Asthma
Conditions
Keywords
Asthma, Pharmacokinetics, Epinephrine, Bronchodilator, metered dose inhaler
Brief summary
This study examines the pharmacokinetic profile of Armstrong's proposed Epinephrine Inhalation Aerosol USP, an HFA-MDI (E004), in healthy male and female adult volunteers. Safety of E004 will also be evaluated, under augmented dose conditions.
Detailed description
This study is a randomized, evaluator-blind, single dose, three-arm, crossover, PK study, to be conducted in \ 18 healthy, male and female, adult volunteers. PK will be studied at two dose strengths (Arm T1 and Arm T2). A currently marketed, non-labeled, Epinephrine CFC-MDI will be used as a Reference Control (Arm C). * At the Screening Visit and the beginning of each Study Visit, each subject will be trained on the correct self-administration of MDI. The following three randomized treatments will be self-administered, at three Study Visits: * Treatment T1: Ten (10) inhalations of the low dose E004(125 mcg/inhalation), totaling 1.25 mg of epinephrine; * Treatment T2: Ten (10) inhalations of the high dose E004 (160 mcg/inhalation), totaling 1.60 mg of epinephrine; * Treatment C: Ten (10) inhalations of Epinephrine CFC-MDI (220 mcg/inhalation, totaling 2.2 mg of epinephrine base equivalent). * PK blood samples will be taken from a vein at scheduled time points. * Safety parameters and adverse drug events, if any, will be monitored and documented at each study visit. An End-of-Study (EOS) safety evaluation will be conducted.
Interventions
Single dose 220 mcg/inhalation, 10 inhalations
Sponsors
Amphastar Pharmaceuticals, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 30 Years
Healthy volunteers
Yes
Inclusion criteria
* Generally healthy, male and female adults, 18-30 yrs of age at Screening; * Having no clinically significant respiratory, cardiovascular and other systemic or organic illnesses, per investigator discretion; * Women of child-bearing potential must be non-pregnant, non-lactating, and practicing a clinically acceptable form of birth control; * Having properly consented and satisfied all other inclusion/
Exclusion criteria
as required for this protocol. * Other criteria apply.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Baseline Concentration (C0) of Labeled Epinephrine Total Epinephrine | 0 to 30 minutes prior to dosing | Patient PK blood samples were taken from a vein in a hand or arm via indwelling heparin-anticoagulated IV catheters, or by venipunctures at Baseline (prior to dosing) in each treatment period following a specified washout period (3-14 days), and were analyzed using an established analysis method. Baseline concentration (C0) is the concentration of epinephrine measured in the plasma at this time point. |
| Area Under the Curve From Time Zero to 6 Hours Post-dose (AUC[0-6]) | Pre-dose to 6 hours post-dose | Patient PK blood samples were taken from a vein in a hand or arm via indwelling heparin-anticoagulated IV catheters, or by venipunctures at 0 (baseline), 5, 15, 30, 45, 60, 90, 120, 180, 240, and 360 minutes post-dose in each treatment period and were analyzed using an established analysis method. Area under the curve from time zero to 6 hours post-dose (AUC\[0-6\]) was calculated using the trapezoidal rule. |
| Peak Concentration (Cmax) for Total Epinephrine From Time Zero to 6 Hours Post-dose | Pre-dose to 6 hours post-dose | Patient PK blood samples were taken from a vein in a hand or arm via indwelling heparin-anticoagulated IV catheters, or by venipunctures at 0 (baseline), 5, 15, 30, 45, 60, 90, 120, 180, 240, and 360 minutes post-dose in each treatment period and were analyzed using an established analysis method. Peak (maximum) concentration (Cmax) is the highest concentration of epinephrine measured in plasma during the treatment period. |
| Time to Reach Peak Concentration (Tmax) for Total Epinephrine | Pre-dose to 6 hours post-dose | Patient PK blood samples were taken from a vein in a hand or arm via indwelling heparin-anticoagulated IV catheters, or by venipunctures at 0 (baseline), 5, 15, 30, 45, 60, 90, 120, 180, 240, and 360 minutes post-dose in each treatment period and were analyzed using an established analysis method. tmax is the amount of time it takes for epinephrine to reach peak concentration in plasma during the treatment period. |
| Half-life (t1/2) for Total Epinephrine | Pre-dose to 6 hours post-dose | Patient PK blood samples were taken from a vein in a hand or arm via indwelling heparin-anticoagulated IV catheters, or by venipunctures at 0 (baseline), 5, 15, 30, 45, 60, 90, 120, 180, 240, and 360 minutes post-dose in each treatment period and were analyzed using an established analysis method. Half-life (t1/2) is the amount of time it takes for epinephrine decrease to half the peak concentration in plasma during the treatment period. |
