -1, 1, 2: 1 hour PM; Days 1, 2, 7, 8, 13: 0 hour AM; Day 1: 8 hour AM; Days 1, 2: 4 hour PM | An orthostatic measurement is obtained by subtracting the supine measurement from the standing measurement. |
| Orthostatic Pulse Over Time | Days -1, 1, 2, 7, 8, 13: 1 and 4 hour AM; Days -1, 1, 2, 8, 13: 0 hour PM; Days -1, 1, 2: 1 hour PM; Days 1, 2, 7, 8, 13: 0 hour AM; Day 1: 8 hour AM; Days 1, 2: 4 hour PM | An orthostatic measurement is obtained by subtracting the supine measurement from the standing measurement. |
| Change From Time-Matched Baseline Over Time in Ambulatory Blood Pressure Monitoring (ABPM) 24-hour Averages of Systolic Blood Pressure | Time Matched Baseline (Day -1), Days 1, 7, and 14 | 24-hour average is the average of ABPM assessments over 24 hour intervals from the time of dosing. Time-matched baseline is the 24 hours average during Day -1. |
| Change From Time-Matched Baseline Over Time in ABPM Daytime (12-Hour) Averages of Systolic Blood Pressure | Time Matched Baseline (Day -1), Days 1, 7, and 14 | Daytime 12-hour average is the average of ABPM assessments over daytime 12-hour intervals from the time of dosing. Time-matched baseline is the daytime 12 hours average during Day -1. |
| Change From Time-Matched Baseline Over Time in ABPM Nighttime (12-Hour) Averages of Systolic Blood Pressure | Time Matched Baseline (Day -1), Days 1, 7, and 14 | Nighttime 12-hour average is the average of ABPM assessments over nighttime 12-hour intervals from the time of dosing. Time-matched baseline is the nighttime 12 hours average during Day -1. |
| Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Systolic Blood Pressure | Time-matched baseline (Day -1), Days 1, 7, 14: 0-4, 4-8, 8-12, 12-16, 16-20, 20-24 hours postdose | Postdose is the average of assessments over 4-hour intervals from the time of dosing that day. Time-matched baseline is the corresponding 4-hour average on Day -1. |
| Change From Time-Matched Baseline Over Time in ABPM 24-hour Averages of Mean Arterial Pressure | Time Matched Baseline (Day -1), Days 1, 7, and 14 | 24-hour average is the average of ABPM assessments over 24 hour intervals from the time of dosing. Time-matched baseline is the 24 hours average during Day -1. |
| Change From Time-Matched Baseline Over Time in ABPM Daytime (12-hour) Averages of Mean Arterial Pressure | Time Matched Baseline (Day -1), Days 1, 7, and 14 | Daytime 12-hour average is the average of ABPM assessments over daytime 12-hour intervals from the time of dosing. Time-matched baseline is the daytime 12 hours average during Day -1. |
| Change From Time-Matched Baseline Over Time in ABPM Nighttime (12-Hour) Averages of Mean Arterial Pressure | Time Matched Baseline (Day -1), Days 1, 7, and 14 | Nighttime 12-hour average is the average of ABPM assessments over nighttime 12-hour intervals from the time of dosing. Time-matched baseline is the nighttime 12 hours average during Day -1. |
| Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Mean Arterial Pressure | Time-matched baseline (Day -1), Days 1, 7, 14: 0-4, 4-8, 8-12, 12-16, 16-20, 20-24 hours postdose | Postdose is the average of assessments over 4-hour intervals from the time of dosing that day. Time-matched baseline is the corresponding 4-hour average on Day -1. |
| Change From Time-Matched Baseline Over Time in ABPM 24-hour Averages of Diastolic Blood Pressure | Time Matched Baseline (Day -1), Days 1, 7, and 14 | 24-hour average is the average of ABPM assessments over 24 hour intervals from the time of dosing. Time-matched baseline is the 24 hours average during Day -1. |
| Change From Time-Matched Baseline Over Time in ABPM Daytime (12-hour) Averages of Diastolic Blood Pressure | Time Matched Baseline (Day -1), Days 1, 7, and 14 | Daytime 12-hour average is the average of ABPM assessments over daytime 12-hour intervals from the time of dosing. Time-matched baseline is the daytime 12 hours average during Day -1. |
| Change From Time-Matched Baseline Over Time in ABPM Nighttime (12-Hour) Averages of Diastolic Blood Pressure | Time Matched Baseline (Day -1), Days 1, 7, and 14 | Nighttime 12-hour average is the average of ABPM assessments over nighttime 12-hour intervals from the time of dosing. Time-matched baseline is the nighttime 12 hours average during Day -1. |
| Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Diastolic Blood Pressure | Time-matched baseline (Day -1), Days 1, 7, 14: 0-4, 4-8, 8-12, 12-16, 16-20, 20-24 hours postdose | Postdose is the average of assessments over 4-hour intervals from the time of dosing that day. Time-matched baseline is the corresponding 4-hour average on Day -1. |
| Change From Time-Matched Baseline Over Time in ABPM 24-hour Averages of Pulse | Time Matched Baseline (Day -1), Days 1, 7, and 14 | 24-hour average is the average of ABPM assessments over 24 hour intervals from the time of dosing. Time-matched baseline is the 24 hours average during Day -1. |
| Change From Time-Matched Baseline Over Time in ABPM Daytime (12-hour) Averages of Pulse | Time Matched Baseline (Day -1), Days 1, 7, and 14 | Daytime 12-hour average is the average of ABPM assessments over daytime 12-hour intervals from the time of dosing. Time-matched baseline is the daytime 12 hours average during Day -1. |
| Change From Time-Matched Baseline Over Time in ABPM Nighttime (12-Hour) Averages of Pulse | Time Matched Baseline (Day -1), Days 1, 7, and 14 | Nighttime 12-hour average is the average of ABPM assessments over nighttime 12-hour intervals from the time of dosing. Time-matched baseline is the nighttime 12 hours average during Day -1. |
| Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Pulse | Time-matched baseline (Day -1), Days 1, 7, 14: 0-4, 4-8, 8-12, 12-16, 16-20, 20-24 hours postdose | Postdose is the average of assessments over 4-hour intervals from the time of dosing that day. Time-matched baseline is the corresponding 4-hour average on Day -1. |
| Change From Baseline in Reactive Hyperemia Index (RHI) on Day 13 | Baseline, Day 13 predose AM | RHI is a measure of the extent of vessel dilatation and augmentation in vascular blood flow after a prespecified period of flow interruption. RHI is determined as the ratio of the post-to-pre- occlusion peripheral arterial tonometry amplitude of the tested (occluded) arm, divided by the post to-pre-occlusion ratio of the control arm. RHI values \>1.67 indicate normal endothelial function, while values ≤1.67 indicate endothelial dysfunction. |
| Post-Baseline Platelet Reactivity on Days 8 and 14: P2Y12 Reaction Units (PRU) Assay | Baseline, Day 8, Day 14 | Platelet reactivity, as measured by VerifyNow PRU assay, and presented as number of participants with \< 180 PRU or ≥ 180 PRU post-baseline (Days 8 and 14), by baseline category. The VerifyNow PRU assay measures effects on platelet activation caused by inhibition of the platelet receptor, P2Y12. This receptor is activated by adenosine 5'-diphosphate (ADP) in the cascade leading to platelet aggregation but can be blocked by P2Y12 inhibitor drugs, such as clopidogrel. Blockage of this receptor diminishes platelet activation and the ability of platelets to bind to fibrinogen. VerifyNow PRU assay values \< 180 units indicate impairment of platelet aggregation. |
| Post-Baseline Platelet Reactivity on Days 8 and 14: Aspirin Reaction Units (ARU) Assay | Baseline, Day 8, Day 14 | Platelet reactivity, as measured by VerifyNow ARU assay, and presented as number of participants with ≤ 549 ARU or \> 549 ARU post-baseline (Days 8 and 14), by baseline category. Aspirin irreversibly inhibits cyclooxygenase 1, which converts arachidonic acid to thromboxane A2, which in turn is involved in the activation of the glycoprotein (GP)IIb/IIIa receptor necessary to initiate platelet aggregation. Impairment of platelet aggregation of the aspirin type is defined for the VerifyNow aspirin assay as values ≤ 549 ARU. |
| Change From Study Baseline Over Time in Platelet Function Assessments: PRU Assay | Study Baseline (Day 1 predose), Day 8 (predose AM), Day 14 (predose AM) | The VerifyNow PRU assay measures effects on platelet activation caused by inhibition of the platelet receptor, P2Y12. This receptor is activated by adenosine 5'-diphosphate (ADP) in the cascade leading to platelet aggregation but can be blocked by P2Y12 inhibitor drugs, such as clopidogrel. Blockage of this receptor diminishes platelet activation and the ability of platelets to bind to fibrinogen. VerifyNow PRU assay values \<180 PRU indicate impairment of platelet aggregation. |
| Change From Study Baseline Over Time in Platelet Function Assessments: ARU Assay | Study Baseline (Day 1 predose), Day 8 (pre AM dose), Day 14 (pre AM dose) | Aspirin irreversibly inhibits cyclooxygenase 1, which converts arachidonic acid to thromboxane A2, which in turn is involved in the activation of the GPIIb IIIa receptor necessary to initiate platelet aggregation. Impairment of platelet aggregation of the aspirin type is defined for the VerifyNow aspirin assay as values ≤ 549 ARU. |
| Percent Change From Study Baseline Over Time in HOMA-IR in Participants Without Concomitant Use of Insulin | Study baseline (defined as the last non-missing assessment before the first administration of study drug), Day 8, pre-AM dose, Day 15 | Blood samples were taken for fasting glucose and insulin levels. From these results, insulin resistance was then estimated using the updated homeostasis model assessment method for insulin resistance (HOMA-IR) computer algorithm. A higher HOMA-IR indicates a higher degree of insulin resistance. Typically a cutoff of HOMA-IR for identifying those with insulin resistance is 2.5. |
| IW-1973 Pharmacokinetics: Area Under the Plasma Concentration Time Curve During a Dosing Interval (AUCtau) on Days 1 and 7 | Days 1 and 7 (AM): 1, 3, and 6 hours postdose | Equivalent to AUC from time 0 to the last measurable concentration (AUClast), with time of last measurable concentration (Tlast)=12 hours for BID dosing and Tlast=24 hours for QD dosing. |
| IW-1973 Pharmacokinetics: Maximum Observed Plasma Concentration (Cmax) on Days 1 and 7 | Days 1 and 7 (AM): 1, 3, and 6 hours postdose | — |
| IW-1973 Pharmacokinetics: Time to Cmax on Days 1 and 7 | Days 1 and 7 (AM): 1, 3, and 6 hours postdose | — |
| IW-1973 Pharmacokinetics: Trough Plasma Concentrations at the End of the Dosing Interval (Ctrough) on Days 1, 2, 6, 7 | Days 1 and 7: predose; Day 2 (BID AM): predose; Day 6 (BID PM/QD): predose | — |
| IW-1973 Pharmacokinetics: Area Under the Plasma Concentration Time Curve From Time Zero to the Last Measurable Plasma Concentration (AUClast) on Days 8 and 14 | Day 8 and 14: 1, 3, 6h (± 5 min) postdose | — |
| IW-1973 Pharmacokinetics: AUCtau on Day 14 | Day 14: 1, 3, 6h (± 5 min) postdose | — |
| IW-1973 Pharmacokinetics: Tmax on Days 8 and 14 | Day 8 and 14: 1, 3, 6h (± 5 min) postdose | — |
| IW-1973 Pharmacokinetics: Cmax on Days 8 and 14 | Day 8 and 14: 1, 3, 6h (± 5 min) postdose | — |
| IW-1973 Pharmacokinetics: Ctrough on Days 13 and 14 | Days 13 and 14: predose | — |
| IW-1973 Pharmacokinetics: Apparent Total Body Clearance (CL/F) on Day 14 | Day 14: 1, 3, 6h (± 5 min) postdose | — |
| IW-1973 Pharmacokinetics: Apparent Volume of Distribution During the Terminal Phase (Vz/F) on Day 14 | Day 14: 1, 3, 6h (± 5 min) postdose | — |
| IW-1973 Pharmacokinetics: Apparent Terminal Elimination Phase Half-Life (t1/2) | Day 14 (final dose) time points 12 hours, 24 hours, 7 days after final dose (Day 21), and 28 days after final dose(Day 42) | — |
| Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Discontinuations Due to TEAEs | From first dose of study drug to End of Trial Visit (42 [± 3] days) | An adverse event (AE) is any untoward medical occurrence, which does not necessarily have to have a causal relationship with study treatment. An SAE is defined as any AE occurring at any dose that results in any of the following outcomes: death; life-threatening; hospitalization or prolongation of existing hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect; important medical events. TEAEs are defined as those AEs that started or worsened in severity after the initiation of study drug administration. AEs of clinical interest (AECI) included those related to bleeding and to hypotension. Study drug causality as assessed by the Investigator who was blinded to study drug assignment. |
| Number of Participants With Clinically Meaningful Postbaseline Laboratory Test Results | From first dose of study drug to End of Trial Visit (42 [± 3] days) | — |
| Number of Participants With Notable Changes in Postbaseline Blood Pressure and Heart Rate Values | From first dose of study drug to End of Trial Visit (42 [± 3] days) | Supine systolic blood pressure (SSBP): ≥ 180 mmHg and increase (↑) from baseline (BL) ≥ 30 mmHg; ≤ 90 mmHg and decrease (↓) from BL ≥ 30 mmHg. Supine diastolic blood pressure (SDBP): ≥ 105 mmHg and ↑ from BL ≥ 20 mmHg; ≤ 50 mmHg and ↓ from BL ≥ 20 mmHg. Supine heart rate (SHR): ≥ 110 bpm and ↑ from BL ≥ 20 bpm; ≤ 50 bpm and ↓ from BL ≥ 20 bpm. Standing systolic blood pressure (StSBP): ≥ 180 mmHg and increase (↑) from baseline (BL) ≥ 30 mmHg; ≤ 90 mmHg and decrease (↓) from BL ≥ 30 mmHg. Standing Diastolic Blood Pressure (StDBP): ≥ 105 mmHg and ↑ from BL ≥ 20 mmHg; ≤ 50 mmHg and ↓ from BL ≥ 20 mmHg. Standing heart rate (StHR): ≥ 110 bpm and ↑ from BL ≥ 20 bpm; ≤ 50 bpm and ↓ from BL ≥ 20 bpm. Orthostatic systolic blood pressure (SBP): ↓ \> 20 mmHg from supine to standing. Orthostatic diastolic blood pressure (DBP): ↓ \> 15 mmHg from supine to standing. Orthostatic HR: ↓ \> 30 bpm from supine to standing. |
| Number of Participants With Clinically Significant Post-Randomization Physical Examination Findings | Post-randomization to End of Trial Visit (42 [± 3] days) | Physical examinations included examination and assessment of the following: general appearance, lymph nodes, skin, cardiovascular system, head, eyes, ears, nose, and throat, central nervous system, respiratory system, neck, peripheral nervous system, abdomen/liver/spleen, musculoskeletal system. |
| Number of Participants With Clinically Significant Postbaseline 12-Lead Electrocardiogram (ECG) Results | From first dose of study drug to End of Trial Visit (42 [± 3] days) | — |
| Change From Study Baseline Over Time in Estimated Glomerular Filtration Rate (eGFR) | Study Baseline, Day 15/Discharge, Day 42/End of Trial | — |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Placebo oral tablet taken in AM and in PM on Days 1-14. | 6 |
| IW-1973 40 mg BID/QD IW-1973 20 mg oral tablet taken in AM and 20 mg oral tablet taken in PM on Days 1-7.
IW-1973 40 mg oral tablet taken QD in AM and placebo oral tablet taken QD in PM on Days 8-14. | 10 |
| IW-1973 40 mg QD/QD IW-1973 40 mg oral tablet taken QD in AM and placebo taken QD in PM on Days 1-14. | 10 |
| Total | 26 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | Placebo | IW-1973 40 mg BID/QD | IW-1973 40 mg QD/QD | Total |
|---|---|---|---|---|
| Age, Customized 40 to < 65 years old | 4 Participants | 6 Participants | 7 Participants | 17 Participants |
| Age, Customized >= 65 years old | 2 Participants | 4 Participants | 3 Participants | 9 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 5 Participants | 2 Participants | 3 Participants | 10 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 1 Participants | 8 Participants | 7 Participants | 16 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Percentage of Participants With Baseline Supine BP Less Than 130/80 mmHg | 33.3 percentage of participants | 80.0 percentage of participants | 60.0 percentage of participants | 70.0 percentage of participants |
| Race/Ethnicity, Customized Asian | 0 Participants | 1 Participants | 2 Participants | 3 Participants |
| Race/Ethnicity, Customized Black or African American | 0 Participants | 2 Participants | 1 Participants | 3 Participants |
| Race/Ethnicity, Customized White | 6 Participants | 7 Participants | 7 Participants | 20 Participants |
| Sex: Female, Male Female | 4 Participants | 4 Participants | 5 Participants | 13 Participants |
| Sex: Female, Male Male | 2 Participants | 6 Participants | 5 Participants | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 10 | 0 / 10 |
| other Total, other adverse events | 5 / 6 | 6 / 10 | 8 / 10 |
| serious Total, serious adverse events | 0 / 6 | 1 / 10 | 0 / 10 |
Outcome results
Primary
Change From Baseline in Reactive Hyperemia Index (RHI) on Day 13
RHI is a measure of the extent of vessel dilatation and augmentation in vascular blood flow after a prespecified period of flow interruption. RHI is determined as the ratio of the post-to-pre- occlusion peripheral arterial tonometry amplitude of the tested (occluded) arm, divided by the post to-pre-occlusion ratio of the control arm. RHI values \>1.67 indicate normal endothelial function, while values ≤1.67 indicate endothelial dysfunction.
Time frame: Baseline, Day 13 predose AM
Population: PD Population: all participants who received at least 1 dose of study drug and had at least 1 postdose PD assessment. Participants with an assessment.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Reactive Hyperemia Index (RHI) on Day 13 | Baseline | 2.327 ratio | Standard Error 1.118 |
| Placebo | Change From Baseline in Reactive Hyperemia Index (RHI) on Day 13 | Day 13 predose AM | 0.282 ratio | Standard Error 0.219 |
| IW-1973 40 mg BID/QD | Change From Baseline in Reactive Hyperemia Index (RHI) on Day 13 | Day 13 predose AM | -0.006 ratio | Standard Error 0.163 |
| IW-1973 40 mg BID/QD | Change From Baseline in Reactive Hyperemia Index (RHI) on Day 13 | Baseline | 1.918 ratio | Standard Error 0.587 |
| IW-1973 40 mg QD/QD | Change From Baseline in Reactive Hyperemia Index (RHI) on Day 13 | Baseline | 1.683 ratio | Standard Error 0.379 |
| IW-1973 40 mg QD/QD | Change From Baseline in Reactive Hyperemia Index (RHI) on Day 13 | Day 13 predose AM | 0.177 ratio | Standard Error 0.176 |
| IW-1973 40 mg Total Daily Dose (Overall) | Change From Baseline in Reactive Hyperemia Index (RHI) on Day 13 | Baseline | 1.807 ratio | Standard Error 0.501 |
| IW-1973 40 mg Total Daily Dose (Overall) | Change From Baseline in Reactive Hyperemia Index (RHI) on Day 13 | Day 13 predose AM | 0.086 ratio | Standard Error 0.12 |
95% CI: [-0.857, 0.282]
95% CI: [-0.708, 0.498]
95% CI: [-0.727, 0.335]
Primary
Change From Study Baseline Over Time in Estimated Glomerular Filtration Rate (eGFR)
Time frame: Study Baseline, Day 15/Discharge, Day 42/End of Trial
Population: Safety Population: participants who received at least 1 dose of study drug.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Study Baseline Over Time in Estimated Glomerular Filtration Rate (eGFR) | Day 15/Discharge | 0.158 mL/min/1.73m^2 | Standard Deviation 4.05 |
| Placebo | Change From Study Baseline Over Time in Estimated Glomerular Filtration Rate (eGFR) | Study Baseline | 103.045 mL/min/1.73m^2 | Standard Deviation 7.542 |
| Placebo | Change From Study Baseline Over Time in Estimated Glomerular Filtration Rate (eGFR) | Day 42/End of Trial | -3.727 mL/min/1.73m^2 | Standard Deviation 10.262 |
| IW-1973 40 mg BID/QD | Change From Study Baseline Over Time in Estimated Glomerular Filtration Rate (eGFR) | Day 15/Discharge | -2.232 mL/min/1.73m^2 | Standard Deviation 7.275 |
| IW-1973 40 mg BID/QD | Change From Study Baseline Over Time in Estimated Glomerular Filtration Rate (eGFR) | Study Baseline | 89.014 mL/min/1.73m^2 | Standard Deviation 19.729 |
| IW-1973 40 mg BID/QD | Change From Study Baseline Over Time in Estimated Glomerular Filtration Rate (eGFR) | Day 42/End of Trial | -8.905 mL/min/1.73m^2 | Standard Deviation 4.293 |
| IW-1973 40 mg QD/QD | Change From Study Baseline Over Time in Estimated Glomerular Filtration Rate (eGFR) | Study Baseline | 80.373 mL/min/1.73m^2 | Standard Deviation 19.716 |
| IW-1973 40 mg QD/QD | Change From Study Baseline Over Time in Estimated Glomerular Filtration Rate (eGFR) | Day 42/End of Trial | -5.587 mL/min/1.73m^2 | Standard Deviation 6.196 |
| IW-1973 40 mg QD/QD | Change From Study Baseline Over Time in Estimated Glomerular Filtration Rate (eGFR) | Day 15/Discharge | 1.663 mL/min/1.73m^2 | Standard Deviation 5.803 |
Primary
Change From Study Baseline Over Time in Platelet Function Assessments: ARU Assay
Aspirin irreversibly inhibits cyclooxygenase 1, which converts arachidonic acid to thromboxane A2, which in turn is involved in the activation of the GPIIb IIIa receptor necessary to initiate platelet aggregation. Impairment of platelet aggregation of the aspirin type is defined for the VerifyNow aspirin assay as values ≤ 549 ARU.
Time frame: Study Baseline (Day 1 predose), Day 8 (pre AM dose), Day 14 (pre AM dose)
Population: PD Population: all participants who received at least 1 dose of study drug and had at least 1 postdose PD assessment. Participants with a baseline (BL) and postbaseline (PBL) assessment at given time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Study Baseline Over Time in Platelet Function Assessments: ARU Assay | Change at Day 14 | 10.2 ARU | Standard Deviation 19.8 |
| Placebo | Change From Study Baseline Over Time in Platelet Function Assessments: ARU Assay | Change at Day 8 | -8.0 ARU | Standard Deviation 58.5 |
| Placebo | Change From Study Baseline Over Time in Platelet Function Assessments: ARU Assay | Study Baseline (Day 1 predose) | 571.4 ARU | Standard Deviation 82.5 |
| IW-1973 40 mg BID/QD | Change From Study Baseline Over Time in Platelet Function Assessments: ARU Assay | Change at Day 14 | 30.2 ARU | Standard Deviation 34.9 |
| IW-1973 40 mg BID/QD | Change From Study Baseline Over Time in Platelet Function Assessments: ARU Assay | Study Baseline (Day 1 predose) | 557.4 ARU | Standard Deviation 76.3 |
| IW-1973 40 mg BID/QD | Change From Study Baseline Over Time in Platelet Function Assessments: ARU Assay | Change at Day 8 | -16.2 ARU | Standard Deviation 50.9 |
| IW-1973 40 mg QD/QD | Change From Study Baseline Over Time in Platelet Function Assessments: ARU Assay | Change at Day 8 | 18.7 ARU | Standard Deviation 29.4 |
| IW-1973 40 mg QD/QD | Change From Study Baseline Over Time in Platelet Function Assessments: ARU Assay | Study Baseline (Day 1 predose) | 524.6 ARU | Standard Deviation 89.5 |
| IW-1973 40 mg QD/QD | Change From Study Baseline Over Time in Platelet Function Assessments: ARU Assay | Change at Day 14 | -11.7 ARU | Standard Deviation 34.9 |
Primary
Change From Study Baseline Over Time in Platelet Function Assessments: PRU Assay
The VerifyNow PRU assay measures effects on platelet activation caused by inhibition of the platelet receptor, P2Y12. This receptor is activated by adenosine 5'-diphosphate (ADP) in the cascade leading to platelet aggregation but can be blocked by P2Y12 inhibitor drugs, such as clopidogrel. Blockage of this receptor diminishes platelet activation and the ability of platelets to bind to fibrinogen. VerifyNow PRU assay values \<180 PRU indicate impairment of platelet aggregation.
Time frame: Study Baseline (Day 1 predose), Day 8 (predose AM), Day 14 (predose AM)
Population: PD Population: all participants who received at least 1 dose of study drug and had at least 1 postdose PD assessment. Participants with a baseline (BL) and postbaseline (PBL) assessment at given time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Study Baseline Over Time in Platelet Function Assessments: PRU Assay | Change at Day 8 | -9.4 PRU | Standard Deviation 47.8 |
| Placebo | Change From Study Baseline Over Time in Platelet Function Assessments: PRU Assay | Study Baseline (Day 1 predose) | 304.0 PRU | Standard Deviation 48.8 |
| Placebo | Change From Study Baseline Over Time in Platelet Function Assessments: PRU Assay | Change at Day 14 | -4.4 PRU | Standard Deviation 38.1 |
| IW-1973 40 mg BID/QD | Change From Study Baseline Over Time in Platelet Function Assessments: PRU Assay | Change at Day 8 | 8.2 PRU | Standard Deviation 31.4 |
| IW-1973 40 mg BID/QD | Change From Study Baseline Over Time in Platelet Function Assessments: PRU Assay | Study Baseline (Day 1 predose) | 283.6 PRU | Standard Deviation 43.1 |
| IW-1973 40 mg BID/QD | Change From Study Baseline Over Time in Platelet Function Assessments: PRU Assay | Change at Day 14 | 24.4 PRU | Standard Deviation 38.2 |
| IW-1973 40 mg QD/QD | Change From Study Baseline Over Time in Platelet Function Assessments: PRU Assay | Study Baseline (Day 1 predose) | 294.4 PRU | Standard Deviation 36.9 |
| IW-1973 40 mg QD/QD | Change From Study Baseline Over Time in Platelet Function Assessments: PRU Assay | Change at Day 14 | 8.5 PRU | Standard Deviation 24.5 |
| IW-1973 40 mg QD/QD | Change From Study Baseline Over Time in Platelet Function Assessments: PRU Assay | Change at Day 8 | -0.7 PRU | Standard Deviation 36.4 |
Primary
Change From Study Baseline Over Time in Supine Diastolic Blood Pressure
Time frame: Study Baseline (Day 1 predose AM); Days 2-14: predose AM; Days 1, 2, 7, 8, 13: postdose AM 1 hour and 4 hour; Day 1: postdose AM 8 hour; Days 1, 2, 8, 13: predose PM; Days 1, 2: postdose PM 1 hour; Days 2, 3: postdose PM 4 hour; Days 15, 21, 42
Population: PD Population: all participants who received at least 1 dose of study drug and had at least 1 postdose PD assessment.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Study Baseline Over Time in Supine Diastolic Blood Pressure | Day 3 predose AM | -0.8 mmHg | Standard Error 2.5 |
| Placebo | Change From Study Baseline Over Time in Supine Diastolic Blood Pressure | Day 21/Follow-Up | 0.1 mmHg | Standard Error 1.8 |
| Placebo | Change From Study Baseline Over Time in Supine Diastolic Blood Pressure | Day 9 predose AM | 0.6 mmHg | Standard Error 2.1 |
| Placebo | Change From Study Baseline Over Time in Supine Diastolic Blood Pressure | Day 3 postdose PM: 4 hour | -5.5 mmHg | Standard Error 3 |
| Placebo | Change From Study Baseline Over Time in Supine Diastolic Blood Pressure | Study Baseline (Day 1 predose AM) | 80.3 mmHg | Standard Error 6.9 |
| Placebo | Change From Study Baseline Over Time in Supine Diastolic Blood Pressure | Day 8 predose PM | -3.3 mmHg | Standard Error 2.9 |
| Placebo | Change From Study Baseline Over Time in Supine Diastolic Blood Pressure | Day 4 predose AM | 0.3 mmHg | Standard Error 2.2 |
| Placebo | Change From Study Baseline Over Time in Supine Diastolic Blood Pressure | Day 1 postdose PM: 1 hour | -0.9 mmHg | Standard Error 3.4 |
| Placebo | Change From Study Baseline Over Time in Supine Diastolic Blood Pressure | Day 8 postdose AM: 4 hour | -3.6 mmHg | Standard Error 2.8 |
| Placebo | Change From Study Baseline Over Time in Supine Diastolic Blood Pressure | Day 5 predose AM | 1.8 mmHg | Standard Error 2.2 |
| Placebo | Change From Study Baseline Over Time in Supine Diastolic Blood Pressure | Day 1 postdose AM: 4 hour | -0.3 mmHg | Standard Error 2.4 |
| Placebo | Change From Study Baseline Over Time in Supine Diastolic Blood Pressure | Day 8 postdose AM: 1 hour | 0 mmHg | Standard Error 2.4 |
| Placebo | Change From Study Baseline Over Time in Supine Diastolic Blood Pressure | Day 6 predose AM | -0.5 mmHg | Standard Error 1.9 |
| Placebo | Change From Study Baseline Over Time in Supine Diastolic Blood Pressure | Day 13 predose PM | 0.1 mmHg | Standard Error 2.7 |
| Placebo | Change From Study Baseline Over Time in Supine Diastolic Blood Pressure | Day 8 predose AM | 0.6 mmHg | Standard Error 2.7 |
| Placebo | Change From Study Baseline Over Time in Supine Diastolic Blood Pressure | Day 7 predose AM | 0.9 mmHg | Standard Error 2.9 |
| Placebo | Change From Study Baseline Over Time in Supine Diastolic Blood Pressure | Day 2 predose AM | 3.1 mmHg | Standard Error 2 |
| Placebo | Change From Study Baseline Over Time in Supine Diastolic Blood Pressure | Day 7 postdose AM: 4 hour | -6.1 mmHg | Standard Error 3.5 |
| Placebo | Change From Study Baseline Over Time in Supine Diastolic Blood Pressure | Day 7 postdose AM: 1 hour | -1.7 mmHg | Standard Error 2.4 |
| Placebo | Change From Study Baseline Over Time in Supine Diastolic Blood Pressure | Day 1 postdose AM: 1 hour | -3.1 mmHg | Standard Error 2.4 |
| Placebo | Change From Study Baseline Over Time in Supine Diastolic Blood Pressure | Day 13 postdose AM: 4 hour | -2.5 mmHg | Standard Error 2.9 |
| Placebo | Change From Study Baseline Over Time in Supine Diastolic Blood Pressure | Day 2 postdose AM: 1 hour | -1.4 mmHg | Standard Error 2.4 |
| Placebo | Change From Study Baseline Over Time in Supine Diastolic Blood Pressure | Day 15/Discharge | -0.9 mmHg | Standard Error 2.4 |
| Placebo | Change From Study Baseline Over Time in Supine Diastolic Blood Pressure | Day 13 postdose AM: 1 hour | -2.0 mmHg | Standard Error 2.1 |
| Placebo | Change From Study Baseline Over Time in Supine Diastolic Blood Pressure | Day 2 postdose AM: 4 hour | 2.2 mmHg | Standard Error 3.4 |
| Placebo | Change From Study Baseline Over Time in Supine Diastolic Blood Pressure | Day 1 postdose AM: 8 hour | 0.9 mmHg | Standard Error 2.3 |
| Placebo | Change From Study Baseline Over Time in Supine Diastolic Blood Pressure | Day 13 predose AM | 0.1 mmHg | Standard Error 2.2 |
| Placebo | Change From Study Baseline Over Time in Supine Diastolic Blood Pressure | Day 2 predose PM | 1.9 mmHg | Standard Error 2.3 |
| Placebo | Change From Study Baseline Over Time in Supine Diastolic Blood Pressure | Day 42/End of Trial | 0.7 mmHg | Standard Error 3.3 |
| Placebo | Change From Study Baseline Over Time in Supine Diastolic Blood Pressure | Day 12 predose AM | -1.1 mmHg | Standard Error 2 |
| Placebo | Change From Study Baseline Over Time in Supine Diastolic Blood Pressure | Day 2 postdose PM: 1 hour | -2.2 mmHg | Standard Error 2.6 |
| Placebo | Change From Study Baseline Over Time in Supine Diastolic Blood Pressure | Day 14 predose AM | -4.4 mmHg | Standard Error 3.1 |
| Placebo | Change From Study Baseline Over Time in Supine Diastolic Blood Pressure | Day 11 predose AM | 2.2 mmHg | Standard Error 2.5 |
| Placebo | Change From Study Baseline Over Time in Supine Diastolic Blood Pressure | Day 2 postdose PM: 4 hour | -3.9 mmHg | Standard Error 2.7 |
| Placebo | Change From Study Baseline Over Time in Supine Diastolic Blood Pressure | Day 1 predose PM | -1.3 mmHg | Standard Error 2.2 |
| Placebo | Change From Study Baseline Over Time in Supine Diastolic Blood Pressure | Day 10 predose AM | 0.1 mmHg | Standard Error 2.4 |
| IW-1973 40 mg BID/QD | Change From Study Baseline Over Time in Supine Diastolic Blood Pressure | Day 13 predose PM | -7.8 mmHg | Standard Error 2 |
| IW-1973 40 mg BID/QD | Change From Study Baseline Over Time in Supine Diastolic Blood Pressure | Study Baseline (Day 1 predose AM) | 75.5 mmHg | Standard Error 4.4 |
| IW-1973 40 mg BID/QD | Change From Study Baseline Over Time in Supine Diastolic Blood Pressure | Day 1 postdose AM: 1 hour | -5.7 mmHg | Standard Error 1.8 |
| IW-1973 40 mg BID/QD | Change From Study Baseline Over Time in Supine Diastolic Blood Pressure | Day 1 postdose AM: 4 hour | -3.2 mmHg | Standard Error 1.8 |
| IW-1973 40 mg BID/QD | Change From Study Baseline Over Time in Supine Diastolic Blood Pressure | Day 1 postdose AM: 8 hour | -4.6 mmHg | Standard Error 1.7 |
| IW-1973 40 mg BID/QD | Change From Study Baseline Over Time in Supine Diastolic Blood Pressure | Day 1 predose PM | -4.9 mmHg | Standard Error 1.6 |
| IW-1973 40 mg BID/QD | Change From Study Baseline Over Time in Supine Diastolic Blood Pressure | Day 1 postdose PM: 1 hour | -5.9 mmHg | Standard Error 2.5 |
| IW-1973 40 mg BID/QD | Change From Study Baseline Over Time in Supine Diastolic Blood Pressure | Day 2 predose AM | -1.3 mmHg | Standard Error 1.5 |
