Age-Related Macular Degeneration
Conditions
Keywords
LHA510, First in human, Safety, Tolerability, Pharmacokinetics, Elderly, Age-Related Macular Degeneration, AMD, Ocular, Eye drop
Brief summary
The purpose of this first-in-human study is to assess the local ocular and systemic safety and tolerability of LHA510 eye drops when administered at various concentrations and dosing frequencies.
Detailed description
This first-in-human study was conducted in two parts. Part 1 was a single ascending dose (SAD) design to assess the local ocular and systemic safety and tolerability of a single topical eye drop of LHA510 administered at various concentrations. Four separate cohorts of unique elderly subjects (55 to 80 years) were utilized, with each cohort randomized to receive either topical LHA510 or vehicle in a 3:1 ratio as a single dose. A disposition evaluation was performed 7 days later. Part 2 was a multiple ascending dose (MAD) design to assess the local ocular and systemic safety and tolerability of LHA510 administered at various concentrations and dosing frequencies. Six separate cohorts of unique AMD subjects were utilized, with each cohort randomized to receive either topical LHA510 or vehicle in a 3:1 ratio for 7 days. A disposition evaluation was performed 14 days after the first dose of study drug. A review of all available safety data was conducted by the Sponsor and the PI(s) prior to dose escalation (cohort progression). The same concentrations levels were used in Part 1 and Part 2 and are ordered as Lowest, Next Lowest, Next Highest, and Highest.
Interventions
Ophthalmic suspension in 4 concentration levels topically administered in Part 1 and Part 2
DRUGLHA510 Vehicle
Inactive ingredients used for masking purposes
Sponsors
Alcon Research
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
55 Years to 80 Years
Healthy volunteers
Yes
Inclusion criteria
* Provide written informed consent. * Vital signs within the following ranges: * oral body temperature between 35.0-37.5 °C * systolic blood pressure, 90-150 mm Hg * diastolic blood pressure, 50-90 mm Hg * pulse rate, 40 - 100 bpm. * Weigh at least 50 kg. * Able to communicate well with the investigator. * Able to understand and comply with the requirements of the study. Additional eligibility criteria for Part 2 (AMD subjects): * Evidence of AMD in one or both eyes. * Age 55-90. * Other protocol-defined inclusion criteria may apply.
Exclusion criteria
* Any currently active ocular condition that requires use of topical eye drops. * Use of contact lens over the course of the study. * Abnormal corneal examination results at screening or eligibility. * History of any ocular surgery within the past 6 months prior to study participation. * Use of other investigational drugs within 30 days of enrollment. * History of hypersensitivity or allergy to any of the study drugs (including fluorescein) or to drugs of similar chemical classes. * History of clinically significant ECG abnormalities, or any ECG abnormality at screening or eligibility. * Known history or current clinically significant arrhythmias. * History of malignancy of any organ system (other than localized basal cell carcinoma of the skin), treated or untreated, within the past 5 years. * Pregnant or nursing (lactating) women. * Women of child-bearing potential. * Use of any prohibited medication as specified in the protocol. * Donation or loss of 400 ml or more of blood within eight (8) weeks prior to initial dosing. * Low hemoglobin levels at screening or eligibility as specified in the protocol. * Significant illness as specified in the protocol. * History of drug or alcohol abuse within the 12 months prior to dosing. Additional
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects With a Serious Adverse Event That, in the Opinion of the Investigator, is Related to the Study Drug, Part 1 | From time of consent until 30 days after stopping the trial/study drug | A serious adverse event (SAE) was defined as any event which is fatal or life-threatening, which requires or prolongs hospitalization, which is significantly or permanently disabling or incapacitating, which constitutes a congenital anomaly or a birth defect, or which is medically significant, may jeopardize the subject and may require medical or surgical intervention to prevent one of the outcomes listed above. |
| Number of Subjects With a Serious Adverse Event That, in the Opinion of the Investigator, is Related to the Study Drug, Part 2 | From time of consent until 30 days after stopping the trial/study drug | A serious adverse event (SAE) was defined as any event which is fatal or life-threatening, which requires or prolongs hospitalization, which is significantly or permanently disabling or incapacitating, which constitutes a congenital anomaly or a birth defect, or which is medically significant, may jeopardize the subject and may require medical or surgical intervention to prevent one of the outcomes listed above. |
| Number of Subjects Experiencing a Non-serious Adverse Event, Part I | From time of consent until 30 days after stopping the trial/study drug | An adverse event (AE) was defined as any untoward medical occurrence in a subject who is administered a study treatment regardless of whether or not the event has a causal relationship with the treatment. An AE, therefore, could be any unfavorable or unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the study treatment, whether or not related to the treatment. |
| Number of Subjects Experiencing a Non-serious Adverse Event, Part 2 | From time of consent until 30 days after stopping the trial/study drug | An adverse event (AE) was defined as any untoward medical occurrence in a subject who is administered a study treatment regardless of whether or not the event has a causal relationship with the treatment. An AE, therefore, could be any unfavorable or unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the study treatment, whether or not related to the treatment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The Terminal Elimination Half-life [Time] (T1/2), Part 2 | Up to Day 15 | Plasma concentrations were quantitated using a high performance liquid chromatography/tandem mass spectometry method. Timepoints of assessment for Arms 1-4 were Days 1 and 7: 0h (pre-dose), 0.25h, 0.5h, 1h, 2h, 4h, 6h, 8h, 12h and 24h post-dose; and Day 15: 0h. Timepoints of assessment for LHA Highest BID were Days 1 and 7: 0h (pre-dose), 0.25h, 0.5h, 1h, 2h, 4h, 6h, 8h and 12h post-dose; and Day 15: 0h. Timepoints of assessment for LHA510 Highest TID were Days 1 and 7: 0h (pre-dose), 0.25h, 0.5h, 1h, 2h, 4h, 0h (pre-2nd dose), 0.5h, 2h, 0h (pre-3rd dose), 0.25h, 0.5h, 1h, 2h, 4h, 12h post-dose; and Day 15: 0h. |
| Change From Baseline in Diastolic Blood Pressure at Each Post Dose Timepoint, Part 1 | Day 1: 0.25h, 0.5h, 1h, 2h, 4h, 6h, 8h, 12h and 24h post-dose | Diastolic blood pressure (pressure in the arteries when the heart rests between beats) was measured using an automated validated device, with an appropriately sized cuff, and assessed in the sitting position after the subject had rested for at least 3 minutes, and again (when required) after 3 minutes in the standing position. |
| Change From Baseline in Systolic Blood Pressure at Each Post Dose Timepoint, Part 1 | Day 1: 0.25h, 0.5h, 1h, 2h, 4h, 6h, 8h, 12h and 24h post-dose | Systolic blood pressure (pressure when the heart is contracting) was measured using an automated validated device, with an appropriately sized cuff, and assessed in the sitting position after the subject had rested for at least 3 minutes, and again (when required) after 3 minutes in the standing position. |
| The Observed Maximum Plasma (or Serum or Blood) Concentration Following Drug Administration [Mass / Volume] (Cmax), Part 2 | Up to Day 15 | Plasma concentrations were quantitated using a high performance liquid chromatography/tandem mass spectometry method.Timepoints of assessment for Arms 1-4 were Days 1 and 7: 0h (pre-dose), 0.25h, 0.5h, 1h, 2h, 4h, 6h, 8h, 12h and 24h post-dose; and Day 15: 0h. Timepoints of assessment for LHA Highest BID were Days 1 and 7: 0h (pre-dose), 0.25h, 0.5h, 1h, 2h, 4h, 6h, 8h and 12h post-dose; and Day 15: 0h. Timepoints of assessment for LHA510 Highest TID were Days 1 and 7: 0h (pre-dose), 0.25h, 0.5h, 1h, 2h, 4h, 0h (pre-2nd dose), 0.5h, 2h, 0h (pre-3rd dose), 0.25h, 0.5h, 1h, 2h, 4h, 12h post-dose; and Day 15: 0h. |
| Change From Baseline in Systolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 1 and 7: 0.25h, 0.5h, 1h, 2h, 4h, 6h, 8h, 12h and 24h post-dose | Systolic blood pressure (pressure when the heart is contracting) was measured using an automated validated device, with an appropriately sized cuff, and assessed in the sitting position after the subject had rested for at least 3 minutes, and again (when required) after 3 minutes in the standing position. |
| Change From Mean Arterial Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 1 and 7: 0.25h, 0.5h, 1h, 2h, 4h, 6h, 8h, 12h and 24h post-dose | Mean arterial blood pressure (average pressure in the arteries during one cardiac cycle) was measured using an automated validated device, with an appropriately sized cuff, and assessed in the sitting position after the subject had rested for at least 3 minutes, and again (when required) after 3 minutes in the standing position. |
| Change From Baseline in Diastolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 1 and 7: 0.25h, 0.5h, 1h, 2h, 4h, 6h, 8h, 12h and 24h post-dose | Diastolic blood pressure (pressure in the arteries when the heart rests between beats) was measured using an automated validated device, with an appropriately sized cuff, and assessed in the sitting position after the subject had rested for at least 3 minutes, and again (when required) after 3 minutes in the standing position. |
| The Time to Reach the Maximum Concentration After Drug Administration [Time] (Tmax), Part 2 | Up to Day 15 | Plasma concentrations were quantitated using a high performance liquid chromatography/tandem mass spectometry method. Timepoints of assessment for Arms 1-4 were Days 1 and 7: 0h (pre-dose), 0.25h, 0.5h, 1h, 2h, 4h, 6h, 8h, 12h and 24h post-dose; and Day 15: 0h. Timepoints of assessment for LHA Highest BID were Days 1 and 7: 0h (pre-dose), 0.25h, 0.5h, 1h, 2h, 4h, 6h, 8h and 12h post-dose; and Day 15: 0h. Timepoints of assessment for LHA510 Highest TID were Days 1 and 7: 0h (pre-dose), 0.25h, 0.5h, 1h, 2h, 4h, 0h (pre-2nd dose), 0.5h, 2h, 0h (pre-3rd dose), 0.25h, 0.5h, 1h, 2h, 4h, 12h post-dose; and Day 15: 0h. |
| Change From Baseline in Mean Arterial Blood Pressure at Each Post Dose Timepoint, Part 1 | Day 1: 0.25h, 0.5h, 1h, 2h, 4h, 6h, 8h, 12h and 24h post-dose | Mean arterial blood pressure (average pressure in the arteries during one cardiac cycle) was measured using an automated validated device, with an appropriately sized cuff, and assessed in the sitting position after the subject had rested for at least 3 minutes, and again (when required) after 3 minutes in the standing position. |
| The Area Under the Plasma (or Serum or Blood) Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration [Mass x Time/Volume] (AUClast), Part 2 | Up to Day 15 | Plasma concentrations were quantitated using a high performance liquid chromatography/tandem mass spectometry method. Timepoints of assessment for Arms 1-4 were Days 1 and 7: 0h (pre-dose), 0.25h, 0.5h, 1h, 2h, 4h, 6h, 8h, 12h and 24h post-dose; and Day 15: 0h. Timepoints of assessment for LHA Highest BID were Days 1 and 7: 0h (pre-dose), 0.25h, 0.5h, 1h, 2h, 4h, 6h, 8h and 12h post-dose; and Day 15: 0h. Timepoints of assessment for LHA510 Highest TID were Days 1 and 7: 0h (pre-dose), 0.25h, 0.5h, 1h, 2h, 4h, 0h (pre-2nd dose), 0.5h, 2h, 0h (pre-3rd dose), 0.25h, 0.5h, 1h, 2h, 4h, 12h post-dose; and Day 15: 0h. |
Participant flow
Recruitment details
Subjects were recruited from a single investigational site located in the US.
Pre-assignment details
Of the 110 enrolled, 30 subjects were exited as screen failures prior to randomization. This reporting group includes all randomized subjects (80).
Participants by arm
| Arm | Count |
|---|---|
| LHA510 Lowest, Part 1 1 drop instilled in the study eye as a single dose | 6 |
| LHA510 Next Lowest, Part 1 1 drop instilled in the study eye as a single dose | 6 |
| LHA510 Next Highest, Part 1 1 drop instilled in the study eye as a single dose | 6 |
| LHA510 Highest, Part 1 1 drop instilled in the study eye as a single dose | 6 |
| Vehicle, Part 1 1 drop instilled in the study eye as a single dose | 8 |
| LHA510 Lowest, Part 2 1 drop instilled in the study eye once daily for 7 days | 6 |
| LHA510 Next Lowest, Part 2 1 drop instilled in the study eye once daily for 7 days | 6 |
| LHA510 Next Highest, Part 2 1 drop instilled in the study eye once daily for 7 days | 6 |
| LHA510 Highest, Part 2 1 drop instilled in the study eye once daily for 7 days | 6 |
| LHA510 Highest BID, Part 2 1 drop instilled in the study eye twice daily for 7 days | 6 |
| LHA510 Highest TID, Part 2 1 drop instilled in the study eye three times daily for 7 days | 6 |
| Vehicle, Part 2 1 drop instilled in the study eye once, twice, or three times daily for 7 days | 12 |
| Total | 80 |
Baseline characteristics
| Characteristic | LHA510 Lowest, Part 1 | LHA510 Next Lowest, Part 1 | LHA510 Next Highest, Part 1 | LHA510 Highest, Part 1 | Vehicle, Part 1 | LHA510 Lowest, Part 2 | LHA510 Next Lowest, Part 2 | LHA510 Next Highest, Part 2 | LHA510 Highest, Part 2 | LHA510 Highest BID, Part 2 | LHA510 Highest TID, Part 2 | Vehicle, Part 2 | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Customized 55-64 years | 2 participants | 3 participants | 4 participants | 2 participants | 2 participants | 0 participants | 0 participants | 0 participants | 0 participants | 1 participants | 0 participants | 0 participants | 14 participants |
| Age, Customized ≥ 65 years | 4 participants | 3 participants | 2 participants | 4 participants | 6 participants | 6 participants | 6 participants | 6 participants | 6 participants | 5 participants | 6 participants | 12 participants | 66 participants |
| Sex: Female, Male Female | 3 Participants | 2 Participants | 3 Participants | 4 Participants | 4 Participants | 4 Participants | 3 Participants | 2 Participants | 3 Participants | 3 Participants | 2 Participants | 8 Participants | 41 Participants |
| Sex: Female, Male Male | 3 Participants | 4 Participants | 3 Participants | 2 Participants | 4 Participants | 2 Participants | 3 Participants | 4 Participants | 3 Participants | 3 Participants | 4 Participants | 4 Participants | 39 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk | EG011 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 2 / 6 | 1 / 6 | 0 / 6 | 1 / 6 | 1 / 8 | 3 / 6 | 1 / 6 | 1 / 6 | 2 / 6 | 2 / 6 | 1 / 6 | 3 / 12 |
| serious Total, serious adverse events | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 8 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 12 |
Outcome results
Primary
Number of Subjects Experiencing a Non-serious Adverse Event, Part 2
An adverse event (AE) was defined as any untoward medical occurrence in a subject who is administered a study treatment regardless of whether or not the event has a causal relationship with the treatment. An AE, therefore, could be any unfavorable or unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the study treatment, whether or not related to the treatment.