| Concentration vs. Time for Total Epinephrine From Time Zero to 6 Hours Post-dose | Pre-dose to 6 hours post-dose | Patient PK blood samples were taken from a vein in a hand or arm via indwelling heparin-anticoagulated IV catheters, or by venipunctures at 0 (baseline), 5, 15, 30, 45, 60, 90, 120, 180, 240, and 360 minutes post-dose in each treatment period and were analyzed using an established analysis method. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Serum Potassium Levels | Pre-dose (baseline) to 360 minutes post-dose | Blood samples used to measure subject serum glucose and potassium levels were collected prior to study drug dosing (baseline) and up to 360 minutes post-dose. |
| Hand Tremor Scores | Pre-dose (baseline) to 360 minutes post-dose | Subjects evaluated hand tremor experiences using a scale from 0 to 3 (0: No tremor; 1: Mild, perceivable; 2: Moderate, observable; and 3: Severe, interfering with hand activities). Hand tremors were evaluated prior to study drug dosing (baseline) and up to 360 minutes post-dose. |
| Vital Signs: Systolic Blood Pressure (SBP) | Pre-dose (baseline) to 360 minutes post-dose | Subject vital signs, i.e., blood pressure and heart rate, were measured prior to study drug dosing (baseline) and up to 360 minutes after dosing during the study visit. |
| Number of Subjects With Significant Changes in Laboratory Tests | Approximately 6 weeks | Laboratory tests (CBC, serum comprehensive metabolic panel, urinalysis, and urinary pregnancy test for women of childbearing potential) were performed as a part of Screening and End-of-Study (EOS) procedures. This outcome is a count of the number of subjects that showed a clinically significant change in the EOS laboratory tests compared to the Screening Visit. |
| Number of Subjects With Significant Changes in Physical Examination | Approximately 6 weeks | Physical examinations were performed as a part of Screening and End-of-Study (EOS) procedures. This outcome is a count of the number of subjects that showed a clinically significant change in the EOS physical examination compared to the Screening Visit. |
| Vital Signs: Diastolic Blood Pressure (DBP) | Pre-dose (baseline) to 360 minutes post-dose | Subject vital signs, i.e., blood pressure and heart rate, were measured prior to study drug dosing (baseline) and up to 360 minutes after dosing during the study visit. |
| Vital Signs: Heart Rate (HR) | Pre-dose (baseline) to 360 minutes post-dose | Subject vital signs, i.e., blood pressure and heart rate, were measured prior to study drug dosing (baseline) and up to 360 minutes after dosing during the study visit. |
| ECG: QT Interval | Pre-dose (baseline) to 360 minutes post-dose | Subject QT and QTc Intervals were recorded using a 12-Lead ECG prior to study drug dosing (baseline) and up to 360 minutes after dosing during the study visit. |
| ECG: QTc Interval | Pre-dose (baseline) to 360 minutes post-dose | Subject QT and QTc Intervals were recorded using a 12-Lead ECG prior to study drug dosing (baseline) and up to 360 minutes after dosing during the study visit. |
| Serum Glucose Levels | Pre-dose (baseline) to 360 minutes post-dose | Blood samples used to measure subject serum glucose and potassium levels were collected prior to study drug dosing (baseline) and up to 360 minutes post-dose. |
Countries
United States
Participant flow
Recruitment details
Participants were recruited from a specialty clinic in Cypress, CA between 04/29/2010 and 05/27/2010
Pre-assignment details
A total of 38 subjects were screened, 24 subjects passed screening, consented and were randomized for participation in the study. The IRB approval date was 04/29/2010, the last subject was screened on 05/27/2010.
Participants by arm
| Arm | Count |
|---|---|
| C, T1, T2 Subjects received one of the three treatments during each study visit, separated by a washout period of 3-14 days. Visit 1: Treatment C: Ten (10) inhalations of Epinephrine CFC-MDI (220 mcg/inhalation), totaling 2.20 mg of epinephrine, in 5 min; Visit 2: Treatment T1: Ten (10) inhalations of the low dose E004 (125 mcg/inhalation), totaling 1.25 mg of epinephrine, in 5 min; Visit 3: Treatment T2: Ten (10) inhalations of the high dose E004 (160 mcg/inhalation), totaling 1.60 mg of epinephrine, in 5 min. | 4 |
| C, T2, T1 Subjects received one of the three treatments during each study visit, separated by a washout period of 3-14 days. Visit 1: Treatment C: Ten (10) inhalations of Epinephrine CFC-MDI (220 mcg/inhalation), totaling 2.20 mg of epinephrine, in 5 min; Visit 2: Treatment T2: Ten (10) inhalations of the high dose E004 (160 mcg/inhalation), totaling 1.60 mg of epinephrine, in 5 min; Visit 3: Treatment T1: Ten (10) inhalations of the low dose E004 (125 mcg/inhalation), totaling 1.25 mg of epinephrine, in 5 min. | 4 |