| IW-1973 40 mg BID/QD | Change From Study Baseline Over Time in Supine Diastolic Blood Pressure | Day 2 postdose AM: 1 hour | -8.1 mmHg | Standard Error 1.8 |
| IW-1973 40 mg BID/QD | Change From Study Baseline Over Time in Supine Diastolic Blood Pressure | Day 2 postdose AM: 4 hour | -3.1 mmHg | Standard Error 2.5 |
| IW-1973 40 mg BID/QD | Change From Study Baseline Over Time in Supine Diastolic Blood Pressure | Day 2 predose PM | -3.7 mmHg | Standard Error 1.7 |
| IW-1973 40 mg BID/QD | Change From Study Baseline Over Time in Supine Diastolic Blood Pressure | Day 2 postdose PM: 1 hour | -2.7 mmHg | Standard Error 1.9 |
| IW-1973 40 mg BID/QD | Change From Study Baseline Over Time in Supine Diastolic Blood Pressure | Day 2 postdose PM: 4 hour | -6.3 mmHg | Standard Error 2 |
| IW-1973 40 mg BID/QD | Change From Study Baseline Over Time in Supine Diastolic Blood Pressure | Day 3 predose AM | -0.6 mmHg | Standard Error 1.8 |
| IW-1973 40 mg BID/QD | Change From Study Baseline Over Time in Supine Diastolic Blood Pressure | Day 3 postdose PM: 4 hour | -4.0 mmHg | Standard Error 2.2 |
| IW-1973 40 mg BID/QD | Change From Study Baseline Over Time in Supine Diastolic Blood Pressure | Day 4 predose AM | -4.0 mmHg | Standard Error 1.6 |
| IW-1973 40 mg BID/QD | Change From Study Baseline Over Time in Supine Diastolic Blood Pressure | Day 5 predose AM | -0.6 mmHg | Standard Error 1.6 |
| IW-1973 40 mg BID/QD | Change From Study Baseline Over Time in Supine Diastolic Blood Pressure | Day 6 predose AM | -3.3 mmHg | Standard Error 1.4 |
| IW-1973 40 mg BID/QD | Change From Study Baseline Over Time in Supine Diastolic Blood Pressure | Day 7 predose AM | -3.2 mmHg | Standard Error 2.1 |
| IW-1973 40 mg BID/QD | Change From Study Baseline Over Time in Supine Diastolic Blood Pressure | Day 7 postdose AM: 1 hour | -6.0 mmHg | Standard Error 1.8 |
| IW-1973 40 mg BID/QD | Change From Study Baseline Over Time in Supine Diastolic Blood Pressure | Day 7 postdose AM: 4 hour | -5.1 mmHg | Standard Error 2.6 |
| IW-1973 40 mg BID/QD | Change From Study Baseline Over Time in Supine Diastolic Blood Pressure | Day 8 predose AM | -3.9 mmHg | Standard Error 1.9 |
| IW-1973 40 mg BID/QD | Change From Study Baseline Over Time in Supine Diastolic Blood Pressure | Day 8 postdose AM: 1 hour | -9.3 mmHg | Standard Error 1.8 |
| IW-1973 40 mg BID/QD | Change From Study Baseline Over Time in Supine Diastolic Blood Pressure | Day 8 postdose AM: 4 hour | -8.9 mmHg | Standard Error 2 |
| IW-1973 40 mg BID/QD | Change From Study Baseline Over Time in Supine Diastolic Blood Pressure | Day 8 predose PM | -4.1 mmHg | Standard Error 2.1 |
| IW-1973 40 mg BID/QD | Change From Study Baseline Over Time in Supine Diastolic Blood Pressure | Day 9 predose AM | -4.3 mmHg | Standard Error 1.5 |
| IW-1973 40 mg BID/QD | Change From Study Baseline Over Time in Supine Diastolic Blood Pressure | Day 10 predose AM | -3.7 mmHg | Standard Error 1.7 |
| IW-1973 40 mg BID/QD | Change From Study Baseline Over Time in Supine Diastolic Blood Pressure | Day 11 predose AM | -6.4 mmHg | Standard Error 1.8 |
| IW-1973 40 mg BID/QD | Change From Study Baseline Over Time in Supine Diastolic Blood Pressure | Day 12 predose AM | -3.5 mmHg | Standard Error 1.5 |
| IW-1973 40 mg BID/QD | Change From Study Baseline Over Time in Supine Diastolic Blood Pressure | Day 13 predose AM | -4.8 mmHg | Standard Error 1.6 |
| IW-1973 40 mg BID/QD | Change From Study Baseline Over Time in Supine Diastolic Blood Pressure | Day 13 postdose AM: 1 hour | -11.0 mmHg | Standard Error 1.6 |
| IW-1973 40 mg BID/QD | Change From Study Baseline Over Time in Supine Diastolic Blood Pressure | Day 13 postdose AM: 4 hour | -8.6 mmHg | Standard Error 2.1 |
| IW-1973 40 mg BID/QD | Change From Study Baseline Over Time in Supine Diastolic Blood Pressure | Day 14 predose AM | -6.1 mmHg | Standard Error 2.3 |
| IW-1973 40 mg BID/QD | Change From Study Baseline Over Time in Supine Diastolic Blood Pressure | Day 15/Discharge | -3.5 mmHg | Standard Error 1.8 |
| IW-1973 40 mg BID/QD | Change From Study Baseline Over Time in Supine Diastolic Blood Pressure | Day 21/Follow-Up | -0.7 mmHg | Standard Error 1.3 |
| IW-1973 40 mg BID/QD | Change From Study Baseline Over Time in Supine Diastolic Blood Pressure | Day 42/End of Trial | 2.8 mmHg | Standard Error 2.4 |
| IW-1973 40 mg QD/QD | Change From Study Baseline Over Time in Supine Diastolic Blood Pressure | Day 3 predose AM | -0.5 mmHg | Standard Error 1.8 |
| IW-1973 40 mg QD/QD | Change From Study Baseline Over Time in Supine Diastolic Blood Pressure | Day 21/Follow-Up | 0.3 mmHg | Standard Error 1.3 |
| IW-1973 40 mg QD/QD | Change From Study Baseline Over Time in Supine Diastolic Blood Pressure | Day 9 predose AM | -1.6 mmHg | Standard Error 1.5 |
| IW-1973 40 mg QD/QD | Change From Study Baseline Over Time in Supine Diastolic Blood Pressure | Day 2 postdose PM: 4 hour | -5.4 mmHg | Standard Error 2 |
| IW-1973 40 mg QD/QD | Change From Study Baseline Over Time in Supine Diastolic Blood Pressure | Day 14 predose AM | -4.1 mmHg | Standard Error 2.3 |
| IW-1973 40 mg QD/QD | Change From Study Baseline Over Time in Supine Diastolic Blood Pressure | Day 10 predose AM | -5.0 mmHg | Standard Error 1.8 |
| IW-1973 40 mg QD/QD | Change From Study Baseline Over Time in Supine Diastolic Blood Pressure | Day 2 postdose PM: 1 hour | -4.4 mmHg | Standard Error 1.9 |
| IW-1973 40 mg QD/QD | Change From Study Baseline Over Time in Supine Diastolic Blood Pressure | Day 1 postdose AM: 4 hour | -7.4 mmHg | Standard Error 1.8 |
| IW-1973 40 mg QD/QD | Change From Study Baseline Over Time in Supine Diastolic Blood Pressure | Day 11 predose AM | -3.1 mmHg | Standard Error 1.9 |
| IW-1973 40 mg QD/QD | Change From Study Baseline Over Time in Supine Diastolic Blood Pressure | Day 2 predose PM | -2.6 mmHg | Standard Error 1.7 |
| IW-1973 40 mg QD/QD | Change From Study Baseline Over Time in Supine Diastolic Blood Pressure | Study Baseline (Day 1 predose AM) | 74.8 mmHg | Standard Error 5.9 |
| IW-1973 40 mg QD/QD | Change From Study Baseline Over Time in Supine Diastolic Blood Pressure | Day 12 predose AM | -5.6 mmHg | Standard Error 1.5 |
| IW-1973 40 mg QD/QD | Change From Study Baseline Over Time in Supine Diastolic Blood Pressure | Day 2 postdose AM: 4 hour | -6.2 mmHg | Standard Error 2.5 |
| IW-1973 40 mg QD/QD | Change From Study Baseline Over Time in Supine Diastolic Blood Pressure | Day 15/Discharge | -1.6 mmHg | Standard Error 1.8 |
| IW-1973 40 mg QD/QD | Change From Study Baseline Over Time in Supine Diastolic Blood Pressure | Day 13 predose AM | -4.4 mmHg | Standard Error 1.6 |
| IW-1973 40 mg QD/QD | Change From Study Baseline Over Time in Supine Diastolic Blood Pressure | Day 2 postdose AM: 1 hour | -6.7 mmHg | Standard Error 1.8 |
| IW-1973 40 mg QD/QD | Change From Study Baseline Over Time in Supine Diastolic Blood Pressure | Day 1 postdose AM: 1 hour | -5.1 mmHg | Standard Error 1.8 |
| IW-1973 40 mg QD/QD | Change From Study Baseline Over Time in Supine Diastolic Blood Pressure | Day 13 postdose AM: 1 hour | -10.5 mmHg | Standard Error 1.6 |
| IW-1973 40 mg QD/QD | Change From Study Baseline Over Time in Supine Diastolic Blood Pressure | Day 2 predose AM | 0 mmHg | Standard Error 1.5 |
| IW-1973 40 mg QD/QD | Change From Study Baseline Over Time in Supine Diastolic Blood Pressure | Day 42/End of Trial | 1.5 mmHg | Standard Error 2.4 |
| IW-1973 40 mg QD/QD | Change From Study Baseline Over Time in Supine Diastolic Blood Pressure | Day 7 postdose AM: 1 hour | -7.4 mmHg | Standard Error 1.8 |
| IW-1973 40 mg QD/QD | Change From Study Baseline Over Time in Supine Diastolic Blood Pressure | Day 7 predose AM | -3.4 mmHg | Standard Error 2.1 |
| IW-1973 40 mg QD/QD | Change From Study Baseline Over Time in Supine Diastolic Blood Pressure | Day 13 postdose AM: 4 hour | -9.0 mmHg | Standard Error 2.2 |
| IW-1973 40 mg QD/QD | Change From Study Baseline Over Time in Supine Diastolic Blood Pressure | Day 7 postdose AM: 4 hour | -5.9 mmHg | Standard Error 2.6 |
| IW-1973 40 mg QD/QD | Change From Study Baseline Over Time in Supine Diastolic Blood Pressure | Day 6 predose AM | -5.2 mmHg | Standard Error 1.4 |
| IW-1973 40 mg QD/QD | Change From Study Baseline Over Time in Supine Diastolic Blood Pressure | Day 1 postdose PM: 1 hour | -3.7 mmHg | Standard Error 2.5 |
| IW-1973 40 mg QD/QD | Change From Study Baseline Over Time in Supine Diastolic Blood Pressure | Day 8 predose AM | -2.2 mmHg | Standard Error 2 |
| IW-1973 40 mg QD/QD | Change From Study Baseline Over Time in Supine Diastolic Blood Pressure | Day 5 predose AM | -5.3 mmHg | Standard Error 1.6 |
| IW-1973 40 mg QD/QD | Change From Study Baseline Over Time in Supine Diastolic Blood Pressure | Day 1 predose PM | -3.5 mmHg | Standard Error 1.6 |
| IW-1973 40 mg QD/QD | Change From Study Baseline Over Time in Supine Diastolic Blood Pressure | Day 8 postdose AM: 1 hour | -8.3 mmHg | Standard Error 1.8 |
| IW-1973 40 mg QD/QD | Change From Study Baseline Over Time in Supine Diastolic Blood Pressure | Day 4 predose AM | -4.2 mmHg | Standard Error 1.6 |
| IW-1973 40 mg QD/QD | Change From Study Baseline Over Time in Supine Diastolic Blood Pressure | Day 13 predose PM | -7.0 mmHg | Standard Error 2 |
| IW-1973 40 mg QD/QD | Change From Study Baseline Over Time in Supine Diastolic Blood Pressure | Day 8 postdose AM: 4 hour | -4.9 mmHg | Standard Error 2.1 |
| IW-1973 40 mg QD/QD | Change From Study Baseline Over Time in Supine Diastolic Blood Pressure | Day 3 postdose PM: 4 hour | -6.7 mmHg | Standard Error 2.2 |
| IW-1973 40 mg QD/QD | Change From Study Baseline Over Time in Supine Diastolic Blood Pressure | Day 1 postdose AM: 8 hour | -3.7 mmHg | Standard Error 1.7 |
| IW-1973 40 mg QD/QD | Change From Study Baseline Over Time in Supine Diastolic Blood Pressure | Day 8 predose PM | -3.0 mmHg | Standard Error 2.1 |
Comparison: Day 1, post-dose AM 1 hour95% CI: [-8.9, 3.8]
Comparison: Day 1, post-dose AM 1 hour95% CI: [-8.4, 4.5]
Comparison: Day 1, post-dose AM 4 hour95% CI: [-9.2, 3.4]
Comparison: Day 1, post-dose AM 4 hour95% CI: [-13.5, -0.6]
Comparison: Day 1, post-dose AM 8 hour95% CI: [-11.5, 0.6]
Comparison: Day 1, post-dose AM 8 hour95% CI: [-10.8, 1.5]
Comparison: Day 1, pre-dose PM95% CI: [-9.4, 2.2]
Comparison: Day 1, pre-dose PM95% CI: [-8, 3.7]
Comparison: Day 1, post-dose PM 1 hour95% CI: [-13.8, 3.9]
Comparison: Day 1, post-dose PM 1 hour95% CI: [-11.7, 6.2]
Comparison: Day 2, pre-dose AM95% CI: [-9.7, 0.9]
Comparison: Day 2, pre-dose AM95% CI: [-8.5, 2.2]
Comparison: Day 2, post-dose AM 1 hour95% CI: [-13.1, -0.3]
Comparison: Day 2, post-dose AM 1 hour95% CI: [-11.8, 1.2]
Comparison: Day 2, post-dose AM 4 hour95% CI: [-14.2, 3.5]
Comparison: Day 2, post-dose AM 4 hour95% CI: [-17.5, 0.5]
Comparison: Day 2, pre-dose PM95% CI: [-11.6, 0.2]
Comparison: Day 2, pre-dose PM95% CI: [-10.6, 1.5]
Comparison: Day 2, post-dose PM 1 hour95% CI: [-7.4, 6.4]
Comparison: Day 2, post-dose PM 1 hour95% CI: [-9.3, 4.7]
Comparison: Day 2, post-dose PM 4 hour95% CI: [-9.4, 4.6]
Comparison: Day 2, post-dose PM 4 hour95% CI: [-8.7, 5.6]
Comparison: Day 3, pre-dose AM95% CI: [-6.2, 6.7]
Comparison: Day 3, pre-dose AM95% CI: [-6.2, 6.8]
Comparison: Day 3, post-dose PM 4 hour95% CI: [-6.4, 9.4]
Comparison: Day 3, post-dose PM 4 hour95% CI: [-9.3, 6.8]
Comparison: Day 4, pre-dose AM95% CI: [-10, 1.4]
Comparison: Day 4, pre-dose AM95% CI: [-10.3, 1.3]
Comparison: Day 5, pre-dose AM95% CI: [-8.2, 3.3]
Comparison: Day 5, pre-dose AM95% CI: [-13, -1.3]
Comparison: Day 6, pre-dose AM95% CI: [-7.7, 2.2]
Comparison: Day 6, pre-dose AM95% CI: [-9.7, 0.3]
Comparison: Day 7, pre-dose AM95% CI: [-11.6, 3.5]
Comparison: Day 7, pre-dose AM95% CI: [-12, 3.3]
Comparison: Day 7, post-dose AM 1 hour95% CI: [-10.6, 1.9]
Comparison: Day 7, post-dose AM 1 hour95% CI: [-12, 0.7]
Comparison: Day 7, post-dose AM 4 hour95% CI: [-8.3, 10.3]
Comparison: Day 7, post-dose AM 4 hour95% CI: [-9.2, 9.7]
Comparison: Day 8, pre-dose AM95% CI: [-11.5, 2.3]
Comparison: Day 8, pre-dose AM95% CI: [-9.9, 4.2]
Comparison: Day 8, post-dose AM 1 hour95% CI: [-15.5, -3]
Comparison: Day 8, post-dose AM 1 hour95% CI: [-14.6, -1.9]
Comparison: Day 8, post-dose AM 4 hour95% CI: [-12.6, 2]
Comparison: Day 8, post-dose AM 4 hour95% CI: [-8.7, 6.1]
Comparison: Day 8, pre-dose PM95% CI: [-8.2, 6.7]
Comparison: Day 8, pre-dose PM95% CI: [-7.3, 7.9]
Comparison: Day 9, pre-dose AM95% CI: [-10.3, 0.6]
Comparison: Day 9, pre-dose AM95% CI: [-7.7, 3.4]
Comparison: Day 10, pre-dose95% CI: [-10, 2.3]
Comparison: Day 10, pre-dose AM95% CI: [-11.4, 1.2]
Comparison: Day 11, pre-dose AM95% CI: [-15.2, -2.2]
Comparison: Day 11, pre-dose AM95% CI: [-12, 1.3]
Comparison: Day 12, pre-dose AM95% CI: [-7.6, 2.8]
Comparison: Day 12, pre-dose AM95% CI: [-9.7, 0.8]
Comparison: Day 13, pre-dose AM95% CI: [-10.7, 0.8]
Comparison: Day 13, pre-dose AM95% CI: [-10.4, 1.3]
Comparison: Day 13, post-dose AM 1 hour95% CI: [-14.6, -3.4]
Comparison: Day 13, post-dose AM 1 hour95% CI: [-14.2, -2.8]
Comparison: Day 13, post-dose AM 4 hour95% CI: [-13.8, 1.5]
Comparison: Day 13, post-dose AM 4 hour95% CI: [-14.3, 1.2]
Comparison: Day 13, pre-dose PM95% CI: [-15, -1]
Comparison: Day 13, pre-dose PM95% CI: [-14.2, 0]
Comparison: Day 14, pre-dose AM95% CI: [-9.8, 6.4]
Comparison: Day 14, pre-dose AM95% CI: [-8, 8.5]
Comparison: Day 15, Discharge95% CI: [-9, 3.7]
Comparison: Day 15, Discharge95% CI: [-7.1, 5.8]
Comparison: Day 21, Follow-up95% CI: [-5.5, 3.9]
Comparison: Day 21, Follow-up95% CI: [-4.6, 4.9]
Comparison: Day 42, End of trial95% CI: [-6.5, 10.7]
Comparison: Day 42, End of trial95% CI: [-7.9, 9.6]
Primary
Change From Study Baseline Over Time in Supine Pulse
Time frame: Study Baseline (Day 1 predose AM); Days 2-14: predose AM; Days 1, 2, 7, 8, 13: postdose AM 1 hour and 4 hour; Day 1: postdose AM 8 hour; Days 1, 2, 8, 13: predose PM; Days 1, 2: postdose PM 1 hour; Days 2, 3: postdose PM 4 hour; Days 15, 21, 42
Population: PD Population: all participants who received at least 1 dose of study drug and had at least 1 postdose PD assessment.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Study Baseline Over Time in Supine Pulse | Day 3 predose AM | 0.2 bpm | Standard Error 2.3 |
| Placebo | Change From Study Baseline Over Time in Supine Pulse | Day 21/Follow-Up | -1.3 bpm | Standard Error 4.1 |
| Placebo | Change From Study Baseline Over Time in Supine Pulse | Day 9 predose AM | -1.8 bpm | Standard Error 2.9 |
| Placebo | Change From Study Baseline Over Time in Supine Pulse | Day 3 postdose PM: 4 hour | 3.0 bpm | Standard Error 2.9 |
| Placebo | Change From Study Baseline Over Time in Supine Pulse | Study Baseline (Day 1 predose AM) | 70.3 bpm | Standard Error 13.7 |
| Placebo | Change From Study Baseline Over Time in Supine Pulse | Day 8 predose PM | 2.7 bpm | Standard Error 3.2 |
| Placebo | Change From Study Baseline Over Time in Supine Pulse | Day 4 predose AM | -4.1 bpm | Standard Error 2.6 |
| Placebo | Change From Study Baseline Over Time in Supine Pulse | Day 1 postdose PM: 1 hour | 2.3 bpm | Standard Error 2.8 |
| Placebo | Change From Study Baseline Over Time in Supine Pulse | Day 8 postdose AM: 4 hour | -0.6 bpm | Standard Error 3 |
| Placebo | Change From Study Baseline Over Time in Supine Pulse | Day 5 predose AM | -3.3 bpm | Standard Error 2.3 |
| Placebo | Change From Study Baseline Over Time in Supine Pulse | Day 1 postdose AM: 4 hour | 4.3 bpm | Standard Error 3.4 |
| Placebo | Change From Study Baseline Over Time in Supine Pulse | Day 8 postdose AM: 1 hour | 2.7 bpm | Standard Error 3.8 |
| Placebo | Change From Study Baseline Over Time in Supine Pulse | Day 6 predose AM | -0.8 bpm | Standard Error 2.9 |
| Placebo | Change From Study Baseline Over Time in Supine Pulse | Day 13 predose PM | 5.0 bpm | Standard Error 3 |
| Placebo | Change From Study Baseline Over Time in Supine Pulse | Day 8 predose AM | -2.8 bpm | Standard Error 2.6 |
| Placebo | Change From Study Baseline Over Time in Supine Pulse | Day 7 predose AM | -4.0 bpm | Standard Error 2.5 |
| Placebo | Change From Study Baseline Over Time in Supine Pulse | Day 2 predose AM | -2.6 bpm | Standard Error 2.3 |
| Placebo | Change From Study Baseline Over Time in Supine Pulse | Day 7 postdose AM: 4 hour | -2.6 bpm | Standard Error 2.6 |
| Placebo | Change From Study Baseline Over Time in Supine Pulse | Day 7 postdose AM: 1 hour | 0.2 bpm | Standard Error 4.2 |
| Placebo | Change From Study Baseline Over Time in Supine Pulse | Day 1 postdose AM: 1 hour | 1.0 bpm | Standard Error 4.1 |
| Placebo | Change From Study Baseline Over Time in Supine Pulse | Day 13 postdose AM: 4 hour | -0.8 bpm | Standard Error 2.5 |
| Placebo | Change From Study Baseline Over Time in Supine Pulse | Day 2 postdose AM: 1 hour | 7.0 bpm | Standard Error 4.1 |
| Placebo | Change From Study Baseline Over Time in Supine Pulse | Day 15/Discharge | 1.1 bpm | Standard Error 2.9 |
| Placebo | Change From Study Baseline Over Time in Supine Pulse | Day 13 postdose AM: 1 hour | 0.3 bpm | Standard Error 3.2 |
| Placebo | Change From Study Baseline Over Time in Supine Pulse | Day 2 postdose AM: 4 hour | 3.2 bpm | Standard Error 3 |
| Placebo | Change From Study Baseline Over Time in Supine Pulse | Day 1 postdose AM: 8 hour | 2.8 bpm | Standard Error 2.8 |
| Placebo | Change From Study Baseline Over Time in Supine Pulse | Day 13 predose AM | -0.2 bpm | Standard Error 3.6 |
| Placebo | Change From Study Baseline Over Time in Supine Pulse | Day 2 predose PM | 7.9 bpm | Standard Error 2.7 |
| Placebo | Change From Study Baseline Over Time in Supine Pulse | Day 42/End of Trial | 0.4 bpm | Standard Error 3.6 |
| Placebo | Change From Study Baseline Over Time in Supine Pulse | Day 12 predose AM | -0.6 bpm | Standard Error 4 |
| Placebo | Change From Study Baseline Over Time in Supine Pulse | Day 2 postdose PM: 1 hour | 7.2 bpm | Standard Error 3.6 |
| Placebo | Change From Study Baseline Over Time in Supine Pulse | Day 14 predose AM | -3.1 bpm | Standard Error 3 |
| Placebo | Change From Study Baseline Over Time in Supine Pulse | Day 11 predose AM | 2.2 bpm | Standard Error 3.6 |
| Placebo | Change From Study Baseline Over Time in Supine Pulse | Day 2 postdose PM: 4 hour | 1.9 bpm | Standard Error 2.4 |
| Placebo | Change From Study Baseline Over Time in Supine Pulse | Day 1 predose PM | 0 bpm | Standard Error 2.7 |
| Placebo | Change From Study Baseline Over Time in Supine Pulse | Day 10 predose AM | -3.0 bpm | Standard Error 3.2 |
| IW-1973 40 mg BID/QD | Change From Study Baseline Over Time in Supine Pulse | Day 13 predose PM | 4.5 bpm | Standard Error 2.3 |
| IW-1973 40 mg BID/QD | Change From Study Baseline Over Time in Supine Pulse | Study Baseline (Day 1 predose AM) | 70.3 bpm | Standard Error 10.9 |
| IW-1973 40 mg BID/QD | Change From Study Baseline Over Time in Supine Pulse | Day 1 postdose AM: 1 hour | 7.2 bpm | Standard Error 3.1 |
| IW-1973 40 mg BID/QD | Change From Study Baseline Over Time in Supine Pulse | Day 1 postdose AM: 4 hour | 4.3 bpm | Standard Error 2.7 |
| IW-1973 40 mg BID/QD | Change From Study Baseline Over Time in Supine Pulse | Day 1 postdose AM: 8 hour | 2.6 bpm | Standard Error 2.2 |
| IW-1973 40 mg BID/QD | Change From Study Baseline Over Time in Supine Pulse | Day 1 predose PM | 5.1 bpm | Standard Error 2.1 |
| IW-1973 40 mg BID/QD | Change From Study Baseline Over Time in Supine Pulse | Day 1 postdose PM: 1 hour | 4.6 bpm | Standard Error 2.2 |
| IW-1973 40 mg BID/QD | Change From Study Baseline Over Time in Supine Pulse | Day 2 predose AM | -1.7 bpm | Standard Error 1.8 |
| IW-1973 40 mg BID/QD | Change From Study Baseline Over Time in Supine Pulse | Day 2 postdose AM: 1 hour | 9.5 bpm | Standard Error 3.1 |
| IW-1973 40 mg BID/QD | Change From Study Baseline Over Time in Supine Pulse | Day 2 postdose AM: 4 hour | 6.5 bpm | Standard Error 2.3 |
| IW-1973 40 mg BID/QD | Change From Study Baseline Over Time in Supine Pulse | Day 2 predose PM | 6.5 bpm | Standard Error 2.1 |
| IW-1973 40 mg BID/QD | Change From Study Baseline Over Time in Supine Pulse | Day 2 postdose PM: 1 hour | 7.3 bpm | Standard Error 2.8 |
| IW-1973 40 mg BID/QD | Change From Study Baseline Over Time in Supine Pulse | Day 2 postdose PM: 4 hour | 3.0 bpm | Standard Error 1.8 |
| IW-1973 40 mg BID/QD | Change From Study Baseline Over Time in Supine Pulse | Day 3 predose AM | -1.2 bpm | Standard Error 1.8 |
| IW-1973 40 mg BID/QD | Change From Study Baseline Over Time in Supine Pulse | Day 3 postdose PM: 4 hour | 0.7 bpm | Standard Error 2.2 |
| IW-1973 40 mg BID/QD | Change From Study Baseline Over Time in Supine Pulse | Day 4 predose AM | 2.8 bpm | Standard Error 2 |
| IW-1973 40 mg BID/QD | Change From Study Baseline Over Time in Supine Pulse | Day 5 predose AM | -0.4 bpm | Standard Error 1.8 |
| IW-1973 40 mg BID/QD | Change From Study Baseline Over Time in Supine Pulse | Day 6 predose AM | 1.5 bpm | Standard Error 2.3 |
| IW-1973 40 mg BID/QD | Change From Study Baseline Over Time in Supine Pulse | Day 7 predose AM | 1.1 bpm | Standard Error 2 |
| IW-1973 40 mg BID/QD | Change From Study Baseline Over Time in Supine Pulse | Day 7 postdose AM: 1 hour | 9.5 bpm | Standard Error 3.2 |
| IW-1973 40 mg BID/QD | Change From Study Baseline Over Time in Supine Pulse | Day 7 postdose AM: 4 hour | 4.4 bpm | Standard Error 2 |
| IW-1973 40 mg BID/QD | Change From Study Baseline Over Time in Supine Pulse | Day 8 predose AM | -0.9 bpm | Standard Error 2 |
| IW-1973 40 mg BID/QD | Change From Study Baseline Over Time in Supine Pulse | Day 8 postdose AM: 1 hour | 12.4 bpm | Standard Error 2.9 |
| IW-1973 40 mg BID/QD | Change From Study Baseline Over Time in Supine Pulse | Day 8 postdose AM: 4 hour | 7.1 bpm | Standard Error 2.3 |
| IW-1973 40 mg BID/QD | Change From Study Baseline Over Time in Supine Pulse | Day 8 predose PM | 6.0 bpm | Standard Error 2.5 |
| IW-1973 40 mg BID/QD | Change From Study Baseline Over Time in Supine Pulse | Day 9 predose AM | -0.3 bpm | Standard Error 2.3 |
| IW-1973 40 mg BID/QD | Change From Study Baseline Over Time in Supine Pulse | Day 10 predose AM | 1.3 bpm | Standard Error 2.4 |
| IW-1973 40 mg BID/QD | Change From Study Baseline Over Time in Supine Pulse | Day 11 predose AM | 0.7 bpm | Standard Error 2.8 |
| IW-1973 40 mg BID/QD | Change From Study Baseline Over Time in Supine Pulse | Day 12 predose AM | 2.3 bpm | Standard Error 3.1 |
| IW-1973 40 mg BID/QD | Change From Study Baseline Over Time in Supine Pulse | Day 13 predose AM | 0.8 bpm | Standard Error 2.8 |
| IW-1973 40 mg BID/QD | Change From Study Baseline Over Time in Supine Pulse | Day 13 postdose AM: 1 hour | 7.3 bpm | Standard Error 2.5 |
| IW-1973 40 mg BID/QD | Change From Study Baseline Over Time in Supine Pulse | Day 13 postdose AM: 4 hour | 4.8 bpm | Standard Error 2 |
| IW-1973 40 mg BID/QD | Change From Study Baseline Over Time in Supine Pulse | Day 14 predose AM | 0.7 bpm | Standard Error 2.3 |
| IW-1973 40 mg BID/QD | Change From Study Baseline Over Time in Supine Pulse | Day 15/Discharge | 0.7 bpm | Standard Error 2.3 |
| IW-1973 40 mg BID/QD | Change From Study Baseline Over Time in Supine Pulse | Day 21/Follow-Up | -2.0 bpm | Standard Error 3.2 |
| IW-1973 40 mg BID/QD | Change From Study Baseline Over Time in Supine Pulse | Day 42/End of Trial | 0.6 bpm | Standard Error 2.8 |
| IW-1973 40 mg QD/QD | Change From Study Baseline Over Time in Supine Pulse | Day 3 predose AM | -0.2 bpm | Standard Error 1.8 |
| IW-1973 40 mg QD/QD | Change From Study Baseline Over Time in Supine Pulse | Day 21/Follow-Up | 5.4 bpm | Standard Error 3.2 |
| IW-1973 40 mg QD/QD | Change From Study Baseline Over Time in Supine Pulse | Day 9 predose AM | 0.5 bpm | Standard Error 2.3 |
| IW-1973 40 mg QD/QD | Change From Study Baseline Over Time in Supine Pulse | Day 2 postdose PM: 4 hour | 4.8 bpm | Standard Error 1.8 |
| IW-1973 40 mg QD/QD | Change From Study Baseline Over Time in Supine Pulse | Day 14 predose AM | 0.1 bpm | Standard Error 2.3 |
| IW-1973 40 mg QD/QD | Change From Study Baseline Over Time in Supine Pulse | Day 10 predose AM | 2.1 bpm | Standard Error 2.4 |
| IW-1973 40 mg QD/QD | Change From Study Baseline Over Time in Supine Pulse | Day 2 postdose PM: 1 hour | 7.0 bpm | Standard Error 2.8 |
| IW-1973 40 mg QD/QD | Change From Study Baseline Over Time in Supine Pulse | Day 1 postdose AM: 4 hour | 8.8 bpm | Standard Error 2.7 |
| IW-1973 40 mg QD/QD | Change From Study Baseline Over Time in Supine Pulse | Day 11 predose AM | 1.4 bpm | Standard Error 2.8 |
| IW-1973 40 mg QD/QD | Change From Study Baseline Over Time in Supine Pulse | Day 2 predose PM | 6.6 bpm | Standard Error 2.1 |
| IW-1973 40 mg QD/QD | Change From Study Baseline Over Time in Supine Pulse | Study Baseline (Day 1 predose AM) | 70.0 bpm | Standard Error 10.3 |
| IW-1973 40 mg QD/QD | Change From Study Baseline Over Time in Supine Pulse | Day 12 predose AM | 0.6 bpm | Standard Error 3.1 |
| IW-1973 40 mg QD/QD | Change From Study Baseline Over Time in Supine Pulse | Day 2 postdose AM: 4 hour | 10.2 bpm | Standard Error 2.3 |
| IW-1973 40 mg QD/QD | Change From Study Baseline Over Time in Supine Pulse | Day 15/Discharge | 1.5 bpm | Standard Error 2.3 |
| IW-1973 40 mg QD/QD | Change From Study Baseline Over Time in Supine Pulse | Day 13 predose AM | -0.1 bpm | Standard Error 2.8 |
| IW-1973 40 mg QD/QD | Change From Study Baseline Over Time in Supine Pulse | Day 2 postdose AM: 1 hour | 11.3 bpm | Standard Error 3.1 |
| IW-1973 40 mg QD/QD | Change From Study Baseline Over Time in Supine Pulse | Day 1 postdose AM: 1 hour | 10.2 bpm | Standard Error 3.1 |
| IW-1973 40 mg QD/QD | Change From Study Baseline Over Time in Supine Pulse | Day 13 postdose AM: 1 hour | 10.2 bpm | Standard Error 2.5 |
| IW-1973 40 mg QD/QD | Change From Study Baseline Over Time in Supine Pulse | Day 2 predose AM | -1.9 bpm | Standard Error 1.8 |
| IW-1973 40 mg QD/QD | Change From Study Baseline Over Time in Supine Pulse | Day 42/End of Trial | 1.2 bpm | Standard Error 2.8 |
| IW-1973 40 mg QD/QD | Change From Study Baseline Over Time in Supine Pulse | Day 7 postdose AM: 1 hour | 13.2 bpm | Standard Error 3.2 |
| IW-1973 40 mg QD/QD | Change From Study Baseline Over Time in Supine Pulse | Day 7 predose AM | 1.0 bpm | Standard Error 2 |
| IW-1973 40 mg QD/QD | Change From Study Baseline Over Time in Supine Pulse | Day 13 postdose AM: 4 hour | 6.4 bpm | Standard Error 2 |
| IW-1973 40 mg QD/QD | Change From Study Baseline Over Time in Supine Pulse | Day 7 postdose AM: 4 hour | 8.8 bpm | Standard Error 2 |
| IW-1973 40 mg QD/QD | Change From Study Baseline Over Time in Supine Pulse | Day 6 predose AM | -1.5 bpm | Standard Error 2.3 |
| IW-1973 40 mg QD/QD | Change From Study Baseline Over Time in Supine Pulse | Day 1 postdose PM: 1 hour | 3.7 bpm | Standard Error 2.2 |
| IW-1973 40 mg QD/QD | Change From Study Baseline Over Time in Supine Pulse | Day 8 predose AM | 1.3 bpm | Standard Error 2 |
| IW-1973 40 mg QD/QD | Change From Study Baseline Over Time in Supine Pulse | Day 5 predose AM | -0.6 bpm | Standard Error 1.8 |
| IW-1973 40 mg QD/QD | Change From Study Baseline Over Time in Supine Pulse | Day 1 predose PM | 5.3 bpm | Standard Error 2.1 |
| IW-1973 40 mg QD/QD | Change From Study Baseline Over Time in Supine Pulse | Day 8 postdose AM: 1 hour | 12.3 bpm | Standard Error 2.9 |
| IW-1973 40 mg QD/QD | Change From Study Baseline Over Time in Supine Pulse | Day 4 predose AM | 0.9 bpm | Standard Error 2 |
| IW-1973 40 mg QD/QD | Change From Study Baseline Over Time in Supine Pulse | Day 13 predose PM | 7.0 bpm | Standard Error 2.3 |
| IW-1973 40 mg QD/QD | Change From Study Baseline Over Time in Supine Pulse | Day 8 postdose AM: 4 hour | 7.7 bpm | Standard Error 2.3 |
| IW-1973 40 mg QD/QD | Change From Study Baseline Over Time in Supine Pulse | Day 3 postdose PM: 4 hour | 5.2 bpm | Standard Error 2.2 |
| IW-1973 40 mg QD/QD | Change From Study Baseline Over Time in Supine Pulse | Day 1 postdose AM: 8 hour | 4.5 bpm | Standard Error 2.2 |
| IW-1973 40 mg QD/QD | Change From Study Baseline Over Time in Supine Pulse | Day 8 predose PM | 5.7 bpm | Standard Error 2.5 |
Comparison: Day 2, pre-dose PM95% CI: [-8.5, 5.9]
Comparison: Day 2, post-dose AM 1 hour95% CI: [-6.3, 15]
Comparison: Day 2, post-dose AM 4 hour95% CI: [-4.6, 11.2]
Comparison: Day 2, post-dose AM 4 hour95% CI: [-1, 14.9]
Comparison: Day 1, post-dose AM 1 hour95% CI: [-4.4, 16.8]
Comparison: Day 1, post-dose AM 1 hour95% CI: [-1.5, 19.8]
Comparison: Day 1, post-dose AM 4 hour95% CI: [-9, 9]
Comparison: Day 1, post-dose AM 4 hour95% CI: [-4.6, 13.4]
Comparison: Day 1, post-dose AM 8 hour95% CI: [-7.5, 7.1]
Comparison: Day 1, post-dose AM 8 hour95% CI: [-5.7, 8.9]
Comparison: Day 1, pre-dose PM95% CI: [-2, 12.1]
Comparison: Day 1, pre-dose PM95% CI: [-1.8, 12.3]
Comparison: Day 1, post-dose PM 1 hour95% CI: [-5.1, 9.6]
Comparison: Day 1, post-dose PM 1 hour95% CI: [-6, 8.7]
Comparison: Day 2, pre-dose AM95% CI: [-5, 6.9]
Comparison: Day 2, pre-dose AM95% CI: [-5.3, 6.6]
Comparison: Day 2, post-dose AM 1 hour95% CI: [-8.1, 13.2]
Comparison: Day 2, pre-dose PM95% CI: [-8.5, 5.9]
Comparison: Day 2, post-dose PM 1 hour95% CI: [-9.2, 9.5]
Comparison: Day 2, post-dose PM 1 hour95% CI: [-9.5, 9.2]
Comparison: Day 2, post-dose PM 4 hour95% CI: [-5.1, 7.4]
Comparison: Day 2, post-dose PM 4 hour95% CI: [-3.4, 9.2]
Comparison: Day 3, pre-dose AM95% CI: [-7.5, 4.8]
Comparison: Day 3, pre-dose AM95% CI: [-6.5, 5.8]
Comparison: Day 3, post-dose PM 4 hour95% CI: [-9.9, 5.3]
Comparison: Day 3, post-dose PM 4 hour95% CI: [-5.4, 9.8]
Comparison: Day 4, pre-dose AM95% CI: [0.2, 13.7]
Comparison: Day 4, pre-dose AM95% CI: [-1.7, 11.8]
Comparison: Day 5, pre-dose AM95% CI: [-3.1, 9]
Comparison: Day 5, pre-dose AM95% CI: [-3.4, 8.7]
Comparison: Day 6, pre-dose AM95% CI: [-5.4, 10]
Comparison: Day 6, pre-dose AM95% CI: [-8.4, 7]
Comparison: Day 7, pre-dose AM95% CI: [-1.6, 11.8]
Comparison: Day 7, pre-dose AM95% CI: [-1.7, 11.7]
Comparison: Day 7, post-dose AM 1 hour95% CI: [-1.6, 20.2]
Comparison: Day 7, post-dose AM 1 hour95% CI: [2.1, 23.9]
Comparison: Day 7, post-dose AM 4 hour95% CI: [0.2, 13.9]
Comparison: Day 7, post-dose AM 4 hour95% CI: [4.6, 18.3]
Comparison: Day 8, pre-dose AM95% CI: [-4.8, 8.6]
Comparison: Day 8, pre-dose95% CI: [-2.6, 10.8]
Comparison: Day 8, post-dose AM 1 hour95% CI: [-0.1, 19.6]
Comparison: Day 8, post-dose AM 1 hour95% CI: [-0.3, 19.4]
Comparison: Day 8, post-dose AM 4 hour95% CI: [0, 15.5]
Comparison: Day 8, post-dose AM 4 hour95% CI: [0.6, 16.1]
Comparison: Day 8, pre-dose PM95% CI: [-5.1, 11.7]
Comparison: Day 8, pre-dose PM95% CI: [-5.4, 11.3]
Comparison: Day 9, pre-dose AM95% CI: [-6.1, 9.1]
Comparison: Day 9, pre-dose AM95% CI: [-5.3, 9.9]
Comparison: Day 10, pre-dose95% CI: [-4, 12.6]
Comparison: Day 10, pre-dose AM95% CI: [-3.2, 13.4]
Comparison: Day 11, pre-dose AM95% CI: [-11, 8]
Comparison: Day 11, pre-dose AM95% CI: [-10.3, 8.6]
Comparison: Day 12, pre-dose AM95% CI: [-7.7, 13.4]
Comparison: Day 12, pre-dose AM95% CI: [-9.4, 11.8]
Comparison: Day 13, pre-dose AM95% CI: [-8.4, 10.3]
Comparison: Day 13, pre-dose AM95% CI: [-9.3, 9.4]
Comparison: Day 13, post-dose AM 1 hour95% CI: [-1.3, 15.3]
Comparison: Day 13, post-dose AM 1 hour95% CI: [1.6, 18.2]
Comparison: Day 13, post-dose AM 4 hour95% CI: [-1, 12.3]
Comparison: Day 13, post-dose AM 4 hour95% CI: [0.5, 13.9]
Comparison: Day 13, pre-dose PM95% CI: [-8.4, 7.4]
Comparison: Day 13, pre-dose PM95% CI: [-6, 9.9]
Comparison: Day 14, pre-dose AM95% CI: [-4, 11.8]
Comparison: Day 14, pre-dose AM95% CI: [-4.6, 11.2]
Comparison: Day 15, Discharge95% CI: [-8, 7.3]