Time frame: From time of consent until 30 days after stopping the trial/study drug
Population: This analysis population includes all enrolled subjects in Part 2.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| LHA510 Lowest, Part 1 | Number of Subjects Experiencing a Non-serious Adverse Event, Part 2 | 3 participants |
| LHA510 Next Lowest, Part 1 | Number of Subjects Experiencing a Non-serious Adverse Event, Part 2 | 1 participants |
| LHA510 Next Highest, Part 1 | Number of Subjects Experiencing a Non-serious Adverse Event, Part 2 | 1 participants |
| LHA510 Highest, Part 1 | Number of Subjects Experiencing a Non-serious Adverse Event, Part 2 | 2 participants |
| Vehicle, Part 1 | Number of Subjects Experiencing a Non-serious Adverse Event, Part 2 | 2 participants |
| LHA510 Highest TID, Part 2 | Number of Subjects Experiencing a Non-serious Adverse Event, Part 2 | 1 participants |
| Vehicle, Part 2 | Number of Subjects Experiencing a Non-serious Adverse Event, Part 2 | 3 participants |
Primary
Number of Subjects Experiencing a Non-serious Adverse Event, Part I
An adverse event (AE) was defined as any untoward medical occurrence in a subject who is administered a study treatment regardless of whether or not the event has a causal relationship with the treatment. An AE, therefore, could be any unfavorable or unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the study treatment, whether or not related to the treatment.
Time frame: From time of consent until 30 days after stopping the trial/study drug
Population: This analysis population includes all enrolled subjects in Part 1.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| LHA510 Lowest, Part 1 | Number of Subjects Experiencing a Non-serious Adverse Event, Part I | 2 participants |
| LHA510 Next Lowest, Part 1 | Number of Subjects Experiencing a Non-serious Adverse Event, Part I | 1 participants |
| LHA510 Next Highest, Part 1 | Number of Subjects Experiencing a Non-serious Adverse Event, Part I | 0 participants |
| LHA510 Highest, Part 1 | Number of Subjects Experiencing a Non-serious Adverse Event, Part I | 1 participants |
| Vehicle, Part 1 | Number of Subjects Experiencing a Non-serious Adverse Event, Part I | 1 participants |
Primary
Number of Subjects With a Serious Adverse Event That, in the Opinion of the Investigator, is Related to the Study Drug, Part 1
A serious adverse event (SAE) was defined as any event which is fatal or life-threatening, which requires or prolongs hospitalization, which is significantly or permanently disabling or incapacitating, which constitutes a congenital anomaly or a birth defect, or which is medically significant, may jeopardize the subject and may require medical or surgical intervention to prevent one of the outcomes listed above.
Time frame: From time of consent until 30 days after stopping the trial/study drug
Population: This analysis population includes all enrolled subjects in Part 1.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| LHA510 Lowest, Part 1 | Number of Subjects With a Serious Adverse Event That, in the Opinion of the Investigator, is Related to the Study Drug, Part 1 | 0 participants |
| LHA510 Next Lowest, Part 1 | Number of Subjects With a Serious Adverse Event That, in the Opinion of the Investigator, is Related to the Study Drug, Part 1 | 0 participants |
| LHA510 Next Highest, Part 1 | Number of Subjects With a Serious Adverse Event That, in the Opinion of the Investigator, is Related to the Study Drug, Part 1 | 0 participants |
| LHA510 Highest, Part 1 | Number of Subjects With a Serious Adverse Event That, in the Opinion of the Investigator, is Related to the Study Drug, Part 1 | 0 participants |
| Vehicle, Part 1 | Number of Subjects With a Serious Adverse Event That, in the Opinion of the Investigator, is Related to the Study Drug, Part 1 | 0 participants |
Primary
Number of Subjects With a Serious Adverse Event That, in the Opinion of the Investigator, is Related to the Study Drug, Part 2
A serious adverse event (SAE) was defined as any event which is fatal or life-threatening, which requires or prolongs hospitalization, which is significantly or permanently disabling or incapacitating, which constitutes a congenital anomaly or a birth defect, or which is medically significant, may jeopardize the subject and may require medical or surgical intervention to prevent one of the outcomes listed above.
Time frame: From time of consent until 30 days after stopping the trial/study drug
Population: This analysis population includes all enrolled subjects in Part 2.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| LHA510 Lowest, Part 1 | Number of Subjects With a Serious Adverse Event That, in the Opinion of the Investigator, is Related to the Study Drug, Part 2 | 0 participants |
| LHA510 Next Lowest, Part 1 | Number of Subjects With a Serious Adverse Event That, in the Opinion of the Investigator, is Related to the Study Drug, Part 2 | 0 participants |
| LHA510 Next Highest, Part 1 | Number of Subjects With a Serious Adverse Event That, in the Opinion of the Investigator, is Related to the Study Drug, Part 2 | 0 participants |
| LHA510 Highest, Part 1 | Number of Subjects With a Serious Adverse Event That, in the Opinion of the Investigator, is Related to the Study Drug, Part 2 | 0 participants |
| Vehicle, Part 1 | Number of Subjects With a Serious Adverse Event That, in the Opinion of the Investigator, is Related to the Study Drug, Part 2 | 0 participants |
| LHA510 Highest TID, Part 2 | Number of Subjects With a Serious Adverse Event That, in the Opinion of the Investigator, is Related to the Study Drug, Part 2 | 0 participants |
| Vehicle, Part 2 | Number of Subjects With a Serious Adverse Event That, in the Opinion of the Investigator, is Related to the Study Drug, Part 2 | 0 participants |
Secondary
Change From Baseline in Diastolic Blood Pressure at Each Post Dose Timepoint, Part 1
Diastolic blood pressure (pressure in the arteries when the heart rests between beats) was measured using an automated validated device, with an appropriately sized cuff, and assessed in the sitting position after the subject had rested for at least 3 minutes, and again (when required) after 3 minutes in the standing position.
Time frame: Day 1: 0.25h, 0.5h, 1h, 2h, 4h, 6h, 8h, 12h and 24h post-dose
Population: This analysis population includes all enrolled subjects in Part 1.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| LHA510 Lowest, Part 1 | Change From Baseline in Diastolic Blood Pressure at Each Post Dose Timepoint, Part 1 | Day 1, 0.50 hours | 3.4 mmHg | Standard Error 3.19 |
| LHA510 Lowest, Part 1 | Change From Baseline in Diastolic Blood Pressure at Each Post Dose Timepoint, Part 1 | Day 1, 0.25 hours | 5.2 mmHg | Standard Error 3.19 |
| LHA510 Lowest, Part 1 | Change From Baseline in Diastolic Blood Pressure at Each Post Dose Timepoint, Part 1 | Day 1, 2.00 hours | -3.8 mmHg | Standard Error 3.19 |
| LHA510 Lowest, Part 1 | Change From Baseline in Diastolic Blood Pressure at Each Post Dose Timepoint, Part 1 | Day 1, 24.00 hours | 8.2 mmHg | Standard Error 3.19 |
| LHA510 Lowest, Part 1 | Change From Baseline in Diastolic Blood Pressure at Each Post Dose Timepoint, Part 1 | Day 1, 12.00 hours | 3.7 mmHg | Standard Error 3.19 |
| LHA510 Lowest, Part 1 | Change From Baseline in Diastolic Blood Pressure at Each Post Dose Timepoint, Part 1 | Day 1, 8.00 hours | 3.6 mmHg | Standard Error 3.19 |
| LHA510 Lowest, Part 1 | Change From Baseline in Diastolic Blood Pressure at Each Post Dose Timepoint, Part 1 | Day 1, 6.00 hours | -1.1 mmHg | Standard Error 3.19 |
| LHA510 Lowest, Part 1 | Change From Baseline in Diastolic Blood Pressure at Each Post Dose Timepoint, Part 1 | Day 1, 1.00 hours | 3.9 mmHg | Standard Error 3.19 |
| LHA510 Lowest, Part 1 | Change From Baseline in Diastolic Blood Pressure at Each Post Dose Timepoint, Part 1 | Day 1, 4.00 hours | 5.4 mmHg | Standard Error 3.19 |
| LHA510 Next Lowest, Part 1 | Change From Baseline in Diastolic Blood Pressure at Each Post Dose Timepoint, Part 1 | Day 1, 8.00 hours | 1.5 mmHg | Standard Error 3.35 |
| LHA510 Next Lowest, Part 1 | Change From Baseline in Diastolic Blood Pressure at Each Post Dose Timepoint, Part 1 | Day 1, 12.00 hours | 1.7 mmHg | Standard Error 3.35 |
| LHA510 Next Lowest, Part 1 | Change From Baseline in Diastolic Blood Pressure at Each Post Dose Timepoint, Part 1 | Day 1, 1.00 hours | 2.2 mmHg | Standard Error 3.35 |
| LHA510 Next Lowest, Part 1 | Change From Baseline in Diastolic Blood Pressure at Each Post Dose Timepoint, Part 1 | Day 1, 2.00 hours | -1.0 mmHg | Standard Error 3.35 |
| LHA510 Next Lowest, Part 1 | Change From Baseline in Diastolic Blood Pressure at Each Post Dose Timepoint, Part 1 | Day 1, 0.50 hours | -0.2 mmHg | Standard Error 3.35 |
| LHA510 Next Lowest, Part 1 | Change From Baseline in Diastolic Blood Pressure at Each Post Dose Timepoint, Part 1 | Day 1, 0.25 hours | -5.5 mmHg | Standard Error 3.35 |
| LHA510 Next Lowest, Part 1 | Change From Baseline in Diastolic Blood Pressure at Each Post Dose Timepoint, Part 1 | Day 1, 4.00 hours | 3.7 mmHg | Standard Error 3.35 |
| LHA510 Next Lowest, Part 1 | Change From Baseline in Diastolic Blood Pressure at Each Post Dose Timepoint, Part 1 | Day 1, 6.00 hours | 1.2 mmHg | Standard Error 3.35 |
| LHA510 Next Lowest, Part 1 | Change From Baseline in Diastolic Blood Pressure at Each Post Dose Timepoint, Part 1 | Day 1, 24.00 hours | 5.5 mmHg | Standard Error 3.35 |
| LHA510 Next Highest, Part 1 | Change From Baseline in Diastolic Blood Pressure at Each Post Dose Timepoint, Part 1 | Day 1, 4.00 hours | 4.3 mmHg | Standard Error 3.14 |
| LHA510 Next Highest, Part 1 | Change From Baseline in Diastolic Blood Pressure at Each Post Dose Timepoint, Part 1 | Day 1, 0.50 hours | 5.6 mmHg | Standard Error 3.14 |
| LHA510 Next Highest, Part 1 | Change From Baseline in Diastolic Blood Pressure at Each Post Dose Timepoint, Part 1 | Day 1, 24.00 hours | 6.1 mmHg | Standard Error 3.14 |
| LHA510 Next Highest, Part 1 | Change From Baseline in Diastolic Blood Pressure at Each Post Dose Timepoint, Part 1 | Day 1, 12.00 hours | 4.1 mmHg | Standard Error 3.14 |
| LHA510 Next Highest, Part 1 | Change From Baseline in Diastolic Blood Pressure at Each Post Dose Timepoint, Part 1 | Day 1, 2.00 hours | -1.6 mmHg | Standard Error 3.14 |
| LHA510 Next Highest, Part 1 | Change From Baseline in Diastolic Blood Pressure at Each Post Dose Timepoint, Part 1 | Day 1, 8.00 hours | 4.6 mmHg | Standard Error 3.14 |
| LHA510 Next Highest, Part 1 | Change From Baseline in Diastolic Blood Pressure at Each Post Dose Timepoint, Part 1 | Day 1, 6.00 hours | 2.9 mmHg | Standard Error 3.14 |
| LHA510 Next Highest, Part 1 | Change From Baseline in Diastolic Blood Pressure at Each Post Dose Timepoint, Part 1 | Day 1, 1.00 hours | 5.3 mmHg | Standard Error 3.14 |
| LHA510 Next Highest, Part 1 | Change From Baseline in Diastolic Blood Pressure at Each Post Dose Timepoint, Part 1 | Day 1, 0.25 hours | 2.8 mmHg | Standard Error 3.14 |
| LHA510 Highest, Part 1 | Change From Baseline in Diastolic Blood Pressure at Each Post Dose Timepoint, Part 1 | Day 1, 24.00 hours | 5.3 mmHg | Standard Error 3.12 |
| LHA510 Highest, Part 1 | Change From Baseline in Diastolic Blood Pressure at Each Post Dose Timepoint, Part 1 | Day 1, 0.50 hours | 7.6 mmHg | Standard Error 3.12 |
| LHA510 Highest, Part 1 | Change From Baseline in Diastolic Blood Pressure at Each Post Dose Timepoint, Part 1 | Day 1, 1.00 hours | 5.1 mmHg | Standard Error 3.12 |
| LHA510 Highest, Part 1 | Change From Baseline in Diastolic Blood Pressure at Each Post Dose Timepoint, Part 1 | Day 1, 2.00 hours | -0.9 mmHg | Standard Error 3.12 |
| LHA510 Highest, Part 1 | Change From Baseline in Diastolic Blood Pressure at Each Post Dose Timepoint, Part 1 | Day 1, 4.00 hours | 4.1 mmHg | Standard Error 3.12 |
| LHA510 Highest, Part 1 | Change From Baseline in Diastolic Blood Pressure at Each Post Dose Timepoint, Part 1 | Day 1, 6.00 hours | 3.1 mmHg | Standard Error 3.12 |
| LHA510 Highest, Part 1 | Change From Baseline in Diastolic Blood Pressure at Each Post Dose Timepoint, Part 1 | Day 1, 8.00 hours | 2.5 mmHg | Standard Error 3.12 |
| LHA510 Highest, Part 1 | Change From Baseline in Diastolic Blood Pressure at Each Post Dose Timepoint, Part 1 | Day 1, 12.00 hours | -2.2 mmHg | Standard Error 3.12 |
| LHA510 Highest, Part 1 | Change From Baseline in Diastolic Blood Pressure at Each Post Dose Timepoint, Part 1 | Day 1, 0.25 hours | 4.1 mmHg | Standard Error 3.12 |
| Vehicle, Part 1 | Change From Baseline in Diastolic Blood Pressure at Each Post Dose Timepoint, Part 1 | Day 1, 8.00 hours | 0.0 mmHg | Standard Error 2.7 |
| Vehicle, Part 1 | Change From Baseline in Diastolic Blood Pressure at Each Post Dose Timepoint, Part 1 | Day 1, 6.00 hours | -6.1 mmHg | Standard Error 2.7 |
| Vehicle, Part 1 | Change From Baseline in Diastolic Blood Pressure at Each Post Dose Timepoint, Part 1 | Day 1, 4.00 hours | 2.4 mmHg | Standard Error 2.7 |
| Vehicle, Part 1 | Change From Baseline in Diastolic Blood Pressure at Each Post Dose Timepoint, Part 1 | Day 1, 2.00 hours | -6.5 mmHg | Standard Error 2.7 |
| Vehicle, Part 1 | Change From Baseline in Diastolic Blood Pressure at Each Post Dose Timepoint, Part 1 | Day 1, 24.00 hours | 4.0 mmHg | Standard Error 2.7 |
| Vehicle, Part 1 | Change From Baseline in Diastolic Blood Pressure at Each Post Dose Timepoint, Part 1 | Day 1, 1.00 hours | -1.4 mmHg | Standard Error 2.7 |
| Vehicle, Part 1 | Change From Baseline in Diastolic Blood Pressure at Each Post Dose Timepoint, Part 1 | Day 1, 0.50 hours | 2.1 mmHg | Standard Error 2.7 |
| Vehicle, Part 1 | Change From Baseline in Diastolic Blood Pressure at Each Post Dose Timepoint, Part 1 | Day 1, 0.25 hours | -5.2 mmHg | Standard Error 2.7 |
| Vehicle, Part 1 | Change From Baseline in Diastolic Blood Pressure at Each Post Dose Timepoint, Part 1 | Day 1, 12.00 hours | -3.9 mmHg | Standard Error 2.7 |
Secondary
Change From Baseline in Diastolic Blood Pressure at Each Post Dose Timepoint, Part 2
Diastolic blood pressure (pressure in the arteries when the heart rests between beats) was measured using an automated validated device, with an appropriately sized cuff, and assessed in the sitting position after the subject had rested for at least 3 minutes, and again (when required) after 3 minutes in the standing position.