| T1, C, T2 Subjects received one of the three treatments during each study visit, separated by a washout period of 3-14 days. Visit 1: Treatment T1: Ten (10) inhalations of the low dose E004 (125 mcg/inhalation), totaling 1.25 mg of epinephrine, in 5 min; Visit 2: Treatment C: Ten (10) inhalations of Epinephrine CFC-MDI (220 mcg/inhalation), totaling 2.20 mg of epinephrine, in 5 min; Visit 3: Treatment T2: Ten (10) inhalations of the high dose E004 (160 mcg/inhalation), totaling 1.60 mg of epinephrine, in 5 min. | 4 |
| T1, T2, C Subjects received one of the three treatments during each study visit, separated by a washout period of 3-14 days. Visit 1: Treatment T1: Ten (10) inhalations of the low dose E004 (125 mcg/inhalation), totaling 1.25 mg of epinephrine, in 5 min; Visit 2: Treatment T2: Ten (10) inhalations of the high dose E004 (160 mcg/inhalation), totaling 1.60 mg of epinephrine, in 5 min; Visit 3: Treatment C: Ten (10) inhalations of Epinephrine CFC-MDI (220 mcg/inhalation), totaling 2.20 mg of epinephrine, in 5 min. | 4 |
| T2, C, T1 Subjects received one of the three treatments during each study visit, separated by a washout period of 3-14 days. Visit 1: Treatment T2: Ten (10) inhalations of the high dose E004 (160 mcg/inhalation), totaling 1.60 mg of epinephrine, in 5 min; Visit 2: Treatment C: Ten (10) inhalations of Epinephrine CFC-MDI (220 mcg/inhalation), totaling 2.20 mg of epinephrine, in 5 min; Visit 3: Treatment T1: Ten (10) inhalations of the low dose E004 (125 mcg/inhalation), totaling 1.25 mg of epinephrine, in 5 min. | 4 |
| T2, T1, C Subjects received one of the three treatments during each study visit, separated by a washout period of 3-14 days. Visit 1: Treatment T2: Ten (10) inhalations of the high dose E004 (160 mcg/inhalation), totaling 1.60 mg of epinephrine, in 5 min; Visit 2: Treatment T1: Ten (10) inhalations of the low dose E004 (125 mcg/inhalation), totaling 1.25 mg of epinephrine, in 5 min; Visit 3 Treatment C: Ten (10) inhalations of Epinephrine CFC-MDI (220 mcg/inhalation), totaling 2.20 mg of epinephrine, in 5 min. | 4 |
| Total | 24 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| 3-14 Day Washout | Withdrawal by Subject | 0 | 0 | 1 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | C, T2, T1 | T1, C, T2 | T1, T2, C | C, T1, T2 | T2, C, T1 | T2, T1, C | Total |
|---|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 4 Participants | 4 Participants | 4 Participants | 4 Participants | 4 Participants | 4 Participants | 24 Participants |
| Age, Continuous | 25.3 years STANDARD_DEVIATION 4.27 | 24.0 years STANDARD_DEVIATION 3.37 | 21.8 years STANDARD_DEVIATION 1.71 | 24.0 years STANDARD_DEVIATION 2.94 | 25.3 years STANDARD_DEVIATION 0.5 | 22.0 years STANDARD_DEVIATION 3.56 | 23.7 years STANDARD_DEVIATION 3.01 |
| Region of Enrollment United States | 4 participants | 4 participants | 4 participants | 4 participants | 4 participants | 4 participants | 24 participants |
| Sex: Female, Male Female | 2 Participants | 1 Participants | 2 Participants | 1 Participants | 1 Participants | 2 Participants | 9 Participants |
| Sex: Female, Male Male | 2 Participants | 3 Participants | 2 Participants | 3 Participants | 3 Participants | 2 Participants | 15 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 1 / 24 | 1 / 23 | 1 / 22 |
| serious Total, serious adverse events | 0 / 24 | 0 / 23 | 0 / 22 |
Outcome results
Primary
Area Under the Curve From Time Zero to 6 Hours Post-dose (AUC[0-6])
Patient PK blood samples were taken from a vein in a hand or arm via indwelling heparin-anticoagulated IV catheters, or by venipunctures at 0 (baseline), 5, 15, 30, 45, 60, 90, 120, 180, 240, and 360 minutes post-dose in each treatment period and were analyzed using an established analysis method. Area under the curve from time zero to 6 hours post-dose (AUC\[0-6\]) was calculated using the trapezoidal rule.
Time frame: Pre-dose to 6 hours post-dose
Population: Patients who: 1) have taken the valid pre-dose baseline PK sample 2) have correctly taken the randomized study-drug treatment 3) have at least four of the five post-dose PK measurements between 5 and 60 min post-dose available and 4) have a minimum of eight of the ten post-dose PK measurements for the entire 6 hour post-dose PK sampling period.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment T1 | Area Under the Curve From Time Zero to 6 Hours Post-dose (AUC[0-6]) | 7938 pg*min/mL | Standard Deviation 5023 |
| Treatment T2 | Area Under the Curve From Time Zero to 6 Hours Post-dose (AUC[0-6]) | 9438 pg*min/mL | Standard Deviation 4819 |
| Treatment C | Area Under the Curve From Time Zero to 6 Hours Post-dose (AUC[0-6]) | 7218 pg*min/mL | Standard Deviation 6489 |
Primary
Baseline Concentration (C0) of Labeled Epinephrine Total Epinephrine
Patient PK blood samples were taken from a vein in a hand or arm via indwelling heparin-anticoagulated IV catheters, or by venipunctures at Baseline (prior to dosing) in each treatment period following a specified washout period (3-14 days), and were analyzed using an established analysis method. Baseline concentration (C0) is the concentration of epinephrine measured in the plasma at this time point.