Comparison: Day 15, Discharge95% CI: [-7.2, 8.1]
Comparison: Day 21, Follow-up95% CI: [-11.5, 10.2]
Comparison: Day 21, Follow-up95% CI: [-4.1, 17.5]
Comparison: Day 42, End of trial95% CI: [-9.1, 9.6]
Comparison: Day 42, End of trial95% CI: [-8.5, 10.2]
Primary
Change From Study Baseline Over Time in Supine Systolic Blood Pressure
Time frame: Study Baseline (Day 1 predose AM); Days 2-14: predose AM; Days 1, 2, 7, 8, 13: postdose AM 1 hour and 4 hour; Day 1: postdose AM 8 hour; Days 1, 2, 8, 13: predose PM; Days 1, 2: postdose PM 1 hour; Days 2, 3: postdose PM 4 hour; Days 15, 21, 42
Population: Pharmacodynamic (PD) Population: all participants who received at least 1 dose of study drug and had at least 1 postdose PD assessment.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Study Baseline Over Time in Supine Systolic Blood Pressure | Day 8 predose PM | -4.5 mmHg | Standard Error 5.5 |
| Placebo | Change From Study Baseline Over Time in Supine Systolic Blood Pressure | Day 3 predose AM | -0.8 mmHg | Standard Error 4 |
| Placebo | Change From Study Baseline Over Time in Supine Systolic Blood Pressure | Day 42/End of Trial | 3.3 mmHg | Standard Error 6.2 |
| Placebo | Change From Study Baseline Over Time in Supine Systolic Blood Pressure | Day 8 postdose AM: 4 hour | -5.2 mmHg | Standard Error 6.1 |
| Placebo | Change From Study Baseline Over Time in Supine Systolic Blood Pressure | Day 3 postdose PM: 4 hour | -5.8 mmHg | Standard Error 4.8 |
| Placebo | Change From Study Baseline Over Time in Supine Systolic Blood Pressure | Day 13 predose PM | -1.9 mmHg | Standard Error 4 |
| Placebo | Change From Study Baseline Over Time in Supine Systolic Blood Pressure | Day 8 postdose AM: 1 hour | -2.0 mmHg | Standard Error 5.3 |
| Placebo | Change From Study Baseline Over Time in Supine Systolic Blood Pressure | Day 4 predose AM | -0.8 mmHg | Standard Error 3.3 |
| Placebo | Change From Study Baseline Over Time in Supine Systolic Blood Pressure | Day 1 postdose AM: 1 hour | -6.8 mmHg | Standard Error 4.8 |
| Placebo | Change From Study Baseline Over Time in Supine Systolic Blood Pressure | Day 8 predose AM | 3.7 mmHg | Standard Error 4.6 |
| Placebo | Change From Study Baseline Over Time in Supine Systolic Blood Pressure | Day 5 predose AM | -0.2 mmHg | Standard Error 3.6 |
| Placebo | Change From Study Baseline Over Time in Supine Systolic Blood Pressure | Day 13 postdose AM: 4 hour | -3.9 mmHg | Standard Error 6.3 |
| Placebo | Change From Study Baseline Over Time in Supine Systolic Blood Pressure | Day 7 postdose AM: 4 hour | 1.3 mmHg | Standard Error 4.8 |
| Placebo | Change From Study Baseline Over Time in Supine Systolic Blood Pressure | Day 6 predose AM | -4.3 mmHg | Standard Error 4.1 |
| Placebo | Change From Study Baseline Over Time in Supine Systolic Blood Pressure | Day 1 postdose PM: 1 hour | -0.6 mmHg | Standard Error 5.6 |
| Placebo | Change From Study Baseline Over Time in Supine Systolic Blood Pressure | Day 7 postdose AM: 1 hour | -5.3 mmHg | Standard Error 4.4 |
| Placebo | Change From Study Baseline Over Time in Supine Systolic Blood Pressure | Day 7 predose AM | -4.3 mmHg | Standard Error 4.8 |
| Placebo | Change From Study Baseline Over Time in Supine Systolic Blood Pressure | Study Baseline (Day 1 predose AM) | 130.2 mmHg | Standard Error 11.1 |
| Placebo | Change From Study Baseline Over Time in Supine Systolic Blood Pressure | Day 13 postdose AM: 1 hour | -2.4 mmHg | Standard Error 4 |
| Placebo | Change From Study Baseline Over Time in Supine Systolic Blood Pressure | Day 2 predose AM | 5.5 mmHg | Standard Error 3.5 |
| Placebo | Change From Study Baseline Over Time in Supine Systolic Blood Pressure | Day 21/Follow-Up | -3.5 mmHg | Standard Error 4.3 |
| Placebo | Change From Study Baseline Over Time in Supine Systolic Blood Pressure | Day 13 predose AM | -1.6 mmHg | Standard Error 3.7 |
| Placebo | Change From Study Baseline Over Time in Supine Systolic Blood Pressure | Day 2 postdose AM: 1 hour | 2.0 mmHg | Standard Error 4.6 |
| Placebo | Change From Study Baseline Over Time in Supine Systolic Blood Pressure | Day 1 postdose AM: 4 hour | 4.4 mmHg | Standard Error 6 |
| Placebo | Change From Study Baseline Over Time in Supine Systolic Blood Pressure | Day 12 predose AM | -6.5 mmHg | Standard Error 4.1 |
| Placebo | Change From Study Baseline Over Time in Supine Systolic Blood Pressure | Day 2 postdose AM: 4 hour | 1.7 mmHg | Standard Error 6.1 |
| Placebo | Change From Study Baseline Over Time in Supine Systolic Blood Pressure | Day 14 predose AM | -3.7 mmHg | Standard Error 5.9 |
| Placebo | Change From Study Baseline Over Time in Supine Systolic Blood Pressure | Day 11 predose AM | 3.8 mmHg | Standard Error 5.4 |
| Placebo | Change From Study Baseline Over Time in Supine Systolic Blood Pressure | Day 2 predose PM | 4.6 mmHg | Standard Error 4.5 |
| Placebo | Change From Study Baseline Over Time in Supine Systolic Blood Pressure | Day 1 predose PM | 1.8 mmHg | Standard Error 6.3 |
| Placebo | Change From Study Baseline Over Time in Supine Systolic Blood Pressure | Day 10 predose AM | -1.3 mmHg | Standard Error 4 |
| Placebo | Change From Study Baseline Over Time in Supine Systolic Blood Pressure | Day 2 postdose PM: 1 hour | -3.8 mmHg | Standard Error 5.3 |
| Placebo | Change From Study Baseline Over Time in Supine Systolic Blood Pressure | Day 15/Discharge | 2.1 mmHg | Standard Error 4.9 |
| Placebo | Change From Study Baseline Over Time in Supine Systolic Blood Pressure | Day 9 predose AM | 3.0 mmHg | Standard Error 3.7 |
| Placebo | Change From Study Baseline Over Time in Supine Systolic Blood Pressure | Day 2 postdose PM: 4 hour | -5.0 mmHg | Standard Error 4.2 |
| Placebo | Change From Study Baseline Over Time in Supine Systolic Blood Pressure | Day 1 postdose AM: 8 hour | 0.5 mmHg | Standard Error 5 |
| IW-1973 40 mg BID/QD | Change From Study Baseline Over Time in Supine Systolic Blood Pressure | Day 2 postdose AM: 4 hour | -7.1 mmHg | Standard Error 4.9 |
| IW-1973 40 mg BID/QD | Change From Study Baseline Over Time in Supine Systolic Blood Pressure | Study Baseline (Day 1 predose AM) | 120.1 mmHg | Standard Error 8.9 |
| IW-1973 40 mg BID/QD | Change From Study Baseline Over Time in Supine Systolic Blood Pressure | Day 1 postdose AM: 1 hour | -7.7 mmHg | Standard Error 3.9 |
| IW-1973 40 mg BID/QD | Change From Study Baseline Over Time in Supine Systolic Blood Pressure | Day 1 postdose AM: 4 hour | -9.5 mmHg | Standard Error 4.9 |
| IW-1973 40 mg BID/QD | Change From Study Baseline Over Time in Supine Systolic Blood Pressure | Day 1 postdose AM: 8 hour | -9.4 mmHg | Standard Error 4 |
| IW-1973 40 mg BID/QD | Change From Study Baseline Over Time in Supine Systolic Blood Pressure | Day 1 predose PM | -6.9 mmHg | Standard Error 5.1 |
| IW-1973 40 mg BID/QD | Change From Study Baseline Over Time in Supine Systolic Blood Pressure | Day 1 postdose PM: 1 hour | -3.9 mmHg | Standard Error 4.5 |
| IW-1973 40 mg BID/QD | Change From Study Baseline Over Time in Supine Systolic Blood Pressure | Day 2 predose AM | -2.9 mmHg | Standard Error 2.8 |
| IW-1973 40 mg BID/QD | Change From Study Baseline Over Time in Supine Systolic Blood Pressure | Day 2 postdose AM: 1 hour | -13.4 mmHg | Standard Error 3.7 |
| IW-1973 40 mg BID/QD | Change From Study Baseline Over Time in Supine Systolic Blood Pressure | Day 2 predose PM | -7.1 mmHg | Standard Error 3.6 |
| IW-1973 40 mg BID/QD | Change From Study Baseline Over Time in Supine Systolic Blood Pressure | Day 2 postdose PM: 1 hour | -2.2 mmHg | Standard Error 4.3 |
| IW-1973 40 mg BID/QD | Change From Study Baseline Over Time in Supine Systolic Blood Pressure | Day 2 postdose PM: 4 hour | -9.7 mmHg | Standard Error 3.4 |
| IW-1973 40 mg BID/QD | Change From Study Baseline Over Time in Supine Systolic Blood Pressure | Day 3 predose AM | -5.5 mmHg | Standard Error 3.2 |
| IW-1973 40 mg BID/QD | Change From Study Baseline Over Time in Supine Systolic Blood Pressure | Day 3 postdose PM: 4 hour | -6.0 mmHg | Standard Error 3.9 |
| IW-1973 40 mg BID/QD | Change From Study Baseline Over Time in Supine Systolic Blood Pressure | Day 4 predose AM | -7.0 mmHg | Standard Error 2.7 |
| IW-1973 40 mg BID/QD | Change From Study Baseline Over Time in Supine Systolic Blood Pressure | Day 5 predose AM | -1.9 mmHg | Standard Error 2.9 |
| IW-1973 40 mg BID/QD | Change From Study Baseline Over Time in Supine Systolic Blood Pressure | Day 6 predose AM | -11.0 mmHg | Standard Error 3.3 |
| IW-1973 40 mg BID/QD | Change From Study Baseline Over Time in Supine Systolic Blood Pressure | Day 7 predose AM | -3.3 mmHg | Standard Error 3.8 |
| IW-1973 40 mg BID/QD | Change From Study Baseline Over Time in Supine Systolic Blood Pressure | Day 7 postdose AM: 1 hour | -8.4 mmHg | Standard Error 3.5 |
| IW-1973 40 mg BID/QD | Change From Study Baseline Over Time in Supine Systolic Blood Pressure | Day 7 postdose AM: 4 hour | -8.2 mmHg | Standard Error 3.9 |
| IW-1973 40 mg BID/QD | Change From Study Baseline Over Time in Supine Systolic Blood Pressure | Day 8 predose AM | -8.0 mmHg | Standard Error 3.7 |
| IW-1973 40 mg BID/QD | Change From Study Baseline Over Time in Supine Systolic Blood Pressure | Day 8 postdose AM: 1 hour | -15.4 mmHg | Standard Error 4.3 |
| IW-1973 40 mg BID/QD | Change From Study Baseline Over Time in Supine Systolic Blood Pressure | Day 8 postdose AM: 4 hour | -15.2 mmHg | Standard Error 4.9 |
| IW-1973 40 mg BID/QD | Change From Study Baseline Over Time in Supine Systolic Blood Pressure | Day 8 predose PM | -8.8 mmHg | Standard Error 4.4 |
| IW-1973 40 mg BID/QD | Change From Study Baseline Over Time in Supine Systolic Blood Pressure | Day 9 predose AM | -9.7 mmHg | Standard Error 3 |
| IW-1973 40 mg BID/QD | Change From Study Baseline Over Time in Supine Systolic Blood Pressure | Day 10 predose AM | -9.3 mmHg | Standard Error 3.2 |
| IW-1973 40 mg BID/QD | Change From Study Baseline Over Time in Supine Systolic Blood Pressure | Day 11 predose AM | -12.3 mmHg | Standard Error 4.4 |
| IW-1973 40 mg BID/QD | Change From Study Baseline Over Time in Supine Systolic Blood Pressure | Day 12 predose AM | -9.8 mmHg | Standard Error 3.3 |
| IW-1973 40 mg BID/QD | Change From Study Baseline Over Time in Supine Systolic Blood Pressure | Day 13 predose AM | -13.5 mmHg | Standard Error 3 |
| IW-1973 40 mg BID/QD | Change From Study Baseline Over Time in Supine Systolic Blood Pressure | Day 13 postdose AM: 1 hour | -16.6 mmHg | Standard Error 3.2 |
| IW-1973 40 mg BID/QD | Change From Study Baseline Over Time in Supine Systolic Blood Pressure | Day 13 postdose AM: 4 hour | -15.6 mmHg | Standard Error 5.1 |
| IW-1973 40 mg BID/QD | Change From Study Baseline Over Time in Supine Systolic Blood Pressure | Day 13 predose PM | -13.2 mmHg | Standard Error 3.2 |
| IW-1973 40 mg BID/QD | Change From Study Baseline Over Time in Supine Systolic Blood Pressure | Day 14 predose AM | -9.5 mmHg | Standard Error 4.7 |
| IW-1973 40 mg BID/QD | Change From Study Baseline Over Time in Supine Systolic Blood Pressure | Day 15/Discharge | -6.0 mmHg | Standard Error 4 |
| IW-1973 40 mg BID/QD | Change From Study Baseline Over Time in Supine Systolic Blood Pressure | Day 21/Follow-Up | 1.3 mmHg | Standard Error 3.5 |
| IW-1973 40 mg BID/QD | Change From Study Baseline Over Time in Supine Systolic Blood Pressure | Day 42/End of Trial | 8.8 mmHg | Standard Error 5 |
| IW-1973 40 mg QD/QD | Change From Study Baseline Over Time in Supine Systolic Blood Pressure | Day 8 predose PM | -5.8 mmHg | Standard Error 4.2 |
| IW-1973 40 mg QD/QD | Change From Study Baseline Over Time in Supine Systolic Blood Pressure | Day 2 postdose PM: 1 hour | -3.1 mmHg | Standard Error 4.1 |
| IW-1973 40 mg QD/QD | Change From Study Baseline Over Time in Supine Systolic Blood Pressure | Day 13 predose PM | -11.8 mmHg | Standard Error 3.1 |
| IW-1973 40 mg QD/QD | Change From Study Baseline Over Time in Supine Systolic Blood Pressure | Day 9 predose AM | -2.1 mmHg | Standard Error 2.9 |
| IW-1973 40 mg QD/QD | Change From Study Baseline Over Time in Supine Systolic Blood Pressure | Day 2 predose PM | -2.4 mmHg | Standard Error 3.4 |
| IW-1973 40 mg QD/QD | Change From Study Baseline Over Time in Supine Systolic Blood Pressure | Day 21/Follow-Up | 1.7 mmHg | Standard Error 3.3 |
| IW-1973 40 mg QD/QD | Change From Study Baseline Over Time in Supine Systolic Blood Pressure | Day 10 predose AM | -5.1 mmHg | Standard Error 3 |
| IW-1973 40 mg QD/QD | Change From Study Baseline Over Time in Supine Systolic Blood Pressure | Day 2 postdose AM: 4 hour | -9.4 mmHg | Standard Error 4.7 |
| IW-1973 40 mg QD/QD | Change From Study Baseline Over Time in Supine Systolic Blood Pressure | Day 14 predose AM | -9.8 mmHg | Standard Error 4.5 |
| IW-1973 40 mg QD/QD | Change From Study Baseline Over Time in Supine Systolic Blood Pressure | Day 11 predose AM | -4.5 mmHg | Standard Error 4.2 |
| IW-1973 40 mg QD/QD | Change From Study Baseline Over Time in Supine Systolic Blood Pressure | Day 2 postdose AM: 1 hour | -7.4 mmHg | Standard Error 3.5 |
| IW-1973 40 mg QD/QD | Change From Study Baseline Over Time in Supine Systolic Blood Pressure | Day 1 postdose AM: 4 hour | -11.1 mmHg | Standard Error 4.6 |
| IW-1973 40 mg QD/QD | Change From Study Baseline Over Time in Supine Systolic Blood Pressure | Day 12 predose AM | -12.0 mmHg | Standard Error 3.1 |
| IW-1973 40 mg QD/QD | Change From Study Baseline Over Time in Supine Systolic Blood Pressure | Day 2 predose AM | -0.2 mmHg | Standard Error 2.7 |
| IW-1973 40 mg QD/QD | Change From Study Baseline Over Time in Supine Systolic Blood Pressure | Study Baseline (Day 1 predose AM) | 128.6 mmHg | Standard Error 10.1 |
| IW-1973 40 mg QD/QD | Change From Study Baseline Over Time in Supine Systolic Blood Pressure | Day 13 predose AM | -8.1 mmHg | Standard Error 2.8 |
| IW-1973 40 mg QD/QD | Change From Study Baseline Over Time in Supine Systolic Blood Pressure | Day 1 postdose PM: 1 hour | -5.0 mmHg | Standard Error 4.3 |
| IW-1973 40 mg QD/QD | Change From Study Baseline Over Time in Supine Systolic Blood Pressure | Day 15/Discharge | -3.0 mmHg | Standard Error 3.8 |
| IW-1973 40 mg QD/QD | Change From Study Baseline Over Time in Supine Systolic Blood Pressure | Day 7 predose AM | -8.1 mmHg | Standard Error 3.7 |
| IW-1973 40 mg QD/QD | Change From Study Baseline Over Time in Supine Systolic Blood Pressure | Day 6 predose AM | -8.6 mmHg | Standard Error 3.2 |
| IW-1973 40 mg QD/QD | Change From Study Baseline Over Time in Supine Systolic Blood Pressure | Day 13 postdose AM: 1 hour | -14.2 mmHg | Standard Error 3.1 |
| IW-1973 40 mg QD/QD | Change From Study Baseline Over Time in Supine Systolic Blood Pressure | Day 7 postdose AM: 1 hour | -11.7 mmHg | Standard Error 3.4 |
| IW-1973 40 mg QD/QD | Change From Study Baseline Over Time in Supine Systolic Blood Pressure | Day 5 predose AM | -10.3 mmHg | Standard Error 2.8 |
| IW-1973 40 mg QD/QD | Change From Study Baseline Over Time in Supine Systolic Blood Pressure | Day 1 predose PM | -1.7 mmHg | Standard Error 4.8 |
| IW-1973 40 mg QD/QD | Change From Study Baseline Over Time in Supine Systolic Blood Pressure | Day 7 postdose AM: 4 hour | -15.9 mmHg | Standard Error 3.7 |
| IW-1973 40 mg QD/QD | Change From Study Baseline Over Time in Supine Systolic Blood Pressure | Day 4 predose AM | -8.9 mmHg | Standard Error 2.6 |
| IW-1973 40 mg QD/QD | Change From Study Baseline Over Time in Supine Systolic Blood Pressure | Day 1 postdose AM: 1 hour | -6.2 mmHg | Standard Error 3.7 |
| IW-1973 40 mg QD/QD | Change From Study Baseline Over Time in Supine Systolic Blood Pressure | Day 8 predose AM | -4.7 mmHg | Standard Error 3.6 |
| IW-1973 40 mg QD/QD | Change From Study Baseline Over Time in Supine Systolic Blood Pressure | Day 3 postdose PM: 4 hour | -8.6 mmHg | Standard Error 3.7 |
| IW-1973 40 mg QD/QD | Change From Study Baseline Over Time in Supine Systolic Blood Pressure | Day 13 postdose AM: 4 hour | -13.7 mmHg | Standard Error 4.8 |
| IW-1973 40 mg QD/QD | Change From Study Baseline Over Time in Supine Systolic Blood Pressure | Day 8 postdose AM: 1 hour | -12.3 mmHg | Standard Error 4.1 |
| IW-1973 40 mg QD/QD | Change From Study Baseline Over Time in Supine Systolic Blood Pressure | Day 3 predose AM | -6.5 mmHg | Standard Error 3.1 |
| IW-1973 40 mg QD/QD | Change From Study Baseline Over Time in Supine Systolic Blood Pressure | Day 1 postdose AM: 8 hour | -2.7 mmHg | Standard Error 3.8 |
| IW-1973 40 mg QD/QD | Change From Study Baseline Over Time in Supine Systolic Blood Pressure | Day 8 postdose AM: 4 hour | -9.8 mmHg | Standard Error 4.7 |
| IW-1973 40 mg QD/QD | Change From Study Baseline Over Time in Supine Systolic Blood Pressure | Day 2 postdose PM: 4 hour | -8.0 mmHg | Standard Error 3.3 |
| IW-1973 40 mg QD/QD | Change From Study Baseline Over Time in Supine Systolic Blood Pressure | Day 42/End of Trial | -1.2 mmHg | Standard Error 4.8 |
Comparison: Day 7 postdose AM 1 hour95% CI: [-17.6, 4.8]
Comparison: Day 7 postdose AM 4 hour95% CI: [-22.7, 3.7]
Comparison: Day 1 postdose AM 1 hour95% CI: [-14.2, 12.4]
Comparison: Day 1 postdose AM 1 hour95% CI: [-11.8, 12.9]
Comparison: Day 1 postdose AM 4 hour95% CI: [-30.6, 2.8]
Comparison: Day 1 postdose AM 4 hour95% CI: [-31, 0]
Comparison: Day 1 postdose AM 8 hour95% CI: [-23.8, 3.9]
Comparison: Day 1 postdose AM 8 hour95% CI: [-16, 9.7]
Comparison: Day 1 predose PM95% CI: [-26.2, 8.6]
Comparison: Day 1 predose PM95% CI: [-19.7, 12.6]
Comparison: Day 1 postdose PM 1 hour95% CI: [-18.7, 12.2]
Comparison: Day 1 postdose PM95% CI: [-18.7, 9.9]
Comparison: Day 2 predose AM95% CI: [-18.2, 1.3]
Comparison: Day 2 predose AM95% CI: [-14.8, 3.3]
Comparison: Day 2 postdose AM 1 hour95% CI: [-28.1, -2.8]
Comparison: Day 2 postdose AM 1 hour95% CI: [-21.1, 2.3]
Comparison: Day 2 postdose AM 4 hour95% CI: [-25.6, 7.9]
Comparison: Day 2 postdose AM 4 hour95% CI: [-26.7, 4.4]
Comparison: Day 2 predose PM95% CI: [-24, 0.6]
Comparison: Day 2 predose PM95% CI: [-18.4, 4.4]
Comparison: Day 2 postdose PM 1 hour95% CI: [-13, 16.2]
Comparison: Day 2 postdose PM 1 hour95% CI: [-12.9, 14.2]
Comparison: Day 2 postdose PM 4 hour95% CI: [-16.4, 7.1]
Comparison: Day 2 postdose PM 4 hour95% CI: [-13.9, 7.9]
Comparison: Day 3 predose AM95% CI: [-15.8, 6.4]
Comparison: Day 3 predose AM95% CI: [-16, 4.5]
Comparison: Day 3 postdose PM 4 hour95% CI: [-13.6, 13.1]
Comparison: Day 3 postdose PM 4 hour95% CI: [-15.2, 9.6]
Comparison: Day 4 predose AM95% CI: [-15.5, 3]
Comparison: Day 4 predose AM95% CI: [-16.6, 0.5]
Comparison: Day 5 predose AM95% CI: [-11.8, 8.4]
Comparison: Day 5 predose AM95% CI: [-19.4, -0.7]
Comparison: Day 6 predose AM95% CI: [-18.1, 4.7]
Comparison: Day 6 predose AM95% CI: [-14.8, 6.3]
Comparison: Day 7 predose AM95% CI: [-12.2, 14.1]
Comparison: Day 7 predose AM95% CI: [-16, 8.4]
Comparison: Day 7 postdose AM 1 hour95% CI: [-15.1, 9.1]
Comparison: Day 7 postdose AM 4 hour95% CI: [-29.5, -5]
Comparison: Day 8 predose AM95% CI: [-24.4, 1.1]
Comparison: Day 8 predose AM95% CI: [-20.2, 3.5]
Comparison: Day 8 postdose AM 1 hour95% CI: [-28.1, 1.4]
Comparison: Day 8 postdose AM 1 hour95% CI: [-24, 3.3]
Comparison: Day 8 postdose AM 4 hour95% CI: [-27, 6.9]
Comparison: Day 8 postdose AM 4 hour95% CI: [-20.4, 11.1]
Comparison: Day 8 predose PM95% CI: [-19.5, 11]
Comparison: Day 8 predose PM95% CI: [-15.4, 12.8]
Comparison: Day 9 predose AM95% CI: [-23, -2.5]
Comparison: Day 13 postdose AM 1 hour95% CI: [-25.4, -3.2]
Comparison: Day 9 predose AM95% CI: [-14.7, 4.3]
Comparison: Day 10 predose AM95% CI: [-19, 2.9]
Comparison: Day 10 predose95% CI: [-14, 6.3]
Comparison: Day 11 predose AM95% CI: [-31, -1.2]
Comparison: Day 11 predose AM95% CI: [-22.1, 5.6]
Comparison: Day 12 predose AM95% CI: [-14.6, 7.9]
Comparison: Day 12 predose AM95% CI: [-15.9, 4.9]
Comparison: Day 13 predose AM95% CI: [-22.1, -1.7]
Comparison: Day 13 predose AM95% CI: [-16, 2.9]
Comparison: Day 13 postdose AM 1 hour95% CI: [-22.1, -1.5]
Comparison: Day 13 postdose AM 4 hour95% CI: [-29, 5.6]
Comparison: Day 13 postdose AM 4 hour95% CI: [-25.9, 6.2]
Comparison: Day 13 postdose PM95% CI: [-22.4, -0.1]
Comparison: Day 13 predose PM95% CI: [-20.2, 0.4]
Comparison: Day 14 predose AM95% CI: [-22, 10.5]
Comparison: Day 14 predose AM95% CI: [-21.1, 9]
Comparison: Day 15 / Discharge95% CI: [-21.7, 5.6]
Comparison: Day 15 / Discharge95% CI: [-17.7, 7.6]
Comparison: Day 21 / Follow-up95% CI: [-7, 16.7]
Comparison: Day 21 / Follow-up95% CI: [-5.8, 16.2]
Comparison: Day 42 / End of Trial95% CI: [-11.7, 22.6]
Comparison: Day 42 / End of Trial95% CI: [-20.4, 11.4]
Primary
Change From Time-Matched Baseline Over Time in ABPM 24-hour Averages of Diastolic Blood Pressure
24-hour average is the average of ABPM assessments over 24 hour intervals from the time of dosing. Time-matched baseline is the 24 hours average during Day -1.
Time frame: Time Matched Baseline (Day -1), Days 1, 7, and 14
Population: PD Population: all participants who received at least 1 dose of study drug and had at least 1 postdose PD assessment.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Time-Matched Baseline Over Time in ABPM 24-hour Averages of Diastolic Blood Pressure | Time Matched Baseline (Day -1) | 77.37 mmHg | Standard Error 9.26 |
| Placebo | Change From Time-Matched Baseline Over Time in ABPM 24-hour Averages of Diastolic Blood Pressure | Change at Day 1 | -1.73 mmHg | Standard Error 1.29 |
| Placebo | Change From Time-Matched Baseline Over Time in ABPM 24-hour Averages of Diastolic Blood Pressure | Change at Day 7 | -1.60 mmHg | Standard Error 1.49 |
| Placebo | Change From Time-Matched Baseline Over Time in ABPM 24-hour Averages of Diastolic Blood Pressure | Change at Day 14 | -1.36 mmHg | Standard Error 2.04 |
| IW-1973 40 mg BID/QD | Change From Time-Matched Baseline Over Time in ABPM 24-hour Averages of Diastolic Blood Pressure | Change at Day 1 | -2.53 mmHg | Standard Error 0.96 |
| IW-1973 40 mg BID/QD | Change From Time-Matched Baseline Over Time in ABPM 24-hour Averages of Diastolic Blood Pressure | Change at Day 7 | -4.27 mmHg | Standard Error 1.12 |
| IW-1973 40 mg BID/QD | Change From Time-Matched Baseline Over Time in ABPM 24-hour Averages of Diastolic Blood Pressure | Change at Day 14 | -5.33 mmHg | Standard Error 1.61 |
| IW-1973 40 mg BID/QD | Change From Time-Matched Baseline Over Time in ABPM 24-hour Averages of Diastolic Blood Pressure | Time Matched Baseline (Day -1) | 71.57 mmHg | Standard Error 8.58 |
| IW-1973 40 mg QD/QD | Change From Time-Matched Baseline Over Time in ABPM 24-hour Averages of Diastolic Blood Pressure | Change at Day 7 | -3.44 mmHg | Standard Error 1.12 |
| IW-1973 40 mg QD/QD | Change From Time-Matched Baseline Over Time in ABPM 24-hour Averages of Diastolic Blood Pressure | Change at Day 1 | -2.82 mmHg | Standard Error 0.96 |
| IW-1973 40 mg QD/QD | Change From Time-Matched Baseline Over Time in ABPM 24-hour Averages of Diastolic Blood Pressure | Change at Day 14 | -5.53 mmHg | Standard Error 1.51 |
| IW-1973 40 mg QD/QD | Change From Time-Matched Baseline Over Time in ABPM 24-hour Averages of Diastolic Blood Pressure | Time Matched Baseline (Day -1) | 71.50 mmHg | Standard Error 6.33 |
| IW-1973 40 mg Total Daily Dose (Overall) | Change From Time-Matched Baseline Over Time in ABPM 24-hour Averages of Diastolic Blood Pressure | Change at Day 14 | -5.43 mmHg | Standard Error 1.11 |
| IW-1973 40 mg Total Daily Dose (Overall) | Change From Time-Matched Baseline Over Time in ABPM 24-hour Averages of Diastolic Blood Pressure | Change at Day 1 | -2.67 mmHg | Standard Error 0.69 |
| IW-1973 40 mg Total Daily Dose (Overall) | Change From Time-Matched Baseline Over Time in ABPM 24-hour Averages of Diastolic Blood Pressure | Time Matched Baseline (Day -1) | 71.53 mmHg | Standard Error 7.34 |
| IW-1973 40 mg Total Daily Dose (Overall) | Change From Time-Matched Baseline Over Time in ABPM 24-hour Averages of Diastolic Blood Pressure | Change at Day 7 | -3.86 mmHg | Standard Error 0.8 |
Comparison: Day 1495% CI: [-9.52, 1.18]
Comparison: Day 195% CI: [-4.17, 2.59]
Comparison: Day 195% CI: [-4.47, 2.29]
Comparison: Day 195% CI: [-4.02, 2.14]
Comparison: Day 795% CI: [-6.6, 1.26]
Comparison: Day 795% CI: [-5.77, 2.1]
Comparison: Day 795% CI: [-5.83, 1.32]
Comparison: Day 1495% CI: [-9.5, 1.56]
Comparison: Day 1495% CI: [-9.01, 0.87]
Primary
Change From Time-Matched Baseline Over Time in ABPM 24-hour Averages of Mean Arterial Pressure
24-hour average is the average of ABPM assessments over 24 hour intervals from the time of dosing. Time-matched baseline is the 24 hours average during Day -1.
Time frame: Time Matched Baseline (Day -1), Days 1, 7, and 14
Population: PD Population: all participants who received at least 1 dose of study drug and had at least 1 postdose PD assessment.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Time-Matched Baseline Over Time in ABPM 24-hour Averages of Mean Arterial Pressure | Time Matched Baseline (Day -1) | 96.44 mmHg | Standard Error 8.38 |
| Placebo | Change From Time-Matched Baseline Over Time in ABPM 24-hour Averages of Mean Arterial Pressure | Change at Day 1 | -0.68 mmHg | Standard Error 1.61 |
| Placebo | Change From Time-Matched Baseline Over Time in ABPM 24-hour Averages of Mean Arterial Pressure | Change at Day 7 | -1.84 mmHg | Standard Error 1.83 |
| Placebo | Change From Time-Matched Baseline Over Time in ABPM 24-hour Averages of Mean Arterial Pressure | Change at Day 14 | -1.55 mmHg | Standard Error 2.28 |
| IW-1973 40 mg BID/QD | Change From Time-Matched Baseline Over Time in ABPM 24-hour Averages of Mean Arterial Pressure | Change at Day 1 | -2.80 mmHg | Standard Error 1.2 |
| IW-1973 40 mg BID/QD | Change From Time-Matched Baseline Over Time in ABPM 24-hour Averages of Mean Arterial Pressure | Change at Day 7 | -5.24 mmHg | Standard Error 1.37 |
| IW-1973 40 mg BID/QD | Change From Time-Matched Baseline Over Time in ABPM 24-hour Averages of Mean Arterial Pressure | Change at Day 14 | -6.50 mmHg | Standard Error 1.79 |
| IW-1973 40 mg BID/QD | Change From Time-Matched Baseline Over Time in ABPM 24-hour Averages of Mean Arterial Pressure | Time Matched Baseline (Day -1) | 90.27 mmHg | Standard Error 6.89 |
| IW-1973 40 mg QD/QD | Change From Time-Matched Baseline Over Time in ABPM 24-hour Averages of Mean Arterial Pressure | Change at Day 7 | -3.46 mmHg | Standard Error 1.35 |
| IW-1973 40 mg QD/QD | Change From Time-Matched Baseline Over Time in ABPM 24-hour Averages of Mean Arterial Pressure | Change at Day 1 | -3.07 mmHg | Standard Error 1.19 |
| IW-1973 40 mg QD/QD | Change From Time-Matched Baseline Over Time in ABPM 24-hour Averages of Mean Arterial Pressure | Change at Day 14 | -6.05 mmHg | Standard Error 1.65 |
| IW-1973 40 mg QD/QD | Change From Time-Matched Baseline Over Time in ABPM 24-hour Averages of Mean Arterial Pressure | Time Matched Baseline (Day -1) | 91.14 mmHg | Standard Error 5.54 |
| IW-1973 40 mg Total Daily Dose (Overall) | Change From Time-Matched Baseline Over Time in ABPM 24-hour Averages of Mean Arterial Pressure | Change at Day 14 | -6.28 mmHg | Standard Error 1.23 |
| IW-1973 40 mg Total Daily Dose (Overall) | Change From Time-Matched Baseline Over Time in ABPM 24-hour Averages of Mean Arterial Pressure | Change at Day 1 | -2.94 mmHg | Standard Error 0.85 |
| IW-1973 40 mg Total Daily Dose (Overall) | Change From Time-Matched Baseline Over Time in ABPM 24-hour Averages of Mean Arterial Pressure | Time Matched Baseline (Day -1) | 90.71 mmHg | Standard Error 6.1 |
| IW-1973 40 mg Total Daily Dose (Overall) | Change From Time-Matched Baseline Over Time in ABPM 24-hour Averages of Mean Arterial Pressure | Change at Day 7 | -4.35 mmHg | Standard Error 0.97 |
Comparison: Day 195% CI: [-6.38, 2.15]
Comparison: Day 195% CI: [-6.59, 1.8]
Comparison: Day 195% CI: [-6.11, 1.6]
Comparison: Day 795% CI: [-8.25, 1.47]
Comparison: Day 795% CI: [-6.4, 3.18]
Comparison: Day 795% CI: [-6.9, 1.9]
Comparison: Day 1495% CI: [-11.22, 1.31]
Comparison: Day 1495% CI: [-10.41, 1.4]
Comparison: Day 1495% CI: [-10.27, 0.81]
Primary
Change From Time-Matched Baseline Over Time in ABPM 24-hour Averages of Pulse
24-hour average is the average of ABPM assessments over 24 hour intervals from the time of dosing. Time-matched baseline is the 24 hours average during Day -1.
Time frame: Time Matched Baseline (Day -1), Days 1, 7, and 14
Population: PD Population: all participants who received at least 1 dose of study drug and had at least 1 postdose PD assessment.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Time-Matched Baseline Over Time in ABPM 24-hour Averages of Pulse | Time Matched Baseline (Day -1) | 75.08 bpm | Standard Error 14.09 |
| Placebo | Change From Time-Matched Baseline Over Time in ABPM 24-hour Averages of Pulse | Change at Day 1 | -0.90 bpm | Standard Error 1.25 |
| Placebo | Change From Time-Matched Baseline Over Time in ABPM 24-hour Averages of Pulse | Change at Day 7 | -1.92 bpm | Standard Error 1.38 |
| Placebo | Change From Time-Matched Baseline Over Time in ABPM 24-hour Averages of Pulse | Change at Day 14 | -0.45 bpm | Standard Error 1.5 |
| IW-1973 40 mg BID/QD | Change From Time-Matched Baseline Over Time in ABPM 24-hour Averages of Pulse | Change at Day 1 | 2.29 bpm | Standard Error 0.97 |
| IW-1973 40 mg BID/QD | Change From Time-Matched Baseline Over Time in ABPM 24-hour Averages of Pulse | Change at Day 7 | 2.67 bpm | Standard Error 1.08 |
| IW-1973 40 mg BID/QD | Change From Time-Matched Baseline Over Time in ABPM 24-hour Averages of Pulse | Change at Day 14 | 2.12 bpm | Standard Error 1.23 |
| IW-1973 40 mg BID/QD | Change From Time-Matched Baseline Over Time in ABPM 24-hour Averages of Pulse | Time Matched Baseline (Day -1) | 72.81 bpm | Standard Error 10.79 |
| IW-1973 40 mg QD/QD | Change From Time-Matched Baseline Over Time in ABPM 24-hour Averages of Pulse | Change at Day 7 | 2.57 bpm | Standard Error 1.07 |
| IW-1973 40 mg QD/QD | Change From Time-Matched Baseline Over Time in ABPM 24-hour Averages of Pulse | Change at Day 1 | 2.64 bpm | Standard Error 0.97 |
| IW-1973 40 mg QD/QD | Change From Time-Matched Baseline Over Time in ABPM 24-hour Averages of Pulse | Change at Day 14 | 2.71 bpm | Standard Error 1.16 |
| IW-1973 40 mg QD/QD | Change From Time-Matched Baseline Over Time in ABPM 24-hour Averages of Pulse | Time Matched Baseline (Day -1) | 75.40 bpm | Standard Error 10.84 |
| IW-1973 40 mg Total Daily Dose (Overall) | Change From Time-Matched Baseline Over Time in ABPM 24-hour Averages of Pulse | Change at Day 14 | 2.42 bpm | Standard Error 0.84 |
| IW-1973 40 mg Total Daily Dose (Overall) | Change From Time-Matched Baseline Over Time in ABPM 24-hour Averages of Pulse | Change at Day 1 | 2.47 bpm | Standard Error 0.69 |
| IW-1973 40 mg Total Daily Dose (Overall) | Change From Time-Matched Baseline Over Time in ABPM 24-hour Averages of Pulse | Time Matched Baseline (Day -1) | 74.10 bpm | Standard Error 10.61 |
| IW-1973 40 mg Total Daily Dose (Overall) | Change From Time-Matched Baseline Over Time in ABPM 24-hour Averages of Pulse | Change at Day 7 | 2.62 bpm | Standard Error 0.76 |
Comparison: Day 195% CI: [-0.1, 6.48]
Comparison: Day 195% CI: [0.25, 6.82]
Comparison: Day 195% CI: [0.4, 6.32]
Comparison: Day 795% CI: [0.95, 8.23]
Comparison: Day 795% CI: [0.86, 8.12]
Comparison: Day 795% CI: [1.27, 7.81]
Comparison: Day 1495% CI: [-1.45, 6.61]
Comparison: Day 1495% CI: [-0.78, 7.11]
Comparison: Day 1495% CI: [-0.71, 6.45]
Primary
Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Diastolic Blood Pressure
Postdose is the average of assessments over 4-hour intervals from the time of dosing that day. Time-matched baseline is the corresponding 4-hour average on Day -1.