Time frame: Day 1 and 7: 0.25h, 0.5h, 1h, 2h, 4h, 6h, 8h, 12h and 24h post-dose
Population: This analysis population includes all enrolled subjects in Part 2.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| LHA510 Lowest, Part 1 | Change From Baseline in Diastolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 1, 0.25 Hours | -1.0 mmHg | Standard Error 2.94 |
| LHA510 Lowest, Part 1 | Change From Baseline in Diastolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 7, 0.50 Hours | -5.9 mmHg | Standard Error 2.94 |
| LHA510 Lowest, Part 1 | Change From Baseline in Diastolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 1, 8.00 Hours | 3.1 mmHg | Standard Error 2.94 |
| LHA510 Lowest, Part 1 | Change From Baseline in Diastolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 1, 2.00 Hours | -9.4 mmHg | Standard Error 2.94 |
| LHA510 Lowest, Part 1 | Change From Baseline in Diastolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 7, 0.25 Hours | -3.4 mmHg | Standard Error 2.94 |
| LHA510 Lowest, Part 1 | Change From Baseline in Diastolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 1, 4.00 Hours | 1.8 mmHg | Standard Error 2.94 |
| LHA510 Lowest, Part 1 | Change From Baseline in Diastolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 7, 1.00 Hours | -6.0 mmHg | Standard Error 2.94 |
| LHA510 Lowest, Part 1 | Change From Baseline in Diastolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 7, 8.00 Hours | -0.7 mmHg | Standard Error 2.94 |
| LHA510 Lowest, Part 1 | Change From Baseline in Diastolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 7, 6.00 Hours | -4.4 mmHg | Standard Error 2.94 |
| LHA510 Lowest, Part 1 | Change From Baseline in Diastolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 1, 12.00 Hours | 2.3 mmHg | Standard Error 2.94 |
| LHA510 Lowest, Part 1 | Change From Baseline in Diastolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 7, 4.00 Hours | -6.0 mmHg | Standard Error 2.94 |
| LHA510 Lowest, Part 1 | Change From Baseline in Diastolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 7, 24.00 Hours | -4.2 mmHg | Standard Error 2.94 |
| LHA510 Lowest, Part 1 | Change From Baseline in Diastolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 7, 2.00 Hours | -4.2 mmHg | Standard Error 2.94 |
| LHA510 Lowest, Part 1 | Change From Baseline in Diastolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 7, 12.00 Hours | -9.5 mmHg | Standard Error 2.94 |
| LHA510 Lowest, Part 1 | Change From Baseline in Diastolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 1, 1.00 Hours | 4.3 mmHg | Standard Error 2.94 |
| LHA510 Lowest, Part 1 | Change From Baseline in Diastolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 1, 0.50 Hours | -1.7 mmHg | Standard Error 2.94 |
| LHA510 Lowest, Part 1 | Change From Baseline in Diastolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 1, 6.00 Hours | -4.9 mmHg | Standard Error 2.94 |
| LHA510 Lowest, Part 1 | Change From Baseline in Diastolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 1, 24.00 Hours | 3.8 mmHg | Standard Error 2.94 |
| LHA510 Next Lowest, Part 1 | Change From Baseline in Diastolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 7, 2.00 Hours | -6.4 mmHg | Standard Error 2.96 |
| LHA510 Next Lowest, Part 1 | Change From Baseline in Diastolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 1, 24.00 Hours | -2.5 mmHg | Standard Error 2.96 |
| LHA510 Next Lowest, Part 1 | Change From Baseline in Diastolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 7, 0.50 Hours | -5.7 mmHg | Standard Error 2.96 |
| LHA510 Next Lowest, Part 1 | Change From Baseline in Diastolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 7, 0.25 Hours | -6.2 mmHg | Standard Error 2.96 |
| LHA510 Next Lowest, Part 1 | Change From Baseline in Diastolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 7, 12.00 Hours | -1.0 mmHg | Standard Error 2.96 |
| LHA510 Next Lowest, Part 1 | Change From Baseline in Diastolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 1, 1.00 Hours | -7.7 mmHg | Standard Error 2.96 |
| LHA510 Next Lowest, Part 1 | Change From Baseline in Diastolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 1, 0.25 Hours | -4.4 mmHg | Standard Error 2.96 |
| LHA510 Next Lowest, Part 1 | Change From Baseline in Diastolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 7, 8.00 Hours | 1.0 mmHg | Standard Error 2.96 |
| LHA510 Next Lowest, Part 1 | Change From Baseline in Diastolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 1, 2.00 Hours | -6.5 mmHg | Standard Error 2.96 |
| LHA510 Next Lowest, Part 1 | Change From Baseline in Diastolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 1, 4.00 Hours | -4.0 mmHg | Standard Error 2.96 |
| LHA510 Next Lowest, Part 1 | Change From Baseline in Diastolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 7, 24.00 Hours | -2.2 mmHg | Standard Error 2.96 |
| LHA510 Next Lowest, Part 1 | Change From Baseline in Diastolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 7, 6.00 Hours | 0.3 mmHg | Standard Error 2.96 |
| LHA510 Next Lowest, Part 1 | Change From Baseline in Diastolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 1, 6.00 Hours | -6.9 mmHg | Standard Error 2.96 |
| LHA510 Next Lowest, Part 1 | Change From Baseline in Diastolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 7, 4.00 Hours | -6.7 mmHg | Standard Error 2.96 |
| LHA510 Next Lowest, Part 1 | Change From Baseline in Diastolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 1, 8.00 Hours | 2.1 mmHg | Standard Error 2.96 |
| LHA510 Next Lowest, Part 1 | Change From Baseline in Diastolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 7, 1.00 Hours | -4.9 mmHg | Standard Error 2.96 |
| LHA510 Next Lowest, Part 1 | Change From Baseline in Diastolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 1, 12.00 Hours | 1.0 mmHg | Standard Error 2.96 |
| LHA510 Next Lowest, Part 1 | Change From Baseline in Diastolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 1, 0.50 Hours | -7.2 mmHg | Standard Error 2.96 |
| LHA510 Next Highest, Part 1 | Change From Baseline in Diastolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 1, 0.50 Hours | -4.5 mmHg | Standard Error 2.95 |
| LHA510 Next Highest, Part 1 | Change From Baseline in Diastolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 1, 6.00 Hours | -3.3 mmHg | Standard Error 2.95 |
| LHA510 Next Highest, Part 1 | Change From Baseline in Diastolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 7, 12.00 Hours | -7.1 mmHg | Standard Error 2.95 |
| LHA510 Next Highest, Part 1 | Change From Baseline in Diastolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 7, 4.00 Hours | -9.3 mmHg | Standard Error 2.95 |
| LHA510 Next Highest, Part 1 | Change From Baseline in Diastolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 1, 24.00 Hours | 3.9 mmHg | Standard Error 2.95 |
| LHA510 Next Highest, Part 1 | Change From Baseline in Diastolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 1, 0.25 Hours | -0.6 mmHg | Standard Error 2.95 |
| LHA510 Next Highest, Part 1 | Change From Baseline in Diastolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 7, 0.25 Hours | -3.3 mmHg | Standard Error 2.95 |
| LHA510 Next Highest, Part 1 | Change From Baseline in Diastolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 7, 1.00 Hours | -4.3 mmHg | Standard Error 2.95 |
| LHA510 Next Highest, Part 1 | Change From Baseline in Diastolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 1, 8.00 Hours | -2.0 mmHg | Standard Error 2.95 |
| LHA510 Next Highest, Part 1 | Change From Baseline in Diastolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 7, 24.00 Hours | -7.5 mmHg | Standard Error 2.95 |
| LHA510 Next Highest, Part 1 | Change From Baseline in Diastolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 1, 2.00 Hours | 1.2 mmHg | Standard Error 2.95 |
| LHA510 Next Highest, Part 1 | Change From Baseline in Diastolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 7, 0.50 Hours | -10.0 mmHg | Standard Error 2.95 |
| LHA510 Next Highest, Part 1 | Change From Baseline in Diastolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 1, 4.00 Hours | -5.5 mmHg | Standard Error 2.95 |
| LHA510 Next Highest, Part 1 | Change From Baseline in Diastolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 7, 2.00 Hours | -8.3 mmHg | Standard Error 2.95 |
| LHA510 Next Highest, Part 1 | Change From Baseline in Diastolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 7, 8.00 Hours | -6.1 mmHg | Standard Error 2.95 |
| LHA510 Next Highest, Part 1 | Change From Baseline in Diastolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 7, 6.00 Hours | -10.3 mmHg | Standard Error 2.95 |
| LHA510 Next Highest, Part 1 | Change From Baseline in Diastolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 1, 12.00 Hours | -1.3 mmHg | Standard Error 2.95 |
| LHA510 Next Highest, Part 1 | Change From Baseline in Diastolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 1, 1.00 Hours | 0.2 mmHg | Standard Error 2.95 |
| LHA510 Highest, Part 1 | Change From Baseline in Diastolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 7, 8.00 Hours | -2.7 mmHg | Standard Error 2.93 |
| LHA510 Highest, Part 1 | Change From Baseline in Diastolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 1, 0.25 Hours | -2.9 mmHg | Standard Error 2.93 |
| LHA510 Highest, Part 1 | Change From Baseline in Diastolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 1, 0.50 Hours | -4.6 mmHg | Standard Error 2.93 |
| LHA510 Highest, Part 1 | Change From Baseline in Diastolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 1, 1.00 Hours | 1.9 mmHg | Standard Error 2.93 |
| LHA510 Highest, Part 1 | Change From Baseline in Diastolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 1, 2.00 Hours | -4.1 mmHg | Standard Error 2.93 |
| LHA510 Highest, Part 1 | Change From Baseline in Diastolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 1, 4.00 Hours | 0.9 mmHg | Standard Error 2.93 |
| LHA510 Highest, Part 1 | Change From Baseline in Diastolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 1, 6.00 Hours | -4.1 mmHg | Standard Error 2.93 |
| LHA510 Highest, Part 1 | Change From Baseline in Diastolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 1, 8.00 Hours | 1.4 mmHg | Standard Error 2.93 |
| LHA510 Highest, Part 1 | Change From Baseline in Diastolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 1, 12.00 Hours | -2.1 mmHg | Standard Error 2.93 |
| LHA510 Highest, Part 1 | Change From Baseline in Diastolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 1, 24.00 Hours | 2.3 mmHg | Standard Error 2.93 |
| LHA510 Highest, Part 1 | Change From Baseline in Diastolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 7, 0.25 Hours | -1.7 mmHg | Standard Error 2.93 |
| LHA510 Highest, Part 1 | Change From Baseline in Diastolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 7, 0.50 Hours | -2.1 mmHg | Standard Error 2.93 |
| LHA510 Highest, Part 1 | Change From Baseline in Diastolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 7, 1.00 Hours | -3.1 mmHg | Standard Error 2.93 |
| LHA510 Highest, Part 1 | Change From Baseline in Diastolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 7, 2.00 Hours | -4.7 mmHg | Standard Error 2.93 |
| LHA510 Highest, Part 1 | Change From Baseline in Diastolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 7, 4.00 Hours | -3.6 mmHg | Standard Error 2.93 |
| LHA510 Highest, Part 1 | Change From Baseline in Diastolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 7, 6.00 Hours | -5.6 mmHg | Standard Error 2.93 |
| LHA510 Highest, Part 1 | Change From Baseline in Diastolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 7, 12.00 Hours | -3.7 mmHg | Standard Error 2.93 |
| LHA510 Highest, Part 1 | Change From Baseline in Diastolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 7, 24.00 Hours | -3.7 mmHg | Standard Error 2.93 |
| Vehicle, Part 1 | Change From Baseline in Diastolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 7, 1.00 Hours | -6.5 mmHg | Standard Error 2.93 |
| Vehicle, Part 1 | Change From Baseline in Diastolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 7, 4.00 Hours | -8.2 mmHg | Standard Error 2.93 |
| Vehicle, Part 1 | Change From Baseline in Diastolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 1, 1.00 Hours | 1.7 mmHg | Standard Error 2.93 |
| Vehicle, Part 1 | Change From Baseline in Diastolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 7, 0.25 Hours | -2.8 mmHg | Standard Error 2.93 |
| Vehicle, Part 1 | Change From Baseline in Diastolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 1, 12.00 Hours | 7.2 mmHg | Standard Error 2.93 |
| Vehicle, Part 1 | Change From Baseline in Diastolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 1, 0.50 Hours | 4.3 mmHg | Standard Error 2.93 |
| Vehicle, Part 1 | Change From Baseline in Diastolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 1, 6.00 Hours | -2.2 mmHg | Standard Error 2.93 |
| Vehicle, Part 1 | Change From Baseline in Diastolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 1, 4.00 Hours | -1.2 mmHg | Standard Error 2.93 |
| Vehicle, Part 1 | Change From Baseline in Diastolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 7, 8.00 Hours | -3.0 mmHg | Standard Error 2.93 |
| Vehicle, Part 1 | Change From Baseline in Diastolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 1, 8.00 Hours | 4.3 mmHg | Standard Error 2.93 |
| Vehicle, Part 1 | Change From Baseline in Diastolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 1, 24.00 Hours | -2.7 mmHg | Standard Error 2.93 |
| Vehicle, Part 1 | Change From Baseline in Diastolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 7, 12.00 Hours | -2.3 mmHg | Standard Error 2.93 |
| Vehicle, Part 1 | Change From Baseline in Diastolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 1, 0.25 Hours | 2.5 mmHg | Standard Error 2.93 |
| Vehicle, Part 1 | Change From Baseline in Diastolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 7, 24.00 Hours | -1.2 mmHg | Standard Error 2.93 |
| Vehicle, Part 1 | Change From Baseline in Diastolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 7, 6.00 Hours | -8.8 mmHg | Standard Error 2.93 |
| Vehicle, Part 1 | Change From Baseline in Diastolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 7, 0.50 Hours | -3.2 mmHg | Standard Error 2.93 |
| Vehicle, Part 1 | Change From Baseline in Diastolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 7, 2.00 Hours | -0.7 mmHg | Standard Error 2.93 |