Time frame: 0 to 30 minutes prior to dosing
Population: Patients who: 1) have taken the valid pre-dose baseline PK sample 2) have correctly taken the randomized study-drug treatment 3) have at least four of the five post-dose PK measurements between 5 and 60 min post-dose available and 4) have a minimum of eight of the ten post-dose PK measurements for the entire 6 hour post-dose PK sampling period.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment T1 | Baseline Concentration (C0) of Labeled Epinephrine Total Epinephrine | 9.3 pg/mL | Standard Deviation 17.7 |
| Treatment T2 | Baseline Concentration (C0) of Labeled Epinephrine Total Epinephrine | 8.9 pg/mL | Standard Deviation 15.8 |
| Treatment C | Baseline Concentration (C0) of Labeled Epinephrine Total Epinephrine | 7.8 pg/mL | Standard Deviation 21.4 |
Primary
Concentration vs. Time for Total Epinephrine From Time Zero to 6 Hours Post-dose
Patient PK blood samples were taken from a vein in a hand or arm via indwelling heparin-anticoagulated IV catheters, or by venipunctures at 0 (baseline), 5, 15, 30, 45, 60, 90, 120, 180, 240, and 360 minutes post-dose in each treatment period and were analyzed using an established analysis method.
Time frame: Pre-dose to 6 hours post-dose
Population: Patients who : 1) have taken the valid pre-dose baseline PK sample 2) have correctly taken the randomized study-drug treatment 3) have at least 4 of the 5 post-dose PK measurements between 5 and 60 minutes post-dose available and 4) have a min of 8 of the 10 post-dose PK measurements for the entire 6 hour post-dose PK sampling period.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment T1 | Concentration vs. Time for Total Epinephrine From Time Zero to 6 Hours Post-dose | Total Epinephrine, 120 min post-dose | 8.7 pg/mL | Standard Deviation 12.8 |
| Treatment T1 | Concentration vs. Time for Total Epinephrine From Time Zero to 6 Hours Post-dose | Total Epinephrine, 45 min post-dose | 8.6 pg/mL | Standard Deviation 14.4 |
| Treatment T1 | Concentration vs. Time for Total Epinephrine From Time Zero to 6 Hours Post-dose | Total Epinephrine, 240 min post-dose | 12.9 pg/mL | Standard Deviation 20.4 |
| Treatment T1 | Concentration vs. Time for Total Epinephrine From Time Zero to 6 Hours Post-dose | Total Epinephrine, 90 min post-dose | 5.7 pg/mL | Standard Deviation 11.6 |
| Treatment T1 | Concentration vs. Time for Total Epinephrine From Time Zero to 6 Hours Post-dose | Total Epinephrine, 60 min post-dose | 7.6 pg/mL | Standard Deviation 14.7 |
| Treatment T1 | Concentration vs. Time for Total Epinephrine From Time Zero to 6 Hours Post-dose | Total Epinephrine, 0 min (Baseline) | 9.3 pg/mL | Standard Deviation 17.7 |
| Treatment T1 | Concentration vs. Time for Total Epinephrine From Time Zero to 6 Hours Post-dose | Total Epinephrine, 15 min post-dose | 48.9 pg/mL | Standard Deviation 33.7 |
| Treatment T1 | Concentration vs. Time for Total Epinephrine From Time Zero to 6 Hours Post-dose | Total Epinephrine, 5 min post-dose | 339.6 pg/mL | Standard Deviation 295.1 |
| Treatment T1 | Concentration vs. Time for Total Epinephrine From Time Zero to 6 Hours Post-dose | Total Epinephrine, 180 min post-dose | 12.0 pg/mL | Standard Deviation 20.2 |
| Treatment T1 | Concentration vs. Time for Total Epinephrine From Time Zero to 6 Hours Post-dose | Total Epinephrine, 30 min post-dose | 12.7 pg/mL | Standard Deviation 18.8 |
| Treatment T1 | Concentration vs. Time for Total Epinephrine From Time Zero to 6 Hours Post-dose | Total Epinephrine, 360 min post-dose | 31.1 pg/mL | Standard Deviation 24 |
| Treatment T2 | Concentration vs. Time for Total Epinephrine From Time Zero to 6 Hours Post-dose | Total Epinephrine, 60 min post-dose | 14.5 pg/mL | Standard Deviation 17.3 |
| Treatment T2 | Concentration vs. Time for Total Epinephrine From Time Zero to 6 Hours Post-dose | Total Epinephrine, 0 min (Baseline) | 8.9 pg/mL | Standard Deviation 15.8 |