Time frame: Time-matched baseline (Day -1), Days 1, 7, 14: 0-4, 4-8, 8-12, 12-16, 16-20, 20-24 hours postdose
Population: PD Population: all participants who received at least 1 dose of study drug and had at least 1 postdose PD assessment.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Diastolic Blood Pressure | Day 1, 0-4 hours | -0.57 mmHg | Standard Error 1.98 |
| Placebo | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Diastolic Blood Pressure | Time Matched Baseline (Day -1): 4-8 hours | 79.85 mmHg | Standard Error 9.34 |
| Placebo | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Diastolic Blood Pressure | Time Matched Baseline (Day -1): 8-12 hours | 83.31 mmHg | Standard Error 8.49 |
| Placebo | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Diastolic Blood Pressure | Time Matched Baseline (Day -1): 12-16 hours | 74.27 mmHg | Standard Error 10.88 |
| Placebo | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Diastolic Blood Pressure | Time Matched Baseline (Day -1): 16-20 hours | 70.07 mmHg | Standard Error 9.16 |
| Placebo | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Diastolic Blood Pressure | Time Matched Baseline (Day -1): 20-24 hours | 77.61 mmHg | Standard Error 10.95 |
| Placebo | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Diastolic Blood Pressure | Time Matched Baseline (Day -1): 0-4 hours | 78.96 mmHg | Standard Error 8.7 |
| Placebo | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Diastolic Blood Pressure | Day 1, 4-8 hours | -1.02 mmHg | Standard Error 2.15 |
| Placebo | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Diastolic Blood Pressure | Day 1, 8-12 hours | -0.08 mmHg | Standard Error 2.64 |
| Placebo | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Diastolic Blood Pressure | Day 1, 12-16 hours | -2.99 mmHg | Standard Error 2.1 |
| Placebo | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Diastolic Blood Pressure | Day 1, 16-20 hours | -1.41 mmHg | Standard Error 2.56 |
| Placebo | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Diastolic Blood Pressure | Day 1, 20-24 hours | -0.13 mmHg | Standard Error 1.89 |
| Placebo | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Diastolic Blood Pressure | Day 7, 0-4 hours | -1.88 mmHg | Standard Error 1.56 |
| Placebo | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Diastolic Blood Pressure | Day 7, 4-8 hours | -2.55 mmHg | Standard Error 2.45 |
| Placebo | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Diastolic Blood Pressure | Day 7, 8-12 hours | -2.16 mmHg | Standard Error 2.01 |
| Placebo | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Diastolic Blood Pressure | Day 7, 12-16 hours | -2.18 mmHg | Standard Error 2.32 |
| Placebo | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Diastolic Blood Pressure | Day 7, 16-20 hours | 2.29 mmHg | Standard Error 2.62 |
| Placebo | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Diastolic Blood Pressure | Day 7, 20-24 hours | -0.13 mmHg | Standard Error 2.37 |
| Placebo | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Diastolic Blood Pressure | Day 14, 0-4 hours | -2.02 mmHg | Standard Error 2.16 |
| Placebo | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Diastolic Blood Pressure | Day 14, 4-8 hours | -1.52 mmHg | Standard Error 1.98 |
| Placebo | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Diastolic Blood Pressure | Day 14, 8-12 hours | -0.98 mmHg | Standard Error 2.99 |
| Placebo | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Diastolic Blood Pressure | Day 14, 12-16 hours | -0.91 mmHg | Standard Error 3.19 |
| Placebo | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Diastolic Blood Pressure | Day 14, 16-20 hours | -0.94 mmHg | Standard Error 2.91 |
| Placebo | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Diastolic Blood Pressure | Day 14, 20-24 hours | 0.50 mmHg | Standard Error 2.64 |
| IW-1973 40 mg BID/QD | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Diastolic Blood Pressure | Day 14, 12-16 hours | -2.32 mmHg | Standard Error 2.59 |
| IW-1973 40 mg BID/QD | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Diastolic Blood Pressure | Time Matched Baseline (Day -1): 0-4 hours | 72.48 mmHg | Standard Error 8.58 |
| IW-1973 40 mg BID/QD | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Diastolic Blood Pressure | Day 7, 0-4 hours | -6.31 mmHg | Standard Error 1.14 |
| IW-1973 40 mg BID/QD | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Diastolic Blood Pressure | Day 7, 16-20 hours | -3.57 mmHg | Standard Error 2.01 |
| IW-1973 40 mg BID/QD | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Diastolic Blood Pressure | Time Matched Baseline (Day -1): 4-8 hours | 73.96 mmHg | Standard Error 8.85 |
| IW-1973 40 mg BID/QD | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Diastolic Blood Pressure | Day 1, 16-20 hours | -1.97 mmHg | Standard Error 1.96 |
| IW-1973 40 mg BID/QD | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Diastolic Blood Pressure | Day 14, 8-12 hours | -8.06 mmHg | Standard Error 2.39 |
| IW-1973 40 mg BID/QD | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Diastolic Blood Pressure | Time Matched Baseline (Day -1): 8-12 hours | 76.47 mmHg | Standard Error 11.76 |
| IW-1973 40 mg BID/QD | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Diastolic Blood Pressure | Day 7, 4-8 hours | -5.94 mmHg | Standard Error 1.83 |
| IW-1973 40 mg BID/QD | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Diastolic Blood Pressure | Day 14, 16-20 hours | -3.30 mmHg | Standard Error 2.34 |
| IW-1973 40 mg BID/QD | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Diastolic Blood Pressure | Time Matched Baseline (Day -1): 12-16 hours | 68.10 mmHg | Standard Error 7.92 |
| IW-1973 40 mg BID/QD | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Diastolic Blood Pressure | Day 1, 12-16 hours | -2.12 mmHg | Standard Error 1.61 |
| IW-1973 40 mg BID/QD | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Diastolic Blood Pressure | Day 7, 20-24 hours | -1.74 mmHg | Standard Error 1.77 |
| IW-1973 40 mg BID/QD | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Diastolic Blood Pressure | Time Matched Baseline (Day -1): 16-20 hours | 67.89 mmHg | Standard Error 10.04 |
| IW-1973 40 mg BID/QD | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Diastolic Blood Pressure | Day 7, 8-12 hours | -4.98 mmHg | Standard Error 1.52 |
| IW-1973 40 mg BID/QD | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Diastolic Blood Pressure | Day 1, 20-24 hours | 1.59 mmHg | Standard Error 1.41 |
| IW-1973 40 mg BID/QD | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Diastolic Blood Pressure | Time Matched Baseline (Day -1): 20-24 hours | 70.57 mmHg | Standard Error 8.35 |
| IW-1973 40 mg BID/QD | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Diastolic Blood Pressure | Day 1, 8-12 hours | -5.18 mmHg | Standard Error 1.99 |
| IW-1973 40 mg BID/QD | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Diastolic Blood Pressure | Day 14, 20-24 hours | 0.06 mmHg | Standard Error 2.08 |
| IW-1973 40 mg BID/QD | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Diastolic Blood Pressure | Day 1, 0-4 hours | -3.15 mmHg | Standard Error 1.45 |
| IW-1973 40 mg BID/QD | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Diastolic Blood Pressure | Day 7, 12-16 hours | -3.37 mmHg | Standard Error 1.78 |
| IW-1973 40 mg BID/QD | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Diastolic Blood Pressure | Day 14, 0-4 hours | -8.92 mmHg | Standard Error 1.66 |
| IW-1973 40 mg BID/QD | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Diastolic Blood Pressure | Day 1, 4-8 hours | -4.88 mmHg | Standard Error 1.61 |
| IW-1973 40 mg BID/QD | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Diastolic Blood Pressure | Day 14, 4-8 hours | -9.77 mmHg | Standard Error 1.56 |
| IW-1973 40 mg QD/QD | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Diastolic Blood Pressure | Day 1, 4-8 hours | -5.75 mmHg | Standard Error 1.61 |
| IW-1973 40 mg QD/QD | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Diastolic Blood Pressure | Day 1, 8-12 hours | -3.04 mmHg | Standard Error 1.99 |
| IW-1973 40 mg QD/QD | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Diastolic Blood Pressure | Day 1, 12-16 hours | -2.44 mmHg | Standard Error 1.59 |
| IW-1973 40 mg QD/QD | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Diastolic Blood Pressure | Day 1, 16-20 hours | -1.87 mmHg | Standard Error 1.99 |
| IW-1973 40 mg QD/QD | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Diastolic Blood Pressure | Day 14, 4-8 hours | -7.07 mmHg | Standard Error 1.47 |
| IW-1973 40 mg QD/QD | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Diastolic Blood Pressure | Day 1, 20-24 hours | 0.12 mmHg | Standard Error 1.4 |
| IW-1973 40 mg QD/QD | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Diastolic Blood Pressure | Day 14, 16-20 hours | -5.44 mmHg | Standard Error 2.24 |
| IW-1973 40 mg QD/QD | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Diastolic Blood Pressure | Day 7, 0-4 hours | -6.05 mmHg | Standard Error 1.15 |
| IW-1973 40 mg QD/QD | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Diastolic Blood Pressure | Day 7, 4-8 hours | -3.61 mmHg | Standard Error 1.84 |
| IW-1973 40 mg QD/QD | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Diastolic Blood Pressure | Day 14, 8-12 hours | -6.83 mmHg | Standard Error 2.24 |
| IW-1973 40 mg QD/QD | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Diastolic Blood Pressure | Day 7, 8-12 hours | -3.52 mmHg | Standard Error 1.51 |
| IW-1973 40 mg QD/QD | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Diastolic Blood Pressure | Day 14, 20-24 hours | -1.48 mmHg | Standard Error 1.95 |
| IW-1973 40 mg QD/QD | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Diastolic Blood Pressure | Day 7, 12-16 hours | -3.45 mmHg | Standard Error 1.75 |
| IW-1973 40 mg QD/QD | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Diastolic Blood Pressure | Time Matched Baseline (Day -1): 0-4 hours | 71.58 mmHg | Standard Error 5.46 |
| IW-1973 40 mg QD/QD | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Diastolic Blood Pressure | Time Matched Baseline (Day -1): 4-8 hours | 73.79 mmHg | Standard Error 6.71 |
| IW-1973 40 mg QD/QD | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Diastolic Blood Pressure | Day 7, 16-20 hours | -3.91 mmHg | Standard Error 2.03 |
| IW-1973 40 mg QD/QD | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Diastolic Blood Pressure | Time Matched Baseline (Day -1): 8-12 hours | 77.13 mmHg | Standard Error 8.49 |
| IW-1973 40 mg QD/QD | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Diastolic Blood Pressure | Day 14, 12-16 hours | -6.07 mmHg | Standard Error 2.4 |
| IW-1973 40 mg QD/QD | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Diastolic Blood Pressure | Time Matched Baseline (Day -1): 12-16 hours | 70.29 mmHg | Standard Error 8.87 |
| IW-1973 40 mg QD/QD | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Diastolic Blood Pressure | Time Matched Baseline (Day -1): 16-20 hours | 64.87 mmHg | Standard Error 8.26 |
| IW-1973 40 mg QD/QD | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Diastolic Blood Pressure | Day 7, 20-24 hours | -0.76 mmHg | Standard Error 1.76 |
| IW-1973 40 mg QD/QD | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Diastolic Blood Pressure | Time Matched Baseline (Day -1): 20-24 hours | 71.04 mmHg | Standard Error 7.34 |
| IW-1973 40 mg QD/QD | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Diastolic Blood Pressure | Day 1, 0-4 hours | -4.63 mmHg | Standard Error 1.47 |
| IW-1973 40 mg QD/QD | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Diastolic Blood Pressure | Day 14, 0-4 hours | -6.06 mmHg | Standard Error 1.57 |
Comparison: Day 1, 0-4 hours95% CI: [-7.76, 2.59]
Comparison: Day 1, 0-4 hours95% CI: [-9.32, 1.19]
Comparison: Day 1, 4-8 hours95% CI: [-9.51, 1.8]
Comparison: Day 1, 4-8 hours95% CI: [-10.4, 0.93]
Comparison: Day 1, 8-12 hours95% CI: [-12.06, 1.86]
Comparison: Day 1, 8-12 hours95% CI: [-9.87, 3.96]
Comparison: Day 1, 12-16 hours95% CI: [-4.7, 6.45]
Comparison: Day 1, 12-16 hours95% CI: [-4.9, 6.01]
Comparison: Day 1, 16-20 hours95% CI: [-7.22, 6.1]
Comparison: Day 1, 16-20 hours95% CI: [-7.27, 6.34]
Comparison: Day 1, 20-24 hours95% CI: [-3.26, 6.69]
Comparison: Day 1, 20-24 hours95% CI: [-4.69, 5.2]
Comparison: Day 7, 0-4 hours95% CI: [-8.5, -0.36]
Comparison: Day 7, 0-4 hours95% CI: [-8.3, -0.03]
Comparison: Day 7, 4-8 hours95% CI: [-9.82, 3.04]
Comparison: Day 7, 4-8 hours95% CI: [-7.51, 5.38]
Comparison: Day 7, 8-12 hours95% CI: [-8.12, 2.48]
Comparison: Day 7, 8-12 hours95% CI: [-6.63, 3.91]
Comparison: Day 7, 12-16 hours95% CI: [-7.35, 4.97]
Comparison: Day 7, 12-16 hours95% CI: [-7.3, 4.77]
Comparison: Day 7, 16-20 hours95% CI: [-12.68, 0.95]
Comparison: Day 7, 16-20 hours95% CI: [-13.16, 0.76]
Comparison: Day 7, 20-24 hours95% CI: [-7.87, 4.65]
Comparison: Day 7, 20-24 hours95% CI: [-6.85, 5.59]
Comparison: Day 14, 0-4 hours95% CI: [-12.74, -1.08]
Comparison: Day 14, 0-4 hours95% CI: [-9.73, 1.66]
Comparison: Day 14, 4-8 hours95% CI: [-13.59, -2.91]
Comparison: Day 14, 4-8 hours95% CI: [-10.76, -0.35]
Comparison: Day 14, 8-12 hours95% CI: [-15.2, 1.05]
Comparison: Day 14, 8-12 hours95% CI: [-13.68, 1.98]
Comparison: Day 14, 12-16 hours95% CI: [-10.14, 7.33]
Comparison: Day 14, 12-16 hours95% CI: [-13.46, 3.14]
Comparison: Day 14, 16-20 hours95% CI: [-10.14, 5.4]
Comparison: Day 14, 16-20 hours95% CI: [-12.25, 3.23]
Comparison: Day 14, 20-24 hours95% CI: [-7.6, 6.72]
Comparison: Day 14, 20-24 hours95% CI: [-8.88, 4.92]
Primary
Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Mean Arterial Pressure
Postdose is the average of assessments over 4-hour intervals from the time of dosing that day. Time-matched baseline is the corresponding 4-hour average on Day -1.
Time frame: Time-matched baseline (Day -1), Days 1, 7, 14: 0-4, 4-8, 8-12, 12-16, 16-20, 20-24 hours postdose
Population: PD Population: all participants who received at least 1 dose of study drug and had at least 1 postdose PD assessment.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Mean Arterial Pressure | Day 1, 0-4 hours | -0.40 mmHg | Standard Error 2.61 |
| Placebo | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Mean Arterial Pressure | Time-matched baseline (Day -1): 4-8 hours | 98.92 mmHg | Standard Error 8.64 |
| Placebo | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Mean Arterial Pressure | Time-matched baseline (Day -1): 8-12 hours | 103.25 mmHg | Standard Error 8.66 |
| Placebo | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Mean Arterial Pressure | Time-matched baseline (Day -1): 12-16 hours | 93.31 mmHg | Standard Error 9.82 |
| Placebo | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Mean Arterial Pressure | Time-matched baseline (Day -1): 16-20 hours | 87.48 mmHg | Standard Error 10.42 |
| Placebo | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Mean Arterial Pressure | Time-matched baseline (Day -1): 20-24 hours | 97.62 mmHg | Standard Error 11.48 |
| Placebo | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Mean Arterial Pressure | Time-matched baseline (Day -1): 0-4 hours | 98.10 mmHg | Standard Error 5.1 |
| Placebo | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Mean Arterial Pressure | Day 1, 4-8 hours | 0.24 mmHg | Standard Error 2.86 |
| Placebo | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Mean Arterial Pressure | Day 1, 8-12 hours | 0.84 mmHg | Standard Error 2.87 |
| Placebo | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Mean Arterial Pressure | Day 1, 12-16 hours | -2.21 mmHg | Standard Error 1.9 |
| Placebo | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Mean Arterial Pressure | Day 1, 16-20 hours | 1.47 mmHg | Standard Error 2.96 |
| Placebo | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Mean Arterial Pressure | Day 1, 20-24 hours | 0.99 mmHg | Standard Error 2.2 |
| Placebo | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Mean Arterial Pressure | Day 7, 0-4 hours | -2.77 mmHg | Standard Error 2.13 |
| Placebo | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Mean Arterial Pressure | Day 7, 4-8 hours | -2.54 mmHg | Standard Error 2.73 |
| Placebo | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Mean Arterial Pressure | Day 7, 8-12 hours | -1.71 mmHg | Standard Error 2.33 |
| Placebo | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Mean Arterial Pressure | Day 7, 12-16 hours | -2.35 mmHg | Standard Error 2.42 |
| Placebo | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Mean Arterial Pressure | Day 7, 16-20 hours | 2.93 mmHg | Standard Error 2.89 |
| Placebo | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Mean Arterial Pressure | Day 7, 20-24 hours | -1.18 mmHg | Standard Error 2.62 |
| Placebo | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Mean Arterial Pressure | Day 14, 0-4 hours | -2.65 mmHg | Standard Error 2.67 |
| Placebo | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Mean Arterial Pressure | Day 14, 4-8 hours | -2.26 mmHg | Standard Error 2.38 |
| Placebo | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Mean Arterial Pressure | Day 14, 8-12 hours | -1.27 mmHg | Standard Error 3.35 |
| Placebo | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Mean Arterial Pressure | Day 14, 12-16 hours | -1.55 mmHg | Standard Error 3.31 |
| Placebo | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Mean Arterial Pressure | Day 14, 16-20 hours | 0.05 mmHg | Standard Error 2.75 |
| Placebo | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Mean Arterial Pressure | Day 14, 20-24 hours | -0.49 mmHg | Standard Error 2.7 |
| IW-1973 40 mg BID/QD | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Mean Arterial Pressure | Day 14, 12-16 hours | -2.91 mmHg | Standard Error 2.71 |
| IW-1973 40 mg BID/QD | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Mean Arterial Pressure | Time-matched baseline (Day -1): 0-4 hours | 91.52 mmHg | Standard Error 7 |
| IW-1973 40 mg BID/QD | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Mean Arterial Pressure | Day 7, 0-4 hours | -7.90 mmHg | Standard Error 1.52 |
| IW-1973 40 mg BID/QD | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Mean Arterial Pressure | Day 7, 16-20 hours | -3.73 mmHg | Standard Error 2.23 |
| IW-1973 40 mg BID/QD | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Mean Arterial Pressure | Time-matched baseline (Day -1): 4-8 hours | 92.27 mmHg | Standard Error 7.73 |
| IW-1973 40 mg BID/QD | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Mean Arterial Pressure | Day 1, 16-20 hours | -0.86 mmHg | Standard Error 2.28 |
| IW-1973 40 mg BID/QD | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Mean Arterial Pressure | Day 14, 8-12 hours | -9.89 mmHg | Standard Error 2.65 |
| IW-1973 40 mg BID/QD | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Mean Arterial Pressure | Time-matched baseline (Day -1): 8-12 hours | 96.20 mmHg | Standard Error 9.5 |
| IW-1973 40 mg BID/QD | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Mean Arterial Pressure | Day 7, 4-8 hours | -6.46 mmHg | Standard Error 2.06 |
| IW-1973 40 mg BID/QD | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Mean Arterial Pressure | Day 14, 16-20 hours | -3.38 mmHg | Standard Error 2.23 |
| IW-1973 40 mg BID/QD | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Mean Arterial Pressure | Time-matched baseline (Day -1): 12-16 hours | 87.07 mmHg | Standard Error 6.75 |
| IW-1973 40 mg BID/QD | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Mean Arterial Pressure | Day 1, 12-16 hours | -1.84 mmHg | Standard Error 1.47 |
| IW-1973 40 mg BID/QD | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Mean Arterial Pressure | Day 7, 20-24 hours | -3.47 mmHg | Standard Error 1.94 |
| IW-1973 40 mg BID/QD | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Mean Arterial Pressure | Time-matched baseline (Day -1): 16-20 hours | 85.54 mmHg | Standard Error 9.68 |
| IW-1973 40 mg BID/QD | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Mean Arterial Pressure | Day 7, 8-12 hours | -6.47 mmHg | Standard Error 1.74 |
| IW-1973 40 mg BID/QD | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Mean Arterial Pressure | Day 1, 20-24 hours | 0.25 mmHg | Standard Error 1.63 |
| IW-1973 40 mg BID/QD | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Mean Arterial Pressure | Time-matched baseline (Day -1): 20-24 hours | 89.30 mmHg | Standard Error 6.4 |
| IW-1973 40 mg BID/QD | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Mean Arterial Pressure | Day 1, 8-12 hours | -5.87 mmHg | Standard Error 2.15 |
| IW-1973 40 mg BID/QD | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Mean Arterial Pressure | Day 14, 20-24 hours | -0.57 mmHg | Standard Error 2.12 |
| IW-1973 40 mg BID/QD | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Mean Arterial Pressure | Day 1, 0-4 hours | -4.84 mmHg | Standard Error 1.86 |
| IW-1973 40 mg BID/QD | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Mean Arterial Pressure | Day 7, 12-16 hours | -4.46 mmHg | Standard Error 1.86 |
| IW-1973 40 mg BID/QD | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Mean Arterial Pressure | Day 14, 0-4 hours | -10.39 mmHg | Standard Error 1.99 |
| IW-1973 40 mg BID/QD | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Mean Arterial Pressure | Day 1, 4-8 hours | -4.98 mmHg | Standard Error 2.15 |
| IW-1973 40 mg BID/QD | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Mean Arterial Pressure | Day 14, 4-8 hours | -11.78 mmHg | Standard Error 1.89 |
| IW-1973 40 mg QD/QD | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Mean Arterial Pressure | Day 1, 4-8 hours | -7.97 mmHg | Standard Error 2.11 |
| IW-1973 40 mg QD/QD | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Mean Arterial Pressure | Day 1, 8-12 hours | -2.30 mmHg | Standard Error 2.14 |
| IW-1973 40 mg QD/QD | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Mean Arterial Pressure | Day 1, 12-16 hours | -2.23 mmHg | Standard Error 1.44 |
| IW-1973 40 mg QD/QD | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Mean Arterial Pressure | Day 1, 16-20 hours | -0.97 mmHg | Standard Error 2.29 |
| IW-1973 40 mg QD/QD | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Mean Arterial Pressure | Day 14, 4-8 hours | -7.91 mmHg | Standard Error 1.74 |
| IW-1973 40 mg QD/QD | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Mean Arterial Pressure | Day 1, 20-24 hours | -0.13 mmHg | Standard Error 1.6 |
| IW-1973 40 mg QD/QD | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Mean Arterial Pressure | Day 14, 16-20 hours | -5.33 mmHg | Standard Error 2.12 |
| IW-1973 40 mg QD/QD | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Mean Arterial Pressure | Day 7, 0-4 hours | -6.41 mmHg | Standard Error 1.53 |
| IW-1973 40 mg QD/QD | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Mean Arterial Pressure | Day 7, 4-8 hours | -4.99 mmHg | Standard Error 2.02 |
| IW-1973 40 mg QD/QD | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Mean Arterial Pressure | Day 14, 8-12 hours | -7.32 mmHg | Standard Error 2.46 |
| IW-1973 40 mg QD/QD | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Mean Arterial Pressure | Day 7, 8-12 hours | -2.96 mmHg | Standard Error 1.73 |
| IW-1973 40 mg QD/QD | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Mean Arterial Pressure | Day 14, 20-24 hours | -2.38 mmHg | Standard Error 1.95 |
| IW-1973 40 mg QD/QD | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Mean Arterial Pressure | Day 7, 12-16 hours | -2.30 mmHg | Standard Error 1.83 |
| IW-1973 40 mg QD/QD | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Mean Arterial Pressure | Time-matched baseline (Day -1): 0-4 hours | 91.16 mmHg | Standard Error 4.64 |
| IW-1973 40 mg QD/QD | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Mean Arterial Pressure | Time-matched baseline (Day -1): 4-8 hours | 93.98 mmHg | Standard Error 4.94 |
| IW-1973 40 mg QD/QD | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Mean Arterial Pressure | Day 7, 16-20 hours | -3.45 mmHg | Standard Error 2.24 |
| IW-1973 40 mg QD/QD | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Mean Arterial Pressure | Time-matched baseline (Day -1): 8-12 hours | 96.76 mmHg | Standard Error 8.22 |
| IW-1973 40 mg QD/QD | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Mean Arterial Pressure | Day 14, 12-16 hours | -6.50 mmHg | Standard Error 2.49 |
| IW-1973 40 mg QD/QD | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Mean Arterial Pressure | Time-matched baseline (Day -1): 12-16 hours | 90.02 mmHg | Standard Error 8.8 |
| IW-1973 40 mg QD/QD | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Mean Arterial Pressure | Time-matched baseline (Day -1): 16-20 hours | 83.70 mmHg | Standard Error 9.24 |
| IW-1973 40 mg QD/QD | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Mean Arterial Pressure | Day 7, 20-24 hours | -1.35 mmHg | Standard Error 1.91 |
| IW-1973 40 mg QD/QD | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Mean Arterial Pressure | Time-matched baseline (Day -1): 20-24 hours | 90.96 mmHg | Standard Error 6.46 |
| IW-1973 40 mg QD/QD | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Mean Arterial Pressure | Day 1, 0-4 hours | -5.57 mmHg | Standard Error 1.88 |
| IW-1973 40 mg QD/QD | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Mean Arterial Pressure | Day 14, 0-4 hours | -6.51 mmHg | Standard Error 1.86 |
Comparison: Day 1, 0-4 hours95% CI: [-11.3, 2.41]
Comparison: Day 1, 0-4 hours95% CI: [-12.1, 1.75]
Comparison: Day 1, 4-8 hours95% CI: [-12.87, 2.42]
Comparison: Day 1, 4-8 hours95% CI: [-15.64, -0.79]
Comparison: Day 1, 8-12 hours95% CI: [-14.29, 0.86]
Comparison: Day 1, 8-12 hours95% CI: [-10.66, 4.38]
Comparison: Day 1, 12-16 hours95% CI: [-4.71, 5.45]
Comparison: Day 1, 12-1695% CI: [-4.94, 4.91]
Comparison: Day 1, 16-20 hours95% CI: [-10.07, 5.41]
Comparison: Day 1, 16-20 hours95% CI: [-10.26, 5.37]
Comparison: Day 1, 20-24 hours95% CI: [-6.62, 5.13]
Comparison: Day 1, 20-24 hours95% CI: [-6.83, 4.58]
Comparison: Day 7, 0-4 hours95% CI: [-10.72, 0.47]
Comparison: Day 7, 0-4 hours95% CI: [-9.29, 2.01]
Comparison: Day 7, 4-8 hours95% CI: [-11.22, 3.38]
Comparison: Day 7, 4-8 hours95% CI: [-9.54, 4.63]
Comparison: Day 7, 8-12 hours95% CI: [-10.9, 1.39]
Comparison: Day 7, 8-12 hours95% CI: [-7.35, 4.85]
Comparison: Day 7, 12-16 hours95% CI: [-8.57, 4.35]
Comparison: Day 7, 12-16 hours95% CI: [-6.21, 6.31]
Comparison: Day 7, 16-20 hours95% CI: [-14.22, 0.9]
Comparison: Day 7, 16-20 hours95% CI: [-14.01, 1.25]
Comparison: Day 7, 20-24 hours95% CI: [-9.3, 4.71]
Comparison: Day 7, 20-24 hours95% CI: [-6.97, 6.64]
Comparison: Day 14, 0-4 hours95% CI: [-15.03, -0.44]
Comparison: Day 14, 0-4 hours95% CI: [-10.88, 3.16]
Comparison: Day 14, 4-895% CI: [-16.1, -2.95]
Comparison: Day 14, 4-8 hours95% CI: [-11.82, 0.5]
Comparison: Day 14, 8-12 hours95% CI: [-17.77, 0.54]
Comparison: Day 14, 8-12 hours95% CI: [-14.79, 2.69]
Comparison: Day 14, 12-16 hours95% CI: [-10.51, 7.79]
Comparison: Day 14, 12-16 hours95% CI: [-13.5, 3.6]
Comparison: Day 14, 16-20 hours95% CI: [-10.81, 3.96]
Comparison: Day 14, 16-20 hours95% CI: [-12.64, 1.89]
Comparison: Day 14, 20-24 hours95% CI: [-7.55, 7.39]
Comparison: Day 14, 20-24 hours95% CI: [-8.89, 5.12]
Primary
Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Pulse
Postdose is the average of assessments over 4-hour intervals from the time of dosing that day. Time-matched baseline is the corresponding 4-hour average on Day -1.
Time frame: Time-matched baseline (Day -1), Days 1, 7, 14: 0-4, 4-8, 8-12, 12-16, 16-20, 20-24 hours postdose
Population: PD Population: all participants who received at least 1 dose of study drug and had at least 1 postdose PD assessment.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Pulse | Day 1, 0-4 hours | 0.87 bpm | Standard Error 2.07 |
| Placebo | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Pulse | Time Matched Baseline (Day -1): 4-8 hours | 77.65 bpm | Standard Error 15.57 |
| Placebo | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Pulse | Time Matched Baseline (Day -1): 8-12 hours | 79.00 bpm | Standard Error 15.5 |
| Placebo | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Pulse | Time Matched Baseline (Day -1): 12-16 hours | 78.60 bpm | Standard Error 15.22 |
| Placebo | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Pulse | Time Matched Baseline (Day -1): 16-20 hours | 72.08 bpm | Standard Error 13.37 |
| Placebo | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Pulse | Time Matched Baseline (Day -1): 20-24 hours | 68.05 bpm | Standard Error 11.26 |
| Placebo | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Pulse | Time Matched Baseline (Day -1): 0-4 hours | 73.52 bpm | Standard Error 14.02 |
| Placebo | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Pulse | Day 1, 4-8 hours | 1.18 bpm | Standard Error 2.76 |
| Placebo | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Pulse | Day 1, 8-12 hours | -0.96 bpm | Standard Error 2.14 |
| Placebo | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Pulse | Day 1, 12-16 hours | -4.33 bpm | Standard Error 1.68 |
| Placebo | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Pulse | Day 1, 16-20 hours | -1.67 bpm | Standard Error 1.24 |
| Placebo | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Pulse | Day 1, 20-24 hours | 0.76 bpm | Standard Error 1.77 |
| Placebo | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Pulse | Day 7, 0-4 hours | -0.09 bpm | Standard Error 2.11 |
| Placebo | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Pulse | Day 7, 4-8 hours | -2.94 bpm | Standard Error 1.72 |
| Placebo | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Pulse | Day 7, 8-12 hours | -2.25 bpm | Standard Error 1.78 |
| Placebo | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Pulse | Day 7, 12-16 hours | -4.05 bpm | Standard Error 1.89 |
| Placebo | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Pulse | Day 14, 16-20 hours | -0.88 bpm | Standard Error 1.98 |
| Placebo | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Pulse | Day 7, 16-20 hours | -2.56 bpm | Standard Error 1.87 |
| Placebo | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Pulse | Day 7, 20-24 hours | 0.23 bpm | Standard Error 1.85 |
| Placebo | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Pulse | Day 14, 0-4 hours | 0.77 bpm | Standard Error 1.95 |
| Placebo | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Pulse | Day 14, 4-8 hours | -2.85 bpm | Standard Error 2.56 |
| Placebo | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Pulse | Day 14, 8-12 hours | 0.89 bpm | Standard Error 1.91 |
| Placebo | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Pulse | Day 14, 12-16 hours | -3.74 bpm | Standard Error 2.33 |
| Placebo | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Pulse | Day 14, 20-24 hours | 4.14 bpm | Standard Error 2.31 |
| IW-1973 40 mg BID/QD | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Pulse | Day 7, 0-4 hours | 4.27 bpm | Standard Error 1.63 |
| IW-1973 40 mg BID/QD | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Pulse | Time Matched Baseline (Day -1): 0-4 hours | 73.89 bpm | Standard Error 12.23 |
| IW-1973 40 mg BID/QD | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Pulse | Day 1, 8-12 hours | -1.33 bpm | Standard Error 1.65 |
| IW-1973 40 mg BID/QD | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Pulse | Day 14, 12-16 hours | 1.35 bpm | Standard Error 1.89 |
| IW-1973 40 mg BID/QD | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Pulse | Time Matched Baseline (Day -1): 4-8 hours | 76.88 bpm | Standard Error 15.09 |
| IW-1973 40 mg BID/QD | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Pulse | Day 14, 4-8 hours | 2.33 bpm | Standard Error 2.09 |
| IW-1973 40 mg BID/QD | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Pulse | Day 7, 16-20 hours | 2.44 bpm | Standard Error 1.45 |
| IW-1973 40 mg BID/QD | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Pulse | Time Matched Baseline (Day -1): 8-12 hours | 77.34 bpm | Standard Error 11.42 |
| IW-1973 40 mg BID/QD | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Pulse | Day 7, 4-8 hours | 1.95 bpm | Standard Error 1.34 |
| IW-1973 40 mg BID/QD | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Pulse | Day 1, 20-24 hours | 2.50 bpm | Standard Error 1.37 |
| IW-1973 40 mg BID/QD | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Pulse | Time Matched Baseline (Day -1): 12-16 hours | 72.93 bpm | Standard Error 9.38 |
| IW-1973 40 mg BID/QD | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Pulse | Day 14, 8-12 hours | 0.68 bpm | Standard Error 1.56 |
| IW-1973 40 mg BID/QD | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Pulse | Day 7, 8-12 hours | 1.79 bpm | Standard Error 1.38 |
| IW-1973 40 mg BID/QD | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Pulse | Time Matched Baseline (Day -1): 16-20 hours | 67.79 bpm | Standard Error 8.8 |
| IW-1973 40 mg BID/QD | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Pulse | Day 1, 12-16 hours | 2.13 bpm | Standard Error 1.3 |
| IW-1973 40 mg BID/QD | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Pulse | Day 7, 20-24 hours | 1.91 bpm | Standard Error 1.44 |
| IW-1973 40 mg BID/QD | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Pulse | Time Matched Baseline (Day -1): 20-24 hours | 67.97 bpm | Standard Error 8.75 |
| IW-1973 40 mg BID/QD | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Pulse | Day 1, 16-20 hours | 1.95 bpm | Standard Error 0.97 |
| IW-1973 40 mg BID/QD | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Pulse | Day 14, 20-24 hours | 2.80 bpm | Standard Error 1.88 |
| IW-1973 40 mg BID/QD | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Pulse | Day 1, 0-4 hours | 7.68 bpm | Standard Error 1.6 |
| IW-1973 40 mg BID/QD | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Pulse | Day 7, 12-16 hours | 2.85 bpm | Standard Error 1.46 |
| IW-1973 40 mg BID/QD | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Pulse | Day 14, 16-20 hours | 0.43 bpm | Standard Error 1.61 |
| IW-1973 40 mg BID/QD | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Pulse | Day 1, 4-8 hours | 0.23 bpm | Standard Error 2.14 |
| IW-1973 40 mg BID/QD | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Pulse | Day 14, 0-4 hours | 4.82 bpm | Standard Error 1.59 |
| IW-1973 40 mg QD/QD | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Pulse | Day 1, 4-8 hours | 3.02 bpm | Standard Error 2.14 |
| IW-1973 40 mg QD/QD | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Pulse | Day 1, 8-12 hours | 2.15 bpm | Standard Error 1.65 |
| IW-1973 40 mg QD/QD | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Pulse | Day 14, 0-4 hours | 4.53 bpm | Standard Error 1.51 |
| IW-1973 40 mg QD/QD | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Pulse | Day 1, 12-16 hours | 1.24 bpm | Standard Error 1.29 |
| IW-1973 40 mg QD/QD | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Pulse | Day 14, 16-20 hours | 2.06 bpm | Standard Error 1.53 |
| IW-1973 40 mg QD/QD | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Pulse | Day 1, 16-20 hours | 0.73 bpm | Standard Error 0.96 |
| IW-1973 40 mg QD/QD | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Pulse | Day 1, 20-24 hours | 1.09 bpm | Standard Error 1.38 |
| IW-1973 40 mg QD/QD | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Pulse | Day 14, 4-8 hours | 2.76 bpm | Standard Error 1.99 |
| IW-1973 40 mg QD/QD | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Pulse | Day 7, 0-4 hours | 5.32 bpm | Standard Error 1.64 |
| IW-1973 40 mg QD/QD | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Pulse | Day 14, 20-24 hours | 3.00 bpm | Standard Error 1.8 |
| IW-1973 40 mg QD/QD | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Pulse | Day 7, 4-8 hours | 1.36 bpm | Standard Error 1.34 |
| IW-1973 40 mg QD/QD | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Pulse | Day 7, 8-12 hours | 0.01 bpm | Standard Error 1.38 |
| IW-1973 40 mg QD/QD | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Pulse | Day 14, 8-12 hours | 2.50 bpm | Standard Error 1.48 |
| IW-1973 40 mg QD/QD | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Pulse | Day 7, 12-16 hours | 2.10 bpm | Standard Error 1.45 |
| IW-1973 40 mg QD/QD | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Pulse | Time Matched Baseline (Day -1): 0-4 hours | 76.46 bpm | Standard Error 9.48 |
| IW-1973 40 mg QD/QD | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Pulse | Time Matched Baseline (Day -1): 4-8 hours | 79.91 bpm | Standard Error 14.33 |
| IW-1973 40 mg QD/QD | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Pulse | Time Matched Baseline (Day -1): 8-12 hours | 78.21 bpm | Standard Error 11.67 |
| IW-1973 40 mg QD/QD | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Pulse | Day 7, 16-20 hours | 2.78 bpm | Standard Error 1.44 |
| IW-1973 40 mg QD/QD | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Pulse | Time Matched Baseline (Day -1): 12-16 hours | 75.36 bpm | Standard Error 11.89 |
| IW-1973 40 mg QD/QD | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Pulse | Day 14, 12-16 hours | 1.56 bpm | Standard Error 1.79 |
| IW-1973 40 mg QD/QD | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Pulse | Time Matched Baseline (Day -1): 16-20 hours | 70.51 bpm | Standard Error 10.23 |
| IW-1973 40 mg QD/QD | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Pulse | Time Matched Baseline (Day -1): 20-24 hours | 71.45 bpm | Standard Error 10.35 |
| IW-1973 40 mg QD/QD | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Pulse | Day 7, 20-24 hours | 4.26 bpm | Standard Error 1.44 |
| IW-1973 40 mg QD/QD | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Pulse | Day 1, 0-4 hours | 7.42 bpm | Standard Error 1.6 |
Comparison: Day 1, 0-4 hours95% CI: [1.4, 12.22]
Comparison: Day 1, 0-4 hours95% CI: [1.12, 11.99]
Comparison: Day 1, 4-8 hours95% CI: [-8.18, 6.28]
Comparison: Day 1, 4-8 hours95% CI: [-5.39, 9.09]
Comparison: Day 1, 8-12 hours95% CI: [-5.98, 5.23]
Comparison: Day 1, 8-12 hours95% CI: [-2.5, 8.7]
Comparison: Day 1, 12-16 hours95% CI: [2.02, 10.89]
Comparison: Day 1, 12-16 hours95% CI: [1.19, 9.95]
Comparison: Day 1, 16-20 hours95% CI: [0.34, 6.91]
Comparison: Day 1, 16-20 hours95% CI: [-0.84, 5.66]
Comparison: Day 1, 20-24 hours95% CI: [-2.89, 6.36]
Comparison: Day 1, 20-24 hours95% CI: [-4.33, 4.99]
Comparison: Day 7, 0-4 hours95% CI: [-1.17, 9.88]
Comparison: Day 7, 0-4 hours95% CI: [-0.14, 10.96]
Comparison: Day 7, 4-8 hours95% CI: [0.36, 9.4]
Comparison: Day 7, 4-8 hours95% CI: [-0.22, 8.83]
Comparison: Day 7, 8-12 hours95% CI: [-0.65, 8.72]
Comparison: Day 7, 8-12 hours95% CI: [-2.42, 6.94]
Comparison: Day 7, 12-16 hours95% CI: [1.91, 11.89]
Comparison: Day 7, 12-16 hours95% CI: [1.22, 11.08]
Comparison: Day 7, 16-20 hours95% CI: [0.05, 9.93]
Comparison: Day 7, 16-20 hours95% CI: [0.45, 10.22]
Comparison: Day 7, 20-24 hours95% CI: [-3.17, 6.52]
Comparison: Day 7, 20-24 hours95% CI: [-0.86, 8.92]
Comparison: Day 14, 0-4 hours95% CI: [-1.18, 9.27]
Comparison: Day 14, 0-4 hours95% CI: [-1.38, 8.9]
Comparison: Day 14, 4-8 hours95% CI: [-1.7, 12.06]
Comparison: Day 14, 4-8 hours95% CI: [-1.14, 12.37]
Comparison: Day 14, 8-12 hours95% CI: [-5.35, 4.92]
Comparison: Day 14, 8-12 hours95% CI: [-3.42, 6.65]
Comparison: Day 14, 12-16 hours95% CI: [-1.19, 11.36]
Comparison: Day 14, 12-16 hours95% CI: [-0.83, 11.42]
Comparison: Day 14, 16-20 hours95% CI: [-4.02, 6.63]
Comparison: Day 14, 16-20 hours95% CI: [-2.26, 8.12]
Comparison: Day 14, 20-24 hours95% CI: [-7.52, 4.85]
Comparison: Day 14, 20-24 hours95% CI: [-7.25, 4.98]
Primary
Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Systolic Blood Pressure
Postdose is the average of assessments over 4-hour intervals from the time of dosing that day. Time-matched baseline is the corresponding 4-hour average on Day -1.