| Vehicle, Part 1 | Change From Baseline in Diastolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 1, 2.00 Hours | -4.2 mmHg | Standard Error 2.93 |
| LHA510 Highest TID, Part 2 | Change From Baseline in Diastolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 7, 1.00 Hours | -2.2 mmHg | Standard Error 2.93 |
| LHA510 Highest TID, Part 2 | Change From Baseline in Diastolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 1, 1.00 Hours | -5.4 mmHg | Standard Error 2.93 |
| LHA510 Highest TID, Part 2 | Change From Baseline in Diastolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 7, 8.00 Hours | 1.3 mmHg | Standard Error 2.93 |
| LHA510 Highest TID, Part 2 | Change From Baseline in Diastolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 1, 0.25 Hours | 0.6 mmHg | Standard Error 2.93 |
| LHA510 Highest TID, Part 2 | Change From Baseline in Diastolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 1, 0.50 Hours | -2.2 mmHg | Standard Error 2.93 |
| LHA510 Highest TID, Part 2 | Change From Baseline in Diastolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 7, 24.00 Hours | -1.4 mmHg | Standard Error 2.93 |
| LHA510 Highest TID, Part 2 | Change From Baseline in Diastolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 1, 6.00 Hours | -5.9 mmHg | Standard Error 2.93 |
| LHA510 Highest TID, Part 2 | Change From Baseline in Diastolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 7, 12.00 Hours | -2.7 mmHg | Standard Error 2.93 |
| LHA510 Highest TID, Part 2 | Change From Baseline in Diastolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 7, 0.25 Hours | -2.4 mmHg | Standard Error 2.93 |
| LHA510 Highest TID, Part 2 | Change From Baseline in Diastolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 1, 24.00 Hours | -0.7 mmHg | Standard Error 2.93 |
| LHA510 Highest TID, Part 2 | Change From Baseline in Diastolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 7, 2.00 Hours | -5.4 mmHg | Standard Error 2.93 |
| LHA510 Highest TID, Part 2 | Change From Baseline in Diastolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 7, 4.00 Hours | -2.4 mmHg | Standard Error 2.93 |
| LHA510 Highest TID, Part 2 | Change From Baseline in Diastolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 1, 12.00 Hours | -0.4 mmHg | Standard Error 2.93 |
| LHA510 Highest TID, Part 2 | Change From Baseline in Diastolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 1, 4.00 Hours | -2.4 mmHg | Standard Error 2.93 |
| LHA510 Highest TID, Part 2 | Change From Baseline in Diastolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 1, 8.00 Hours | 1.3 mmHg | Standard Error 2.93 |
| LHA510 Highest TID, Part 2 | Change From Baseline in Diastolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 7, 0.50 Hours | 1.6 mmHg | Standard Error 2.93 |
| LHA510 Highest TID, Part 2 | Change From Baseline in Diastolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 1, 2.00 Hours | -6.7 mmHg | Standard Error 2.93 |
| LHA510 Highest TID, Part 2 | Change From Baseline in Diastolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 7, 6.00 Hours | -6.4 mmHg | Standard Error 2.93 |
| Vehicle, Part 2 | Change From Baseline in Diastolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 1, 0.25 Hours | -0.5 mmHg | Standard Error 2.07 |
| Vehicle, Part 2 | Change From Baseline in Diastolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 7, 0.50 Hours | -2.8 mmHg | Standard Error 2.07 |
| Vehicle, Part 2 | Change From Baseline in Diastolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 7, 1.00 Hours | -2.9 mmHg | Standard Error 2.07 |
| Vehicle, Part 2 | Change From Baseline in Diastolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 1, 8.00 Hours | 5.7 mmHg | Standard Error 2.07 |
| Vehicle, Part 2 | Change From Baseline in Diastolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 7, 2.00 Hours | -9.6 mmHg | Standard Error 2.07 |
| Vehicle, Part 2 | Change From Baseline in Diastolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 1, 6.00 Hours | -5.3 mmHg | Standard Error 2.07 |
| Vehicle, Part 2 | Change From Baseline in Diastolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 7, 24.00 Hours | 0.4 mmHg | Standard Error 2.07 |
| Vehicle, Part 2 | Change From Baseline in Diastolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 7, 4.00 Hours | -7.8 mmHg | Standard Error 2.07 |
| Vehicle, Part 2 | Change From Baseline in Diastolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 1, 4.00 Hours | -0.2 mmHg | Standard Error 2.07 |
| Vehicle, Part 2 | Change From Baseline in Diastolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 1, 12.00 Hours | 0.4 mmHg | Standard Error 2.07 |
| Vehicle, Part 2 | Change From Baseline in Diastolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 1, 2.00 Hours | -4.9 mmHg | Standard Error 2.07 |
| Vehicle, Part 2 | Change From Baseline in Diastolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 7, 12.00 Hours | -3.0 mmHg | Standard Error 2.07 |
| Vehicle, Part 2 | Change From Baseline in Diastolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 7, 6.00 Hours | -5.3 mmHg | Standard Error 2.07 |
| Vehicle, Part 2 | Change From Baseline in Diastolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 1, 1.00 Hours | 0.3 mmHg | Standard Error 2.07 |
| Vehicle, Part 2 | Change From Baseline in Diastolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 7, 8.00 Hours | -2.4 mmHg | Standard Error 2.07 |
| Vehicle, Part 2 | Change From Baseline in Diastolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 1, 0.50 Hours | 2.4 mmHg | Standard Error 2.07 |
| Vehicle, Part 2 | Change From Baseline in Diastolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 1, 24.00 Hours | 2.7 mmHg | Standard Error 2.07 |
| Vehicle, Part 2 | Change From Baseline in Diastolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 7, 0.25 Hours | -3.6 mmHg | Standard Error 2.07 |
Secondary
Change From Baseline in Mean Arterial Blood Pressure at Each Post Dose Timepoint, Part 1
Mean arterial blood pressure (average pressure in the arteries during one cardiac cycle) was measured using an automated validated device, with an appropriately sized cuff, and assessed in the sitting position after the subject had rested for at least 3 minutes, and again (when required) after 3 minutes in the standing position.
Time frame: Day 1: 0.25h, 0.5h, 1h, 2h, 4h, 6h, 8h, 12h and 24h post-dose
Population: This analysis population includes all enrolled subjects in Part 1.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| LHA510 Lowest, Part 1 | Change From Baseline in Mean Arterial Blood Pressure at Each Post Dose Timepoint, Part 1 | Day 1, 24.00 hours | 8.8 mmHg | Standard Error 3.25 |
| LHA510 Lowest, Part 1 | Change From Baseline in Mean Arterial Blood Pressure at Each Post Dose Timepoint, Part 1 | Day 1, 8.00 hours | 3.9 mmHg | Standard Error 3.25 |
| LHA510 Lowest, Part 1 | Change From Baseline in Mean Arterial Blood Pressure at Each Post Dose Timepoint, Part 1 | Day 1, 12.00 hours | 3.9 mmHg | Standard Error 3.25 |
| LHA510 Lowest, Part 1 | Change From Baseline in Mean Arterial Blood Pressure at Each Post Dose Timepoint, Part 1 | Day 1, 1.00 hours | 3.3 mmHg | Standard Error 3.25 |
| LHA510 Lowest, Part 1 | Change From Baseline in Mean Arterial Blood Pressure at Each Post Dose Timepoint, Part 1 | Day 1, 0.25 hours | 5.2 mmHg | Standard Error 3.25 |
| LHA510 Lowest, Part 1 | Change From Baseline in Mean Arterial Blood Pressure at Each Post Dose Timepoint, Part 1 | Day 1, 2.00 hours | -3.9 mmHg | Standard Error 3.25 |
| LHA510 Lowest, Part 1 | Change From Baseline in Mean Arterial Blood Pressure at Each Post Dose Timepoint, Part 1 | Day 1, 4.00 hours | 1.7 mmHg | Standard Error 3.25 |
| LHA510 Lowest, Part 1 | Change From Baseline in Mean Arterial Blood Pressure at Each Post Dose Timepoint, Part 1 | Day 1, 0.50 hours | 2.0 mmHg | Standard Error 3.25 |
| LHA510 Lowest, Part 1 | Change From Baseline in Mean Arterial Blood Pressure at Each Post Dose Timepoint, Part 1 | Day 1, 6.00 hours | -1.2 mmHg | Standard Error 3.25 |
| LHA510 Next Lowest, Part 1 | Change From Baseline in Mean Arterial Blood Pressure at Each Post Dose Timepoint, Part 1 | Day 1, 6.00 hours | 3.4 mmHg | Standard Error 3.52 |
| LHA510 Next Lowest, Part 1 | Change From Baseline in Mean Arterial Blood Pressure at Each Post Dose Timepoint, Part 1 | Day 1, 4.00 hours | 4.7 mmHg | Standard Error 3.52 |
| LHA510 Next Lowest, Part 1 | Change From Baseline in Mean Arterial Blood Pressure at Each Post Dose Timepoint, Part 1 | Day 1, 8.00 hours | 1.6 mmHg | Standard Error 3.52 |
| LHA510 Next Lowest, Part 1 | Change From Baseline in Mean Arterial Blood Pressure at Each Post Dose Timepoint, Part 1 | Day 1, 0.50 hours | -0.9 mmHg | Standard Error 3.52 |
| LHA510 Next Lowest, Part 1 | Change From Baseline in Mean Arterial Blood Pressure at Each Post Dose Timepoint, Part 1 | Day 1, 2.00 hours | 0.3 mmHg | Standard Error 3.52 |
| LHA510 Next Lowest, Part 1 | Change From Baseline in Mean Arterial Blood Pressure at Each Post Dose Timepoint, Part 1 | Day 1, 0.25 hours | -4.4 mmHg | Standard Error 3.52 |
| LHA510 Next Lowest, Part 1 | Change From Baseline in Mean Arterial Blood Pressure at Each Post Dose Timepoint, Part 1 | Day 1, 1.00 hours | 1.5 mmHg | Standard Error 3.52 |
| LHA510 Next Lowest, Part 1 | Change From Baseline in Mean Arterial Blood Pressure at Each Post Dose Timepoint, Part 1 | Day 1, 12.00 hours | 4.2 mmHg | Standard Error 3.52 |
| LHA510 Next Lowest, Part 1 | Change From Baseline in Mean Arterial Blood Pressure at Each Post Dose Timepoint, Part 1 | Day 1, 24.00 hours | 6.0 mmHg | Standard Error 3.52 |
| LHA510 Next Highest, Part 1 | Change From Baseline in Mean Arterial Blood Pressure at Each Post Dose Timepoint, Part 1 | Day 1, 0.25 hours | 2.4 mmHg | Standard Error 3.31 |
| LHA510 Next Highest, Part 1 | Change From Baseline in Mean Arterial Blood Pressure at Each Post Dose Timepoint, Part 1 | Day 1, 1.00 hours | 4.3 mmHg | Standard Error 3.31 |
| LHA510 Next Highest, Part 1 | Change From Baseline in Mean Arterial Blood Pressure at Each Post Dose Timepoint, Part 1 | Day 1, 2.00 hours | -0.5 mmHg | Standard Error 3.31 |
| LHA510 Next Highest, Part 1 | Change From Baseline in Mean Arterial Blood Pressure at Each Post Dose Timepoint, Part 1 | Day 1, 24.00 hours | 5.3 mmHg | Standard Error 3.31 |
| LHA510 Next Highest, Part 1 | Change From Baseline in Mean Arterial Blood Pressure at Each Post Dose Timepoint, Part 1 | Day 1, 8.00 hours | 4.2 mmHg | Standard Error 3.31 |
| LHA510 Next Highest, Part 1 | Change From Baseline in Mean Arterial Blood Pressure at Each Post Dose Timepoint, Part 1 | Day 1, 0.50 hours | 4.0 mmHg | Standard Error 3.31 |
| LHA510 Next Highest, Part 1 | Change From Baseline in Mean Arterial Blood Pressure at Each Post Dose Timepoint, Part 1 | Day 1, 12.00 hours | 2.2 mmHg | Standard Error 3.31 |
| LHA510 Next Highest, Part 1 | Change From Baseline in Mean Arterial Blood Pressure at Each Post Dose Timepoint, Part 1 | Day 1, 4.00 hours | 4.8 mmHg | Standard Error 3.31 |
| LHA510 Next Highest, Part 1 | Change From Baseline in Mean Arterial Blood Pressure at Each Post Dose Timepoint, Part 1 | Day 1, 6.00 hours | 2.6 mmHg | Standard Error 3.31 |
| LHA510 Highest, Part 1 | Change From Baseline in Mean Arterial Blood Pressure at Each Post Dose Timepoint, Part 1 | Day 1, 24.00 hours | 6.7 mmHg | Standard Error 3.26 |
| LHA510 Highest, Part 1 | Change From Baseline in Mean Arterial Blood Pressure at Each Post Dose Timepoint, Part 1 | Day 1, 0.25 hours | 4.7 mmHg | Standard Error 3.26 |
| LHA510 Highest, Part 1 | Change From Baseline in Mean Arterial Blood Pressure at Each Post Dose Timepoint, Part 1 | Day 1, 0.50 hours | 7.6 mmHg | Standard Error 3.26 |
| LHA510 Highest, Part 1 | Change From Baseline in Mean Arterial Blood Pressure at Each Post Dose Timepoint, Part 1 | Day 1, 1.00 hours | 4.6 mmHg | Standard Error 3.26 |
| LHA510 Highest, Part 1 | Change From Baseline in Mean Arterial Blood Pressure at Each Post Dose Timepoint, Part 1 | Day 1, 2.00 hours | 2.9 mmHg | Standard Error 3.26 |
| LHA510 Highest, Part 1 | Change From Baseline in Mean Arterial Blood Pressure at Each Post Dose Timepoint, Part 1 | Day 1, 4.00 hours | 4.8 mmHg | Standard Error 3.26 |
| LHA510 Highest, Part 1 | Change From Baseline in Mean Arterial Blood Pressure at Each Post Dose Timepoint, Part 1 | Day 1, 6.00 hours | 4.0 mmHg | Standard Error 3.26 |
| LHA510 Highest, Part 1 | Change From Baseline in Mean Arterial Blood Pressure at Each Post Dose Timepoint, Part 1 | Day 1, 8.00 hours | 6.6 mmHg | Standard Error 3.26 |
| LHA510 Highest, Part 1 | Change From Baseline in Mean Arterial Blood Pressure at Each Post Dose Timepoint, Part 1 | Day 1, 12.00 hours | 0.5 mmHg | Standard Error 3.26 |
| Vehicle, Part 1 | Change From Baseline in Mean Arterial Blood Pressure at Each Post Dose Timepoint, Part 1 | Day 1, 6.00 hours | -5.6 mmHg | Standard Error 2.81 |
| Vehicle, Part 1 | Change From Baseline in Mean Arterial Blood Pressure at Each Post Dose Timepoint, Part 1 | Day 1, 4.00 hours | 1.3 mmHg | Standard Error 2.81 |
| Vehicle, Part 1 | Change From Baseline in Mean Arterial Blood Pressure at Each Post Dose Timepoint, Part 1 | Day 1, 2.00 hours | -3.9 mmHg | Standard Error 2.81 |
| Vehicle, Part 1 | Change From Baseline in Mean Arterial Blood Pressure at Each Post Dose Timepoint, Part 1 | Day 1, 1.00 hours | 0.6 mmHg | Standard Error 2.81 |
| Vehicle, Part 1 | Change From Baseline in Mean Arterial Blood Pressure at Each Post Dose Timepoint, Part 1 | Day 1, 24.00 hours | 3.4 mmHg | Standard Error 2.81 |
| Vehicle, Part 1 | Change From Baseline in Mean Arterial Blood Pressure at Each Post Dose Timepoint, Part 1 | Day 1, 0.50 hours | 3.1 mmHg | Standard Error 2.81 |
| Vehicle, Part 1 | Change From Baseline in Mean Arterial Blood Pressure at Each Post Dose Timepoint, Part 1 | Day 1, 0.25 hours | -3.4 mmHg | Standard Error 2.81 |
| Vehicle, Part 1 | Change From Baseline in Mean Arterial Blood Pressure at Each Post Dose Timepoint, Part 1 | Day 1, 12.00 hours | -3.2 mmHg | Standard Error 2.81 |
| Vehicle, Part 1 | Change From Baseline in Mean Arterial Blood Pressure at Each Post Dose Timepoint, Part 1 | Day 1, 8.00 hours | -0.8 mmHg | Standard Error 2.81 |
Secondary
Change From Baseline in Systolic Blood Pressure at Each Post Dose Timepoint, Part 1
Systolic blood pressure (pressure when the heart is contracting) was measured using an automated validated device, with an appropriately sized cuff, and assessed in the sitting position after the subject had rested for at least 3 minutes, and again (when required) after 3 minutes in the standing position.