| Treatment T2 | Concentration vs. Time for Total Epinephrine From Time Zero to 6 Hours Post-dose | Total Epinephrine, 5 min post-dose | 442.4 pg/mL | Standard Deviation 330.8 |
| Treatment T2 | Concentration vs. Time for Total Epinephrine From Time Zero to 6 Hours Post-dose | Total Epinephrine, 15 min post-dose | 62.4 pg/mL | Standard Deviation 42.5 |
| Treatment T2 | Concentration vs. Time for Total Epinephrine From Time Zero to 6 Hours Post-dose | Total Epinephrine, 30 min post-dose | 17.4 pg/mL | Standard Deviation 18.3 |
| Treatment T2 | Concentration vs. Time for Total Epinephrine From Time Zero to 6 Hours Post-dose | Total Epinephrine, 45 min post-dose | 13.0 pg/mL | Standard Deviation 17.2 |
| Treatment T2 | Concentration vs. Time for Total Epinephrine From Time Zero to 6 Hours Post-dose | Total Epinephrine, 90 min post-dose | 13.7 pg/mL | Standard Deviation 14.8 |
| Treatment T2 | Concentration vs. Time for Total Epinephrine From Time Zero to 6 Hours Post-dose | Total Epinephrine, 120 min post-dose | 15.5 pg/mL | Standard Deviation 19.7 |
| Treatment T2 | Concentration vs. Time for Total Epinephrine From Time Zero to 6 Hours Post-dose | Total Epinephrine, 180 min post-dose | 10.4 pg/mL | Standard Deviation 15.2 |
| Treatment T2 | Concentration vs. Time for Total Epinephrine From Time Zero to 6 Hours Post-dose | Total Epinephrine, 240 min post-dose | 11.5 pg/mL | Standard Deviation 14.9 |
| Treatment T2 | Concentration vs. Time for Total Epinephrine From Time Zero to 6 Hours Post-dose | Total Epinephrine, 360 min post-dose | 29.4 pg/mL | Standard Deviation 23 |
| Treatment C | Concentration vs. Time for Total Epinephrine From Time Zero to 6 Hours Post-dose | Total Epinephrine, 240 min post-dose | 9.8 pg/mL | Standard Deviation 18.1 |
| Treatment C | Concentration vs. Time for Total Epinephrine From Time Zero to 6 Hours Post-dose | Total Epinephrine, 120 min post-dose | 13.1 pg/mL | Standard Deviation 17.6 |
| Treatment C | Concentration vs. Time for Total Epinephrine From Time Zero to 6 Hours Post-dose | Total Epinephrine, 15 min post-dose | 38.5 pg/mL | Standard Deviation 21.2 |
| Treatment C | Concentration vs. Time for Total Epinephrine From Time Zero to 6 Hours Post-dose | Total Epinephrine, 0 min (Baseline) | 7.8 pg/mL | Standard Deviation 21.4 |
| Treatment C | Concentration vs. Time for Total Epinephrine From Time Zero to 6 Hours Post-dose | Total Epinephrine, 180 min post-dose | 8.4 pg/mL | Standard Deviation 15.2 |
| Treatment C | Concentration vs. Time for Total Epinephrine From Time Zero to 6 Hours Post-dose | Total Epinephrine, 5 min post-dose | 130.2 pg/mL | Standard Deviation 101.8 |
| Treatment C | Concentration vs. Time for Total Epinephrine From Time Zero to 6 Hours Post-dose | Total Epinephrine, 60 min post-dose | 18.0 pg/mL | Standard Deviation 18.6 |
| Treatment C | Concentration vs. Time for Total Epinephrine From Time Zero to 6 Hours Post-dose | Total Epinephrine, 45 min post-dose | 20.9 pg/mL | Standard Deviation 18.6 |
| Treatment C | Concentration vs. Time for Total Epinephrine From Time Zero to 6 Hours Post-dose | Total Epinephrine, 360 min post-dose | 38.3 pg/mL | Standard Deviation 40.8 |
| Treatment C | Concentration vs. Time for Total Epinephrine From Time Zero to 6 Hours Post-dose | Total Epinephrine, 90 min post-dose | 16.7 pg/mL | Standard Deviation 16.6 |
| Treatment C | Concentration vs. Time for Total Epinephrine From Time Zero to 6 Hours Post-dose | Total Epinephrine, 30 min post-dose | 16.8 pg/mL | Standard Deviation 17.6 |
Primary
Half-life (t1/2) for Total Epinephrine
Patient PK blood samples were taken from a vein in a hand or arm via indwelling heparin-anticoagulated IV catheters, or by venipunctures at 0 (baseline), 5, 15, 30, 45, 60, 90, 120, 180, 240, and 360 minutes post-dose in each treatment period and were analyzed using an established analysis method. Half-life (t1/2) is the amount of time it takes for epinephrine decrease to half the peak concentration in plasma during the treatment period.