Time frame: Time-matched baseline (Day -1), Days 1, 7, 14: 0-4, 4-8, 8-12, 12-16, 16-20, 20-24 hours postdose
Population: PD Population: all participants who received at least 1 dose of study drug and had at least 1 postdose PD assessment.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Systolic Blood Pressure | Day 1, 0-4 hours | -1.61 mmHg | Standard Error 3.02 |
| Placebo | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Systolic Blood Pressure | Time-matched baseline (Day -1): 4-8 hours | 136.10 mmHg | Standard Error 9.69 |
| Placebo | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Systolic Blood Pressure | Time-matched baseline (Day -1): 8-12 hours | 140.46 mmHg | Standard Error 9.12 |
| Placebo | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Systolic Blood Pressure | Time-matched baseline (Day -1): 12-16 hours | 130.31 mmHg | Standard Error 9.75 |
| Placebo | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Systolic Blood Pressure | Time-matched baseline (Day -1): 16-20 hours | 120.34 mmHg | Standard Error 8.79 |
| Placebo | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Systolic Blood Pressure | Time-matched baseline (Day -1): 20-24 hours | 132.10 mmHg | Standard Error 11.62 |
| Placebo | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Systolic Blood Pressure | Time-matched baseline (Day -1): 0-4 hours | 134.45 mmHg | Standard Error 8.01 |
| Placebo | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Systolic Blood Pressure | Day 1, 4-8 hours | -0.62 mmHg | Standard Error 3.51 |
| Placebo | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Systolic Blood Pressure | Day 1, 8-12 hours | 1.21 mmHg | Standard Error 3.8 |
| Placebo | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Systolic Blood Pressure | Day 1, 12-16 hours | -4.83 mmHg | Standard Error 3.04 |
| Placebo | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Systolic Blood Pressure | Day 1, 16-20 hours | 3.77 mmHg | Standard Error 4.12 |
| Placebo | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Systolic Blood Pressure | Day 1, 20-24 hours | 2.08 mmHg | Standard Error 3.04 |
| Placebo | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Systolic Blood Pressure | Day 7, 0-4 hours | -5.14 mmHg | Standard Error 3.14 |
| Placebo | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Systolic Blood Pressure | Day 7, 4-8 hours | -6.24 mmHg | Standard Error 3.44 |
| Placebo | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Systolic Blood Pressure | Day 7, 8-12 hours | -3.70 mmHg | Standard Error 3.65 |
| Placebo | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Systolic Blood Pressure | Day 7, 12-16 hours | -4.46 mmHg | Standard Error 3.66 |
| Placebo | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Systolic Blood Pressure | Day 7, 16-20 hours | 2.75 mmHg | Standard Error 3.98 |
| Placebo | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Systolic Blood Pressure | Day 7, 20-24 hours | -1.10 mmHg | Standard Error 3.74 |
| Placebo | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Systolic Blood Pressure | Day 14, 0-4 hours | -6.67 mmHg | Standard Error 3.92 |
| Placebo | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Systolic Blood Pressure | Day 14, 4-8 hours | -7.36 mmHg | Standard Error 3.62 |
| Placebo | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Systolic Blood Pressure | Day 14, 8-12 hours | -4.42 mmHg | Standard Error 4.41 |
| Placebo | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Systolic Blood Pressure | Day 14, 12-16 hours | -5.28 mmHg | Standard Error 4.14 |
| Placebo | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Systolic Blood Pressure | Day 14, 16-20 hours | -1.06 mmHg | Standard Error 3.53 |
| Placebo | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Systolic Blood Pressure | Day 14, 20-24 hours | -2.98 mmHg | Standard Error 3.82 |
| IW-1973 40 mg BID/QD | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Systolic Blood Pressure | Day 14, 12-16 hours | -3.52 mmHg | Standard Error 3.43 |
| IW-1973 40 mg BID/QD | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Systolic Blood Pressure | Time-matched baseline (Day -1): 0-4 hours | 128.18 mmHg | Standard Error 9.9 |
| IW-1973 40 mg BID/QD | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Systolic Blood Pressure | Day 7, 0-4 hours | -10.68 mmHg | Standard Error 2.35 |
| IW-1973 40 mg BID/QD | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Systolic Blood Pressure | Day 7, 16-20 hours | -5.14 mmHg | Standard Error 3.08 |
| IW-1973 40 mg BID/QD | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Systolic Blood Pressure | Time-matched baseline (Day -1): 4-8 hours | 130.04 mmHg | Standard Error 13.15 |
| IW-1973 40 mg BID/QD | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Systolic Blood Pressure | Day 1, 16-20 hours | -0.66 mmHg | Standard Error 3.19 |
| IW-1973 40 mg BID/QD | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Systolic Blood Pressure | Day 14, 8-12 hours | -11.43 mmHg | Standard Error 3.58 |
| IW-1973 40 mg BID/QD | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Systolic Blood Pressure | Time-matched baseline (Day -1): 8-12 hours | 133.67 mmHg | Standard Error 11.9 |
| IW-1973 40 mg BID/QD | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Systolic Blood Pressure | Day 7, 4-8 hours | -9.13 mmHg | Standard Error 2.65 |
| IW-1973 40 mg BID/QD | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Systolic Blood Pressure | Day 14, 16-20 hours | -2.79 mmHg | Standard Error 2.89 |
| IW-1973 40 mg BID/QD | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Systolic Blood Pressure | Time-matched baseline (Day -1): 12-16 hours | 124.00 mmHg | Standard Error 11.93 |
| IW-1973 40 mg BID/QD | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Systolic Blood Pressure | Day 1, 12-16 hours | -1.46 mmHg | Standard Error 2.37 |
| IW-1973 40 mg BID/QD | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Systolic Blood Pressure | Day 7, 20-24 hours | -4.94 mmHg | Standard Error 2.91 |
| IW-1973 40 mg BID/QD | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Systolic Blood Pressure | Time-matched baseline (Day -1): 16-20 hours | 119.75 mmHg | Standard Error 14.51 |
| IW-1973 40 mg BID/QD | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Systolic Blood Pressure | Day 7, 8-12 hours | -7.93 mmHg | Standard Error 2.8 |
| IW-1973 40 mg BID/QD | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Systolic Blood Pressure | Day 1, 20-24 hours | 1.27 mmHg | Standard Error 2.37 |
| IW-1973 40 mg BID/QD | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Systolic Blood Pressure | Time-matched baseline (Day -1): 20-24 hours | 122.77 mmHg | Standard Error 9.6 |
| IW-1973 40 mg BID/QD | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Systolic Blood Pressure | Day 1, 8-12 hours | -8.14 mmHg | Standard Error 2.91 |
| IW-1973 40 mg BID/QD | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Systolic Blood Pressure | Day 14, 20-24 hours | -1.00 mmHg | Standard Error 3.17 |
| IW-1973 40 mg BID/QD | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Systolic Blood Pressure | Day 1, 0-4 hours | -7.15 mmHg | Standard Error 2.27 |
| IW-1973 40 mg BID/QD | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Systolic Blood Pressure | Day 7, 12-16 hours | -5.03 mmHg | Standard Error 2.86 |
| IW-1973 40 mg BID/QD | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Systolic Blood Pressure | Day 14, 0-4 hours | -13.80 mmHg | Standard Error 3.1 |
| IW-1973 40 mg BID/QD | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Systolic Blood Pressure | Day 1, 4-8 hours | -8.67 mmHg | Standard Error 2.7 |
| IW-1973 40 mg BID/QD | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Systolic Blood Pressure | Day 14, 4-8 hours | -13.67 mmHg | Standard Error 2.95 |
| IW-1973 40 mg QD/QD | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Systolic Blood Pressure | Day 1, 4-8 hours | -8.89 mmHg | Standard Error 2.67 |
| IW-1973 40 mg QD/QD | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Systolic Blood Pressure | Day 1, 8-12 hours | -1.84 mmHg | Standard Error 2.88 |
| IW-1973 40 mg QD/QD | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Systolic Blood Pressure | Day 1, 12-16 hours | -2.00 mmHg | Standard Error 2.34 |
| IW-1973 40 mg QD/QD | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Systolic Blood Pressure | Day 1, 16-20 hours | -1.08 mmHg | Standard Error 3.19 |
| IW-1973 40 mg QD/QD | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Systolic Blood Pressure | Day 14, 4-8 hours | -8.53 mmHg | Standard Error 2.75 |
| IW-1973 40 mg QD/QD | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Systolic Blood Pressure | Day 1, 20-24 hours | -0.55 mmHg | Standard Error 2.27 |
| IW-1973 40 mg QD/QD | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Systolic Blood Pressure | Day 14, 16-20 hours | -6.61 mmHg | Standard Error 2.74 |
| IW-1973 40 mg QD/QD | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Systolic Blood Pressure | Day 7, 0-4 hours | -5.15 mmHg | Standard Error 2.35 |
| IW-1973 40 mg QD/QD | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Systolic Blood Pressure | Day 7, 4-8 hours | -4.07 mmHg | Standard Error 2.62 |
| IW-1973 40 mg QD/QD | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Systolic Blood Pressure | Day 14, 8-12 hours | -8.53 mmHg | Standard Error 3.31 |
| IW-1973 40 mg QD/QD | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Systolic Blood Pressure | Day 7, 8-12 hours | -2.33 mmHg | Standard Error 2.76 |
| IW-1973 40 mg QD/QD | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Systolic Blood Pressure | Day 14, 20-24 hours | -1.91 mmHg | Standard Error 2.84 |
| IW-1973 40 mg QD/QD | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Systolic Blood Pressure | Day 7, 12-16 hours | -1.97 mmHg | Standard Error 2.82 |
| IW-1973 40 mg QD/QD | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Systolic Blood Pressure | Time-matched baseline (Day -1): 0-4 hours | 128.38 mmHg | Standard Error 7.33 |
| IW-1973 40 mg QD/QD | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Systolic Blood Pressure | Time-matched baseline (Day -1): 4-8 hours | 132.53 mmHg | Standard Error 6.83 |
| IW-1973 40 mg QD/QD | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Systolic Blood Pressure | Day 7, 16-20 hours | -3.74 mmHg | Standard Error 3.08 |
| IW-1973 40 mg QD/QD | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Systolic Blood Pressure | Time-matched baseline (Day -1): 8-12 hours | 135.93 mmHg | Standard Error 8.51 |
| IW-1973 40 mg QD/QD | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Systolic Blood Pressure | Day 14, 12-16 hours | -8.75 mmHg | Standard Error 3.18 |
| IW-1973 40 mg QD/QD | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Systolic Blood Pressure | Time-matched baseline (Day -1): 12-16 hours | 128.44 mmHg | Standard Error 11.32 |
| IW-1973 40 mg QD/QD | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Systolic Blood Pressure | Time-matched baseline (Day -1): 16-20 hours | 120.41 mmHg | Standard Error 11 |
| IW-1973 40 mg QD/QD | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Systolic Blood Pressure | Day 7, 20-24 hours | -0.33 mmHg | Standard Error 2.8 |
| IW-1973 40 mg QD/QD | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Systolic Blood Pressure | Time-matched baseline (Day -1): 20-24 hours | 128.13 mmHg | Standard Error 7.19 |
| IW-1973 40 mg QD/QD | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Systolic Blood Pressure | Day 1, 0-4 hours | -4.08 mmHg | Standard Error 2.27 |
| IW-1973 40 mg QD/QD | Change From Time-Matched Baseline Over Time in ABPM 4-hour Averages of Systolic Blood Pressure | Day 14, 0-4 hours | -5.01 mmHg | Standard Error 2.9 |
Comparison: Day 1, 0-4 hours95% CI: [-13.51, 2.41]
Comparison: Day 1, 0-4 hours95% CI: [-10.41, 5.47]
Comparison: Day 1, 4-8 hours95% CI: [-17.36, 1.25]
Comparison: Day 1, 4-8 hours95% CI: [-17.42, 0.87]
Comparison: Day 1, 8-12 hours95% CI: [-19.43, 0.74]
Comparison: Day 1, 8-12 hours95% CI: [-12.95, 6.84]
Comparison: Day 1, 12-16 hours95% CI: [-4.74, 11.47]
Comparison: Day 1, 12-16 hours95% CI: [-5.1, 10.75]
Comparison: Day 1, 16-20 hours95% CI: [-15.23, 6.37]
Comparison: Day 1, 16-20 hours95% CI: [-15.65, 5.94]
Comparison: Day 1, 20-24 hours95% CI: [-9.1, 7.47]
Comparison: Day 1, 20-24 hours95% CI: [-10.42, 5.16]
Comparison: Day 7, 0-4 hours95% CI: [-13.8, 2.72]
Comparison: Day 7, 0-4 hours95% CI: [-8.25, 8.23]
Comparison: Day 7, 4-8 hours95% CI: [-12.01, 6.23]
Comparison: Day 7, 4-8 hours95% CI: [-6.78, 11.13]
Comparison: Day 7, 8-12 hours95% CI: [-13.93, 5.47]
Comparison: Day 7, 8-12 hours95% CI: [-8.14, 10.88]
Comparison: Day 7, 12-16 hours95% CI: [-10.32, 9.18]
Comparison: Day 7, 12-16 hours95% CI: [-7.04, 12.02]
Comparison: Day 7, 16-20 hours95% CI: [-18.33, 2.55]
Comparison: Day 7, 16-20 hours95% CI: [-16.92, 3.95]
Comparison: Day 7, 20-24 hours95% CI: [-14.03, 6.35]
Comparison: Day 7, 20-24 hours95% CI: [-8.8, 10.35]
Comparison: Day 14, 0-4 hours95% CI: [-17.79, 3.53]
Comparison: Day 14, 0-4 hours95% CI: [-8.59, 11.91]
Comparison: Day 14, 4-8 hours95% CI: [-16.17, 3.55]
Comparison: Day 14, 4-8 hours95% CI: [-10.6, 8.27]
Comparison: Day 14, 8-12 hours95% CI: [-19.13, 5.11]
Comparison: Day 14, 8-12 hours95% CI: [-15.55, 7.34]
Comparison: Day 14, 12-16 hours95% CI: [-9.63, 13.17]
Comparison: Day 14, 12-16 hours95% CI: [-14.25, 7.31]
Comparison: Day 14, 16-20 hours95% CI: [-11.24, 7.77]
Comparison: Day 14, 16-20 hours95% CI: [-14.83, 3.73]
Comparison: Day 14, 20-24 hours95% CI: [-8.85, 12.81]
Comparison: Day 14, 20-24 hours95% CI: [-8.68, 10.82]
Primary
Change From Time-Matched Baseline Over Time in ABPM Daytime (12-hour) Averages of Diastolic Blood Pressure
Daytime 12-hour average is the average of ABPM assessments over daytime 12-hour intervals from the time of dosing. Time-matched baseline is the daytime 12 hours average during Day -1.
Time frame: Time Matched Baseline (Day -1), Days 1, 7, and 14
Population: PD Population: all participants who received at least 1 dose of study drug and had at least 1 postdose PD assessment.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Time-Matched Baseline Over Time in ABPM Daytime (12-hour) Averages of Diastolic Blood Pressure | Time Matched Baseline (Day -1) | 80.71 mmHg | Standard Error 8.65 |
| Placebo | Change From Time-Matched Baseline Over Time in ABPM Daytime (12-hour) Averages of Diastolic Blood Pressure | Change at Day 1 | -0.88 mmHg | Standard Error 1.76 |
| Placebo | Change From Time-Matched Baseline Over Time in ABPM Daytime (12-hour) Averages of Diastolic Blood Pressure | Change at Day 7 | -2.36 mmHg | Standard Error 1.61 |
| Placebo | Change From Time-Matched Baseline Over Time in ABPM Daytime (12-hour) Averages of Diastolic Blood Pressure | Change at Day 14 | -1.59 mmHg | Standard Error 2.03 |
| IW-1973 40 mg BID/QD | Change From Time-Matched Baseline Over Time in ABPM Daytime (12-hour) Averages of Diastolic Blood Pressure | Change at Day 14 | -8.88 mmHg | Standard Error 1.59 |
| IW-1973 40 mg BID/QD | Change From Time-Matched Baseline Over Time in ABPM Daytime (12-hour) Averages of Diastolic Blood Pressure | Time Matched Baseline (Day -1) | 74.31 mmHg | Standard Error 9.19 |
| IW-1973 40 mg BID/QD | Change From Time-Matched Baseline Over Time in ABPM Daytime (12-hour) Averages of Diastolic Blood Pressure | Change at Day 7 | -5.66 mmHg | Standard Error 1.2 |
| IW-1973 40 mg BID/QD | Change From Time-Matched Baseline Over Time in ABPM Daytime (12-hour) Averages of Diastolic Blood Pressure | Change at Day 1 | -4.28 mmHg | Standard Error 1.31 |
| IW-1973 40 mg QD/QD | Change From Time-Matched Baseline Over Time in ABPM Daytime (12-hour) Averages of Diastolic Blood Pressure | Change at Day 14 | -6.69 mmHg | Standard Error 1.5 |
| IW-1973 40 mg QD/QD | Change From Time-Matched Baseline Over Time in ABPM Daytime (12-hour) Averages of Diastolic Blood Pressure | Change at Day 1 | -4.47 mmHg | Standard Error 1.31 |
| IW-1973 40 mg QD/QD | Change From Time-Matched Baseline Over Time in ABPM Daytime (12-hour) Averages of Diastolic Blood Pressure | Change at Day 7 | -4.36 mmHg | Standard Error 1.2 |
| IW-1973 40 mg QD/QD | Change From Time-Matched Baseline Over Time in ABPM Daytime (12-hour) Averages of Diastolic Blood Pressure | Time Matched Baseline (Day -1) | 74.20 mmHg | Standard Error 6.45 |
Comparison: Day 195% CI: [-8.01, 1.21]
Comparison: Day 195% CI: [-8.21, 1.02]
Comparison: Day 795% CI: [-7.53, 0.92]
Comparison: Day 795% CI: [-6.24, 2.23]
Comparison: Day 1495% CI: [-12.8, -1.79]
Comparison: Day 1495% CI: [-10.43, 0.23]
Primary
Change From Time-Matched Baseline Over Time in ABPM Daytime (12-hour) Averages of Mean Arterial Pressure
Daytime 12-hour average is the average of ABPM assessments over daytime 12-hour intervals from the time of dosing. Time-matched baseline is the daytime 12 hours average during Day -1.
Time frame: Time Matched Baseline (Day -1), Days 1, 7, and 14
Population: PD Population: all participants who received at least 1 dose of study drug and had at least 1 postdose PD assessment.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Time-Matched Baseline Over Time in ABPM Daytime (12-hour) Averages of Mean Arterial Pressure | Time Matched Baseline (Day -1) | 100.09 mmHg | Standard Error 7.14 |
| Placebo | Change From Time-Matched Baseline Over Time in ABPM Daytime (12-hour) Averages of Mean Arterial Pressure | Change at Day 1 | -0.20 mmHg | Standard Error 2.24 |
| Placebo | Change From Time-Matched Baseline Over Time in ABPM Daytime (12-hour) Averages of Mean Arterial Pressure | Change at Day 7 | -2.60 mmHg | Standard Error 2.01 |
| Placebo | Change From Time-Matched Baseline Over Time in ABPM Daytime (12-hour) Averages of Mean Arterial Pressure | Change at Day 14 | -1.97 mmHg | Standard Error 2.5 |
| IW-1973 40 mg BID/QD | Change From Time-Matched Baseline Over Time in ABPM Daytime (12-hour) Averages of Mean Arterial Pressure | Change at Day 14 | -10.71 mmHg | Standard Error 1.94 |
| IW-1973 40 mg BID/QD | Change From Time-Matched Baseline Over Time in ABPM Daytime (12-hour) Averages of Mean Arterial Pressure | Time Matched Baseline (Day -1) | 93.31 mmHg | Standard Error 7.36 |
| IW-1973 40 mg BID/QD | Change From Time-Matched Baseline Over Time in ABPM Daytime (12-hour) Averages of Mean Arterial Pressure | Change at Day 7 | -6.82 mmHg | Standard Error 1.48 |
| IW-1973 40 mg BID/QD | Change From Time-Matched Baseline Over Time in ABPM Daytime (12-hour) Averages of Mean Arterial Pressure | Change at Day 1 | -5.07 mmHg | Standard Error 1.65 |
| IW-1973 40 mg QD/QD | Change From Time-Matched Baseline Over Time in ABPM Daytime (12-hour) Averages of Mean Arterial Pressure | Change at Day 14 | -7.31 mmHg | Standard Error 1.79 |
| IW-1973 40 mg QD/QD | Change From Time-Matched Baseline Over Time in ABPM Daytime (12-hour) Averages of Mean Arterial Pressure | Change at Day 1 | -5.22 mmHg | Standard Error 1.63 |
| IW-1973 40 mg QD/QD | Change From Time-Matched Baseline Over Time in ABPM Daytime (12-hour) Averages of Mean Arterial Pressure | Change at Day 7 | -4.75 mmHg | Standard Error 1.46 |
| IW-1973 40 mg QD/QD | Change From Time-Matched Baseline Over Time in ABPM Daytime (12-hour) Averages of Mean Arterial Pressure | Time Matched Baseline (Day -1) | 94.00 mmHg | Standard Error 5.54 |
Comparison: Day 195% CI: [-10.8, 1.06]
Comparison: Day 195% CI: [-10.87, 0.83]
Comparison: Day 795% CI: [-9.55, 1.1]
Comparison: Day 795% CI: [-7.4, 3.11]
Comparison: Day 1495% CI: [-15.64, -1.85]
Comparison: Day 1495% CI: [-11.84, 1.15]
Primary
Change From Time-Matched Baseline Over Time in ABPM Daytime (12-hour) Averages of Pulse
Daytime 12-hour average is the average of ABPM assessments over daytime 12-hour intervals from the time of dosing. Time-matched baseline is the daytime 12 hours average during Day -1.
Time frame: Time Matched Baseline (Day -1), Days 1, 7, and 14
Population: PD Population: all participants who received at least 1 dose of study drug and had at least 1 postdose PD assessment.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Time-Matched Baseline Over Time in ABPM Daytime (12-hour) Averages of Pulse | Time Matched Baseline (Day -1) | 76.81 bpm | Standard Error 15 |
| Placebo | Change From Time-Matched Baseline Over Time in ABPM Daytime (12-hour) Averages of Pulse | Change at Day 1 | 0.14 bpm | Standard Error 1.84 |
| Placebo | Change From Time-Matched Baseline Over Time in ABPM Daytime (12-hour) Averages of Pulse | Change at Day 7 | -1.80 bpm | Standard Error 1.51 |
| Placebo | Change From Time-Matched Baseline Over Time in ABPM Daytime (12-hour) Averages of Pulse | Change at Day 14 | -0.46 bpm | Standard Error 1.59 |
| IW-1973 40 mg BID/QD | Change From Time-Matched Baseline Over Time in ABPM Daytime (12-hour) Averages of Pulse | Change at Day 14 | 2.66 bpm | Standard Error 1.3 |
| IW-1973 40 mg BID/QD | Change From Time-Matched Baseline Over Time in ABPM Daytime (12-hour) Averages of Pulse | Time Matched Baseline (Day -1) | 75.98 bpm | Standard Error 12.84 |
| IW-1973 40 mg BID/QD | Change From Time-Matched Baseline Over Time in ABPM Daytime (12-hour) Averages of Pulse | Change at Day 7 | 2.75 bpm | Standard Error 1.17 |
| IW-1973 40 mg BID/QD | Change From Time-Matched Baseline Over Time in ABPM Daytime (12-hour) Averages of Pulse | Change at Day 1 | 2.30 bpm | Standard Error 1.42 |
| IW-1973 40 mg QD/QD | Change From Time-Matched Baseline Over Time in ABPM Daytime (12-hour) Averages of Pulse | Change at Day 14 | 3.28 bpm | Standard Error 1.23 |
| IW-1973 40 mg QD/QD | Change From Time-Matched Baseline Over Time in ABPM Daytime (12-hour) Averages of Pulse | Change at Day 1 | 4.23 bpm | Standard Error 1.43 |
| IW-1973 40 mg QD/QD | Change From Time-Matched Baseline Over Time in ABPM Daytime (12-hour) Averages of Pulse | Change at Day 7 | 2.22 bpm | Standard Error 1.17 |
| IW-1973 40 mg QD/QD | Change From Time-Matched Baseline Over Time in ABPM Daytime (12-hour) Averages of Pulse | Time Matched Baseline (Day -1) | 78.18 bpm | Standard Error 11.47 |
Comparison: Day 195% CI: [-2.65, 6.99]
Comparison: Day 195% CI: [-0.73, 8.91]
Comparison: Day 795% CI: [0.6, 8.51]
Comparison: Day 795% CI: [0.07, 7.98]
Comparison: Day 1495% CI: [-1.15, 7.39]
Comparison: Day 1495% CI: [-0.44, 7.92]
Primary
Change From Time-Matched Baseline Over Time in ABPM Daytime (12-Hour) Averages of Systolic Blood Pressure
Daytime 12-hour average is the average of ABPM assessments over daytime 12-hour intervals from the time of dosing. Time-matched baseline is the daytime 12 hours average during Day -1.
Time frame: Time Matched Baseline (Day -1), Days 1, 7, and 14
Population: PD Population: all participants who received at least 1 dose of study drug and had at least 1 postdose PD assessment.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Time-Matched Baseline Over Time in ABPM Daytime (12-Hour) Averages of Systolic Blood Pressure | Time Matched Baseline (Day -1) | 136.99 mmHg | Standard Error 8.42 |
| Placebo | Change From Time-Matched Baseline Over Time in ABPM Daytime (12-Hour) Averages of Systolic Blood Pressure | Change at Day 1 | -0.74 mmHg | Standard Error 2.81 |
| Placebo | Change From Time-Matched Baseline Over Time in ABPM Daytime (12-Hour) Averages of Systolic Blood Pressure | Change at Day 7 | -5.27 mmHg | Standard Error 2.89 |
| Placebo | Change From Time-Matched Baseline Over Time in ABPM Daytime (12-Hour) Averages of Systolic Blood Pressure | Change at Day 14 | -6.37 mmHg | Standard Error 3.62 |
| IW-1973 40 mg BID/QD | Change From Time-Matched Baseline Over Time in ABPM Daytime (12-Hour) Averages of Systolic Blood Pressure | Change at Day 14 | -12.81 mmHg | Standard Error 2.92 |
| IW-1973 40 mg BID/QD | Change From Time-Matched Baseline Over Time in ABPM Daytime (12-Hour) Averages of Systolic Blood Pressure | Time Matched Baseline (Day -1) | 130.64 mmHg | Standard Error 10.82 |
| IW-1973 40 mg BID/QD | Change From Time-Matched Baseline Over Time in ABPM Daytime (12-Hour) Averages of Systolic Blood Pressure | Change at Day 7 | -9.09 mmHg | Standard Error 2.2 |
| IW-1973 40 mg BID/QD | Change From Time-Matched Baseline Over Time in ABPM Daytime (12-Hour) Averages of Systolic Blood Pressure | Change at Day 1 | -7.80 mmHg | Standard Error 2.14 |
| IW-1973 40 mg QD/QD | Change From Time-Matched Baseline Over Time in ABPM Daytime (12-Hour) Averages of Systolic Blood Pressure | Change at Day 14 | -7.40 mmHg | Standard Error 2.71 |
| IW-1973 40 mg QD/QD | Change From Time-Matched Baseline Over Time in ABPM Daytime (12-Hour) Averages of Systolic Blood Pressure | Change at Day 1 | -4.93 mmHg | Standard Error 2.12 |
| IW-1973 40 mg QD/QD | Change From Time-Matched Baseline Over Time in ABPM Daytime (12-Hour) Averages of Systolic Blood Pressure | Change at Day 7 | -3.85 mmHg | Standard Error 2.17 |
| IW-1973 40 mg QD/QD | Change From Time-Matched Baseline Over Time in ABPM Daytime (12-Hour) Averages of Systolic Blood Pressure | Time Matched Baseline (Day -1) | 132.28 mmHg | Standard Error 7.07 |
Comparison: Day 195% CI: [-14.52, 0.4]
Comparison: Day 195% CI: [-11.52, 3.14]
Comparison: Day 795% CI: [-11.47, 3.83]
Comparison: Day 795% CI: [-6.1, 8.94]
Comparison: Day 1495% CI: [-16.36, 3.47]
Comparison: Day 1495% CI: [-10.44, 8.38]
Primary
Change From Time-Matched Baseline Over Time in ABPM Nighttime (12-Hour) Averages of Diastolic Blood Pressure
Nighttime 12-hour average is the average of ABPM assessments over nighttime 12-hour intervals from the time of dosing. Time-matched baseline is the nighttime 12 hours average during Day -1.
Time frame: Time Matched Baseline (Day -1), Days 1, 7, and 14
Population: PD Population: all participants who received at least 1 dose of study drug and had at least 1 postdose PD assessment.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Time-Matched Baseline Over Time in ABPM Nighttime (12-Hour) Averages of Diastolic Blood Pressure | Time Matched Baseline (Day -1) | 73.42 mmHg | Standard Error 10.04 |
| Placebo | Change From Time-Matched Baseline Over Time in ABPM Nighttime (12-Hour) Averages of Diastolic Blood Pressure | Change at Day 1 | -2.02 mmHg | Standard Error 1.51 |
| Placebo | Change From Time-Matched Baseline Over Time in ABPM Nighttime (12-Hour) Averages of Diastolic Blood Pressure | Change at Day 7 | -0.42 mmHg | Standard Error 1.94 |
| Placebo | Change From Time-Matched Baseline Over Time in ABPM Nighttime (12-Hour) Averages of Diastolic Blood Pressure | Change at Day 14 | -0.81 mmHg | Standard Error 2.41 |
| IW-1973 40 mg BID/QD | Change From Time-Matched Baseline Over Time in ABPM Nighttime (12-Hour) Averages of Diastolic Blood Pressure | Change at Day 14 | -1.84 mmHg | Standard Error 1.92 |
| IW-1973 40 mg BID/QD | Change From Time-Matched Baseline Over Time in ABPM Nighttime (12-Hour) Averages of Diastolic Blood Pressure | Time Matched Baseline (Day -1) | 68.44 mmHg | Standard Error 8.6 |
| IW-1973 40 mg BID/QD | Change From Time-Matched Baseline Over Time in ABPM Nighttime (12-Hour) Averages of Diastolic Blood Pressure | Change at Day 7 | -2.96 mmHg | Standard Error 1.47 |
| IW-1973 40 mg BID/QD | Change From Time-Matched Baseline Over Time in ABPM Nighttime (12-Hour) Averages of Diastolic Blood Pressure | Change at Day 1 | -1.03 mmHg | Standard Error 1.14 |
| IW-1973 40 mg QD/QD | Change From Time-Matched Baseline Over Time in ABPM Nighttime (12-Hour) Averages of Diastolic Blood Pressure | Change at Day 14 | -4.48 mmHg | Standard Error 1.81 |
| IW-1973 40 mg QD/QD | Change From Time-Matched Baseline Over Time in ABPM Nighttime (12-Hour) Averages of Diastolic Blood Pressure | Change at Day 1 | -1.46 mmHg | Standard Error 1.14 |
| IW-1973 40 mg QD/QD | Change From Time-Matched Baseline Over Time in ABPM Nighttime (12-Hour) Averages of Diastolic Blood Pressure | Change at Day 7 | -2.68 mmHg | Standard Error 1.47 |
| IW-1973 40 mg QD/QD | Change From Time-Matched Baseline Over Time in ABPM Nighttime (12-Hour) Averages of Diastolic Blood Pressure | Time Matched Baseline (Day -1) | 68.36 mmHg | Standard Error 6.8 |
Comparison: Day 195% CI: [-2.97, 4.95]
Comparison: Day 195% CI: [-3.41, 4.52]
Comparison: Day 795% CI: [-7.63, 2.56]
Comparison: Day 795% CI: [-7.36, 2.85]
Comparison: Day 1495% CI: [-7.55, 5.49]
Comparison: Day 1495% CI: [-10, 2.65]
Primary
Change From Time-Matched Baseline Over Time in ABPM Nighttime (12-Hour) Averages of Mean Arterial Pressure
Nighttime 12-hour average is the average of ABPM assessments over nighttime 12-hour intervals from the time of dosing. Time-matched baseline is the nighttime 12 hours average during Day -1.