Time frame: Day 1: 0.25h, 0.5h, 1h, 2h, 4h, 6h, 8h, 12h and 24h post-dose
Population: This analysis population includes all enrolled subjects in Part 1.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| LHA510 Lowest, Part 1 | Change From Baseline in Systolic Blood Pressure at Each Post Dose Timepoint, Part 1 | Day 1, 0.25 hours | 4.7 mmHg | Standard Error 5 |
| LHA510 Lowest, Part 1 | Change From Baseline in Systolic Blood Pressure at Each Post Dose Timepoint, Part 1 | Day 1, 8.00 hours | 4.0 mmHg | Standard Error 5 |
| LHA510 Lowest, Part 1 | Change From Baseline in Systolic Blood Pressure at Each Post Dose Timepoint, Part 1 | Day 1, 6.00 hours | -2.0 mmHg | Standard Error 5 |
| LHA510 Lowest, Part 1 | Change From Baseline in Systolic Blood Pressure at Each Post Dose Timepoint, Part 1 | Day 1, 12.00 hours | 3.9 mmHg | Standard Error 5 |
| LHA510 Lowest, Part 1 | Change From Baseline in Systolic Blood Pressure at Each Post Dose Timepoint, Part 1 | Day 1, 2.00 hours | -4.6 mmHg | Standard Error 5 |
| LHA510 Lowest, Part 1 | Change From Baseline in Systolic Blood Pressure at Each Post Dose Timepoint, Part 1 | Day 1, 0.50 hours | -1.3 mmHg | Standard Error 5 |
| LHA510 Lowest, Part 1 | Change From Baseline in Systolic Blood Pressure at Each Post Dose Timepoint, Part 1 | Day 1, 1.00 hours | 1.7 mmHg | Standard Error 5 |
| LHA510 Lowest, Part 1 | Change From Baseline in Systolic Blood Pressure at Each Post Dose Timepoint, Part 1 | Day 1, 24.00 hours | 9.4 mmHg | Standard Error 5 |
| LHA510 Lowest, Part 1 | Change From Baseline in Systolic Blood Pressure at Each Post Dose Timepoint, Part 1 | Day 1, 4.00 hours | -6.3 mmHg | Standard Error 5 |
| LHA510 Next Lowest, Part 1 | Change From Baseline in Systolic Blood Pressure at Each Post Dose Timepoint, Part 1 | Day 1, 0.50 hours | 0.1 mmHg | Standard Error 5.11 |
| LHA510 Next Lowest, Part 1 | Change From Baseline in Systolic Blood Pressure at Each Post Dose Timepoint, Part 1 | Day 1, 4.00 hours | 9.3 mmHg | Standard Error 5.11 |
| LHA510 Next Lowest, Part 1 | Change From Baseline in Systolic Blood Pressure at Each Post Dose Timepoint, Part 1 | Day 1, 8.00 hours | 4.3 mmHg | Standard Error 5.11 |
| LHA510 Next Lowest, Part 1 | Change From Baseline in Systolic Blood Pressure at Each Post Dose Timepoint, Part 1 | Day 1, 6.00 hours | 10.5 mmHg | Standard Error 5.11 |
| LHA510 Next Lowest, Part 1 | Change From Baseline in Systolic Blood Pressure at Each Post Dose Timepoint, Part 1 | Day 1, 1.00 hours | 2.8 mmHg | Standard Error 5.11 |
| LHA510 Next Lowest, Part 1 | Change From Baseline in Systolic Blood Pressure at Each Post Dose Timepoint, Part 1 | Day 1, 0.25 hours | 0.5 mmHg | Standard Error 5.11 |
| LHA510 Next Lowest, Part 1 | Change From Baseline in Systolic Blood Pressure at Each Post Dose Timepoint, Part 1 | Day 1, 2.00 hours | 5.3 mmHg | Standard Error 5.11 |
| LHA510 Next Lowest, Part 1 | Change From Baseline in Systolic Blood Pressure at Each Post Dose Timepoint, Part 1 | Day 1, 24.00 hours | 9.6 mmHg | Standard Error 5.11 |
| LHA510 Next Lowest, Part 1 | Change From Baseline in Systolic Blood Pressure at Each Post Dose Timepoint, Part 1 | Day 1, 12.00 hours | 11.8 mmHg | Standard Error 5.11 |
| LHA510 Next Highest, Part 1 | Change From Baseline in Systolic Blood Pressure at Each Post Dose Timepoint, Part 1 | Day 1, 0.25 hours | 0.5 mmHg | Standard Error 5.05 |
| LHA510 Next Highest, Part 1 | Change From Baseline in Systolic Blood Pressure at Each Post Dose Timepoint, Part 1 | Day 1, 8.00 hours | 2.2 mmHg | Standard Error 5.05 |
| LHA510 Next Highest, Part 1 | Change From Baseline in Systolic Blood Pressure at Each Post Dose Timepoint, Part 1 | Day 1, 12.00 hours | -3.0 mmHg | Standard Error 5.05 |
| LHA510 Next Highest, Part 1 | Change From Baseline in Systolic Blood Pressure at Each Post Dose Timepoint, Part 1 | Day 1, 1.00 hours | 1.2 mmHg | Standard Error 5.05 |
| LHA510 Next Highest, Part 1 | Change From Baseline in Systolic Blood Pressure at Each Post Dose Timepoint, Part 1 | Day 1, 0.50 hours | -0.3 mmHg | Standard Error 5.05 |
| LHA510 Next Highest, Part 1 | Change From Baseline in Systolic Blood Pressure at Each Post Dose Timepoint, Part 1 | Day 1, 2.00 hours | 0.5 mmHg | Standard Error 5.05 |
| LHA510 Next Highest, Part 1 | Change From Baseline in Systolic Blood Pressure at Each Post Dose Timepoint, Part 1 | Day 1, 4.00 hours | 4.7 mmHg | Standard Error 5.05 |
| LHA510 Next Highest, Part 1 | Change From Baseline in Systolic Blood Pressure at Each Post Dose Timepoint, Part 1 | Day 1, 6.00 hours | 0.7 mmHg | Standard Error 5.05 |
| LHA510 Next Highest, Part 1 | Change From Baseline in Systolic Blood Pressure at Each Post Dose Timepoint, Part 1 | Day 1, 24.00 hours | 2.3 mmHg | Standard Error 5.05 |
| LHA510 Highest, Part 1 | Change From Baseline in Systolic Blood Pressure at Each Post Dose Timepoint, Part 1 | Day 1, 24.00 hours | 8.9 mmHg | Standard Error 4.97 |
| LHA510 Highest, Part 1 | Change From Baseline in Systolic Blood Pressure at Each Post Dose Timepoint, Part 1 | Day 1, 0.25 hours | 5.3 mmHg | Standard Error 4.97 |
| LHA510 Highest, Part 1 | Change From Baseline in Systolic Blood Pressure at Each Post Dose Timepoint, Part 1 | Day 1, 0.50 hours | 6.9 mmHg | Standard Error 4.97 |
| LHA510 Highest, Part 1 | Change From Baseline in Systolic Blood Pressure at Each Post Dose Timepoint, Part 1 | Day 1, 1.00 hours | 2.9 mmHg | Standard Error 4.97 |
| LHA510 Highest, Part 1 | Change From Baseline in Systolic Blood Pressure at Each Post Dose Timepoint, Part 1 | Day 1, 2.00 hours | 9.8 mmHg | Standard Error 4.97 |
| LHA510 Highest, Part 1 | Change From Baseline in Systolic Blood Pressure at Each Post Dose Timepoint, Part 1 | Day 1, 4.00 hours | 5.4 mmHg | Standard Error 4.97 |
| LHA510 Highest, Part 1 | Change From Baseline in Systolic Blood Pressure at Each Post Dose Timepoint, Part 1 | Day 1, 6.00 hours | 4.9 mmHg | Standard Error 4.97 |
| LHA510 Highest, Part 1 | Change From Baseline in Systolic Blood Pressure at Each Post Dose Timepoint, Part 1 | Day 1, 8.00 hours | 14.1 mmHg | Standard Error 4.97 |
| LHA510 Highest, Part 1 | Change From Baseline in Systolic Blood Pressure at Each Post Dose Timepoint, Part 1 | Day 1, 12.00 hours | 5.3 mmHg | Standard Error 4.97 |
| Vehicle, Part 1 | Change From Baseline in Systolic Blood Pressure at Each Post Dose Timepoint, Part 1 | Day 1, 12.00 hours | -1.9 mmHg | Standard Error 4.32 |
| Vehicle, Part 1 | Change From Baseline in Systolic Blood Pressure at Each Post Dose Timepoint, Part 1 | Day 1, 8.00 hours | -2.6 mmHg | Standard Error 4.32 |
| Vehicle, Part 1 | Change From Baseline in Systolic Blood Pressure at Each Post Dose Timepoint, Part 1 | Day 1, 6.00 hours | -4.6 mmHg | Standard Error 4.32 |
| Vehicle, Part 1 | Change From Baseline in Systolic Blood Pressure at Each Post Dose Timepoint, Part 1 | Day 1, 4.00 hours | -0.9 mmHg | Standard Error 4.32 |
| Vehicle, Part 1 | Change From Baseline in Systolic Blood Pressure at Each Post Dose Timepoint, Part 1 | Day 1, 24.00 hours | 2.1 mmHg | Standard Error 4.32 |
| Vehicle, Part 1 | Change From Baseline in Systolic Blood Pressure at Each Post Dose Timepoint, Part 1 | Day 1, 2.00 hours | 1.3 mmHg | Standard Error 4.32 |
| Vehicle, Part 1 | Change From Baseline in Systolic Blood Pressure at Each Post Dose Timepoint, Part 1 | Day 1, 1.00 hours | 4.4 mmHg | Standard Error 4.32 |
| Vehicle, Part 1 | Change From Baseline in Systolic Blood Pressure at Each Post Dose Timepoint, Part 1 | Day 1, 0.50 hours | 4.9 mmHg | Standard Error 4.32 |
| Vehicle, Part 1 | Change From Baseline in Systolic Blood Pressure at Each Post Dose Timepoint, Part 1 | Day 1, 0.25 hours | 0.2 mmHg | Standard Error 4.32 |
Secondary
Change From Baseline in Systolic Blood Pressure at Each Post Dose Timepoint, Part 2
Systolic blood pressure (pressure when the heart is contracting) was measured using an automated validated device, with an appropriately sized cuff, and assessed in the sitting position after the subject had rested for at least 3 minutes, and again (when required) after 3 minutes in the standing position.