Time frame: Pre-dose to 6 hours post-dose
Population: Patients who: 1) have taken the valid pre-dose baseline PK sample 2) have correctly taken the randomized study-drug treatment 3) have at least 4 of the 5 post-dose PK measurements between 5 and 60 min post-dose available; and 4) have a min of 8 of the 10 post-dose PK measurements for the entire 6 hour post-dose PK sampling period.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment T1 | Half-life (t1/2) for Total Epinephrine | 125.9 min | Full Range 183.3 |
| Treatment T2 | Half-life (t1/2) for Total Epinephrine | 158.8 min | Full Range 238 |
| Treatment C | Half-life (t1/2) for Total Epinephrine | 237.3 min | Full Range 175.2 |
Primary
Peak Concentration (Cmax) for Total Epinephrine From Time Zero to 6 Hours Post-dose
Patient PK blood samples were taken from a vein in a hand or arm via indwelling heparin-anticoagulated IV catheters, or by venipunctures at 0 (baseline), 5, 15, 30, 45, 60, 90, 120, 180, 240, and 360 minutes post-dose in each treatment period and were analyzed using an established analysis method. Peak (maximum) concentration (Cmax) is the highest concentration of epinephrine measured in plasma during the treatment period.
Time frame: Pre-dose to 6 hours post-dose
Population: Patients who: 1) have taken the valid pre-dose baseline PK sample 2) have correctly taken the randomized study-drug treatment 3) have at least four of the five post-dose PK measurements between 5 and 60 min post-dose available and 4) have a minimum of eight of the ten post-dose PK measurements for the entire 6 hour post-dose PK sampling period.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment T1 | Peak Concentration (Cmax) for Total Epinephrine From Time Zero to 6 Hours Post-dose | 340 pg/mL | Standard Deviation 294 |
| Treatment T2 | Peak Concentration (Cmax) for Total Epinephrine From Time Zero to 6 Hours Post-dose | 444 pg/mL | Standard Deviation 328 |
| Treatment C | Peak Concentration (Cmax) for Total Epinephrine From Time Zero to 6 Hours Post-dose | 139 pg/mL | Standard Deviation 98 |
Primary
Time to Reach Peak Concentration (Tmax) for Total Epinephrine
Patient PK blood samples were taken from a vein in a hand or arm via indwelling heparin-anticoagulated IV catheters, or by venipunctures at 0 (baseline), 5, 15, 30, 45, 60, 90, 120, 180, 240, and 360 minutes post-dose in each treatment period and were analyzed using an established analysis method. tmax is the amount of time it takes for epinephrine to reach peak concentration in plasma during the treatment period.
Time frame: Pre-dose to 6 hours post-dose
Population: Patients who : 1) have taken the valid pre-dose baseline PK sample 2) have correctly taken the randomized study-drug treatment 3) have at least four of the five post-dose PK measurements between 5 and 60 min post-dose available and 4) have a minimum of eight of the ten post-dose PK measurements for the entire 6 hour post-dose PK sampling period.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment T1 | Time to Reach Peak Concentration (Tmax) for Total Epinephrine | 34.6 min | Standard Deviation 100.2 |
| Treatment T2 | Time to Reach Peak Concentration (Tmax) for Total Epinephrine | 37.0 min | Standard Deviation 104.5 |
| Treatment C | Time to Reach Peak Concentration (Tmax) for Total Epinephrine | 38.0 min | Standard Deviation 104.3 |
Secondary
ECG: QTc Interval
Subject QT and QTc Intervals were recorded using a 12-Lead ECG prior to study drug dosing (baseline) and up to 360 minutes after dosing during the study visit.
Time frame: Pre-dose (baseline) to 360 minutes post-dose
Population: Subjects who have taken any amount of study drug treatment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment T1 | ECG: QTc Interval | Pre-dose (Baseline) | 407 msec | Standard Deviation 16.9 |
| Treatment T1 | ECG: QTc Interval | 30 min post-dose | 408 msec | Standard Deviation 15.2 |
| Treatment T1 | ECG: QTc Interval | 90 min post-dose | 401 msec | Standard Deviation 16.9 |
| Treatment T1 | ECG: QTc Interval | 360 min post-dose | 403 msec | Standard Deviation 18.2 |
| Treatment T2 | ECG: QTc Interval | 360 min post-dose | 403 msec | Standard Deviation 17.9 |
| Treatment T2 | ECG: QTc Interval | Pre-dose (Baseline) | 407 msec | Standard Deviation 20 |
| Treatment T2 | ECG: QTc Interval | 90 min post-dose | 401 msec | Standard Deviation 18.1 |
| Treatment T2 | ECG: QTc Interval | 30 min post-dose | 411 msec | Standard Deviation 19.4 |
| Treatment C | ECG: QTc Interval | 360 min post-dose | 402 msec | Standard Deviation 15.7 |
| Treatment C | ECG: QTc Interval | 30 min post-dose | 412 msec | Standard Deviation 22.3 |
| Treatment C | ECG: QTc Interval | 90 min post-dose | 403 msec | Standard Deviation 14.1 |
| Treatment C | ECG: QTc Interval | Pre-dose (Baseline) | 403 msec | Standard Deviation 16.2 |
Secondary
ECG: QT Interval
Subject QT and QTc Intervals were recorded using a 12-Lead ECG prior to study drug dosing (baseline) and up to 360 minutes after dosing during the study visit.