Time frame: Time Matched Baseline (Day -1), Days 1, 7, and 14
Population: PD Population: all participants who received at least 1 dose of study drug and had at least 1 postdose PD assessment.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Time-Matched Baseline Over Time in ABPM Nighttime (12-Hour) Averages of Mean Arterial Pressure | Time Matched Baseline (Day -1) | 91.93 mmHg | Standard Error 10.03 |
| Placebo | Change From Time-Matched Baseline Over Time in ABPM Nighttime (12-Hour) Averages of Mean Arterial Pressure | Change at Day 1 | -0.39 mmHg | Standard Error 1.67 |
| Placebo | Change From Time-Matched Baseline Over Time in ABPM Nighttime (12-Hour) Averages of Mean Arterial Pressure | Change at Day 7 | -0.47 mmHg | Standard Error 2.07 |
| Placebo | Change From Time-Matched Baseline Over Time in ABPM Nighttime (12-Hour) Averages of Mean Arterial Pressure | Change at Day 14 | -0.54 mmHg | Standard Error 2.46 |
| IW-1973 40 mg BID/QD | Change From Time-Matched Baseline Over Time in ABPM Nighttime (12-Hour) Averages of Mean Arterial Pressure | Change at Day 14 | -2.42 mmHg | Standard Error 1.97 |
| IW-1973 40 mg BID/QD | Change From Time-Matched Baseline Over Time in ABPM Nighttime (12-Hour) Averages of Mean Arterial Pressure | Time Matched Baseline (Day -1) | 86.85 mmHg | Standard Error 7.57 |
| IW-1973 40 mg BID/QD | Change From Time-Matched Baseline Over Time in ABPM Nighttime (12-Hour) Averages of Mean Arterial Pressure | Change at Day 7 | -3.79 mmHg | Standard Error 1.57 |
| IW-1973 40 mg BID/QD | Change From Time-Matched Baseline Over Time in ABPM Nighttime (12-Hour) Averages of Mean Arterial Pressure | Change at Day 1 | -0.84 mmHg | Standard Error 1.27 |
| IW-1973 40 mg QD/QD | Change From Time-Matched Baseline Over Time in ABPM Nighttime (12-Hour) Averages of Mean Arterial Pressure | Change at Day 14 | -4.83 mmHg | Standard Error 1.84 |
| IW-1973 40 mg QD/QD | Change From Time-Matched Baseline Over Time in ABPM Nighttime (12-Hour) Averages of Mean Arterial Pressure | Change at Day 1 | -1.10 mmHg | Standard Error 1.26 |
| IW-1973 40 mg QD/QD | Change From Time-Matched Baseline Over Time in ABPM Nighttime (12-Hour) Averages of Mean Arterial Pressure | Change at Day 7 | -2.20 mmHg | Standard Error 1.56 |
| IW-1973 40 mg QD/QD | Change From Time-Matched Baseline Over Time in ABPM Nighttime (12-Hour) Averages of Mean Arterial Pressure | Time Matched Baseline (Day -1) | 87.77 mmHg | Standard Error 6.37 |
Comparison: Day 195% CI: [-4.86, 3.96]
Comparison: Day 195% CI: [-5.07, 3.65]
Comparison: Day 795% CI: [-8.79, 2.14]
Comparison: Day 795% CI: [-7.14, 3.67]
Comparison: Day 1495% CI: [-8.58, 4.83]
Comparison: Day 1495% CI: [-10.69, 2.1]
Primary
Change From Time-Matched Baseline Over Time in ABPM Nighttime (12-Hour) Averages of Pulse
Nighttime 12-hour average is the average of ABPM assessments over nighttime 12-hour intervals from the time of dosing. Time-matched baseline is the nighttime 12 hours average during Day -1.
Time frame: Time Matched Baseline (Day -1), Days 1, 7, and 14
Population: PD Population: all participants who received at least 1 dose of study drug and had at least 1 postdose PD assessment.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Time-Matched Baseline Over Time in ABPM Nighttime (12-Hour) Averages of Pulse | Time Matched Baseline (Day -1) | 73.43 bpm | Standard Error 13.39 |
| Placebo | Change From Time-Matched Baseline Over Time in ABPM Nighttime (12-Hour) Averages of Pulse | Change at Day 1 | -2.01 bpm | Standard Error 1.21 |
| Placebo | Change From Time-Matched Baseline Over Time in ABPM Nighttime (12-Hour) Averages of Pulse | Change at Day 7 | -2.24 bpm | Standard Error 1.63 |
| Placebo | Change From Time-Matched Baseline Over Time in ABPM Nighttime (12-Hour) Averages of Pulse | Change at Day 14 | -0.40 bpm | Standard Error 1.79 |
| IW-1973 40 mg BID/QD | Change From Time-Matched Baseline Over Time in ABPM Nighttime (12-Hour) Averages of Pulse | Change at Day 14 | 1.48 bpm | Standard Error 1.46 |
| IW-1973 40 mg BID/QD | Change From Time-Matched Baseline Over Time in ABPM Nighttime (12-Hour) Averages of Pulse | Time Matched Baseline (Day -1) | 69.62 bpm | Standard Error 8.91 |
| IW-1973 40 mg BID/QD | Change From Time-Matched Baseline Over Time in ABPM Nighttime (12-Hour) Averages of Pulse | Change at Day 7 | 2.57 bpm | Standard Error 1.27 |
| IW-1973 40 mg BID/QD | Change From Time-Matched Baseline Over Time in ABPM Nighttime (12-Hour) Averages of Pulse | Change at Day 1 | 2.29 bpm | Standard Error 0.94 |
| IW-1973 40 mg QD/QD | Change From Time-Matched Baseline Over Time in ABPM Nighttime (12-Hour) Averages of Pulse | Change at Day 14 | 2.15 bpm | Standard Error 1.38 |
| IW-1973 40 mg QD/QD | Change From Time-Matched Baseline Over Time in ABPM Nighttime (12-Hour) Averages of Pulse | Change at Day 1 | 0.93 bpm | Standard Error 0.94 |
| IW-1973 40 mg QD/QD | Change From Time-Matched Baseline Over Time in ABPM Nighttime (12-Hour) Averages of Pulse | Change at Day 7 | 2.86 bpm | Standard Error 1.26 |
| IW-1973 40 mg QD/QD | Change From Time-Matched Baseline Over Time in ABPM Nighttime (12-Hour) Averages of Pulse | Time Matched Baseline (Day -1) | 72.54 bpm | Standard Error 10.46 |
Comparison: Day 195% CI: [1.1, 7.49]
Comparison: Day 195% CI: [-0.23, 6.1]
Comparison: Day 795% CI: [0.5, 9.11]
Comparison: Day 795% CI: [0.84, 9.36]
Comparison: Day 1495% CI: [-2.93, 6.7]
Comparison: Day 1495% CI: [-2.15, 7.25]
Primary
Change From Time-Matched Baseline Over Time in ABPM Nighttime (12-Hour) Averages of Systolic Blood Pressure
Nighttime 12-hour average is the average of ABPM assessments over nighttime 12-hour intervals from the time of dosing. Time-matched baseline is the nighttime 12 hours average during Day -1.
Time frame: Time Matched Baseline (Day -1), Days 1, 7, and 14
Population: PD Population: all participants who received at least 1 dose of study drug and had at least 1 postdose PD assessment.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Time-Matched Baseline Over Time in ABPM Nighttime (12-Hour) Averages of Systolic Blood Pressure | Time Matched Baseline (Day -1) | 126.76 mmHg | Standard Error 9.36 |
| Placebo | Change From Time-Matched Baseline Over Time in ABPM Nighttime (12-Hour) Averages of Systolic Blood Pressure | Change at Day 1 | 0.11 mmHg | Standard Error 2.55 |
| Placebo | Change From Time-Matched Baseline Over Time in ABPM Nighttime (12-Hour) Averages of Systolic Blood Pressure | Change at Day 7 | -1.42 mmHg | Standard Error 2.93 |
| Placebo | Change From Time-Matched Baseline Over Time in ABPM Nighttime (12-Hour) Averages of Systolic Blood Pressure | Change at Day 14 | -3.25 mmHg | Standard Error 3.17 |
| IW-1973 40 mg BID/QD | Change From Time-Matched Baseline Over Time in ABPM Nighttime (12-Hour) Averages of Systolic Blood Pressure | Change at Day 14 | -2.38 mmHg | Standard Error 2.63 |
| IW-1973 40 mg BID/QD | Change From Time-Matched Baseline Over Time in ABPM Nighttime (12-Hour) Averages of Systolic Blood Pressure | Time Matched Baseline (Day -1) | 121.77 mmHg | Standard Error 12.26 |
| IW-1973 40 mg BID/QD | Change From Time-Matched Baseline Over Time in ABPM Nighttime (12-Hour) Averages of Systolic Blood Pressure | Change at Day 7 | -4.54 mmHg | Standard Error 2.28 |
| IW-1973 40 mg BID/QD | Change From Time-Matched Baseline Over Time in ABPM Nighttime (12-Hour) Averages of Systolic Blood Pressure | Change at Day 1 | -0.11 mmHg | Standard Error 1.98 |
| IW-1973 40 mg QD/QD | Change From Time-Matched Baseline Over Time in ABPM Nighttime (12-Hour) Averages of Systolic Blood Pressure | Change at Day 14 | -6.23 mmHg | Standard Error 2.44 |
| IW-1973 40 mg QD/QD | Change From Time-Matched Baseline Over Time in ABPM Nighttime (12-Hour) Averages of Systolic Blood Pressure | Change at Day 1 | -1.50 mmHg | Standard Error 1.96 |
| IW-1973 40 mg QD/QD | Change From Time-Matched Baseline Over Time in ABPM Nighttime (12-Hour) Averages of Systolic Blood Pressure | Change at Day 7 | -2.25 mmHg | Standard Error 2.25 |
| IW-1973 40 mg QD/QD | Change From Time-Matched Baseline Over Time in ABPM Nighttime (12-Hour) Averages of Systolic Blood Pressure | Time Matched Baseline (Day -1) | 125.26 mmHg | Standard Error 7.24 |
Comparison: Day 195% CI: [-6.97, 6.54]
Comparison: Day 195% CI: [-8.24, 5.03]
Comparison: Day 795% CI: [-10.88, 4.65]
Comparison: Day 795% CI: [-8.45, 6.8]
Comparison: Day 1495% CI: [-7.84, 9.58]
Comparison: Day 1495% CI: [-11.23, 5.26]
Primary
Change From Time-Matched Baseline Over Time in Ambulatory Blood Pressure Monitoring (ABPM) 24-hour Averages of Systolic Blood Pressure
24-hour average is the average of ABPM assessments over 24 hour intervals from the time of dosing. Time-matched baseline is the 24 hours average during Day -1.
Time frame: Time Matched Baseline (Day -1), Days 1, 7, and 14
Population: PD Population: all participants who received at least 1 dose of study drug and had at least 1 postdose PD assessment.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Time-Matched Baseline Over Time in Ambulatory Blood Pressure Monitoring (ABPM) 24-hour Averages of Systolic Blood Pressure | Time Matched Baseline (Day -1) | 132.34 mmHg | Standard Error 8.22 |
| Placebo | Change From Time-Matched Baseline Over Time in Ambulatory Blood Pressure Monitoring (ABPM) 24-hour Averages of Systolic Blood Pressure | Change at Day 1 | -0.60 mmHg | Standard Error 2.39 |
| Placebo | Change From Time-Matched Baseline Over Time in Ambulatory Blood Pressure Monitoring (ABPM) 24-hour Averages of Systolic Blood Pressure | Change at Day 7 | -3.54 mmHg | Standard Error 2.68 |
| Placebo | Change From Time-Matched Baseline Over Time in Ambulatory Blood Pressure Monitoring (ABPM) 24-hour Averages of Systolic Blood Pressure | Change at Day 14 | -4.87 mmHg | Standard Error 3.17 |
| IW-1973 40 mg BID/QD | Change From Time-Matched Baseline Over Time in Ambulatory Blood Pressure Monitoring (ABPM) 24-hour Averages of Systolic Blood Pressure | Change at Day 1 | -3.92 mmHg | Standard Error 1.84 |
| IW-1973 40 mg BID/QD | Change From Time-Matched Baseline Over Time in Ambulatory Blood Pressure Monitoring (ABPM) 24-hour Averages of Systolic Blood Pressure | Change at Day 7 | -6.77 mmHg | Standard Error 2.07 |
| IW-1973 40 mg BID/QD | Change From Time-Matched Baseline Over Time in Ambulatory Blood Pressure Monitoring (ABPM) 24-hour Averages of Systolic Blood Pressure | Change at Day 14 | -7.58 mmHg | Standard Error 2.59 |
| IW-1973 40 mg BID/QD | Change From Time-Matched Baseline Over Time in Ambulatory Blood Pressure Monitoring (ABPM) 24-hour Averages of Systolic Blood Pressure | Time Matched Baseline (Day -1) | 126.40 mmHg | Standard Error 11.07 |
| IW-1973 40 mg QD/QD | Change From Time-Matched Baseline Over Time in Ambulatory Blood Pressure Monitoring (ABPM) 24-hour Averages of Systolic Blood Pressure | Change at Day 7 | -3.03 mmHg | Standard Error 2.04 |
| IW-1973 40 mg QD/QD | Change From Time-Matched Baseline Over Time in Ambulatory Blood Pressure Monitoring (ABPM) 24-hour Averages of Systolic Blood Pressure | Change at Day 1 | -3.15 mmHg | Standard Error 1.81 |
| IW-1973 40 mg QD/QD | Change From Time-Matched Baseline Over Time in Ambulatory Blood Pressure Monitoring (ABPM) 24-hour Averages of Systolic Blood Pressure | Change at Day 14 | -6.74 mmHg | Standard Error 2.39 |
| IW-1973 40 mg QD/QD | Change From Time-Matched Baseline Over Time in Ambulatory Blood Pressure Monitoring (ABPM) 24-hour Averages of Systolic Blood Pressure | Time Matched Baseline (Day -1) | 129.00 mmHg | Standard Error 6.48 |
| IW-1973 40 mg Total Daily Dose (Overall) | Change From Time-Matched Baseline Over Time in Ambulatory Blood Pressure Monitoring (ABPM) 24-hour Averages of Systolic Blood Pressure | Change at Day 14 | -7.16 mmHg | Standard Error 1.75 |
| IW-1973 40 mg Total Daily Dose (Overall) | Change From Time-Matched Baseline Over Time in Ambulatory Blood Pressure Monitoring (ABPM) 24-hour Averages of Systolic Blood Pressure | Change at Day 1 | -3.53 mmHg | Standard Error 1.29 |
| IW-1973 40 mg Total Daily Dose (Overall) | Change From Time-Matched Baseline Over Time in Ambulatory Blood Pressure Monitoring (ABPM) 24-hour Averages of Systolic Blood Pressure | Time Matched Baseline (Day -1) | 127.70 mmHg | Standard Error 8.93 |
| IW-1973 40 mg Total Daily Dose (Overall) | Change From Time-Matched Baseline Over Time in Ambulatory Blood Pressure Monitoring (ABPM) 24-hour Averages of Systolic Blood Pressure | Change at Day 7 | -4.90 mmHg | Standard Error 1.45 |
Comparison: Day 1495% CI: [-9.93, 5.35]
Comparison: Day 195% CI: [-9.68, 3.04]
Comparison: Day 195% CI: [-8.76, 3.66]
Comparison: Day 195% CI: [-8.62, 2.75]
Comparison: Day 795% CI: [-10.37, 3.92]
Comparison: Day 795% CI: [-6.46, 7.49]
Comparison: Day 795% CI: [-7.74, 5.03]
Comparison: Day 1495% CI: [-11.46, 6.04]
Comparison: Day 1495% CI: [-10.09, 6.35]
Primary
IW-1973 Pharmacokinetics: Apparent Terminal Elimination Phase Half-Life (t1/2)
Time frame: Day 14 (final dose) time points 12 hours, 24 hours, 7 days after final dose (Day 21), and 28 days after final dose(Day 42)
Population: PK Population: all participants who received ≥1 dose of IW-1973 and had ≥1 postdose PK parameter assessment without events or deviations affecting the PK results.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | IW-1973 Pharmacokinetics: Apparent Terminal Elimination Phase Half-Life (t1/2) | 197 hours | Standard Deviation 57.4 |
| IW-1973 40 mg BID/QD | IW-1973 Pharmacokinetics: Apparent Terminal Elimination Phase Half-Life (t1/2) | 183 hours | Standard Deviation 43.4 |
Primary
IW-1973 Pharmacokinetics: Apparent Total Body Clearance (CL/F) on Day 14
Time frame: Day 14: 1, 3, 6h (± 5 min) postdose
Population: PK Population: all participants who received ≥1 dose of IW-1973 and had ≥1 postdose PK parameter assessment without events or deviations affecting the PK results.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | IW-1973 Pharmacokinetics: Apparent Total Body Clearance (CL/F) on Day 14 | 20.0 L/h | Standard Deviation 4.34 |
| IW-1973 40 mg BID/QD | IW-1973 Pharmacokinetics: Apparent Total Body Clearance (CL/F) on Day 14 | 14.7 L/h | Standard Deviation 3.89 |
Primary
IW-1973 Pharmacokinetics: Apparent Volume of Distribution During the Terminal Phase (Vz/F) on Day 14
Time frame: Day 14: 1, 3, 6h (± 5 min) postdose
Population: PK Population: all participants who received ≥1 dose of IW-1973 and had ≥1 postdose PK parameter assessment without events or deviations affecting the PK results.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | IW-1973 Pharmacokinetics: Apparent Volume of Distribution During the Terminal Phase (Vz/F) on Day 14 | 5570 L | Standard Deviation 1530 |
| IW-1973 40 mg BID/QD | IW-1973 Pharmacokinetics: Apparent Volume of Distribution During the Terminal Phase (Vz/F) on Day 14 | 3880 L | Standard Deviation 1370 |
Primary
IW-1973 Pharmacokinetics: Area Under the Plasma Concentration Time Curve During a Dosing Interval (AUCtau) on Days 1 and 7
Equivalent to AUC from time 0 to the last measurable concentration (AUClast), with time of last measurable concentration (Tlast)=12 hours for BID dosing and Tlast=24 hours for QD dosing.
Time frame: Days 1 and 7 (AM): 1, 3, and 6 hours postdose
Population: Pharmacokinetic (PK) Population: all participants who received ≥1 dose of IW-1973 and had ≥1 postdose PK parameter assessment without events or deviations affecting the PK results.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | IW-1973 Pharmacokinetics: Area Under the Plasma Concentration Time Curve During a Dosing Interval (AUCtau) on Days 1 and 7 | Day 1 | 362 h*ng/mL | Standard Deviation 88 |
| Placebo | IW-1973 Pharmacokinetics: Area Under the Plasma Concentration Time Curve During a Dosing Interval (AUCtau) on Days 1 and 7 | Day 7 | 795 h*ng/mL | Standard Deviation 186 |
| IW-1973 40 mg BID/QD | IW-1973 Pharmacokinetics: Area Under the Plasma Concentration Time Curve During a Dosing Interval (AUCtau) on Days 1 and 7 | Day 1 | 339 h*ng/mL | Standard Deviation 134 |
| IW-1973 40 mg QD/QD | IW-1973 Pharmacokinetics: Area Under the Plasma Concentration Time Curve During a Dosing Interval (AUCtau) on Days 1 and 7 | Day 1 | 1190 h*ng/mL | Standard Deviation 499 |
| IW-1973 40 mg QD/QD | IW-1973 Pharmacokinetics: Area Under the Plasma Concentration Time Curve During a Dosing Interval (AUCtau) on Days 1 and 7 | Day 7 | 2200 h*ng/mL | Standard Deviation 591 |
Primary
IW-1973 Pharmacokinetics: Area Under the Plasma Concentration Time Curve From Time Zero to the Last Measurable Plasma Concentration (AUClast) on Days 8 and 14
Time frame: Day 8 and 14: 1, 3, 6h (± 5 min) postdose
Population: PK Population: all participants who received ≥1 dose of IW-1973 and had ≥1 postdose PK parameter assessment without events or deviations affecting the PK results.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | IW-1973 Pharmacokinetics: Area Under the Plasma Concentration Time Curve From Time Zero to the Last Measurable Plasma Concentration (AUClast) on Days 8 and 14 | Day 8 | 1210 h*mg/mL | Standard Deviation 264 |
| Placebo | IW-1973 Pharmacokinetics: Area Under the Plasma Concentration Time Curve From Time Zero to the Last Measurable Plasma Concentration (AUClast) on Days 8 and 14 | Day 14 | 17100 h*mg/mL | Standard Deviation 6980 |
| IW-1973 40 mg BID/QD | IW-1973 Pharmacokinetics: Area Under the Plasma Concentration Time Curve From Time Zero to the Last Measurable Plasma Concentration (AUClast) on Days 8 and 14 | Day 8 | 1540 h*mg/mL | Standard Deviation 482 |
| IW-1973 40 mg BID/QD | IW-1973 Pharmacokinetics: Area Under the Plasma Concentration Time Curve From Time Zero to the Last Measurable Plasma Concentration (AUClast) on Days 8 and 14 | Day 14 | 23600 h*mg/mL | Standard Deviation 8950 |
Primary
IW-1973 Pharmacokinetics: AUCtau on Day 14
Time frame: Day 14: 1, 3, 6h (± 5 min) postdose
Population: PK Population: all participants who received ≥1 dose of IW-1973 and had ≥1 postdose PK parameter assessment without events or deviations affecting the PK results.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | IW-1973 Pharmacokinetics: AUCtau on Day 14 | 2080 ng/mL | Standard Deviation 442 |
| IW-1973 40 mg BID/QD | IW-1973 Pharmacokinetics: AUCtau on Day 14 | 2910 ng/mL | Standard Deviation 770 |
Primary
IW-1973 Pharmacokinetics: Cmax on Days 8 and 14
Time frame: Day 8 and 14: 1, 3, 6h (± 5 min) postdose
Population: PK Population: all participants who received ≥1 dose of IW-1973 and had ≥1 postdose PK parameter assessment without events or deviations affecting the PK results.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | IW-1973 Pharmacokinetics: Cmax on Days 8 and 14 | Day 8 | 198 ng/mL | Standard Deviation 56.8 |
| Placebo | IW-1973 Pharmacokinetics: Cmax on Days 8 and 14 | Day 14 | 181 ng/mL | Standard Deviation 46.8 |
| IW-1973 40 mg BID/QD | IW-1973 Pharmacokinetics: Cmax on Days 8 and 14 | Day 8 | 229 ng/mL | Standard Deviation 90.6 |
| IW-1973 40 mg BID/QD | IW-1973 Pharmacokinetics: Cmax on Days 8 and 14 | Day 14 | 250 ng/mL | Standard Deviation 139 |
Primary
IW-1973 Pharmacokinetics: Ctrough on Days 13 and 14
Time frame: Days 13 and 14: predose
Population: PK Population: all participants who received ≥1 dose of IW-1973 and had ≥1 postdose PK parameter assessment without events or deviations affecting the PK results.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | IW-1973 Pharmacokinetics: Ctrough on Days 13 and 14 | Day 13 | 56.8 ng/mL | Standard Deviation 19.5 |
| Placebo | IW-1973 Pharmacokinetics: Ctrough on Days 13 and 14 | Day 14 | 65.7 ng/mL | Standard Deviation 23 |
| IW-1973 40 mg BID/QD | IW-1973 Pharmacokinetics: Ctrough on Days 13 and 14 | Day 13 | 82.4 ng/mL | Standard Deviation 22.7 |
| IW-1973 40 mg BID/QD | IW-1973 Pharmacokinetics: Ctrough on Days 13 and 14 | Day 14 | 90.7 ng/mL | Standard Deviation 26.2 |
Primary
IW-1973 Pharmacokinetics: Maximum Observed Plasma Concentration (Cmax) on Days 1 and 7
Time frame: Days 1 and 7 (AM): 1, 3, and 6 hours postdose
Population: PK Population: all participants who received ≥1 dose of IW-1973 and had ≥1 postdose PK parameter assessment without events or deviations affecting the PK results.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | IW-1973 Pharmacokinetics: Maximum Observed Plasma Concentration (Cmax) on Days 1 and 7 | Day 1 | 73.8 ng/mL | Standard Deviation 18.9 |
| Placebo | IW-1973 Pharmacokinetics: Maximum Observed Plasma Concentration (Cmax) on Days 1 and 7 | Day 7 | 117 ng/mL | Standard Deviation 32.6 |
| IW-1973 40 mg BID/QD | IW-1973 Pharmacokinetics: Maximum Observed Plasma Concentration (Cmax) on Days 1 and 7 | Day 1 | 47.8 ng/mL | Standard Deviation 22.2 |
| IW-1973 40 mg QD/QD | IW-1973 Pharmacokinetics: Maximum Observed Plasma Concentration (Cmax) on Days 1 and 7 | Day 1 | 181 ng/mL | Standard Deviation 107 |
| IW-1973 40 mg QD/QD | IW-1973 Pharmacokinetics: Maximum Observed Plasma Concentration (Cmax) on Days 1 and 7 | Day 7 | 242 ng/mL | Standard Deviation 80 |
Primary
IW-1973 Pharmacokinetics: Time to Cmax on Days 1 and 7
Time frame: Days 1 and 7 (AM): 1, 3, and 6 hours postdose
Population: PK Population: all participants who received ≥1 dose of IW-1973 and had ≥1 postdose PK parameter assessment without events or deviations affecting the PK results.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Placebo | IW-1973 Pharmacokinetics: Time to Cmax on Days 1 and 7 | Day 1 | 1.0 hours |
| Placebo | IW-1973 Pharmacokinetics: Time to Cmax on Days 1 and 7 | Day 7 | 1.0 hours |
| IW-1973 40 mg BID/QD | IW-1973 Pharmacokinetics: Time to Cmax on Days 1 and 7 | Day 1 | 3.0 hours |
| IW-1973 40 mg QD/QD | IW-1973 Pharmacokinetics: Time to Cmax on Days 1 and 7 | Day 1 | 2.0 hours |
| IW-1973 40 mg QD/QD | IW-1973 Pharmacokinetics: Time to Cmax on Days 1 and 7 | Day 7 | 1.0 hours |
Primary
IW-1973 Pharmacokinetics: Tmax on Days 8 and 14
Time frame: Day 8 and 14: 1, 3, 6h (± 5 min) postdose
Population: PK Population: all participants who received ≥1 dose of IW-1973 and had ≥1 postdose PK parameter assessment without events or deviations affecting the PK results.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Placebo | IW-1973 Pharmacokinetics: Tmax on Days 8 and 14 | Day 14 | 1.0 hours |
| Placebo | IW-1973 Pharmacokinetics: Tmax on Days 8 and 14 | Day 8 | 1.0 hours |
| IW-1973 40 mg BID/QD | IW-1973 Pharmacokinetics: Tmax on Days 8 and 14 | Day 14 | 3.0 hours |
| IW-1973 40 mg BID/QD | IW-1973 Pharmacokinetics: Tmax on Days 8 and 14 | Day 8 | 1.0 hours |
Primary
IW-1973 Pharmacokinetics: Trough Plasma Concentrations at the End of the Dosing Interval (Ctrough) on Days 1, 2, 6, 7
Time frame: Days 1 and 7: predose; Day 2 (BID AM): predose; Day 6 (BID PM/QD): predose
Population: PK Population: all participants who received ≥1 dose of IW-1973 and had ≥1 postdose PK parameter assessment without events or deviations affecting the PK results.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | IW-1973 Pharmacokinetics: Trough Plasma Concentrations at the End of the Dosing Interval (Ctrough) on Days 1, 2, 6, 7 | Day 2 | 21.0 ng/mL | Standard Deviation 5.97 |
| Placebo | IW-1973 Pharmacokinetics: Trough Plasma Concentrations at the End of the Dosing Interval (Ctrough) on Days 1, 2, 6, 7 | Day 1 | 11.6 ng/mL | Standard Deviation 4.29 |
| Placebo | IW-1973 Pharmacokinetics: Trough Plasma Concentrations at the End of the Dosing Interval (Ctrough) on Days 1, 2, 6, 7 | Day 7 | 45.6 ng/mL | Standard Deviation 14.5 |
| IW-1973 40 mg BID/QD | IW-1973 Pharmacokinetics: Trough Plasma Concentrations at the End of the Dosing Interval (Ctrough) on Days 1, 2, 6, 7 | Day 6 | 48.4 ng/mL | Standard Deviation 10.1 |
| IW-1973 40 mg BID/QD | IW-1973 Pharmacokinetics: Trough Plasma Concentrations at the End of the Dosing Interval (Ctrough) on Days 1, 2, 6, 7 | Day 1 | 19.6 ng/mL | Standard Deviation 5.04 |
| IW-1973 40 mg BID/QD | IW-1973 Pharmacokinetics: Trough Plasma Concentrations at the End of the Dosing Interval (Ctrough) on Days 1, 2, 6, 7 | Day 7 | 52.4 ng/mL | Standard Deviation 12.8 |
| IW-1973 40 mg QD/QD | IW-1973 Pharmacokinetics: Trough Plasma Concentrations at the End of the Dosing Interval (Ctrough) on Days 1, 2, 6, 7 | Day 1 | 15.6 ng/mL | Standard Deviation 5.24 |
| IW-1973 40 mg QD/QD | IW-1973 Pharmacokinetics: Trough Plasma Concentrations at the End of the Dosing Interval (Ctrough) on Days 1, 2, 6, 7 | Day 7 | 57.2 ng/mL | Standard Deviation 14.9 |
| IW-1973 40 mg QD/QD | IW-1973 Pharmacokinetics: Trough Plasma Concentrations at the End of the Dosing Interval (Ctrough) on Days 1, 2, 6, 7 | Day 6 | 53.7 ng/mL | Standard Deviation 14.5 |
Primary
Number of Participants With Clinically Meaningful Postbaseline Laboratory Test Results
Time frame: From first dose of study drug to End of Trial Visit (42 [± 3] days)
Population: Safety Population: participants who received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Number of Participants With Clinically Meaningful Postbaseline Laboratory Test Results | 0 participants |
| IW-1973 40 mg BID/QD | Number of Participants With Clinically Meaningful Postbaseline Laboratory Test Results | 1 participants |
| IW-1973 40 mg QD/QD | Number of Participants With Clinically Meaningful Postbaseline Laboratory Test Results | 1 participants |
Primary
Number of Participants With Clinically Significant Postbaseline 12-Lead Electrocardiogram (ECG) Results
Time frame: From first dose of study drug to End of Trial Visit (42 [± 3] days)
Population: Safety Population: participants who received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Number of Participants With Clinically Significant Postbaseline 12-Lead Electrocardiogram (ECG) Results | 0 participants |
| IW-1973 40 mg BID/QD | Number of Participants With Clinically Significant Postbaseline 12-Lead Electrocardiogram (ECG) Results | 0 participants |
| IW-1973 40 mg QD/QD | Number of Participants With Clinically Significant Postbaseline 12-Lead Electrocardiogram (ECG) Results | 0 participants |
Primary
Number of Participants With Clinically Significant Post-Randomization Physical Examination Findings
Physical examinations included examination and assessment of the following: general appearance, lymph nodes, skin, cardiovascular system, head, eyes, ears, nose, and throat, central nervous system, respiratory system, neck, peripheral nervous system, abdomen/liver/spleen, musculoskeletal system.
Time frame: Post-randomization to End of Trial Visit (42 [± 3] days)
Population: Safety Population: participants who received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Number of Participants With Clinically Significant Post-Randomization Physical Examination Findings | 0 participants |
| IW-1973 40 mg BID/QD | Number of Participants With Clinically Significant Post-Randomization Physical Examination Findings | 0 participants |
| IW-1973 40 mg QD/QD | Number of Participants With Clinically Significant Post-Randomization Physical Examination Findings | 0 participants |
Primary
Number of Participants With Notable Changes in Postbaseline Blood Pressure and Heart Rate Values
Supine systolic blood pressure (SSBP): ≥ 180 mmHg and increase (↑) from baseline (BL) ≥ 30 mmHg; ≤ 90 mmHg and decrease (↓) from BL ≥ 30 mmHg. Supine diastolic blood pressure (SDBP): ≥ 105 mmHg and ↑ from BL ≥ 20 mmHg; ≤ 50 mmHg and ↓ from BL ≥ 20 mmHg. Supine heart rate (SHR): ≥ 110 bpm and ↑ from BL ≥ 20 bpm; ≤ 50 bpm and ↓ from BL ≥ 20 bpm. Standing systolic blood pressure (StSBP): ≥ 180 mmHg and increase (↑) from baseline (BL) ≥ 30 mmHg; ≤ 90 mmHg and decrease (↓) from BL ≥ 30 mmHg. Standing Diastolic Blood Pressure (StDBP): ≥ 105 mmHg and ↑ from BL ≥ 20 mmHg; ≤ 50 mmHg and ↓ from BL ≥ 20 mmHg. Standing heart rate (StHR): ≥ 110 bpm and ↑ from BL ≥ 20 bpm; ≤ 50 bpm and ↓ from BL ≥ 20 bpm. Orthostatic systolic blood pressure (SBP): ↓ \> 20 mmHg from supine to standing. Orthostatic diastolic blood pressure (DBP): ↓ \> 15 mmHg from supine to standing. Orthostatic HR: ↓ \> 30 bpm from supine to standing.
Time frame: From first dose of study drug to End of Trial Visit (42 [± 3] days)
Population: Safety Population: participants who received at least 1 dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Number of Participants With Notable Changes in Postbaseline Blood Pressure and Heart Rate Values | SHR: ≤ 50 bpm and ↓ from BL ≥ 20 bpm | 1 participants |
| Placebo | Number of Participants With Notable Changes in Postbaseline Blood Pressure and Heart Rate Values | SDBP: ≥ 105 mmHg and ↑ from BL ≥ 20 mmHg | 0 participants |
| Placebo | Number of Participants With Notable Changes in Postbaseline Blood Pressure and Heart Rate Values | StHR: ≥ 120 bpm and ↑ from BL ≥ 25 bpm | 0 participants |
| Placebo | Number of Participants With Notable Changes in Postbaseline Blood Pressure and Heart Rate Values | StSBP: ≥ 180 mmHg and ↑ from BL ≥ 30 mmHg | 0 participants |
| Placebo | Number of Participants With Notable Changes in Postbaseline Blood Pressure and Heart Rate Values | SSBP: ≤ 90 mmHg and ↓ from BL ≥ 30 mmHg | 0 participants |
| Placebo | Number of Participants With Notable Changes in Postbaseline Blood Pressure and Heart Rate Values | StDBP: ≤ 50 mmHg and ↓ from BL ≥ 20 mmHg | 0 participants |
| Placebo | Number of Participants With Notable Changes in Postbaseline Blood Pressure and Heart Rate Values | StSBP: ≤ 90 mmHg and ↓ from BL ≥ 30 mmHg | 0 participants |
| Placebo | Number of Participants With Notable Changes in Postbaseline Blood Pressure and Heart Rate Values | Orthostatic SBP: ↓ > 20 mmHg, Supine to Standing | 2 participants |
| Placebo | Number of Participants With Notable Changes in Postbaseline Blood Pressure and Heart Rate Values | StDBP: ≥ 105 mmHg and ↑ from BL ≥ 20 mmHg | 0 participants |
| Placebo | Number of Participants With Notable Changes in Postbaseline Blood Pressure and Heart Rate Values | SDBP: ≤ 50 mmHg and ↓ from BL ≥ 20 mmHg | 0 participants |
| Placebo | Number of Participants With Notable Changes in Postbaseline Blood Pressure and Heart Rate Values | Orthostatic HR: ↑ > 30 bpm, Supine to Standing | 2 participants |
| Placebo | Number of Participants With Notable Changes in Postbaseline Blood Pressure and Heart Rate Values | SSBP: ≥ 180 mmHg and ↑ from BL ≥ 30 mmHg | 0 participants |
| Placebo | Number of Participants With Notable Changes in Postbaseline Blood Pressure and Heart Rate Values | SHR: ≥ 110 bpm and ↑ from BL ≥ 20 bpm | 1 participants |
| Placebo | Number of Participants With Notable Changes in Postbaseline Blood Pressure and Heart Rate Values | Orthostatic DBP: ↓ > 15 mmHg, Supine to Standing | 1 participants |
| Placebo | Number of Participants With Notable Changes in Postbaseline Blood Pressure and Heart Rate Values | StHR: ≤ 50 bpm and ↓ from BL ≥ 20 bpm | 0 participants |
| IW-1973 40 mg BID/QD | Number of Participants With Notable Changes in Postbaseline Blood Pressure and Heart Rate Values | StHR: ≤ 50 bpm and ↓ from BL ≥ 20 bpm | 0 participants |
| IW-1973 40 mg BID/QD | Number of Participants With Notable Changes in Postbaseline Blood Pressure and Heart Rate Values | SSBP: ≥ 180 mmHg and ↑ from BL ≥ 30 mmHg | 0 participants |
| IW-1973 40 mg BID/QD | Number of Participants With Notable Changes in Postbaseline Blood Pressure and Heart Rate Values | SSBP: ≤ 90 mmHg and ↓ from BL ≥ 30 mmHg | 1 participants |
| IW-1973 40 mg BID/QD | Number of Participants With Notable Changes in Postbaseline Blood Pressure and Heart Rate Values | SDBP: ≥ 105 mmHg and ↑ from BL ≥ 20 mmHg | 0 participants |
| IW-1973 40 mg BID/QD | Number of Participants With Notable Changes in Postbaseline Blood Pressure and Heart Rate Values | SDBP: ≤ 50 mmHg and ↓ from BL ≥ 20 mmHg | 2 participants |
| IW-1973 40 mg BID/QD | Number of Participants With Notable Changes in Postbaseline Blood Pressure and Heart Rate Values | SHR: ≥ 110 bpm and ↑ from BL ≥ 20 bpm | 2 participants |
| IW-1973 40 mg BID/QD | Number of Participants With Notable Changes in Postbaseline Blood Pressure and Heart Rate Values | SHR: ≤ 50 bpm and ↓ from BL ≥ 20 bpm | 0 participants |
| IW-1973 40 mg BID/QD | Number of Participants With Notable Changes in Postbaseline Blood Pressure and Heart Rate Values | StSBP: ≥ 180 mmHg and ↑ from BL ≥ 30 mmHg | 0 participants |
| IW-1973 40 mg BID/QD | Number of Participants With Notable Changes in Postbaseline Blood Pressure and Heart Rate Values | StSBP: ≤ 90 mmHg and ↓ from BL ≥ 30 mmHg | 2 participants |
| IW-1973 40 mg BID/QD | Number of Participants With Notable Changes in Postbaseline Blood Pressure and Heart Rate Values | StDBP: ≥ 105 mmHg and ↑ from BL ≥ 20 mmHg | 0 participants |
| IW-1973 40 mg BID/QD | Number of Participants With Notable Changes in Postbaseline Blood Pressure and Heart Rate Values | StDBP: ≤ 50 mmHg and ↓ from BL ≥ 20 mmHg | 1 participants |
| IW-1973 40 mg BID/QD | Number of Participants With Notable Changes in Postbaseline Blood Pressure and Heart Rate Values | StHR: ≥ 120 bpm and ↑ from BL ≥ 25 bpm | 1 participants |
| IW-1973 40 mg BID/QD | Number of Participants With Notable Changes in Postbaseline Blood Pressure and Heart Rate Values | Orthostatic SBP: ↓ > 20 mmHg, Supine to Standing | 4 participants |
| IW-1973 40 mg BID/QD | Number of Participants With Notable Changes in Postbaseline Blood Pressure and Heart Rate Values | Orthostatic DBP: ↓ > 15 mmHg, Supine to Standing | 1 participants |
| IW-1973 40 mg BID/QD | Number of Participants With Notable Changes in Postbaseline Blood Pressure and Heart Rate Values | Orthostatic HR: ↑ > 30 bpm, Supine to Standing | 2 participants |
| IW-1973 40 mg QD/QD | Number of Participants With Notable Changes in Postbaseline Blood Pressure and Heart Rate Values | SHR: ≤ 50 bpm and ↓ from BL ≥ 20 bpm | 0 participants |
| IW-1973 40 mg QD/QD | Number of Participants With Notable Changes in Postbaseline Blood Pressure and Heart Rate Values | Orthostatic DBP: ↓ > 15 mmHg, Supine to Standing | 0 participants |
| IW-1973 40 mg QD/QD | Number of Participants With Notable Changes in Postbaseline Blood Pressure and Heart Rate Values | StHR: ≥ 120 bpm and ↑ from BL ≥ 25 bpm | 1 participants |
| IW-1973 40 mg QD/QD | Number of Participants With Notable Changes in Postbaseline Blood Pressure and Heart Rate Values | SHR: ≥ 110 bpm and ↑ from BL ≥ 20 bpm | 0 participants |
| IW-1973 40 mg QD/QD | Number of Participants With Notable Changes in Postbaseline Blood Pressure and Heart Rate Values | SDBP: ≤ 50 mmHg and ↓ from BL ≥ 20 mmHg | 0 participants |
| IW-1973 40 mg QD/QD | Number of Participants With Notable Changes in Postbaseline Blood Pressure and Heart Rate Values | StHR: ≤ 50 bpm and ↓ from BL ≥ 20 bpm | 0 participants |
| IW-1973 40 mg QD/QD | Number of Participants With Notable Changes in Postbaseline Blood Pressure and Heart Rate Values | SDBP: ≥ 105 mmHg and ↑ from BL ≥ 20 mmHg | 0 participants |
| IW-1973 40 mg QD/QD | Number of Participants With Notable Changes in Postbaseline Blood Pressure and Heart Rate Values | SSBP: ≥ 180 mmHg and ↑ from BL ≥ 30 mmHg | 0 participants |
| IW-1973 40 mg QD/QD | Number of Participants With Notable Changes in Postbaseline Blood Pressure and Heart Rate Values | Orthostatic SBP: ↓ > 20 mmHg, Supine to Standing | 3 participants |
| IW-1973 40 mg QD/QD | Number of Participants With Notable Changes in Postbaseline Blood Pressure and Heart Rate Values | StSBP: ≤ 90 mmHg and ↓ from BL ≥ 30 mmHg | 0 participants |
| IW-1973 40 mg QD/QD | Number of Participants With Notable Changes in Postbaseline Blood Pressure and Heart Rate Values | SSBP: ≤ 90 mmHg and ↓ from BL ≥ 30 mmHg | 0 participants |
| IW-1973 40 mg QD/QD | Number of Participants With Notable Changes in Postbaseline Blood Pressure and Heart Rate Values | StDBP: ≥ 105 mmHg and ↑ from BL ≥ 20 mmHg | 0 participants |
| IW-1973 40 mg QD/QD | Number of Participants With Notable Changes in Postbaseline Blood Pressure and Heart Rate Values | StSBP: ≥ 180 mmHg and ↑ from BL ≥ 30 mmHg | 0 participants |
| IW-1973 40 mg QD/QD | Number of Participants With Notable Changes in Postbaseline Blood Pressure and Heart Rate Values | Orthostatic HR: ↑ > 30 bpm, Supine to Standing | 1 participants |
| IW-1973 40 mg QD/QD | Number of Participants With Notable Changes in Postbaseline Blood Pressure and Heart Rate Values | StDBP: ≤ 50 mmHg and ↓ from BL ≥ 20 mmHg | 0 participants |
Primary
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Discontinuations Due to TEAEs
An adverse event (AE) is any untoward medical occurrence, which does not necessarily have to have a causal relationship with study treatment. An SAE is defined as any AE occurring at any dose that results in any of the following outcomes: death; life-threatening; hospitalization or prolongation of existing hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect; important medical events. TEAEs are defined as those AEs that started or worsened in severity after the initiation of study drug administration. AEs of clinical interest (AECI) included those related to bleeding and to hypotension. Study drug causality as assessed by the Investigator who was blinded to study drug assignment.