Time frame: Day 1 and 7: 0.25h, 0.5h, 1h, 2h, 4h, 6h, 8h, 12h and 24h post-dose
Population: This analysis population includes all enrolled subjects in Part 2.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| LHA510 Lowest, Part 1 | Change From Baseline in Systolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 7, 8.00 Hours | 0.1 mmHg | Standard Error 5.7 |
| LHA510 Lowest, Part 1 | Change From Baseline in Systolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 7, 1.00 Hours | -1.2 mmHg | Standard Error 5.7 |
| LHA510 Lowest, Part 1 | Change From Baseline in Systolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 7, 24.00 Hours | -0.5 mmHg | Standard Error 5.7 |
| LHA510 Lowest, Part 1 | Change From Baseline in Systolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 1, 6.00 Hours | -3.2 mmHg | Standard Error 5.7 |
| LHA510 Lowest, Part 1 | Change From Baseline in Systolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 1, 24.00 Hours | 5.0 mmHg | Standard Error 5.7 |
| LHA510 Lowest, Part 1 | Change From Baseline in Systolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 1, 1.00 Hours | 7.1 mmHg | Standard Error 5.7 |
| LHA510 Lowest, Part 1 | Change From Baseline in Systolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 7, 12.00 Hours | -4.5 mmHg | Standard Error 5.7 |
| LHA510 Lowest, Part 1 | Change From Baseline in Systolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 7, 6.00 Hours | -0.4 mmHg | Standard Error 5.7 |
| LHA510 Lowest, Part 1 | Change From Baseline in Systolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 1, 0.50 Hours | -3.9 mmHg | Standard Error 5.7 |
| LHA510 Lowest, Part 1 | Change From Baseline in Systolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 1, 8.00 Hours | 5.5 mmHg | Standard Error 5.7 |
| LHA510 Lowest, Part 1 | Change From Baseline in Systolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 7, 0.50 Hours | -5.7 mmHg | Standard Error 5.7 |
| LHA510 Lowest, Part 1 | Change From Baseline in Systolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 7, 2.00 Hours | -5.4 mmHg | Standard Error 5.7 |
| LHA510 Lowest, Part 1 | Change From Baseline in Systolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 1, 0.25 Hours | 12.5 mmHg | Standard Error 5.7 |
| LHA510 Lowest, Part 1 | Change From Baseline in Systolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 1, 2.00 Hours | -0.7 mmHg | Standard Error 5.7 |
| LHA510 Lowest, Part 1 | Change From Baseline in Systolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 1, 4.00 Hours | 5.3 mmHg | Standard Error 5.7 |
| LHA510 Lowest, Part 1 | Change From Baseline in Systolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 1, 12.00 Hours | 5.5 mmHg | Standard Error 5.7 |
| LHA510 Lowest, Part 1 | Change From Baseline in Systolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 7, 4.00 Hours | -4.2 mmHg | Standard Error 5.7 |
| LHA510 Lowest, Part 1 | Change From Baseline in Systolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 7, 0.25 Hours | -5.0 mmHg | Standard Error 5.7 |
| LHA510 Next Lowest, Part 1 | Change From Baseline in Systolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 1, 2.00 Hours | -3.9 mmHg | Standard Error 5.9 |
| LHA510 Next Lowest, Part 1 | Change From Baseline in Systolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 1, 24.00 Hours | 0.1 mmHg | Standard Error 5.9 |
| LHA510 Next Lowest, Part 1 | Change From Baseline in Systolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 7, 0.25 Hours | -7.6 mmHg | Standard Error 5.9 |
| LHA510 Next Lowest, Part 1 | Change From Baseline in Systolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 7, 24.00 Hours | 0.6 mmHg | Standard Error 5.9 |
| LHA510 Next Lowest, Part 1 | Change From Baseline in Systolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 7, 6.00 Hours | 4.3 mmHg | Standard Error 5.9 |
| LHA510 Next Lowest, Part 1 | Change From Baseline in Systolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 1, 1.00 Hours | -13.1 mmHg | Standard Error 5.9 |
| LHA510 Next Lowest, Part 1 | Change From Baseline in Systolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 1, 0.50 Hours | -12.7 mmHg | Standard Error 5.9 |
| LHA510 Next Lowest, Part 1 | Change From Baseline in Systolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 1, 4.00 Hours | -5.4 mmHg | Standard Error 5.9 |
| LHA510 Next Lowest, Part 1 | Change From Baseline in Systolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 7, 1.00 Hours | -9.4 mmHg | Standard Error 5.9 |
| LHA510 Next Lowest, Part 1 | Change From Baseline in Systolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 7, 4.00 Hours | -5.1 mmHg | Standard Error 5.9 |
| LHA510 Next Lowest, Part 1 | Change From Baseline in Systolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 7, 8.00 Hours | 15.6 mmHg | Standard Error 5.9 |
| LHA510 Next Lowest, Part 1 | Change From Baseline in Systolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 1, 6.00 Hours | -15.6 mmHg | Standard Error 5.9 |
| LHA510 Next Lowest, Part 1 | Change From Baseline in Systolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 7, 2.00 Hours | -6.9 mmHg | Standard Error 5.9 |
| LHA510 Next Lowest, Part 1 | Change From Baseline in Systolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 7, 12.00 Hours | 8.4 mmHg | Standard Error 5.9 |
| LHA510 Next Lowest, Part 1 | Change From Baseline in Systolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 1, 0.25 Hours | -11.1 mmHg | Standard Error 5.9 |
| LHA510 Next Lowest, Part 1 | Change From Baseline in Systolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 1, 8.00 Hours | 11.1 mmHg | Standard Error 5.9 |
| LHA510 Next Lowest, Part 1 | Change From Baseline in Systolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 1, 12.00 Hours | 11.8 mmHg | Standard Error 5.9 |
| LHA510 Next Lowest, Part 1 | Change From Baseline in Systolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 7, 0.50 Hours | -6.2 mmHg | Standard Error 5.9 |
| LHA510 Next Highest, Part 1 | Change From Baseline in Systolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 7, 12.00 Hours | -10.9 mmHg | Standard Error 5.7 |
| LHA510 Next Highest, Part 1 | Change From Baseline in Systolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 7, 4.00 Hours | -12.4 mmHg | Standard Error 5.7 |
| LHA510 Next Highest, Part 1 | Change From Baseline in Systolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 7, 6.00 Hours | -18.8 mmHg | Standard Error 5.7 |
| LHA510 Next Highest, Part 1 | Change From Baseline in Systolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 1, 4.00 Hours | -9.9 mmHg | Standard Error 5.7 |
| LHA510 Next Highest, Part 1 | Change From Baseline in Systolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 1, 1.00 Hours | 3.4 mmHg | Standard Error 5.7 |
| LHA510 Next Highest, Part 1 | Change From Baseline in Systolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 1, 0.25 Hours | -4.1 mmHg | Standard Error 5.7 |
| LHA510 Next Highest, Part 1 | Change From Baseline in Systolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 1, 6.00 Hours | -8.6 mmHg | Standard Error 5.7 |
| LHA510 Next Highest, Part 1 | Change From Baseline in Systolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 1, 8.00 Hours | -9.8 mmHg | Standard Error 5.7 |
| LHA510 Next Highest, Part 1 | Change From Baseline in Systolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 1, 12.00 Hours | -8.8 mmHg | Standard Error 5.7 |
| LHA510 Next Highest, Part 1 | Change From Baseline in Systolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 7, 24.00 Hours | -23.1 mmHg | Standard Error 5.7 |
| LHA510 Next Highest, Part 1 | Change From Baseline in Systolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 1, 24.00 Hours | -2.6 mmHg | Standard Error 5.7 |
| LHA510 Next Highest, Part 1 | Change From Baseline in Systolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 7, 0.25 Hours | -9.4 mmHg | Standard Error 5.7 |
| LHA510 Next Highest, Part 1 | Change From Baseline in Systolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 1, 0.50 Hours | -0.4 mmHg | Standard Error 5.7 |
| LHA510 Next Highest, Part 1 | Change From Baseline in Systolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 1, 2.00 Hours | -0.9 mmHg | Standard Error 5.7 |
| LHA510 Next Highest, Part 1 | Change From Baseline in Systolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 7, 0.50 Hours | -14.9 mmHg | Standard Error 5.7 |
| LHA510 Next Highest, Part 1 | Change From Baseline in Systolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 7, 1.00 Hours | -9.4 mmHg | Standard Error 5.7 |
| LHA510 Next Highest, Part 1 | Change From Baseline in Systolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 7, 8.00 Hours | -9.8 mmHg | Standard Error 5.7 |
| LHA510 Next Highest, Part 1 | Change From Baseline in Systolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 7, 2.00 Hours | -9.8 mmHg | Standard Error 5.7 |
| LHA510 Highest, Part 1 | Change From Baseline in Systolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 7, 24.00 Hours | -4.4 mmHg | Standard Error 5.74 |
| LHA510 Highest, Part 1 | Change From Baseline in Systolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 1, 12.00 Hours | -3.9 mmHg | Standard Error 5.74 |
| LHA510 Highest, Part 1 | Change From Baseline in Systolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 1, 2.00 Hours | -6.4 mmHg | Standard Error 5.74 |
| LHA510 Highest, Part 1 | Change From Baseline in Systolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 7, 0.50 Hours | -8.8 mmHg | Standard Error 5.74 |
| LHA510 Highest, Part 1 | Change From Baseline in Systolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 1, 8.00 Hours | -1.4 mmHg | Standard Error 5.74 |
| LHA510 Highest, Part 1 | Change From Baseline in Systolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 1, 1.00 Hours | -8.9 mmHg | Standard Error 5.74 |
| LHA510 Highest, Part 1 | Change From Baseline in Systolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 1, 6.00 Hours | 0.4 mmHg | Standard Error 5.74 |
| LHA510 Highest, Part 1 | Change From Baseline in Systolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 1, 0.25 Hours | -4.8 mmHg | Standard Error 5.74 |
| LHA510 Highest, Part 1 | Change From Baseline in Systolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 1, 4.00 Hours | 0.7 mmHg | Standard Error 5.74 |
| LHA510 Highest, Part 1 | Change From Baseline in Systolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 7, 4.00 Hours | -3.8 mmHg | Standard Error 5.74 |
| LHA510 Highest, Part 1 | Change From Baseline in Systolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 7, 1.00 Hours | -4.6 mmHg | Standard Error 5.74 |
| LHA510 Highest, Part 1 | Change From Baseline in Systolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 1, 0.50 Hours | -11.4 mmHg | Standard Error 5.74 |
| LHA510 Highest, Part 1 | Change From Baseline in Systolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 1, 24.00 Hours | 7.7 mmHg | Standard Error 5.74 |
| LHA510 Highest, Part 1 | Change From Baseline in Systolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 7, 6.00 Hours | -6.6 mmHg | Standard Error 5.74 |
| LHA510 Highest, Part 1 | Change From Baseline in Systolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 7, 0.25 Hours | -2.3 mmHg | Standard Error 5.74 |
| LHA510 Highest, Part 1 | Change From Baseline in Systolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 7, 8.00 Hours | 0.6 mmHg | Standard Error 5.74 |
| LHA510 Highest, Part 1 | Change From Baseline in Systolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 7, 12.00 Hours | -9.6 mmHg | Standard Error 5.74 |
| LHA510 Highest, Part 1 | Change From Baseline in Systolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 7, 2.00 Hours | -6.1 mmHg | Standard Error 5.74 |
| Vehicle, Part 1 | Change From Baseline in Systolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 1, 8.00 Hours | -6.1 mmHg | Standard Error 5.72 |
| Vehicle, Part 1 | Change From Baseline in Systolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 1, 1.00 Hours | -3.1 mmHg | Standard Error 5.72 |
| Vehicle, Part 1 | Change From Baseline in Systolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 1, 2.00 Hours | -5.6 mmHg | Standard Error 5.72 |
| Vehicle, Part 1 | Change From Baseline in Systolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 1, 4.00 Hours | -3.4 mmHg | Standard Error 5.72 |
| Vehicle, Part 1 | Change From Baseline in Systolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 1, 6.00 Hours | -2.2 mmHg | Standard Error 5.72 |
| Vehicle, Part 1 | Change From Baseline in Systolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 1, 12.00 Hours | 3.4 mmHg | Standard Error 5.72 |
| Vehicle, Part 1 | Change From Baseline in Systolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 1, 24.00 Hours | -6.9 mmHg | Standard Error 5.72 |
| Vehicle, Part 1 | Change From Baseline in Systolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 7, 0.25 Hours | -13.7 mmHg | Standard Error 5.72 |
| Vehicle, Part 1 | Change From Baseline in Systolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 7, 0.50 Hours | -9.9 mmHg | Standard Error 5.72 |
| Vehicle, Part 1 | Change From Baseline in Systolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 7, 1.00 Hours | -18.6 mmHg | Standard Error 5.72 |
| Vehicle, Part 1 | Change From Baseline in Systolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 7, 2.00 Hours | -14.7 mmHg | Standard Error 5.72 |
| Vehicle, Part 1 | Change From Baseline in Systolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 7, 4.00 Hours | -9.4 mmHg | Standard Error 5.72 |
| Vehicle, Part 1 | Change From Baseline in Systolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 7, 6.00 Hours | -7.7 mmHg | Standard Error 5.72 |
| Vehicle, Part 1 | Change From Baseline in Systolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 7, 8.00 Hours | -10.9 mmHg | Standard Error 5.72 |
| Vehicle, Part 1 | Change From Baseline in Systolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 7, 12.00 Hours | -7.6 mmHg | Standard Error 5.72 |
| Vehicle, Part 1 | Change From Baseline in Systolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 7, 24.00 Hours | -4.4 mmHg | Standard Error 5.72 |
| Vehicle, Part 1 | Change From Baseline in Systolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 1, 0.25 Hours | 0.6 mmHg | Standard Error 5.72 |
| Vehicle, Part 1 | Change From Baseline in Systolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 1, 0.50 Hours | -5.4 mmHg | Standard Error 5.72 |
| LHA510 Highest TID, Part 2 | Change From Baseline in Systolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 7, 2.00 Hours | -0.4 mmHg | Standard Error 5.69 |
| LHA510 Highest TID, Part 2 | Change From Baseline in Systolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 7, 1.00 Hours | -6.1 mmHg | Standard Error 5.69 |
| LHA510 Highest TID, Part 2 | Change From Baseline in Systolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 1, 2.00 Hours | -10.6 mmHg | Standard Error 5.69 |
| LHA510 Highest TID, Part 2 | Change From Baseline in Systolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 7, 8.00 Hours | 0.1 mmHg | Standard Error 5.69 |
| LHA510 Highest TID, Part 2 | Change From Baseline in Systolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 7, 0.50 Hours | -9.9 mmHg | Standard Error 5.69 |
| LHA510 Highest TID, Part 2 | Change From Baseline in Systolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 7, 0.25 Hours | -11.3 mmHg | Standard Error 5.69 |
| LHA510 Highest TID, Part 2 | Change From Baseline in Systolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 7, 12.00 Hours | -4.9 mmHg | Standard Error 5.69 |
| LHA510 Highest TID, Part 2 | Change From Baseline in Systolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 1, 24.00 Hours | -6.8 mmHg | Standard Error 5.69 |
| LHA510 Highest TID, Part 2 | Change From Baseline in Systolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 1, 12.00 Hours | 1.2 mmHg | Standard Error 5.69 |
| LHA510 Highest TID, Part 2 | Change From Baseline in Systolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 1, 1.00 Hours | -8.9 mmHg | Standard Error 5.69 |
| LHA510 Highest TID, Part 2 | Change From Baseline in Systolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 7, 24.00 Hours | 0.6 mmHg | Standard Error 5.69 |
| LHA510 Highest TID, Part 2 | Change From Baseline in Systolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 1, 6.00 Hours | -6.9 mmHg | Standard Error 5.69 |
| LHA510 Highest TID, Part 2 | Change From Baseline in Systolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 1, 8.00 Hours | 6.1 mmHg | Standard Error 5.69 |
| LHA510 Highest TID, Part 2 | Change From Baseline in Systolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 1, 4.00 Hours | -0.4 mmHg | Standard Error 5.69 |
| LHA510 Highest TID, Part 2 | Change From Baseline in Systolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 1, 0.50 Hours | -5.8 mmHg | Standard Error 5.69 |
| LHA510 Highest TID, Part 2 | Change From Baseline in Systolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 1, 0.25 Hours | -4.1 mmHg | Standard Error 5.69 |
| LHA510 Highest TID, Part 2 | Change From Baseline in Systolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 7, 4.00 Hours | -8.9 mmHg | Standard Error 5.69 |
| LHA510 Highest TID, Part 2 | Change From Baseline in Systolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 7, 6.00 Hours | -5.4 mmHg | Standard Error 5.69 |
| Vehicle, Part 2 | Change From Baseline in Systolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 7, 2.00 Hours | -12.3 mmHg | Standard Error 4.03 |
| Vehicle, Part 2 | Change From Baseline in Systolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 7, 1.00 Hours | -3.9 mmHg | Standard Error 4.03 |
| Vehicle, Part 2 | Change From Baseline in Systolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 7, 24.00 Hours | 7.3 mmHg | Standard Error 4.03 |
| Vehicle, Part 2 | Change From Baseline in Systolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 1, 8.00 Hours | 5.1 mmHg | Standard Error 4.03 |
| Vehicle, Part 2 | Change From Baseline in Systolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 1, 0.25 Hours | 1.0 mmHg | Standard Error 4.03 |
| Vehicle, Part 2 | Change From Baseline in Systolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 7, 8.00 Hours | -0.9 mmHg | Standard Error 4.03 |
| Vehicle, Part 2 | Change From Baseline in Systolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 7, 0.50 Hours | -6.4 mmHg | Standard Error 4.03 |
| Vehicle, Part 2 | Change From Baseline in Systolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 7, 4.00 Hours | -17.4 mmHg | Standard Error 4.03 |
| Vehicle, Part 2 | Change From Baseline in Systolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 7, 0.25 Hours | -3.3 mmHg | Standard Error 4.03 |
| Vehicle, Part 2 | Change From Baseline in Systolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 1, 0.50 Hours | 0.8 mmHg | Standard Error 4.03 |
| Vehicle, Part 2 | Change From Baseline in Systolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 1, 1.00 Hours | 0.8 mmHg | Standard Error 4.03 |
| Vehicle, Part 2 | Change From Baseline in Systolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 1, 6.00 Hours | -10.1 mmHg | Standard Error 4.03 |
| Vehicle, Part 2 | Change From Baseline in Systolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 7, 12.00 Hours | -5.5 mmHg | Standard Error 4.03 |
| Vehicle, Part 2 | Change From Baseline in Systolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 1, 24.00 Hours | 2.6 mmHg | Standard Error 4.03 |
| Vehicle, Part 2 | Change From Baseline in Systolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 1, 4.00 Hours | -0.4 mmHg | Standard Error 4.03 |
| Vehicle, Part 2 | Change From Baseline in Systolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 1, 12.00 Hours | 5.9 mmHg | Standard Error 4.03 |
| Vehicle, Part 2 | Change From Baseline in Systolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 7, 6.00 Hours | -3.3 mmHg | Standard Error 4.03 |
| Vehicle, Part 2 | Change From Baseline in Systolic Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 1, 2.00 Hours | -4.6 mmHg | Standard Error 4.03 |
Secondary
Change From Mean Arterial Blood Pressure at Each Post Dose Timepoint, Part 2
Mean arterial blood pressure (average pressure in the arteries during one cardiac cycle) was measured using an automated validated device, with an appropriately sized cuff, and assessed in the sitting position after the subject had rested for at least 3 minutes, and again (when required) after 3 minutes in the standing position.