Time frame: Pre-dose (baseline) to 360 minutes post-dose
Population: Subjects who have taken any amount of study drug treatment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment T1 | ECG: QT Interval | Pre-dose (Baseline) | 416 msec | Standard Deviation 33.6 |
| Treatment T1 | ECG: QT Interval | 30 min post-dose | 404 msec | Standard Deviation 38.6 |
| Treatment T1 | ECG: QT Interval | 90 min post-dose | 399 msec | Standard Deviation 34.3 |
| Treatment T1 | ECG: QT Interval | 360 min post-dose | 399 msec | Standard Deviation 41.5 |
| Treatment T2 | ECG: QT Interval | 360 min post-dose | 400 msec | Standard Deviation 33.1 |
| Treatment T2 | ECG: QT Interval | Pre-dose (Baseline) | 407 msec | Standard Deviation 30.1 |
| Treatment T2 | ECG: QT Interval | 90 min post-dose | 401 msec | Standard Deviation 32.9 |
| Treatment T2 | ECG: QT Interval | 30 min post-dose | 405 msec | Standard Deviation 32.8 |
| Treatment C | ECG: QT Interval | 360 min post-dose | 400 msec | Standard Deviation 37.7 |
| Treatment C | ECG: QT Interval | 30 min post-dose | 413 msec | Standard Deviation 44.8 |
| Treatment C | ECG: QT Interval | 90 min post-dose | 407 msec | Standard Deviation 41.3 |
| Treatment C | ECG: QT Interval | Pre-dose (Baseline) | 423 msec | Standard Deviation 44.1 |
Secondary
Hand Tremor Scores
Subjects evaluated hand tremor experiences using a scale from 0 to 3 (0: No tremor; 1: Mild, perceivable; 2: Moderate, observable; and 3: Severe, interfering with hand activities). Hand tremors were evaluated prior to study drug dosing (baseline) and up to 360 minutes post-dose.
Time frame: Pre-dose (baseline) to 360 minutes post-dose
Population: Subjects who have taken any amount of study drug treatment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment T1 | Hand Tremor Scores | Pre-dose (Baseline) | 0.0 score on a scale | Standard Deviation 0 |
| Treatment T1 | Hand Tremor Scores | 10 min post-dose | 0.1 score on a scale | Standard Deviation 0.3 |
| Treatment T1 | Hand Tremor Scores | 60 min post-dose | 0.0 score on a scale | Standard Deviation 0 |
| Treatment T1 | Hand Tremor Scores | 360 min post-dose | 0.0 score on a scale | Standard Deviation 0 |
| Treatment T2 | Hand Tremor Scores | 360 min post-dose | 0.0 score on a scale | Standard Deviation 0 |
| Treatment T2 | Hand Tremor Scores | Pre-dose (Baseline) | 0.0 score on a scale | Standard Deviation 0 |
| Treatment T2 | Hand Tremor Scores | 60 min post-dose | 0.0 score on a scale | Standard Deviation 0 |
| Treatment T2 | Hand Tremor Scores | 10 min post-dose | 0.2 score on a scale | Standard Deviation 0.4 |
| Treatment C | Hand Tremor Scores | 360 min post-dose | 0.0 score on a scale | Standard Deviation 0.2 |
| Treatment C | Hand Tremor Scores | 10 min post-dose | 0.1 score on a scale | Standard Deviation 0.4 |
| Treatment C | Hand Tremor Scores | 60 min post-dose | 0.0 score on a scale | Standard Deviation 0.2 |
| Treatment C | Hand Tremor Scores | Pre-dose (Baseline) | 0.0 score on a scale | Standard Deviation 0 |
Secondary
Number of Subjects With Significant Changes in Laboratory Tests
Laboratory tests (CBC, serum comprehensive metabolic panel, urinalysis, and urinary pregnancy test for women of childbearing potential) were performed as a part of Screening and End-of-Study (EOS) procedures. This outcome is a count of the number of subjects that showed a clinically significant change in the EOS laboratory tests compared to the Screening Visit.
Time frame: Approximately 6 weeks
Population: Subjects who have taken any amount of study drug treatment. The Arm/Group is presented as one group because subjects would have received all 3 different study drug treatments prior to EOS due to the crossover study design.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment T1 | Number of Subjects With Significant Changes in Laboratory Tests | 0 Participants |
Secondary
Number of Subjects With Significant Changes in Physical Examination
Physical examinations were performed as a part of Screening and End-of-Study (EOS) procedures. This outcome is a count of the number of subjects that showed a clinically significant change in the EOS physical examination compared to the Screening Visit.
Time frame: Approximately 6 weeks
Population: Subjects who have taken any amount of study drug treatment. The Arm/Group is presented as one group because subjects would have received all 3 different study drug treatments prior to EOS due to the crossover study design.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment T1 | Number of Subjects With Significant Changes in Physical Examination | 0 Participants |
Secondary
Serum Glucose Levels
Blood samples used to measure subject serum glucose and potassium levels were collected prior to study drug dosing (baseline) and up to 360 minutes post-dose.