Time frame: From first dose of study drug to End of Trial Visit (42 [± 3] days)
Population: Safety Population: participants who received at least 1 dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Discontinuations Due to TEAEs | TEAE Resulting in Study Discontinuation | 0 participants |
| Placebo | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Discontinuations Due to TEAEs | Mild TEAE | 5 participants |
| Placebo | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Discontinuations Due to TEAEs | AECI Related to Bleeding | 0 participants |
| Placebo | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Discontinuations Due to TEAEs | TEAE Considered Not Study Drug Related | 4 participants |
| Placebo | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Discontinuations Due to TEAEs | TEAE Considered Study Drug Related | 1 participants |
| Placebo | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Discontinuations Due to TEAEs | TEAE | 5 participants |
| Placebo | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Discontinuations Due to TEAEs | Severe TEAE | 0 participants |
| Placebo | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Discontinuations Due to TEAEs | SAE | 0 participants |
| Placebo | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Discontinuations Due to TEAEs | TEAE Resulting in Death | 0 participants |
| Placebo | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Discontinuations Due to TEAEs | Moderate TEAE | 0 participants |
| Placebo | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Discontinuations Due to TEAEs | AECI Related to Hypotension | 1 participants |
| IW-1973 40 mg BID/QD | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Discontinuations Due to TEAEs | TEAE Considered Study Drug Related | 3 participants |
| IW-1973 40 mg BID/QD | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Discontinuations Due to TEAEs | TEAE | 6 participants |
| IW-1973 40 mg BID/QD | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Discontinuations Due to TEAEs | SAE | 1 participants |
| IW-1973 40 mg BID/QD | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Discontinuations Due to TEAEs | Severe TEAE | 1 participants |
| IW-1973 40 mg BID/QD | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Discontinuations Due to TEAEs | Moderate TEAE | 0 participants |
| IW-1973 40 mg BID/QD | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Discontinuations Due to TEAEs | Mild TEAE | 6 participants |
| IW-1973 40 mg BID/QD | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Discontinuations Due to TEAEs | TEAE Considered Not Study Drug Related | 6 participants |
| IW-1973 40 mg BID/QD | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Discontinuations Due to TEAEs | TEAE Resulting in Study Discontinuation | 1 participants |
| IW-1973 40 mg BID/QD | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Discontinuations Due to TEAEs | TEAE Resulting in Death | 0 participants |
| IW-1973 40 mg BID/QD | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Discontinuations Due to TEAEs | AECI Related to Bleeding | 1 participants |
| IW-1973 40 mg BID/QD | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Discontinuations Due to TEAEs | AECI Related to Hypotension | 1 participants |
| IW-1973 40 mg QD/QD | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Discontinuations Due to TEAEs | AECI Related to Bleeding | 0 participants |
| IW-1973 40 mg QD/QD | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Discontinuations Due to TEAEs | TEAE Resulting in Study Discontinuation | 0 participants |
| IW-1973 40 mg QD/QD | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Discontinuations Due to TEAEs | Severe TEAE | 0 participants |
| IW-1973 40 mg QD/QD | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Discontinuations Due to TEAEs | TEAE | 8 participants |
| IW-1973 40 mg QD/QD | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Discontinuations Due to TEAEs | TEAE Resulting in Death | 0 participants |
| IW-1973 40 mg QD/QD | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Discontinuations Due to TEAEs | SAE | 0 participants |
| IW-1973 40 mg QD/QD | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Discontinuations Due to TEAEs | TEAE Considered Study Drug Related | 6 participants |
| IW-1973 40 mg QD/QD | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Discontinuations Due to TEAEs | Mild TEAE | 8 participants |
| IW-1973 40 mg QD/QD | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Discontinuations Due to TEAEs | AECI Related to Hypotension | 0 participants |
| IW-1973 40 mg QD/QD | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Discontinuations Due to TEAEs | TEAE Considered Not Study Drug Related | 7 participants |
| IW-1973 40 mg QD/QD | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Discontinuations Due to TEAEs | Moderate TEAE | 0 participants |
Primary
Orthostatic Diastolic Blood Pressure Over Time
An orthostatic measurement is obtained by subtracting the supine measurement from the standing measurement.
Time frame: Days -1, 1, 2, 7, 8, 13: 1 and 4 hour AM; Days -1, 1, 2, 8, 13: 0 hour PM; Days -1, 1, 2: 1 hour PM; Days 1, 2, 7, 8, 13: 0 hour AM; Day 1: 8 hour AM; Days 1, 2: 4 hour PM
Population: Safety Population: participants who received at least 1 dose of study drug.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Orthostatic Diastolic Blood Pressure Over Time | Day 13, 0 hour PM | 4.0 mmHg | Standard Deviation 3.2 |
| Placebo | Orthostatic Diastolic Blood Pressure Over Time | Day 7, 4 hour AM | 7.3 mmHg | Standard Deviation 9 |
| Placebo | Orthostatic Diastolic Blood Pressure Over Time | Day 1, 4 hour PM | 6.8 mmHg | Standard Deviation 4.2 |
| Placebo | Orthostatic Diastolic Blood Pressure Over Time | Day -1, 1 hour AM | 1.8 mmHg | Standard Deviation 3 |
| Placebo | Orthostatic Diastolic Blood Pressure Over Time | Day 7, 1 hour AM | 1.8 mmHg | Standard Deviation 2.9 |
| Placebo | Orthostatic Diastolic Blood Pressure Over Time | Day 2, 0 hour AM | 2.7 mmHg | Standard Deviation 2 |
| Placebo | Orthostatic Diastolic Blood Pressure Over Time | Day 1, 0 hour AM | 3.3 mmHg | Standard Deviation 5.2 |
| Placebo | Orthostatic Diastolic Blood Pressure Over Time | Day 7, 0 hour AM | 2.3 mmHg | Standard Deviation 3.4 |
| Placebo | Orthostatic Diastolic Blood Pressure Over Time | Day 2, 1 hour AM | 3.0 mmHg | Standard Deviation 4.1 |
| Placebo | Orthostatic Diastolic Blood Pressure Over Time | Day 13, 4 hour AM | 0.7 mmHg | Standard Deviation 4.5 |
| Placebo | Orthostatic Diastolic Blood Pressure Over Time | Day 2, 4 hour PM | 5.8 mmHg | Standard Deviation 4.3 |
| Placebo | Orthostatic Diastolic Blood Pressure Over Time | Day 2, 4 hour AM | 0.5 mmHg | Standard Deviation 2.4 |
| Placebo | Orthostatic Diastolic Blood Pressure Over Time | Day 13, 0 hour AM | 2.7 mmHg | Standard Deviation 5.1 |
| Placebo | Orthostatic Diastolic Blood Pressure Over Time | Day 2, 1 hour PM | 2.3 mmHg | Standard Deviation 5.6 |
| Placebo | Orthostatic Diastolic Blood Pressure Over Time | Day 2, 0 Hour PM | -2.7 mmHg | Standard Deviation 10.2 |
| Placebo | Orthostatic Diastolic Blood Pressure Over Time | Day 1, 1 hour AM | 5.3 mmHg | Standard Deviation 8.9 |
| Placebo | Orthostatic Diastolic Blood Pressure Over Time | Day -1, 0 hour PM | 8.2 mmHg | Standard Deviation 4.6 |
| Placebo | Orthostatic Diastolic Blood Pressure Over Time | Day 8, 0 hour PM | 5.0 mmHg | Standard Deviation 2.6 |
| Placebo | Orthostatic Diastolic Blood Pressure Over Time | Day 1, 4 hour AM | 4.2 mmHg | Standard Deviation 4.1 |
| Placebo | Orthostatic Diastolic Blood Pressure Over Time | Day -1, 4 hour AM | -0.5 mmHg | Standard Deviation 5.1 |
| Placebo | Orthostatic Diastolic Blood Pressure Over Time | Day 8, 4 hour AM | 4.0 mmHg | Standard Deviation 2.6 |
| Placebo | Orthostatic Diastolic Blood Pressure Over Time | Day 1, 8 hour AM | 5.3 mmHg | Standard Deviation 1.9 |
| Placebo | Orthostatic Diastolic Blood Pressure Over Time | Day 13, 1 hour AM | 3.3 mmHg | Standard Deviation 4.3 |
| Placebo | Orthostatic Diastolic Blood Pressure Over Time | Day 8, 1 hour AM | -1.3 mmHg | Standard Deviation 8.9 |
| Placebo | Orthostatic Diastolic Blood Pressure Over Time | Day 1, 0 hour PM | 10.0 mmHg | Standard Deviation 6.8 |
| Placebo | Orthostatic Diastolic Blood Pressure Over Time | Day -1, 1 hour PM | 5.7 mmHg | Standard Deviation 4.6 |
| Placebo | Orthostatic Diastolic Blood Pressure Over Time | Day 8, 0 hour AM | 3.3 mmHg | Standard Deviation 6.1 |
| Placebo | Orthostatic Diastolic Blood Pressure Over Time | Day 1, 1 hour PM | 3.0 mmHg | Standard Deviation 4.3 |
| IW-1973 40 mg BID/QD | Orthostatic Diastolic Blood Pressure Over Time | Day 13, 0 hour AM | 4.0 mmHg | Standard Deviation 6.8 |
| IW-1973 40 mg BID/QD | Orthostatic Diastolic Blood Pressure Over Time | Day -1, 1 hour AM | 3.3 mmHg | Standard Deviation 6.8 |
| IW-1973 40 mg BID/QD | Orthostatic Diastolic Blood Pressure Over Time | Day -1, 4 hour AM | 3.6 mmHg | Standard Deviation 8.2 |
| IW-1973 40 mg BID/QD | Orthostatic Diastolic Blood Pressure Over Time | Day -1, 0 hour PM | 4.2 mmHg | Standard Deviation 5.6 |
| IW-1973 40 mg BID/QD | Orthostatic Diastolic Blood Pressure Over Time | Day -1, 1 hour PM | 4.0 mmHg | Standard Deviation 6.8 |
| IW-1973 40 mg BID/QD | Orthostatic Diastolic Blood Pressure Over Time | Day 1, 0 hour AM | 4.2 mmHg | Standard Deviation 4.4 |
| IW-1973 40 mg BID/QD | Orthostatic Diastolic Blood Pressure Over Time | Day 1, 1 hour AM | 2.9 mmHg | Standard Deviation 5.1 |
| IW-1973 40 mg BID/QD | Orthostatic Diastolic Blood Pressure Over Time | Day 1, 4 hour AM | 6.1 mmHg | Standard Deviation 5.8 |
| IW-1973 40 mg BID/QD | Orthostatic Diastolic Blood Pressure Over Time | Day 1, 8 hour AM | 3.6 mmHg | Standard Deviation 4.5 |
| IW-1973 40 mg BID/QD | Orthostatic Diastolic Blood Pressure Over Time | Day 1, 0 hour PM | 2.8 mmHg | Standard Deviation 6.3 |
| IW-1973 40 mg BID/QD | Orthostatic Diastolic Blood Pressure Over Time | Day 1, 1 hour PM | 5.2 mmHg | Standard Deviation 9.2 |
| IW-1973 40 mg BID/QD | Orthostatic Diastolic Blood Pressure Over Time | Day 1, 4 hour PM | 3.4 mmHg | Standard Deviation 7.3 |
| IW-1973 40 mg BID/QD | Orthostatic Diastolic Blood Pressure Over Time | Day 2, 0 hour AM | 3.3 mmHg | Standard Deviation 5.2 |
| IW-1973 40 mg BID/QD | Orthostatic Diastolic Blood Pressure Over Time | Day 2, 1 hour AM | 1.8 mmHg | Standard Deviation 5.8 |
| IW-1973 40 mg BID/QD | Orthostatic Diastolic Blood Pressure Over Time | Day 2, 4 hour AM | 3.8 mmHg | Standard Deviation 3.5 |
| IW-1973 40 mg BID/QD | Orthostatic Diastolic Blood Pressure Over Time | Day 2, 0 Hour PM | 3.2 mmHg | Standard Deviation 7.4 |
| IW-1973 40 mg BID/QD | Orthostatic Diastolic Blood Pressure Over Time | Day 2, 1 hour PM | 0.9 mmHg | Standard Deviation 6.1 |
| IW-1973 40 mg BID/QD | Orthostatic Diastolic Blood Pressure Over Time | Day 2, 4 hour PM | 1.3 mmHg | Standard Deviation 10 |
| IW-1973 40 mg BID/QD | Orthostatic Diastolic Blood Pressure Over Time | Day 7, 0 hour AM | 2.9 mmHg | Standard Deviation 7.9 |
| IW-1973 40 mg BID/QD | Orthostatic Diastolic Blood Pressure Over Time | Day 7, 1 hour AM | 3.7 mmHg | Standard Deviation 5.5 |
| IW-1973 40 mg BID/QD | Orthostatic Diastolic Blood Pressure Over Time | Day 7, 4 hour AM | 4.8 mmHg | Standard Deviation 7.4 |
| IW-1973 40 mg BID/QD | Orthostatic Diastolic Blood Pressure Over Time | Day 8, 0 hour AM | 6.2 mmHg | Standard Deviation 7.1 |
| IW-1973 40 mg BID/QD | Orthostatic Diastolic Blood Pressure Over Time | Day 8, 1 hour AM | 2.2 mmHg | Standard Deviation 8.4 |
| IW-1973 40 mg BID/QD | Orthostatic Diastolic Blood Pressure Over Time | Day 8, 4 hour AM | 1.9 mmHg | Standard Deviation 7.3 |
| IW-1973 40 mg BID/QD | Orthostatic Diastolic Blood Pressure Over Time | Day 8, 0 hour PM | 3.8 mmHg | Standard Deviation 4.5 |
| IW-1973 40 mg BID/QD | Orthostatic Diastolic Blood Pressure Over Time | Day 13, 1 hour AM | 5.8 mmHg | Standard Deviation 4.7 |
| IW-1973 40 mg BID/QD | Orthostatic Diastolic Blood Pressure Over Time | Day 13, 4 hour AM | 3.7 mmHg | Standard Deviation 4.3 |
| IW-1973 40 mg BID/QD | Orthostatic Diastolic Blood Pressure Over Time | Day 13, 0 hour PM | 5.1 mmHg | Standard Deviation 6.3 |
| IW-1973 40 mg QD/QD | Orthostatic Diastolic Blood Pressure Over Time | Day 7, 1 hour AM | 2.4 mmHg | Standard Deviation 3.5 |
| IW-1973 40 mg QD/QD | Orthostatic Diastolic Blood Pressure Over Time | Day 1, 1 hour PM | 5.1 mmHg | Standard Deviation 4.3 |
| IW-1973 40 mg QD/QD | Orthostatic Diastolic Blood Pressure Over Time | Day -1, 1 hour AM | 6.3 mmHg | Standard Deviation 5.9 |
| IW-1973 40 mg QD/QD | Orthostatic Diastolic Blood Pressure Over Time | Day 7, 4 hour AM | 3.2 mmHg | Standard Deviation 6.5 |
| IW-1973 40 mg QD/QD | Orthostatic Diastolic Blood Pressure Over Time | Day 1, 0 hour PM | 5.1 mmHg | Standard Deviation 6.2 |
| IW-1973 40 mg QD/QD | Orthostatic Diastolic Blood Pressure Over Time | Day 13, 1 hour AM | 5.0 mmHg | Standard Deviation 7.1 |
| IW-1973 40 mg QD/QD | Orthostatic Diastolic Blood Pressure Over Time | Day 8, 0 hour AM | 4.8 mmHg | Standard Deviation 5.5 |
| IW-1973 40 mg QD/QD | Orthostatic Diastolic Blood Pressure Over Time | Day 1, 8 hour AM | 4.9 mmHg | Standard Deviation 6 |
| IW-1973 40 mg QD/QD | Orthostatic Diastolic Blood Pressure Over Time | Day -1, 4 hour AM | 5.5 mmHg | Standard Deviation 6.4 |
| IW-1973 40 mg QD/QD | Orthostatic Diastolic Blood Pressure Over Time | Day 8, 1 hour AM | 3.8 mmHg | Standard Deviation 6.7 |
| IW-1973 40 mg QD/QD | Orthostatic Diastolic Blood Pressure Over Time | Day 1, 4 hour AM | 7.0 mmHg | Standard Deviation 5 |
| IW-1973 40 mg QD/QD | Orthostatic Diastolic Blood Pressure Over Time | Day 13, 0 hour PM | 3.9 mmHg | Standard Deviation 3.8 |
| IW-1973 40 mg QD/QD | Orthostatic Diastolic Blood Pressure Over Time | Day 8, 4 hour AM | 1.2 mmHg | Standard Deviation 7.3 |
| IW-1973 40 mg QD/QD | Orthostatic Diastolic Blood Pressure Over Time | Day 1, 1 hour AM | 3.4 mmHg | Standard Deviation 5.9 |
| IW-1973 40 mg QD/QD | Orthostatic Diastolic Blood Pressure Over Time | Day 13, 4 hour AM | 5.4 mmHg | Standard Deviation 7.7 |
| IW-1973 40 mg QD/QD | Orthostatic Diastolic Blood Pressure Over Time | Day 8, 0 hour PM | 4.2 mmHg | Standard Deviation 4 |
| IW-1973 40 mg QD/QD | Orthostatic Diastolic Blood Pressure Over Time | Day 2, 0 Hour PM | 4.7 mmHg | Standard Deviation 5.2 |
| IW-1973 40 mg QD/QD | Orthostatic Diastolic Blood Pressure Over Time | Day 2, 4 hour AM | 5.7 mmHg | Standard Deviation 5.3 |
| IW-1973 40 mg QD/QD | Orthostatic Diastolic Blood Pressure Over Time | Day 1, 0 hour AM | 5.4 mmHg | Standard Deviation 4.6 |
| IW-1973 40 mg QD/QD | Orthostatic Diastolic Blood Pressure Over Time | Day 2, 1 hour PM | 5.3 mmHg | Standard Deviation 5.1 |
| IW-1973 40 mg QD/QD | Orthostatic Diastolic Blood Pressure Over Time | Day 2, 1 hour AM | 5.2 mmHg | Standard Deviation 3.2 |
| IW-1973 40 mg QD/QD | Orthostatic Diastolic Blood Pressure Over Time | Day -1, 1 hour PM | 4.5 mmHg | Standard Deviation 4.3 |
| IW-1973 40 mg QD/QD | Orthostatic Diastolic Blood Pressure Over Time | Day 2, 4 hour PM | 8.7 mmHg | Standard Deviation 7.5 |
| IW-1973 40 mg QD/QD | Orthostatic Diastolic Blood Pressure Over Time | Day 2, 0 hour AM | 3.3 mmHg | Standard Deviation 6 |
| IW-1973 40 mg QD/QD | Orthostatic Diastolic Blood Pressure Over Time | Day 13, 0 hour AM | 3.9 mmHg | Standard Deviation 4.1 |
| IW-1973 40 mg QD/QD | Orthostatic Diastolic Blood Pressure Over Time | Day 7, 0 hour AM | 5.6 mmHg | Standard Deviation 6.2 |
| IW-1973 40 mg QD/QD | Orthostatic Diastolic Blood Pressure Over Time | Day 1, 4 hour PM | 7.7 mmHg | Standard Deviation 4.9 |
| IW-1973 40 mg QD/QD | Orthostatic Diastolic Blood Pressure Over Time | Day -1, 0 hour PM | 3.4 mmHg | Standard Deviation 4.4 |
Primary
Orthostatic Pulse Over Time
An orthostatic measurement is obtained by subtracting the supine measurement from the standing measurement.
Time frame: Days -1, 1, 2, 7, 8, 13: 1 and 4 hour AM; Days -1, 1, 2, 8, 13: 0 hour PM; Days -1, 1, 2: 1 hour PM; Days 1, 2, 7, 8, 13: 0 hour AM; Day 1: 8 hour AM; Days 1, 2: 4 hour PM
Population: Safety Population: participants who received at least 1 dose of study drug.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Orthostatic Pulse Over Time | Day 13, 0 hour PM | 9.3 bpm | Standard Deviation 3.4 |
| Placebo | Orthostatic Pulse Over Time | Day 7, 4 hour AM | 10.8 bpm | Standard Deviation 3.3 |
| Placebo | Orthostatic Pulse Over Time | Day 1, 4 hour PM | 16.5 bpm | Standard Deviation 12.7 |
| Placebo | Orthostatic Pulse Over Time | Day -1, 1 hour AM | 9.2 bpm | Standard Deviation 6.4 |
| Placebo | Orthostatic Pulse Over Time | Day 7, 1 hour AM | 11.5 bpm | Standard Deviation 6.3 |
| Placebo | Orthostatic Pulse Over Time | Day 2, 0 hour AM | 9.0 bpm | Standard Deviation 3 |
| Placebo | Orthostatic Pulse Over Time | Day 1, 0 hour AM | 4.8 bpm | Standard Deviation 10.4 |
| Placebo | Orthostatic Pulse Over Time | Day 7, 0 hour AM | 10.8 bpm | Standard Deviation 5.2 |
| Placebo | Orthostatic Pulse Over Time | Day 2, 1 hour AM | 6.5 bpm | Standard Deviation 6 |
| Placebo | Orthostatic Pulse Over Time | Day 13, 4 hour AM | 14.5 bpm | Standard Deviation 8.1 |
| Placebo | Orthostatic Pulse Over Time | Day 2, 4 hour PM | 10.8 bpm | Standard Deviation 6.3 |
| Placebo | Orthostatic Pulse Over Time | Day 2, 4 hour AM | 11.2 bpm | Standard Deviation 9.2 |
| Placebo | Orthostatic Pulse Over Time | Day 13, 0 hour AM | 7.8 bpm | Standard Deviation 14.9 |
| Placebo | Orthostatic Pulse Over Time | Day 2, 1 hour PM | 10.0 bpm | Standard Deviation 5.4 |
| Placebo | Orthostatic Pulse Over Time | Day 2, 0 Hour PM | 6.0 bpm | Standard Deviation 8.6 |
| Placebo | Orthostatic Pulse Over Time | Day 1, 1 hour AM | 8.7 bpm | Standard Deviation 6.6 |
| Placebo | Orthostatic Pulse Over Time | Day -1, 0 hour PM | 15.3 bpm | Standard Deviation 15 |
| Placebo | Orthostatic Pulse Over Time | Day 8, 0 hour PM | 9.3 bpm | Standard Deviation 3.6 |
| Placebo | Orthostatic Pulse Over Time | Day 1, 4 hour AM | 7.7 bpm | Standard Deviation 7.4 |
| Placebo | Orthostatic Pulse Over Time | Day -1, 4 hour AM | 4.7 bpm | Standard Deviation 9.8 |
| Placebo | Orthostatic Pulse Over Time | Day 8, 4 hour AM | 10.7 bpm | Standard Deviation 7.4 |
| Placebo | Orthostatic Pulse Over Time | Day 1, 8 hour AM | 10.0 bpm | Standard Deviation 4.7 |
| Placebo | Orthostatic Pulse Over Time | Day 13, 1 hour AM | 11.0 bpm | Standard Deviation 4.6 |
| Placebo | Orthostatic Pulse Over Time | Day 8, 1 hour AM | 5.3 bpm | Standard Deviation 9.3 |
| Placebo | Orthostatic Pulse Over Time | Day 1, 0 hour PM | 14.8 bpm | Standard Deviation 9.9 |
| Placebo | Orthostatic Pulse Over Time | Day -1, 1 hour PM | 11.3 bpm | Standard Deviation 3.9 |
| Placebo | Orthostatic Pulse Over Time | Day 8, 0 hour AM | 10.3 bpm | Standard Deviation 8.3 |
| Placebo | Orthostatic Pulse Over Time | Day 1, 1 hour PM | 9.3 bpm | Standard Deviation 6.2 |
| IW-1973 40 mg BID/QD | Orthostatic Pulse Over Time | Day 13, 0 hour AM | 9.1 bpm | Standard Deviation 8.6 |
| IW-1973 40 mg BID/QD | Orthostatic Pulse Over Time | Day -1, 1 hour AM | 9.2 bpm | Standard Deviation 4.3 |
| IW-1973 40 mg BID/QD | Orthostatic Pulse Over Time | Day -1, 4 hour AM | 10.9 bpm | Standard Deviation 5.8 |
| IW-1973 40 mg BID/QD | Orthostatic Pulse Over Time | Day -1, 0 hour PM | 10.1 bpm | Standard Deviation 4.7 |
| IW-1973 40 mg BID/QD | Orthostatic Pulse Over Time | Day -1, 1 hour PM | 11.0 bpm | Standard Deviation 4.3 |
| IW-1973 40 mg BID/QD | Orthostatic Pulse Over Time | Day 1, 0 hour AM | 8.8 bpm | Standard Deviation 4.3 |
| IW-1973 40 mg BID/QD | Orthostatic Pulse Over Time | Day 1, 1 hour AM | 9.7 bpm | Standard Deviation 5.9 |
| IW-1973 40 mg BID/QD | Orthostatic Pulse Over Time | Day 1, 4 hour AM | 11.0 bpm | Standard Deviation 6.1 |
| IW-1973 40 mg BID/QD | Orthostatic Pulse Over Time | Day 1, 8 hour AM | 9.9 bpm | Standard Deviation 6.3 |
| IW-1973 40 mg BID/QD | Orthostatic Pulse Over Time | Day 1, 0 hour PM | 9.1 bpm | Standard Deviation 6.6 |
| IW-1973 40 mg BID/QD | Orthostatic Pulse Over Time | Day 1, 1 hour PM | 10.8 bpm | Standard Deviation 7.2 |
| IW-1973 40 mg BID/QD | Orthostatic Pulse Over Time | Day 1, 4 hour PM | 14.5 bpm | Standard Deviation 7.2 |
| IW-1973 40 mg BID/QD | Orthostatic Pulse Over Time | Day 2, 0 hour AM | 10.4 bpm | Standard Deviation 7 |
| IW-1973 40 mg BID/QD | Orthostatic Pulse Over Time | Day 2, 1 hour AM | 11.2 bpm | Standard Deviation 8.7 |
| IW-1973 40 mg BID/QD | Orthostatic Pulse Over Time | Day 2, 4 hour AM | 8.4 bpm | Standard Deviation 6.5 |
| IW-1973 40 mg BID/QD | Orthostatic Pulse Over Time | Day 2, 0 Hour PM | 8.6 bpm | Standard Deviation 5.8 |
| IW-1973 40 mg BID/QD | Orthostatic Pulse Over Time | Day 2, 1 hour PM | 9.4 bpm | Standard Deviation 6.8 |
| IW-1973 40 mg BID/QD | Orthostatic Pulse Over Time | Day 2, 4 hour PM | 15.9 bpm | Standard Deviation 8.6 |
| IW-1973 40 mg BID/QD | Orthostatic Pulse Over Time | Day 7, 0 hour AM | 7.1 bpm | Standard Deviation 8.5 |
| IW-1973 40 mg BID/QD | Orthostatic Pulse Over Time | Day 7, 1 hour AM | 9.5 bpm | Standard Deviation 6.6 |
| IW-1973 40 mg BID/QD | Orthostatic Pulse Over Time | Day 7, 4 hour AM | 8.7 bpm | Standard Deviation 2.6 |
| IW-1973 40 mg BID/QD | Orthostatic Pulse Over Time | Day 8, 0 hour AM | 8.6 bpm | Standard Deviation 8.6 |
| IW-1973 40 mg BID/QD | Orthostatic Pulse Over Time | Day 8, 1 hour AM | 9.5 bpm | Standard Deviation 8.7 |
| IW-1973 40 mg BID/QD | Orthostatic Pulse Over Time | Day 8, 4 hour AM | 8.1 bpm | Standard Deviation 7.8 |
| IW-1973 40 mg BID/QD | Orthostatic Pulse Over Time | Day 8, 0 hour PM | 9.6 bpm | Standard Deviation 5.6 |
| IW-1973 40 mg BID/QD | Orthostatic Pulse Over Time | Day 13, 1 hour AM | 7.9 bpm | Standard Deviation 6 |
| IW-1973 40 mg BID/QD | Orthostatic Pulse Over Time | Day 13, 4 hour AM | 9.1 bpm | Standard Deviation 6 |
| IW-1973 40 mg BID/QD | Orthostatic Pulse Over Time | Day 13, 0 hour PM | 9.3 bpm | Standard Deviation 4.6 |
| IW-1973 40 mg QD/QD | Orthostatic Pulse Over Time | Day 7, 1 hour AM | 10.1 bpm | Standard Deviation 7.9 |
| IW-1973 40 mg QD/QD | Orthostatic Pulse Over Time | Day 1, 1 hour PM | 11.1 bpm | Standard Deviation 6.6 |
| IW-1973 40 mg QD/QD | Orthostatic Pulse Over Time | Day -1, 1 hour AM | 10.2 bpm | Standard Deviation 8.8 |
| IW-1973 40 mg QD/QD | Orthostatic Pulse Over Time | Day 7, 4 hour AM | 9.6 bpm | Standard Deviation 4.7 |
| IW-1973 40 mg QD/QD | Orthostatic Pulse Over Time | Day 1, 0 hour PM | 7.7 bpm | Standard Deviation 4.1 |
| IW-1973 40 mg QD/QD | Orthostatic Pulse Over Time | Day 13, 1 hour AM | 11.2 bpm | Standard Deviation 7.5 |
| IW-1973 40 mg QD/QD | Orthostatic Pulse Over Time | Day 8, 0 hour AM | 9.5 bpm | Standard Deviation 7.8 |
| IW-1973 40 mg QD/QD | Orthostatic Pulse Over Time | Day 1, 8 hour AM | 10.5 bpm | Standard Deviation 4.6 |
| IW-1973 40 mg QD/QD | Orthostatic Pulse Over Time | Day -1, 4 hour AM | 9.5 bpm | Standard Deviation 8.3 |
| IW-1973 40 mg QD/QD | Orthostatic Pulse Over Time | Day 8, 1 hour AM | 10.5 bpm | Standard Deviation 3.3 |
| IW-1973 40 mg QD/QD | Orthostatic Pulse Over Time | Day 1, 4 hour AM | 10.1 bpm | Standard Deviation 8.4 |
| IW-1973 40 mg QD/QD | Orthostatic Pulse Over Time | Day 13, 0 hour PM | 11.2 bpm | Standard Deviation 4.3 |
| IW-1973 40 mg QD/QD | Orthostatic Pulse Over Time | Day 8, 4 hour AM | 7.3 bpm | Standard Deviation 6.1 |
| IW-1973 40 mg QD/QD | Orthostatic Pulse Over Time | Day 1, 1 hour AM | 12.9 bpm | Standard Deviation 6.9 |
| IW-1973 40 mg QD/QD | Orthostatic Pulse Over Time | Day 13, 4 hour AM | 11.5 bpm | Standard Deviation 5.9 |
| IW-1973 40 mg QD/QD | Orthostatic Pulse Over Time | Day 8, 0 hour PM | 8.9 bpm | Standard Deviation 4.7 |
| IW-1973 40 mg QD/QD | Orthostatic Pulse Over Time | Day 2, 0 Hour PM | 9.0 bpm | Standard Deviation 4.2 |
| IW-1973 40 mg QD/QD | Orthostatic Pulse Over Time | Day 2, 4 hour AM | 8.8 bpm | Standard Deviation 6.2 |
| IW-1973 40 mg QD/QD | Orthostatic Pulse Over Time | Day 1, 0 hour AM | 10.3 bpm | Standard Deviation 7.7 |
| IW-1973 40 mg QD/QD | Orthostatic Pulse Over Time | Day 2, 1 hour PM | 7.9 bpm | Standard Deviation 4.6 |
| IW-1973 40 mg QD/QD | Orthostatic Pulse Over Time | Day 2, 1 hour AM | 10.7 bpm | Standard Deviation 5.8 |
| IW-1973 40 mg QD/QD | Orthostatic Pulse Over Time | Day -1, 1 hour PM | 11.4 bpm | Standard Deviation 6 |
| IW-1973 40 mg QD/QD | Orthostatic Pulse Over Time | Day 2, 4 hour PM | 13.6 bpm | Standard Deviation 7.1 |
| IW-1973 40 mg QD/QD | Orthostatic Pulse Over Time | Day 2, 0 hour AM | 10.5 bpm | Standard Deviation 4.7 |
| IW-1973 40 mg QD/QD | Orthostatic Pulse Over Time | Day 13, 0 hour AM | 10.9 bpm | Standard Deviation 5.9 |
| IW-1973 40 mg QD/QD | Orthostatic Pulse Over Time | Day 7, 0 hour AM | 9.7 bpm | Standard Deviation 4.6 |
| IW-1973 40 mg QD/QD | Orthostatic Pulse Over Time | Day 1, 4 hour PM | 16.5 bpm | Standard Deviation 10 |
| IW-1973 40 mg QD/QD | Orthostatic Pulse Over Time | Day -1, 0 hour PM | 9.8 bpm | Standard Deviation 4.9 |
Primary
Orthostatic Systolic Blood Pressure Over Time
An orthostatic measurement is obtained by subtracting the supine measurement from the standing measurement.