Time frame: Day 1 and 7: 0.25h, 0.5h, 1h, 2h, 4h, 6h, 8h, 12h and 24h post-dose
Population: This analysis population includes all enrolled subjects in Part 2.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| LHA510 Lowest, Part 1 | Change From Mean Arterial Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 1, 6.00 Hours | -4.3 mmHg | Standard Error 3.34 |
| LHA510 Lowest, Part 1 | Change From Mean Arterial Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 1, 4.00 Hours | 3.0 mmHg | Standard Error 3.34 |
| LHA510 Lowest, Part 1 | Change From Mean Arterial Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 1, 2.00 Hours | -6.4 mmHg | Standard Error 3.34 |
| LHA510 Lowest, Part 1 | Change From Mean Arterial Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 7, 12.00 Hours | -7.8 mmHg | Standard Error 3.34 |
| LHA510 Lowest, Part 1 | Change From Mean Arterial Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 7, 8.00 Hours | -0.4 mmHg | Standard Error 3.34 |
| LHA510 Lowest, Part 1 | Change From Mean Arterial Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 7, 6.00 Hours | -3.0 mmHg | Standard Error 3.34 |
| LHA510 Lowest, Part 1 | Change From Mean Arterial Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 7, 4.00 Hours | -5.4 mmHg | Standard Error 3.34 |
| LHA510 Lowest, Part 1 | Change From Mean Arterial Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 1, 0.50 Hours | -2.4 mmHg | Standard Error 3.34 |
| LHA510 Lowest, Part 1 | Change From Mean Arterial Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 7, 24.00 Hours | -2.9 mmHg | Standard Error 3.34 |
| LHA510 Lowest, Part 1 | Change From Mean Arterial Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 7, 2.00 Hours | -4.5 mmHg | Standard Error 3.34 |
| LHA510 Lowest, Part 1 | Change From Mean Arterial Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 7, 1.00 Hours | -4.4 mmHg | Standard Error 3.34 |
| LHA510 Lowest, Part 1 | Change From Mean Arterial Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 7, 0.50 Hours | -5.8 mmHg | Standard Error 3.34 |
| LHA510 Lowest, Part 1 | Change From Mean Arterial Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 7, 0.25 Hours | -3.9 mmHg | Standard Error 3.34 |
| LHA510 Lowest, Part 1 | Change From Mean Arterial Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 1, 24.00 Hours | 4.2 mmHg | Standard Error 3.34 |
| LHA510 Lowest, Part 1 | Change From Mean Arterial Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 1, 1.00 Hours | 5.3 mmHg | Standard Error 3.34 |
| LHA510 Lowest, Part 1 | Change From Mean Arterial Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 1, 0.25 Hours | 3.5 mmHg | Standard Error 3.34 |
| LHA510 Lowest, Part 1 | Change From Mean Arterial Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 1, 12.00 Hours | 3.4 mmHg | Standard Error 3.34 |
| LHA510 Lowest, Part 1 | Change From Mean Arterial Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 1, 8.00 Hours | 4.0 mmHg | Standard Error 3.34 |
| LHA510 Next Lowest, Part 1 | Change From Mean Arterial Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 1, 1.00 Hours | -9.7 mmHg | Standard Error 3.41 |
| LHA510 Next Lowest, Part 1 | Change From Mean Arterial Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 1, 0.25 Hours | -6.8 mmHg | Standard Error 3.41 |
| LHA510 Next Lowest, Part 1 | Change From Mean Arterial Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 1, 0.50 Hours | -9.2 mmHg | Standard Error 3.41 |
| LHA510 Next Lowest, Part 1 | Change From Mean Arterial Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 1, 2.00 Hours | -5.8 mmHg | Standard Error 3.41 |
| LHA510 Next Lowest, Part 1 | Change From Mean Arterial Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 1, 4.00 Hours | -4.7 mmHg | Standard Error 3.41 |
| LHA510 Next Lowest, Part 1 | Change From Mean Arterial Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 1, 6.00 Hours | -10.0 mmHg | Standard Error 3.41 |
| LHA510 Next Lowest, Part 1 | Change From Mean Arterial Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 1, 8.00 Hours | 4.9 mmHg | Standard Error 3.41 |
| LHA510 Next Lowest, Part 1 | Change From Mean Arterial Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 1, 12.00 Hours | 4.4 mmHg | Standard Error 3.41 |
| LHA510 Next Lowest, Part 1 | Change From Mean Arterial Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 1, 24.00 Hours | -1.8 mmHg | Standard Error 3.41 |
| LHA510 Next Lowest, Part 1 | Change From Mean Arterial Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 7, 0.25 Hours | -6.8 mmHg | Standard Error 3.41 |
| LHA510 Next Lowest, Part 1 | Change From Mean Arterial Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 7, 0.50 Hours | -6.1 mmHg | Standard Error 3.41 |
| LHA510 Next Lowest, Part 1 | Change From Mean Arterial Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 7, 1.00 Hours | -6.6 mmHg | Standard Error 3.41 |
| LHA510 Next Lowest, Part 1 | Change From Mean Arterial Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 7, 2.00 Hours | -6.7 mmHg | Standard Error 3.41 |
| LHA510 Next Lowest, Part 1 | Change From Mean Arterial Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 7, 4.00 Hours | -6.3 mmHg | Standard Error 3.41 |
| LHA510 Next Lowest, Part 1 | Change From Mean Arterial Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 7, 6.00 Hours | 1.4 mmHg | Standard Error 3.41 |
| LHA510 Next Lowest, Part 1 | Change From Mean Arterial Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 7, 8.00 Hours | 5.7 mmHg | Standard Error 3.41 |
| LHA510 Next Lowest, Part 1 | Change From Mean Arterial Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 7, 12.00 Hours | 1.9 mmHg | Standard Error 3.41 |
| LHA510 Next Lowest, Part 1 | Change From Mean Arterial Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 7, 24.00 Hours | -1.5 mmHg | Standard Error 3.41 |
| LHA510 Next Highest, Part 1 | Change From Mean Arterial Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 7, 0.50 Hours | -11.6 mmHg | Standard Error 3.35 |
| LHA510 Next Highest, Part 1 | Change From Mean Arterial Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 1, 8.00 Hours | -4.5 mmHg | Standard Error 3.35 |
| LHA510 Next Highest, Part 1 | Change From Mean Arterial Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 7, 2.00 Hours | -8.7 mmHg | Standard Error 3.35 |
| LHA510 Next Highest, Part 1 | Change From Mean Arterial Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 1, 0.50 Hours | -3.1 mmHg | Standard Error 3.35 |
| LHA510 Next Highest, Part 1 | Change From Mean Arterial Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 1, 0.25 Hours | -1.7 mmHg | Standard Error 3.35 |
| LHA510 Next Highest, Part 1 | Change From Mean Arterial Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 7, 1.00 Hours | -5.9 mmHg | Standard Error 3.35 |
| LHA510 Next Highest, Part 1 | Change From Mean Arterial Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 1, 1.00 Hours | 1.3 mmHg | Standard Error 3.35 |
| LHA510 Next Highest, Part 1 | Change From Mean Arterial Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 1, 12.00 Hours | -3.7 mmHg | Standard Error 3.35 |
| LHA510 Next Highest, Part 1 | Change From Mean Arterial Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 1, 6.00 Hours | -5.0 mmHg | Standard Error 3.35 |
| LHA510 Next Highest, Part 1 | Change From Mean Arterial Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 1, 2.00 Hours | 0.6 mmHg | Standard Error 3.35 |
| LHA510 Next Highest, Part 1 | Change From Mean Arterial Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 7, 8.00 Hours | -7.3 mmHg | Standard Error 3.35 |
| LHA510 Next Highest, Part 1 | Change From Mean Arterial Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 1, 24.00 Hours | 1.8 mmHg | Standard Error 3.35 |
| LHA510 Next Highest, Part 1 | Change From Mean Arterial Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 1, 4.00 Hours | -6.9 mmHg | Standard Error 3.35 |
| LHA510 Next Highest, Part 1 | Change From Mean Arterial Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 7, 6.00 Hours | -13.1 mmHg | Standard Error 3.35 |
| LHA510 Next Highest, Part 1 | Change From Mean Arterial Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 7, 0.25 Hours | -5.3 mmHg | Standard Error 3.35 |
| LHA510 Next Highest, Part 1 | Change From Mean Arterial Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 7, 4.00 Hours | -10.3 mmHg | Standard Error 3.35 |
| LHA510 Next Highest, Part 1 | Change From Mean Arterial Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 7, 24.00 Hours | -12.6 mmHg | Standard Error 3.35 |
| LHA510 Next Highest, Part 1 | Change From Mean Arterial Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 7, 12.00 Hours | -8.3 mmHg | Standard Error 3.35 |
| LHA510 Highest, Part 1 | Change From Mean Arterial Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 7, 24.00 Hours | -3.9 mmHg | Standard Error 3.33 |
| LHA510 Highest, Part 1 | Change From Mean Arterial Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 7, 0.50 Hours | -4.3 mmHg | Standard Error 3.33 |
| LHA510 Highest, Part 1 | Change From Mean Arterial Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 7, 8.00 Hours | -1.6 mmHg | Standard Error 3.33 |
| LHA510 Highest, Part 1 | Change From Mean Arterial Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 7, 4.00 Hours | -3.6 mmHg | Standard Error 3.33 |
| LHA510 Highest, Part 1 | Change From Mean Arterial Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 1, 4.00 Hours | 0.9 mmHg | Standard Error 3.33 |
| LHA510 Highest, Part 1 | Change From Mean Arterial Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 1, 0.50 Hours | -6.8 mmHg | Standard Error 3.33 |
| LHA510 Highest, Part 1 | Change From Mean Arterial Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 7, 2.00 Hours | -5.1 mmHg | Standard Error 3.33 |
| LHA510 Highest, Part 1 | Change From Mean Arterial Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 1, 24.00 Hours | 4.1 mmHg | Standard Error 3.33 |
| LHA510 Highest, Part 1 | Change From Mean Arterial Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 7, 1.00 Hours | -3.5 mmHg | Standard Error 3.33 |
| LHA510 Highest, Part 1 | Change From Mean Arterial Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 1, 8.00 Hours | 0.5 mmHg | Standard Error 3.33 |
| LHA510 Highest, Part 1 | Change From Mean Arterial Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 1, 6.00 Hours | -2.5 mmHg | Standard Error 3.33 |
| LHA510 Highest, Part 1 | Change From Mean Arterial Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 1, 0.25 Hours | -3.5 mmHg | Standard Error 3.33 |
| LHA510 Highest, Part 1 | Change From Mean Arterial Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 1, 2.00 Hours | -4.8 mmHg | Standard Error 3.33 |
| LHA510 Highest, Part 1 | Change From Mean Arterial Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 7, 0.25 Hours | -1.9 mmHg | Standard Error 3.33 |
| LHA510 Highest, Part 1 | Change From Mean Arterial Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 7, 12.00 Hours | -5.6 mmHg | Standard Error 3.33 |
| LHA510 Highest, Part 1 | Change From Mean Arterial Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 7, 6.00 Hours | -5.9 mmHg | Standard Error 3.33 |
| LHA510 Highest, Part 1 | Change From Mean Arterial Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 1, 12.00 Hours | -2.6 mmHg | Standard Error 3.33 |
| LHA510 Highest, Part 1 | Change From Mean Arterial Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 1, 1.00 Hours | -1.6 mmHg | Standard Error 3.33 |
| Vehicle, Part 1 | Change From Mean Arterial Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 1, 1.00 Hours | 0.1 mmHg | Standard Error 3.33 |
| Vehicle, Part 1 | Change From Mean Arterial Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 1, 6.00 Hours | -2.1 mmHg | Standard Error 3.33 |
| Vehicle, Part 1 | Change From Mean Arterial Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 1, 8.00 Hours | 0.9 mmHg | Standard Error 3.33 |
| Vehicle, Part 1 | Change From Mean Arterial Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 1, 12.00 Hours | 6.0 mmHg | Standard Error 3.33 |
| Vehicle, Part 1 | Change From Mean Arterial Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 7, 12.00 Hours | -4.0 mmHg | Standard Error 3.33 |
| Vehicle, Part 1 | Change From Mean Arterial Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 1, 24.00 Hours | -4.0 mmHg | Standard Error 3.33 |
| Vehicle, Part 1 | Change From Mean Arterial Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 7, 0.25 Hours | -6.4 mmHg | Standard Error 3.33 |
| Vehicle, Part 1 | Change From Mean Arterial Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 1, 0.50 Hours | 1.1 mmHg | Standard Error 3.33 |
| Vehicle, Part 1 | Change From Mean Arterial Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 7, 0.50 Hours | -5.4 mmHg | Standard Error 3.33 |
| Vehicle, Part 1 | Change From Mean Arterial Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 7, 1.00 Hours | -10.5 mmHg | Standard Error 3.33 |
| Vehicle, Part 1 | Change From Mean Arterial Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 7, 2.00 Hours | -5.3 mmHg | Standard Error 3.33 |
| Vehicle, Part 1 | Change From Mean Arterial Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 7, 4.00 Hours | -8.5 mmHg | Standard Error 3.33 |
| Vehicle, Part 1 | Change From Mean Arterial Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 7, 6.00 Hours | -8.4 mmHg | Standard Error 3.33 |
| Vehicle, Part 1 | Change From Mean Arterial Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 1, 0.25 Hours | 1.9 mmHg | Standard Error 3.33 |
| Vehicle, Part 1 | Change From Mean Arterial Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 7, 24.00 Hours | -2.2 mmHg | Standard Error 3.33 |
| Vehicle, Part 1 | Change From Mean Arterial Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 7, 8.00 Hours | -5.6 mmHg | Standard Error 3.33 |
| Vehicle, Part 1 | Change From Mean Arterial Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 1, 2.00 Hours | -4.6 mmHg | Standard Error 3.33 |
| Vehicle, Part 1 | Change From Mean Arterial Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 1, 4.00 Hours | -1.9 mmHg | Standard Error 3.33 |
| LHA510 Highest TID, Part 2 | Change From Mean Arterial Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 1, 0.25 Hours | -1.0 mmHg | Standard Error 3.33 |
| LHA510 Highest TID, Part 2 | Change From Mean Arterial Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 1, 4.00 Hours | -1.8 mmHg | Standard Error 3.33 |
| LHA510 Highest TID, Part 2 | Change From Mean Arterial Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 7, 8.00 Hours | 0.8 mmHg | Standard Error 3.33 |
| LHA510 Highest TID, Part 2 | Change From Mean Arterial Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 1, 0.50 Hours | -3.4 mmHg | Standard Error 3.33 |
| LHA510 Highest TID, Part 2 | Change From Mean Arterial Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 7, 12.00 Hours | -3.5 mmHg | Standard Error 3.33 |
| LHA510 Highest TID, Part 2 | Change From Mean Arterial Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 1, 12.00 Hours | 0.1 mmHg | Standard Error 3.33 |
| LHA510 Highest TID, Part 2 | Change From Mean Arterial Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 1, 24.00 Hours | -2.8 mmHg | Standard Error 3.33 |
| LHA510 Highest TID, Part 2 | Change From Mean Arterial Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 1, 8.00 Hours | 2.8 mmHg | Standard Error 3.33 |
| LHA510 Highest TID, Part 2 | Change From Mean Arterial Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 1, 2.00 Hours | -8.1 mmHg | Standard Error 3.33 |
| LHA510 Highest TID, Part 2 | Change From Mean Arterial Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 7, 6.00 Hours | -6.1 mmHg | Standard Error 3.33 |
| LHA510 Highest TID, Part 2 | Change From Mean Arterial Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 7, 1.00 Hours | -3.6 mmHg | Standard Error 3.33 |
| LHA510 Highest TID, Part 2 | Change From Mean Arterial Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 7, 4.00 Hours | -4.6 mmHg | Standard Error 3.33 |
| LHA510 Highest TID, Part 2 | Change From Mean Arterial Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 1, 6.00 Hours | -6.3 mmHg | Standard Error 3.33 |
| LHA510 Highest TID, Part 2 | Change From Mean Arterial Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 7, 24.00 Hours | -0.8 mmHg | Standard Error 3.33 |
| LHA510 Highest TID, Part 2 | Change From Mean Arterial Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 7, 0.50 Hours | -2.3 mmHg | Standard Error 3.33 |
| LHA510 Highest TID, Part 2 | Change From Mean Arterial Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 7, 0.25 Hours | -5.4 mmHg | Standard Error 3.33 |
| LHA510 Highest TID, Part 2 | Change From Mean Arterial Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 1, 1.00 Hours | -6.6 mmHg | Standard Error 3.33 |
| LHA510 Highest TID, Part 2 | Change From Mean Arterial Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 7, 2.00 Hours | -3.8 mmHg | Standard Error 3.33 |
| Vehicle, Part 2 | Change From Mean Arterial Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 1, 12.00 Hours | 2.2 mmHg | Standard Error 2.35 |
| Vehicle, Part 2 | Change From Mean Arterial Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 1, 0.25 Hours | -0.0 mmHg | Standard Error 2.35 |
| Vehicle, Part 2 | Change From Mean Arterial Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 7, 0.25 Hours | -3.5 mmHg | Standard Error 2.35 |
| Vehicle, Part 2 | Change From Mean Arterial Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 7, 4.00 Hours | -11.0 mmHg | Standard Error 2.35 |
| Vehicle, Part 2 | Change From Mean Arterial Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 1, 24.00 Hours | 2.6 mmHg | Standard Error 2.35 |
| Vehicle, Part 2 | Change From Mean Arterial Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 1, 6.00 Hours | -6.9 mmHg | Standard Error 2.35 |
| Vehicle, Part 2 | Change From Mean Arterial Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 7, 6.00 Hours | -4.6 mmHg | Standard Error 2.35 |
| Vehicle, Part 2 | Change From Mean Arterial Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 1, 0.50 Hours | 1.8 mmHg | Standard Error 2.35 |
| Vehicle, Part 2 | Change From Mean Arterial Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 7, 2.00 Hours | -10.5 mmHg | Standard Error 2.35 |
| Vehicle, Part 2 | Change From Mean Arterial Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 1, 1.00 Hours | 0.4 mmHg | Standard Error 2.35 |
| Vehicle, Part 2 | Change From Mean Arterial Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 7, 8.00 Hours | -1.9 mmHg | Standard Error 2.35 |
| Vehicle, Part 2 | Change From Mean Arterial Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 1, 8.00 Hours | 5.5 mmHg | Standard Error 2.35 |
| Vehicle, Part 2 | Change From Mean Arterial Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 1, 4.00 Hours | -0.3 mmHg | Standard Error 2.35 |
| Vehicle, Part 2 | Change From Mean Arterial Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 1, 2.00 Hours | -4.8 mmHg | Standard Error 2.35 |
| Vehicle, Part 2 | Change From Mean Arterial Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 7, 1.00 Hours | -3.3 mmHg | Standard Error 2.35 |
| Vehicle, Part 2 | Change From Mean Arterial Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 7, 0.50 Hours | -4.0 mmHg | Standard Error 2.35 |
| Vehicle, Part 2 | Change From Mean Arterial Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 7, 24.00 Hours | 2.7 mmHg | Standard Error 2.35 |
| Vehicle, Part 2 | Change From Mean Arterial Blood Pressure at Each Post Dose Timepoint, Part 2 | Day 7, 12.00 Hours | -3.8 mmHg | Standard Error 2.35 |
Secondary
The Area Under the Plasma (or Serum or Blood) Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration [Mass x Time/Volume] (AUClast), Part 2
Plasma concentrations were quantitated using a high performance liquid chromatography/tandem mass spectometry method. Timepoints of assessment for Arms 1-4 were Days 1 and 7: 0h (pre-dose), 0.25h, 0.5h, 1h, 2h, 4h, 6h, 8h, 12h and 24h post-dose; and Day 15: 0h. Timepoints of assessment for LHA Highest BID were Days 1 and 7: 0h (pre-dose), 0.25h, 0.5h, 1h, 2h, 4h, 6h, 8h and 12h post-dose; and Day 15: 0h. Timepoints of assessment for LHA510 Highest TID were Days 1 and 7: 0h (pre-dose), 0.25h, 0.5h, 1h, 2h, 4h, 0h (pre-2nd dose), 0.5h, 2h, 0h (pre-3rd dose), 0.25h, 0.5h, 1h, 2h, 4h, 12h post-dose; and Day 15: 0h.
Time frame: Up to Day 15
Population: This analysis population includes all enrolled subjects in Part 2.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| LHA510 Lowest, Part 1 | The Area Under the Plasma (or Serum or Blood) Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration [Mass x Time/Volume] (AUClast), Part 2 | NA ng*h/mL |
| LHA510 Next Lowest, Part 1 | The Area Under the Plasma (or Serum or Blood) Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration [Mass x Time/Volume] (AUClast), Part 2 | NA ng*h/mL |
| LHA510 Next Highest, Part 1 | The Area Under the Plasma (or Serum or Blood) Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration [Mass x Time/Volume] (AUClast), Part 2 | NA ng*h/mL |
| LHA510 Highest, Part 1 | The Area Under the Plasma (or Serum or Blood) Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration [Mass x Time/Volume] (AUClast), Part 2 | NA ng*h/mL |
| Vehicle, Part 1 | The Area Under the Plasma (or Serum or Blood) Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration [Mass x Time/Volume] (AUClast), Part 2 | NA ng*h/mL |
| LHA510 Highest TID, Part 2 | The Area Under the Plasma (or Serum or Blood) Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration [Mass x Time/Volume] (AUClast), Part 2 | NA ng*h/mL |
Secondary
The Observed Maximum Plasma (or Serum or Blood) Concentration Following Drug Administration [Mass / Volume] (Cmax), Part 2
Plasma concentrations were quantitated using a high performance liquid chromatography/tandem mass spectometry method.Timepoints of assessment for Arms 1-4 were Days 1 and 7: 0h (pre-dose), 0.25h, 0.5h, 1h, 2h, 4h, 6h, 8h, 12h and 24h post-dose; and Day 15: 0h. Timepoints of assessment for LHA Highest BID were Days 1 and 7: 0h (pre-dose), 0.25h, 0.5h, 1h, 2h, 4h, 6h, 8h and 12h post-dose; and Day 15: 0h. Timepoints of assessment for LHA510 Highest TID were Days 1 and 7: 0h (pre-dose), 0.25h, 0.5h, 1h, 2h, 4h, 0h (pre-2nd dose), 0.5h, 2h, 0h (pre-3rd dose), 0.25h, 0.5h, 1h, 2h, 4h, 12h post-dose; and Day 15: 0h.
Time frame: Up to Day 15
Population: This analysis population includes all enrolled subjects in Part 2.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| LHA510 Lowest, Part 1 | The Observed Maximum Plasma (or Serum or Blood) Concentration Following Drug Administration [Mass / Volume] (Cmax), Part 2 | NA ng/mL |
| LHA510 Next Lowest, Part 1 | The Observed Maximum Plasma (or Serum or Blood) Concentration Following Drug Administration [Mass / Volume] (Cmax), Part 2 | NA ng/mL |
| LHA510 Next Highest, Part 1 | The Observed Maximum Plasma (or Serum or Blood) Concentration Following Drug Administration [Mass / Volume] (Cmax), Part 2 | NA ng/mL |
| LHA510 Highest, Part 1 | The Observed Maximum Plasma (or Serum or Blood) Concentration Following Drug Administration [Mass / Volume] (Cmax), Part 2 | NA ng/mL |
| Vehicle, Part 1 | The Observed Maximum Plasma (or Serum or Blood) Concentration Following Drug Administration [Mass / Volume] (Cmax), Part 2 | NA ng/mL |
| LHA510 Highest TID, Part 2 | The Observed Maximum Plasma (or Serum or Blood) Concentration Following Drug Administration [Mass / Volume] (Cmax), Part 2 | NA ng/mL |
Secondary
The Terminal Elimination Half-life [Time] (T1/2), Part 2
Plasma concentrations were quantitated using a high performance liquid chromatography/tandem mass spectometry method. Timepoints of assessment for Arms 1-4 were Days 1 and 7: 0h (pre-dose), 0.25h, 0.5h, 1h, 2h, 4h, 6h, 8h, 12h and 24h post-dose; and Day 15: 0h. Timepoints of assessment for LHA Highest BID were Days 1 and 7: 0h (pre-dose), 0.25h, 0.5h, 1h, 2h, 4h, 6h, 8h and 12h post-dose; and Day 15: 0h. Timepoints of assessment for LHA510 Highest TID were Days 1 and 7: 0h (pre-dose), 0.25h, 0.5h, 1h, 2h, 4h, 0h (pre-2nd dose), 0.5h, 2h, 0h (pre-3rd dose), 0.25h, 0.5h, 1h, 2h, 4h, 12h post-dose; and Day 15: 0h.
Time frame: Up to Day 15
Population: This analysis population includes all enrolled subjects in Part 2.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| LHA510 Lowest, Part 1 | The Terminal Elimination Half-life [Time] (T1/2), Part 2 | NA hour |
| LHA510 Next Lowest, Part 1 | The Terminal Elimination Half-life [Time] (T1/2), Part 2 | NA hour |
| LHA510 Next Highest, Part 1 | The Terminal Elimination Half-life [Time] (T1/2), Part 2 | NA hour |
| LHA510 Highest, Part 1 | The Terminal Elimination Half-life [Time] (T1/2), Part 2 | NA hour |
| Vehicle, Part 1 | The Terminal Elimination Half-life [Time] (T1/2), Part 2 | NA hour |
| LHA510 Highest TID, Part 2 | The Terminal Elimination Half-life [Time] (T1/2), Part 2 | NA hour |
Secondary
The Time to Reach the Maximum Concentration After Drug Administration [Time] (Tmax), Part 2
Plasma concentrations were quantitated using a high performance liquid chromatography/tandem mass spectometry method. Timepoints of assessment for Arms 1-4 were Days 1 and 7: 0h (pre-dose), 0.25h, 0.5h, 1h, 2h, 4h, 6h, 8h, 12h and 24h post-dose; and Day 15: 0h. Timepoints of assessment for LHA Highest BID were Days 1 and 7: 0h (pre-dose), 0.25h, 0.5h, 1h, 2h, 4h, 6h, 8h and 12h post-dose; and Day 15: 0h. Timepoints of assessment for LHA510 Highest TID were Days 1 and 7: 0h (pre-dose), 0.25h, 0.5h, 1h, 2h, 4h, 0h (pre-2nd dose), 0.5h, 2h, 0h (pre-3rd dose), 0.25h, 0.5h, 1h, 2h, 4h, 12h post-dose; and Day 15: 0h.
Time frame: Up to Day 15
Population: This analysis population includes all enrolled subjects in Part 2.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| LHA510 Lowest, Part 1 | The Time to Reach the Maximum Concentration After Drug Administration [Time] (Tmax), Part 2 | NA hour |
| LHA510 Next Lowest, Part 1 | The Time to Reach the Maximum Concentration After Drug Administration [Time] (Tmax), Part 2 | NA hour |
| LHA510 Next Highest, Part 1 | The Time to Reach the Maximum Concentration After Drug Administration [Time] (Tmax), Part 2 | NA hour |
| LHA510 Highest, Part 1 | The Time to Reach the Maximum Concentration After Drug Administration [Time] (Tmax), Part 2 | NA hour |
| Vehicle, Part 1 | The Time to Reach the Maximum Concentration After Drug Administration [Time] (Tmax), Part 2 | NA hour |
| LHA510 Highest TID, Part 2 | The Time to Reach the Maximum Concentration After Drug Administration [Time] (Tmax), Part 2 | NA hour |