Time frame: Days -1, 1, 2, 7, 8, 13: 1 and 4 hour AM; Days -1, 1, 2, 8, 13: 0 hour PM; Days -1, 1, 2: 1 hour PM; Days 1, 2, 7, 8, 13: 0 hour AM; Day 1: 8 hour AM; Days 1, 2: 4 hour PM
Population: Safety Population: participants who received at least 1 dose of study drug.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Orthostatic Systolic Blood Pressure Over Time | Day 13, 0 hour PM | 3.8 mmHg | Standard Deviation 9.1 |
| Placebo | Orthostatic Systolic Blood Pressure Over Time | Day 7, 4 hour AM | -1.2 mmHg | Standard Deviation 10.8 |
| Placebo | Orthostatic Systolic Blood Pressure Over Time | Day 1, 4 hour PM | 4.3 mmHg | Standard Deviation 14.4 |
| Placebo | Orthostatic Systolic Blood Pressure Over Time | Day -1, 1 hour AM | -0.8 mmHg | Standard Deviation 11.9 |
| Placebo | Orthostatic Systolic Blood Pressure Over Time | Day 7, 1 hour AM | -2.0 mmHg | Standard Deviation 6.8 |
| Placebo | Orthostatic Systolic Blood Pressure Over Time | Day 2, 0 hour AM | -2.7 mmHg | Standard Deviation 11 |
| Placebo | Orthostatic Systolic Blood Pressure Over Time | Day 1, 0 hour AM | 1.3 mmHg | Standard Deviation 9.6 |
| Placebo | Orthostatic Systolic Blood Pressure Over Time | Day 7, 0 hour AM | 1.0 mmHg | Standard Deviation 7.6 |
| Placebo | Orthostatic Systolic Blood Pressure Over Time | Day 2, 1 hour AM | -4.7 mmHg | Standard Deviation 15 |
| Placebo | Orthostatic Systolic Blood Pressure Over Time | Day 13, 4 hour AM | 0.8 mmHg | Standard Deviation 7.4 |
| Placebo | Orthostatic Systolic Blood Pressure Over Time | Day 2, 4 hour PM | 0.8 mmHg | Standard Deviation 6.8 |
| Placebo | Orthostatic Systolic Blood Pressure Over Time | Day 2, 4 hour AM | -1.7 mmHg | Standard Deviation 11.4 |
| Placebo | Orthostatic Systolic Blood Pressure Over Time | Day 13, 0 hour AM | -2.0 mmHg | Standard Deviation 5.2 |
| Placebo | Orthostatic Systolic Blood Pressure Over Time | Day 2, 1 hour PM | 2.7 mmHg | Standard Deviation 14.4 |
| Placebo | Orthostatic Systolic Blood Pressure Over Time | Day 2, 0 Hour PM | -6.0 mmHg | Standard Deviation 14.9 |
| Placebo | Orthostatic Systolic Blood Pressure Over Time | Day 1, 1 hour AM | 9.7 mmHg | Standard Deviation 7.9 |
| Placebo | Orthostatic Systolic Blood Pressure Over Time | Day -1, 0 hour PM | 3.0 mmHg | Standard Deviation 10.5 |
| Placebo | Orthostatic Systolic Blood Pressure Over Time | Day 8, 0 hour PM | 1.0 mmHg | Standard Deviation 8.4 |
| Placebo | Orthostatic Systolic Blood Pressure Over Time | Day 1, 4 hour AM | 3.0 mmHg | Standard Deviation 14.6 |
| Placebo | Orthostatic Systolic Blood Pressure Over Time | Day -1, 4 hour AM | 0.3 mmHg | Standard Deviation 6.4 |
| Placebo | Orthostatic Systolic Blood Pressure Over Time | Day 8, 4 hour AM | 1.0 mmHg | Standard Deviation 12.3 |
| Placebo | Orthostatic Systolic Blood Pressure Over Time | Day 1, 8 hour AM | 5.3 mmHg | Standard Deviation 6.4 |
| Placebo | Orthostatic Systolic Blood Pressure Over Time | Day 13, 1 hour AM | -1.5 mmHg | Standard Deviation 12.8 |
| Placebo | Orthostatic Systolic Blood Pressure Over Time | Day 8, 1 hour AM | -2.5 mmHg | Standard Deviation 8.5 |
| Placebo | Orthostatic Systolic Blood Pressure Over Time | Day 1, 0 hour PM | 10.2 mmHg | Standard Deviation 10.5 |
| Placebo | Orthostatic Systolic Blood Pressure Over Time | Day -1, 1 hour PM | 3.8 mmHg | Standard Deviation 9 |
| Placebo | Orthostatic Systolic Blood Pressure Over Time | Day 8, 0 hour AM | -4.0 mmHg | Standard Deviation 13.7 |
| Placebo | Orthostatic Systolic Blood Pressure Over Time | Day 1, 1 hour PM | 5.7 mmHg | Standard Deviation 10.2 |
| IW-1973 40 mg BID/QD | Orthostatic Systolic Blood Pressure Over Time | Day 13, 0 hour AM | 6.2 mmHg | Standard Deviation 13.7 |
| IW-1973 40 mg BID/QD | Orthostatic Systolic Blood Pressure Over Time | Day -1, 1 hour AM | 2.0 mmHg | Standard Deviation 12.1 |
| IW-1973 40 mg BID/QD | Orthostatic Systolic Blood Pressure Over Time | Day -1, 4 hour AM | 2.9 mmHg | Standard Deviation 9.9 |
| IW-1973 40 mg BID/QD | Orthostatic Systolic Blood Pressure Over Time | Day -1, 0 hour PM | 1.7 mmHg | Standard Deviation 12.4 |
| IW-1973 40 mg BID/QD | Orthostatic Systolic Blood Pressure Over Time | Day -1, 1 hour PM | 5.3 mmHg | Standard Deviation 13.8 |
| IW-1973 40 mg BID/QD | Orthostatic Systolic Blood Pressure Over Time | Day 1, 0 hour AM | 5.2 mmHg | Standard Deviation 11.8 |
| IW-1973 40 mg BID/QD | Orthostatic Systolic Blood Pressure Over Time | Day 1, 1 hour AM | 3.7 mmHg | Standard Deviation 15.8 |
| IW-1973 40 mg BID/QD | Orthostatic Systolic Blood Pressure Over Time | Day 1, 4 hour AM | 12.1 mmHg | Standard Deviation 11.3 |
| IW-1973 40 mg BID/QD | Orthostatic Systolic Blood Pressure Over Time | Day 1, 8 hour AM | 4.7 mmHg | Standard Deviation 12.4 |
| IW-1973 40 mg BID/QD | Orthostatic Systolic Blood Pressure Over Time | Day 1, 0 hour PM | 4.1 mmHg | Standard Deviation 17 |
| IW-1973 40 mg BID/QD | Orthostatic Systolic Blood Pressure Over Time | Day 1, 1 hour PM | 0.7 mmHg | Standard Deviation 18 |
| IW-1973 40 mg BID/QD | Orthostatic Systolic Blood Pressure Over Time | Day 1, 4 hour PM | 0.4 mmHg | Standard Deviation 14.8 |
| IW-1973 40 mg BID/QD | Orthostatic Systolic Blood Pressure Over Time | Day 2, 0 hour AM | 2.5 mmHg | Standard Deviation 13.5 |
| IW-1973 40 mg BID/QD | Orthostatic Systolic Blood Pressure Over Time | Day 2, 1 hour AM | 2.9 mmHg | Standard Deviation 8.5 |
| IW-1973 40 mg BID/QD | Orthostatic Systolic Blood Pressure Over Time | Day 2, 4 hour AM | 5.8 mmHg | Standard Deviation 6.8 |
| IW-1973 40 mg BID/QD | Orthostatic Systolic Blood Pressure Over Time | Day 2, 0 Hour PM | 6.6 mmHg | Standard Deviation 11.9 |
| IW-1973 40 mg BID/QD | Orthostatic Systolic Blood Pressure Over Time | Day 2, 1 hour PM | 5.0 mmHg | Standard Deviation 14.3 |
| IW-1973 40 mg BID/QD | Orthostatic Systolic Blood Pressure Over Time | Day 2, 4 hour PM | -0.7 mmHg | Standard Deviation 18.9 |
| IW-1973 40 mg BID/QD | Orthostatic Systolic Blood Pressure Over Time | Day 7, 0 hour AM | 2.5 mmHg | Standard Deviation 19.1 |
| IW-1973 40 mg BID/QD | Orthostatic Systolic Blood Pressure Over Time | Day 7, 1 hour AM | 6.3 mmHg | Standard Deviation 11.7 |
| IW-1973 40 mg BID/QD | Orthostatic Systolic Blood Pressure Over Time | Day 7, 4 hour AM | 4.7 mmHg | Standard Deviation 11.3 |
| IW-1973 40 mg BID/QD | Orthostatic Systolic Blood Pressure Over Time | Day 8, 0 hour AM | 6.5 mmHg | Standard Deviation 11.9 |
| IW-1973 40 mg BID/QD | Orthostatic Systolic Blood Pressure Over Time | Day 8, 1 hour AM | 5.9 mmHg | Standard Deviation 14.7 |
| IW-1973 40 mg BID/QD | Orthostatic Systolic Blood Pressure Over Time | Day 8, 4 hour AM | 2.9 mmHg | Standard Deviation 10.3 |
| IW-1973 40 mg BID/QD | Orthostatic Systolic Blood Pressure Over Time | Day 8, 0 hour PM | 5.0 mmHg | Standard Deviation 9.7 |
| IW-1973 40 mg BID/QD | Orthostatic Systolic Blood Pressure Over Time | Day 13, 1 hour AM | 8.3 mmHg | Standard Deviation 13.7 |
| IW-1973 40 mg BID/QD | Orthostatic Systolic Blood Pressure Over Time | Day 13, 4 hour AM | 4.1 mmHg | Standard Deviation 10.9 |
| IW-1973 40 mg BID/QD | Orthostatic Systolic Blood Pressure Over Time | Day 13, 0 hour PM | 4.8 mmHg | Standard Deviation 14.2 |
| IW-1973 40 mg QD/QD | Orthostatic Systolic Blood Pressure Over Time | Day 7, 1 hour AM | -2.5 mmHg | Standard Deviation 8 |
| IW-1973 40 mg QD/QD | Orthostatic Systolic Blood Pressure Over Time | Day 1, 1 hour PM | 4.1 mmHg | Standard Deviation 11.4 |
| IW-1973 40 mg QD/QD | Orthostatic Systolic Blood Pressure Over Time | Day -1, 1 hour AM | 5.6 mmHg | Standard Deviation 11.5 |
| IW-1973 40 mg QD/QD | Orthostatic Systolic Blood Pressure Over Time | Day 7, 4 hour AM | 4.7 mmHg | Standard Deviation 14.1 |
| IW-1973 40 mg QD/QD | Orthostatic Systolic Blood Pressure Over Time | Day 1, 0 hour PM | 0.2 mmHg | Standard Deviation 10.3 |
| IW-1973 40 mg QD/QD | Orthostatic Systolic Blood Pressure Over Time | Day 13, 1 hour AM | 1.4 mmHg | Standard Deviation 12.1 |
| IW-1973 40 mg QD/QD | Orthostatic Systolic Blood Pressure Over Time | Day 8, 0 hour AM | -1.1 mmHg | Standard Deviation 5.7 |
| IW-1973 40 mg QD/QD | Orthostatic Systolic Blood Pressure Over Time | Day 1, 8 hour AM | 5.1 mmHg | Standard Deviation 11.5 |
| IW-1973 40 mg QD/QD | Orthostatic Systolic Blood Pressure Over Time | Day -1, 4 hour AM | 2.3 mmHg | Standard Deviation 11.5 |
| IW-1973 40 mg QD/QD | Orthostatic Systolic Blood Pressure Over Time | Day 8, 1 hour AM | 1.7 mmHg | Standard Deviation 12.6 |
| IW-1973 40 mg QD/QD | Orthostatic Systolic Blood Pressure Over Time | Day 1, 4 hour AM | 5.8 mmHg | Standard Deviation 8.3 |
| IW-1973 40 mg QD/QD | Orthostatic Systolic Blood Pressure Over Time | Day 13, 0 hour PM | 3.2 mmHg | Standard Deviation 10.3 |
| IW-1973 40 mg QD/QD | Orthostatic Systolic Blood Pressure Over Time | Day 8, 4 hour AM | -1.7 mmHg | Standard Deviation 16 |
| IW-1973 40 mg QD/QD | Orthostatic Systolic Blood Pressure Over Time | Day 1, 1 hour AM | 2.5 mmHg | Standard Deviation 11.5 |
| IW-1973 40 mg QD/QD | Orthostatic Systolic Blood Pressure Over Time | Day 13, 4 hour AM | 2.2 mmHg | Standard Deviation 11.7 |
| IW-1973 40 mg QD/QD | Orthostatic Systolic Blood Pressure Over Time | Day 8, 0 hour PM | 4.2 mmHg | Standard Deviation 8.8 |
| IW-1973 40 mg QD/QD | Orthostatic Systolic Blood Pressure Over Time | Day 2, 0 Hour PM | 2.3 mmHg | Standard Deviation 10.4 |
| IW-1973 40 mg QD/QD | Orthostatic Systolic Blood Pressure Over Time | Day 2, 4 hour AM | 4.6 mmHg | Standard Deviation 10.6 |
| IW-1973 40 mg QD/QD | Orthostatic Systolic Blood Pressure Over Time | Day 1, 0 hour AM | 3.7 mmHg | Standard Deviation 12.7 |
| IW-1973 40 mg QD/QD | Orthostatic Systolic Blood Pressure Over Time | Day 2, 1 hour PM | 0.5 mmHg | Standard Deviation 14 |
| IW-1973 40 mg QD/QD | Orthostatic Systolic Blood Pressure Over Time | Day 2, 1 hour AM | 2.2 mmHg | Standard Deviation 8.6 |
| IW-1973 40 mg QD/QD | Orthostatic Systolic Blood Pressure Over Time | Day -1, 1 hour PM | 3.1 mmHg | Standard Deviation 11.5 |
| IW-1973 40 mg QD/QD | Orthostatic Systolic Blood Pressure Over Time | Day 2, 4 hour PM | 7.1 mmHg | Standard Deviation 13.1 |
| IW-1973 40 mg QD/QD | Orthostatic Systolic Blood Pressure Over Time | Day 2, 0 hour AM | 1.1 mmHg | Standard Deviation 10.3 |
| IW-1973 40 mg QD/QD | Orthostatic Systolic Blood Pressure Over Time | Day 13, 0 hour AM | 1.3 mmHg | Standard Deviation 7.4 |
| IW-1973 40 mg QD/QD | Orthostatic Systolic Blood Pressure Over Time | Day 7, 0 hour AM | 4.9 mmHg | Standard Deviation 10.7 |
| IW-1973 40 mg QD/QD | Orthostatic Systolic Blood Pressure Over Time | Day 1, 4 hour PM | 6.4 mmHg | Standard Deviation 5.3 |
| IW-1973 40 mg QD/QD | Orthostatic Systolic Blood Pressure Over Time | Day -1, 0 hour PM | -0.1 mmHg | Standard Deviation 7.3 |
Primary
Percentage of Participants With Postdose Supine Blood Pressure Less Than 130/80 mmHg Over Time
Time frame: Baseline, Days 1-14, Day 15, 21, 42
Population: PD Population: all participants who received at least 1 dose of study drug and had at least 1 postdose PD assessment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Percentage of Participants With Postdose Supine Blood Pressure Less Than 130/80 mmHg Over Time | Day 4 | 50.0 percentage of participants |
| Placebo | Percentage of Participants With Postdose Supine Blood Pressure Less Than 130/80 mmHg Over Time | Day 1 | 100 percentage of participants |
| Placebo | Percentage of Participants With Postdose Supine Blood Pressure Less Than 130/80 mmHg Over Time | Day 2 | 66.7 percentage of participants |
| Placebo | Percentage of Participants With Postdose Supine Blood Pressure Less Than 130/80 mmHg Over Time | Day 3 | 66.7 percentage of participants |
| Placebo | Percentage of Participants With Postdose Supine Blood Pressure Less Than 130/80 mmHg Over Time | Baseline | 33.3 percentage of participants |
| Placebo | Percentage of Participants With Postdose Supine Blood Pressure Less Than 130/80 mmHg Over Time | Day 5 | 50.0 percentage of participants |
| Placebo | Percentage of Participants With Postdose Supine Blood Pressure Less Than 130/80 mmHg Over Time | Day 6 | 66.7 percentage of participants |
| Placebo | Percentage of Participants With Postdose Supine Blood Pressure Less Than 130/80 mmHg Over Time | Day 7 | 50.0 percentage of participants |
| Placebo | Percentage of Participants With Postdose Supine Blood Pressure Less Than 130/80 mmHg Over Time | Day 8 | 83.3 percentage of participants |
| Placebo | Percentage of Participants With Postdose Supine Blood Pressure Less Than 130/80 mmHg Over Time | Day 9 | 33.3 percentage of participants |
| Placebo | Percentage of Participants With Postdose Supine Blood Pressure Less Than 130/80 mmHg Over Time | Day 10 | 33.3 percentage of participants |
| Placebo | Percentage of Participants With Postdose Supine Blood Pressure Less Than 130/80 mmHg Over Time | Day 11 | 50.0 percentage of participants |
| Placebo | Percentage of Participants With Postdose Supine Blood Pressure Less Than 130/80 mmHg Over Time | Day 12 | 50.0 percentage of participants |
| Placebo | Percentage of Participants With Postdose Supine Blood Pressure Less Than 130/80 mmHg Over Time | Day 13 | 66.7 percentage of participants |
| Placebo | Percentage of Participants With Postdose Supine Blood Pressure Less Than 130/80 mmHg Over Time | Day 14 | 50.0 percentage of participants |
| Placebo | Percentage of Participants With Postdose Supine Blood Pressure Less Than 130/80 mmHg Over Time | Day 15 / Discharge | 33.3 percentage of participants |
| Placebo | Percentage of Participants With Postdose Supine Blood Pressure Less Than 130/80 mmHg Over Time | Day 21 / Follow-Up | 50.0 percentage of participants |
| Placebo | Percentage of Participants With Postdose Supine Blood Pressure Less Than 130/80 mmHg Over Time | Day 42 / End of Trial | 33.3 percentage of participants |
| IW-1973 40 mg BID/QD | Percentage of Participants With Postdose Supine Blood Pressure Less Than 130/80 mmHg Over Time | Day 42 / End of Trial | 40.0 percentage of participants |
| IW-1973 40 mg BID/QD | Percentage of Participants With Postdose Supine Blood Pressure Less Than 130/80 mmHg Over Time | Baseline | 80.0 percentage of participants |
| IW-1973 40 mg BID/QD | Percentage of Participants With Postdose Supine Blood Pressure Less Than 130/80 mmHg Over Time | Day 9 | 100 percentage of participants |
| IW-1973 40 mg BID/QD | Percentage of Participants With Postdose Supine Blood Pressure Less Than 130/80 mmHg Over Time | Day 12 | 90.0 percentage of participants |
| IW-1973 40 mg BID/QD | Percentage of Participants With Postdose Supine Blood Pressure Less Than 130/80 mmHg Over Time | Day 1 | 100 percentage of participants |
| IW-1973 40 mg BID/QD | Percentage of Participants With Postdose Supine Blood Pressure Less Than 130/80 mmHg Over Time | Day 14 | 90.0 percentage of participants |
| IW-1973 40 mg BID/QD | Percentage of Participants With Postdose Supine Blood Pressure Less Than 130/80 mmHg Over Time | Day 15 / Discharge | 100 percentage of participants |
| IW-1973 40 mg BID/QD | Percentage of Participants With Postdose Supine Blood Pressure Less Than 130/80 mmHg Over Time | Day 2 | 100 percentage of participants |
| IW-1973 40 mg BID/QD | Percentage of Participants With Postdose Supine Blood Pressure Less Than 130/80 mmHg Over Time | Day 10 | 100 percentage of participants |
| IW-1973 40 mg BID/QD | Percentage of Participants With Postdose Supine Blood Pressure Less Than 130/80 mmHg Over Time | Day 21 / Follow-Up | 80.0 percentage of participants |
| IW-1973 40 mg BID/QD | Percentage of Participants With Postdose Supine Blood Pressure Less Than 130/80 mmHg Over Time | Day 3 | 100 percentage of participants |
| IW-1973 40 mg BID/QD | Percentage of Participants With Postdose Supine Blood Pressure Less Than 130/80 mmHg Over Time | Day 8 | 90.0 percentage of participants |
| IW-1973 40 mg BID/QD | Percentage of Participants With Postdose Supine Blood Pressure Less Than 130/80 mmHg Over Time | Day 13 | 100 percentage of participants |
| IW-1973 40 mg BID/QD | Percentage of Participants With Postdose Supine Blood Pressure Less Than 130/80 mmHg Over Time | Day 4 | 100 percentage of participants |
| IW-1973 40 mg BID/QD | Percentage of Participants With Postdose Supine Blood Pressure Less Than 130/80 mmHg Over Time | Day 7 | 90.0 percentage of participants |
| IW-1973 40 mg BID/QD | Percentage of Participants With Postdose Supine Blood Pressure Less Than 130/80 mmHg Over Time | Day 11 | 100 percentage of participants |
| IW-1973 40 mg BID/QD | Percentage of Participants With Postdose Supine Blood Pressure Less Than 130/80 mmHg Over Time | Day 5 | 70.0 percentage of participants |
| IW-1973 40 mg BID/QD | Percentage of Participants With Postdose Supine Blood Pressure Less Than 130/80 mmHg Over Time | Day 6 | 90.0 percentage of participants |
| IW-1973 40 mg QD/QD | Percentage of Participants With Postdose Supine Blood Pressure Less Than 130/80 mmHg Over Time | Day 5 | 90.0 percentage of participants |
| IW-1973 40 mg QD/QD | Percentage of Participants With Postdose Supine Blood Pressure Less Than 130/80 mmHg Over Time | Day 6 | 90.0 percentage of participants |
| IW-1973 40 mg QD/QD | Percentage of Participants With Postdose Supine Blood Pressure Less Than 130/80 mmHg Over Time | Day 7 | 90.0 percentage of participants |
| IW-1973 40 mg QD/QD | Percentage of Participants With Postdose Supine Blood Pressure Less Than 130/80 mmHg Over Time | Day 14 | 80.0 percentage of participants |
| IW-1973 40 mg QD/QD | Percentage of Participants With Postdose Supine Blood Pressure Less Than 130/80 mmHg Over Time | Day 8 | 100 percentage of participants |
| IW-1973 40 mg QD/QD | Percentage of Participants With Postdose Supine Blood Pressure Less Than 130/80 mmHg Over Time | Day 42 / End of Trial | 60.0 percentage of participants |
| IW-1973 40 mg QD/QD | Percentage of Participants With Postdose Supine Blood Pressure Less Than 130/80 mmHg Over Time | Day 9 | 70.0 percentage of participants |
| IW-1973 40 mg QD/QD | Percentage of Participants With Postdose Supine Blood Pressure Less Than 130/80 mmHg Over Time | Day 10 | 70.0 percentage of participants |
| IW-1973 40 mg QD/QD | Percentage of Participants With Postdose Supine Blood Pressure Less Than 130/80 mmHg Over Time | Day 15 / Discharge | 70.0 percentage of participants |
| IW-1973 40 mg QD/QD | Percentage of Participants With Postdose Supine Blood Pressure Less Than 130/80 mmHg Over Time | Day 11 | 70.0 percentage of participants |
| IW-1973 40 mg QD/QD | Percentage of Participants With Postdose Supine Blood Pressure Less Than 130/80 mmHg Over Time | Baseline | 60.0 percentage of participants |
| IW-1973 40 mg QD/QD | Percentage of Participants With Postdose Supine Blood Pressure Less Than 130/80 mmHg Over Time | Day 1 | 100 percentage of participants |
| IW-1973 40 mg QD/QD | Percentage of Participants With Postdose Supine Blood Pressure Less Than 130/80 mmHg Over Time | Day 12 | 80.0 percentage of participants |
| IW-1973 40 mg QD/QD | Percentage of Participants With Postdose Supine Blood Pressure Less Than 130/80 mmHg Over Time | Day 2 | 100 percentage of participants |
| IW-1973 40 mg QD/QD | Percentage of Participants With Postdose Supine Blood Pressure Less Than 130/80 mmHg Over Time | Day 3 | 90.0 percentage of participants |
| IW-1973 40 mg QD/QD | Percentage of Participants With Postdose Supine Blood Pressure Less Than 130/80 mmHg Over Time | Day 4 | 90.0 percentage of participants |
| IW-1973 40 mg QD/QD | Percentage of Participants With Postdose Supine Blood Pressure Less Than 130/80 mmHg Over Time | Day 13 | 100 percentage of participants |
| IW-1973 40 mg QD/QD | Percentage of Participants With Postdose Supine Blood Pressure Less Than 130/80 mmHg Over Time | Day 21 / Follow-Up | 50.0 percentage of participants |
Primary
Percent Change From Study Baseline Over Time in HOMA-IR in Participants Without Concomitant Use of Insulin
Blood samples were taken for fasting glucose and insulin levels. From these results, insulin resistance was then estimated using the updated homeostasis model assessment method for insulin resistance (HOMA-IR) computer algorithm. A higher HOMA-IR indicates a higher degree of insulin resistance. Typically a cutoff of HOMA-IR for identifying those with insulin resistance is 2.5.
Time frame: Study baseline (defined as the last non-missing assessment before the first administration of study drug), Day 8, pre-AM dose, Day 15
Population: PD Population: all participants who received at least 1 dose of study drug and had at least 1 postdose PD assessment. Participants with a baseline (BL) and postbaseline (PBL) assessment at given time point who did not use concomitant insulin.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Percent Change From Study Baseline Over Time in HOMA-IR in Participants Without Concomitant Use of Insulin | Study Baseline (Day 1 predose) | 7.350 percent change | Standard Error 5.236 |
| Placebo | Percent Change From Study Baseline Over Time in HOMA-IR in Participants Without Concomitant Use of Insulin | Day 15 | -12.839 percent change | Standard Error 12.565 |
| Placebo | Percent Change From Study Baseline Over Time in HOMA-IR in Participants Without Concomitant Use of Insulin | Day 8 | -4.284 percent change | Standard Error 20.823 |
| IW-1973 40 mg BID/QD | Percent Change From Study Baseline Over Time in HOMA-IR in Participants Without Concomitant Use of Insulin | Study Baseline (Day 1 predose) | 6.646 percent change | Standard Error 3.403 |
| IW-1973 40 mg BID/QD | Percent Change From Study Baseline Over Time in HOMA-IR in Participants Without Concomitant Use of Insulin | Day 15 | -38.228 percent change | Standard Error 11.263 |
| IW-1973 40 mg BID/QD | Percent Change From Study Baseline Over Time in HOMA-IR in Participants Without Concomitant Use of Insulin | Day 8 | -27.473 percent change | Standard Error 18.639 |
| IW-1973 40 mg QD/QD | Percent Change From Study Baseline Over Time in HOMA-IR in Participants Without Concomitant Use of Insulin | Day 8 | -18.318 percent change | Standard Error 15.735 |
| IW-1973 40 mg QD/QD | Percent Change From Study Baseline Over Time in HOMA-IR in Participants Without Concomitant Use of Insulin | Study Baseline (Day 1 predose) | 7.187 percent change | Standard Error 5.684 |
| IW-1973 40 mg QD/QD | Percent Change From Study Baseline Over Time in HOMA-IR in Participants Without Concomitant Use of Insulin | Day 15 | -34.015 percent change | Standard Error 10.27 |
| IW-1973 40 mg Total Daily Dose (Overall) | Percent Change From Study Baseline Over Time in HOMA-IR in Participants Without Concomitant Use of Insulin | Study Baseline (Day 1 predose) | 6.962 percent change | Standard Error 4.681 |
| IW-1973 40 mg Total Daily Dose (Overall) | Percent Change From Study Baseline Over Time in HOMA-IR in Participants Without Concomitant Use of Insulin | Day 15 | -36.121 percent change | Standard Error 7.609 |
| IW-1973 40 mg Total Daily Dose (Overall) | Percent Change From Study Baseline Over Time in HOMA-IR in Participants Without Concomitant Use of Insulin | Day 8 | -22.895 percent change | Standard Error 12.191 |
Comparison: Day 895% CI: [-70.883, 42.817]
Comparison: Day 895% CI: [-71.204, 33.982]
Comparison: Day 1595% CI: [-62.551, 11.774]
Comparison: Day 1595% CI: [-56.879, 14.527]
Comparison: Day 1595% CI: [-55.618, 9.053]
Comparison: Day 895% CI: [-84.13, 37.753]
Primary
Post-Baseline Platelet Reactivity on Days 8 and 14: Aspirin Reaction Units (ARU) Assay
Platelet reactivity, as measured by VerifyNow ARU assay, and presented as number of participants with ≤ 549 ARU or \> 549 ARU post-baseline (Days 8 and 14), by baseline category. Aspirin irreversibly inhibits cyclooxygenase 1, which converts arachidonic acid to thromboxane A2, which in turn is involved in the activation of the glycoprotein (GP)IIb/IIIa receptor necessary to initiate platelet aggregation. Impairment of platelet aggregation of the aspirin type is defined for the VerifyNow aspirin assay as values ≤ 549 ARU.
Time frame: Baseline, Day 8, Day 14
Population: PD Population: all participants who received at least 1 dose of study drug and had at least 1 postdose PD assessment. Participants with a baseline (BL) and postbaseline (PBL) assessment at given time point, by specific BL category (≤ 549 or \> 549 ARU).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Post-Baseline Platelet Reactivity on Days 8 and 14: Aspirin Reaction Units (ARU) Assay | Baseline: ≤ 549 ARU | 2 Participants |
| Placebo | Post-Baseline Platelet Reactivity on Days 8 and 14: Aspirin Reaction Units (ARU) Assay | Baseline: > 549 ARU | 3 Participants |
| Placebo | Post-Baseline Platelet Reactivity on Days 8 and 14: Aspirin Reaction Units (ARU) Assay | Day 8: ≤ 549 BL, ≤ 549 PBL | 2 Participants |
| Placebo | Post-Baseline Platelet Reactivity on Days 8 and 14: Aspirin Reaction Units (ARU) Assay | Day 8: ≤ 549 BL, > 549 PBL | 0 Participants |
| Placebo | Post-Baseline Platelet Reactivity on Days 8 and 14: Aspirin Reaction Units (ARU) Assay | Day 8: > 549 BL, ≤ 549 PBL | 1 Participants |
| Placebo | Post-Baseline Platelet Reactivity on Days 8 and 14: Aspirin Reaction Units (ARU) Assay | Day 8: > 549 BL, > 549 PBL | 2 Participants |
| Placebo | Post-Baseline Platelet Reactivity on Days 8 and 14: Aspirin Reaction Units (ARU) Assay | Day 14: ≤ 549 BL, ≤ 549 PBL | 2 Participants |
| Placebo | Post-Baseline Platelet Reactivity on Days 8 and 14: Aspirin Reaction Units (ARU) Assay | Day 14: ≤ 549 BL, > 549 PBL | 0 Participants |
| Placebo | Post-Baseline Platelet Reactivity on Days 8 and 14: Aspirin Reaction Units (ARU) Assay | Day 14: > 549 BL, ≤ 549 PBL | 0 Participants |
| Placebo | Post-Baseline Platelet Reactivity on Days 8 and 14: Aspirin Reaction Units (ARU) Assay | Day 14: > 549 BL, > 549 PBL | 3 Participants |
| IW-1973 40 mg BID/QD | Post-Baseline Platelet Reactivity on Days 8 and 14: Aspirin Reaction Units (ARU) Assay | Day 14: > 549 BL, ≤ 549 PBL | 0 Participants |
| IW-1973 40 mg BID/QD | Post-Baseline Platelet Reactivity on Days 8 and 14: Aspirin Reaction Units (ARU) Assay | Baseline: ≤ 549 ARU | 5 Participants |
| IW-1973 40 mg BID/QD | Post-Baseline Platelet Reactivity on Days 8 and 14: Aspirin Reaction Units (ARU) Assay | Day 8: > 549 BL, > 549 PBL | 3 Participants |
| IW-1973 40 mg BID/QD | Post-Baseline Platelet Reactivity on Days 8 and 14: Aspirin Reaction Units (ARU) Assay | Day 8: > 549 BL, ≤ 549 PBL | 2 Participants |
| IW-1973 40 mg BID/QD | Post-Baseline Platelet Reactivity on Days 8 and 14: Aspirin Reaction Units (ARU) Assay | Baseline: > 549 ARU | 5 Participants |
| IW-1973 40 mg BID/QD | Post-Baseline Platelet Reactivity on Days 8 and 14: Aspirin Reaction Units (ARU) Assay | Day 14: > 549 BL, > 549 PBL | 5 Participants |
| IW-1973 40 mg BID/QD | Post-Baseline Platelet Reactivity on Days 8 and 14: Aspirin Reaction Units (ARU) Assay | Day 14: ≤ 549 BL, > 549 PBL | 3 Participants |
| IW-1973 40 mg BID/QD | Post-Baseline Platelet Reactivity on Days 8 and 14: Aspirin Reaction Units (ARU) Assay | Day 8: ≤ 549 BL, ≤ 549 PBL | 5 Participants |
| IW-1973 40 mg BID/QD | Post-Baseline Platelet Reactivity on Days 8 and 14: Aspirin Reaction Units (ARU) Assay | Day 14: ≤ 549 BL, ≤ 549 PBL | 2 Participants |
| IW-1973 40 mg BID/QD | Post-Baseline Platelet Reactivity on Days 8 and 14: Aspirin Reaction Units (ARU) Assay | Day 8: ≤ 549 BL, > 549 PBL | 0 Participants |
| IW-1973 40 mg QD/QD | Post-Baseline Platelet Reactivity on Days 8 and 14: Aspirin Reaction Units (ARU) Assay | Day 14: ≤ 549 BL, > 549 PBL | 0 Participants |
| IW-1973 40 mg QD/QD | Post-Baseline Platelet Reactivity on Days 8 and 14: Aspirin Reaction Units (ARU) Assay | Day 8: ≤ 549 BL, > 549 PBL | 0 Participants |
| IW-1973 40 mg QD/QD | Post-Baseline Platelet Reactivity on Days 8 and 14: Aspirin Reaction Units (ARU) Assay | Day 8: > 549 BL, ≤ 549 PBL | 0 Participants |
| IW-1973 40 mg QD/QD | Post-Baseline Platelet Reactivity on Days 8 and 14: Aspirin Reaction Units (ARU) Assay | Day 8: > 549 BL, > 549 PBL | 4 Participants |
| IW-1973 40 mg QD/QD | Post-Baseline Platelet Reactivity on Days 8 and 14: Aspirin Reaction Units (ARU) Assay | Day 14: > 549 BL, ≤ 549 PBL | 1 Participants |
| IW-1973 40 mg QD/QD | Post-Baseline Platelet Reactivity on Days 8 and 14: Aspirin Reaction Units (ARU) Assay | Day 14: ≤ 549 BL, ≤ 549 PBL | 6 Participants |
| IW-1973 40 mg QD/QD | Post-Baseline Platelet Reactivity on Days 8 and 14: Aspirin Reaction Units (ARU) Assay | Baseline: ≤ 549 ARU | 6 Participants |
| IW-1973 40 mg QD/QD | Post-Baseline Platelet Reactivity on Days 8 and 14: Aspirin Reaction Units (ARU) Assay | Day 14: > 549 BL, > 549 PBL | 3 Participants |
| IW-1973 40 mg QD/QD | Post-Baseline Platelet Reactivity on Days 8 and 14: Aspirin Reaction Units (ARU) Assay | Baseline: > 549 ARU | 4 Participants |
| IW-1973 40 mg QD/QD | Post-Baseline Platelet Reactivity on Days 8 and 14: Aspirin Reaction Units (ARU) Assay | Day 8: ≤ 549 BL, ≤ 549 PBL | 6 Participants |
Primary
Post-Baseline Platelet Reactivity on Days 8 and 14: P2Y12 Reaction Units (PRU) Assay
Platelet reactivity, as measured by VerifyNow PRU assay, and presented as number of participants with \< 180 PRU or ≥ 180 PRU post-baseline (Days 8 and 14), by baseline category. The VerifyNow PRU assay measures effects on platelet activation caused by inhibition of the platelet receptor, P2Y12. This receptor is activated by adenosine 5'-diphosphate (ADP) in the cascade leading to platelet aggregation but can be blocked by P2Y12 inhibitor drugs, such as clopidogrel. Blockage of this receptor diminishes platelet activation and the ability of platelets to bind to fibrinogen. VerifyNow PRU assay values \< 180 units indicate impairment of platelet aggregation.
Time frame: Baseline, Day 8, Day 14
Population: PD Population: all participants who received at least 1 dose of study drug and had at least 1 postdose PD assessment. Participants with a baseline (BL) and postbaseline (PBL) assessment at given time point, by specific BL category \< 180 or ≥ 180 PRU.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Post-Baseline Platelet Reactivity on Days 8 and 14: P2Y12 Reaction Units (PRU) Assay | Baseline: <180 PRU | 0 Participants |
| Placebo | Post-Baseline Platelet Reactivity on Days 8 and 14: P2Y12 Reaction Units (PRU) Assay | Baseline: ≥180 PRU | 5 Participants |
| Placebo | Post-Baseline Platelet Reactivity on Days 8 and 14: P2Y12 Reaction Units (PRU) Assay | PRU Day 8: ≥180 BL, <180 PBL | 0 Participants |
| Placebo | Post-Baseline Platelet Reactivity on Days 8 and 14: P2Y12 Reaction Units (PRU) Assay | PRU Day 8: ≥180 BL, ≥180 PBL | 5 Participants |
| Placebo | Post-Baseline Platelet Reactivity on Days 8 and 14: P2Y12 Reaction Units (PRU) Assay | PRU Day 14: ≥180 BL, <180 PBL | 0 Participants |
| Placebo | Post-Baseline Platelet Reactivity on Days 8 and 14: P2Y12 Reaction Units (PRU) Assay | PRU Day 14: ≥180 BL, ≥180 PBL | 5 Participants |
| IW-1973 40 mg BID/QD | Post-Baseline Platelet Reactivity on Days 8 and 14: P2Y12 Reaction Units (PRU) Assay | PRU Day 14: ≥180 BL, ≥180 PBL | 10 Participants |
| IW-1973 40 mg BID/QD | Post-Baseline Platelet Reactivity on Days 8 and 14: P2Y12 Reaction Units (PRU) Assay | Baseline: <180 PRU | 0 Participants |
| IW-1973 40 mg BID/QD | Post-Baseline Platelet Reactivity on Days 8 and 14: P2Y12 Reaction Units (PRU) Assay | PRU Day 8: ≥180 BL, ≥180 PBL | 10 Participants |
| IW-1973 40 mg BID/QD | Post-Baseline Platelet Reactivity on Days 8 and 14: P2Y12 Reaction Units (PRU) Assay | PRU Day 14: ≥180 BL, <180 PBL | 0 Participants |
| IW-1973 40 mg BID/QD | Post-Baseline Platelet Reactivity on Days 8 and 14: P2Y12 Reaction Units (PRU) Assay | Baseline: ≥180 PRU | 10 Participants |
| IW-1973 40 mg BID/QD | Post-Baseline Platelet Reactivity on Days 8 and 14: P2Y12 Reaction Units (PRU) Assay | PRU Day 8: ≥180 BL, <180 PBL | 0 Participants |
| IW-1973 40 mg QD/QD | Post-Baseline Platelet Reactivity on Days 8 and 14: P2Y12 Reaction Units (PRU) Assay | Baseline: ≥180 PRU | 10 Participants |
| IW-1973 40 mg QD/QD | Post-Baseline Platelet Reactivity on Days 8 and 14: P2Y12 Reaction Units (PRU) Assay | PRU Day 8: ≥180 BL, <180 PBL | 0 Participants |
| IW-1973 40 mg QD/QD | Post-Baseline Platelet Reactivity on Days 8 and 14: P2Y12 Reaction Units (PRU) Assay | PRU Day 14: ≥180 BL, ≥180 PBL | 10 Participants |
| IW-1973 40 mg QD/QD | Post-Baseline Platelet Reactivity on Days 8 and 14: P2Y12 Reaction Units (PRU) Assay | PRU Day 8: ≥180 BL, ≥180 PBL | 10 Participants |
| IW-1973 40 mg QD/QD | Post-Baseline Platelet Reactivity on Days 8 and 14: P2Y12 Reaction Units (PRU) Assay | Baseline: <180 PRU | 0 Participants |
| IW-1973 40 mg QD/QD | Post-Baseline Platelet Reactivity on Days 8 and 14: P2Y12 Reaction Units (PRU) Assay | PRU Day 14: ≥180 BL, <180 PBL | 0 Participants |