Time frame: Pre-dose (baseline) to 360 minutes post-dose
Population: Subjects who have taken any amount of study drug treatment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment T1 | Serum Glucose Levels | Pre-dose (Baseline) | 83 mg/dL | Standard Deviation 6.9 |
| Treatment T1 | Serum Glucose Levels | 15 min post-dose | 101 mg/dL | Standard Deviation 17 |
| Treatment T1 | Serum Glucose Levels | 30 min post-dose | 94 mg/dL | Standard Deviation 16.4 |
| Treatment T1 | Serum Glucose Levels | 60 min post-dose | 86 mg/dL | Standard Deviation 8.9 |
| Treatment T1 | Serum Glucose Levels | 120 min post-dose | 81 mg/dL | Standard Deviation 6.8 |
| Treatment T1 | Serum Glucose Levels | 360 min post-dose | 82 mg/dL | Standard Deviation 7.9 |
| Treatment T2 | Serum Glucose Levels | 360 min post-dose | 82 mg/dL | Standard Deviation 9.4 |
| Treatment T2 | Serum Glucose Levels | Pre-dose (Baseline) | 83 mg/dL | Standard Deviation 9.1 |
| Treatment T2 | Serum Glucose Levels | 60 min post-dose | 86 mg/dL | Standard Deviation 10.8 |
| Treatment T2 | Serum Glucose Levels | 120 min post-dose | 82 mg/dL | Standard Deviation 6.1 |
| Treatment T2 | Serum Glucose Levels | 15 min post-dose | 105 mg/dL | Standard Deviation 11.6 |
| Treatment T2 | Serum Glucose Levels | 30 min post-dose | 99 mg/dL | Standard Deviation 12.1 |
| Treatment C | Serum Glucose Levels | 15 min post-dose | 96 mg/dL | Standard Deviation 11 |
| Treatment C | Serum Glucose Levels | 30 min post-dose | 98 mg/dL | Standard Deviation 10.7 |
| Treatment C | Serum Glucose Levels | 360 min post-dose | 80 mg/dL | Standard Deviation 7.1 |
| Treatment C | Serum Glucose Levels | 60 min post-dose | 94 mg/dL | Standard Deviation 12.5 |
| Treatment C | Serum Glucose Levels | Pre-dose (Baseline) | 84 mg/dL | Standard Deviation 6.2 |
| Treatment C | Serum Glucose Levels | 120 min post-dose | 83 mg/dL | Standard Deviation 5.3 |
Secondary
Serum Potassium Levels
Blood samples used to measure subject serum glucose and potassium levels were collected prior to study drug dosing (baseline) and up to 360 minutes post-dose.
Time frame: Pre-dose (baseline) to 360 minutes post-dose
Population: Subjects who have taken any amount of study drug treatment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment T1 | Serum Potassium Levels | Pre-dose (Baseline) | 4 mmol/L | Standard Deviation 0.2 |
| Treatment T1 | Serum Potassium Levels | 15 min post-dose | 4 mmol/L | Standard Deviation 0.3 |
| Treatment T1 | Serum Potassium Levels | 30 min post-dose | 4 mmol/L | Standard Deviation 0.5 |
| Treatment T1 | Serum Potassium Levels | 60 min post-dose | 4 mmol/L | Standard Deviation 0.2 |
| Treatment T1 | Serum Potassium Levels | 120 min post-dose | 4 mmol/L | Standard Deviation 0.3 |
| Treatment T1 | Serum Potassium Levels | 360 min post-dose | 4 mmol/L | Standard Deviation 0.3 |
| Treatment T2 | Serum Potassium Levels | 360 min post-dose | 4 mmol/L | Standard Deviation 0.3 |
| Treatment T2 | Serum Potassium Levels | Pre-dose (Baseline) | 4 mmol/L | Standard Deviation 0.3 |
| Treatment T2 | Serum Potassium Levels | 60 min post-dose | 4 mmol/L | Standard Deviation 0.3 |
| Treatment T2 | Serum Potassium Levels | 120 min post-dose | 4 mmol/L | Standard Deviation 0.3 |
| Treatment T2 | Serum Potassium Levels | 15 min post-dose | 4 mmol/L | Standard Deviation 0.3 |
| Treatment T2 | Serum Potassium Levels | 30 min post-dose | 4 mmol/L | Standard Deviation 0.3 |
| Treatment C | Serum Potassium Levels | 15 min post-dose | 4 mmol/L | Standard Deviation 0.3 |
| Treatment C | Serum Potassium Levels | 30 min post-dose | 4 mmol/L | Standard Deviation 0.3 |
| Treatment C | Serum Potassium Levels | 360 min post-dose | 4 mmol/L | Standard Deviation 0.2 |
| Treatment C | Serum Potassium Levels | 60 min post-dose | 4 mmol/L | Standard Deviation 0.2 |
| Treatment C | Serum Potassium Levels | Pre-dose (Baseline) | 4 mmol/L | Standard Deviation 0.2 |
| Treatment C | Serum Potassium Levels | 120 min post-dose | 4 mmol/L | Standard Deviation 0.3 |
Secondary
Vital Signs: Diastolic Blood Pressure (DBP)
Subject vital signs, i.e., blood pressure and heart rate, were measured prior to study drug dosing (baseline) and up to 360 minutes after dosing during the study visit.
Time frame: Pre-dose (baseline) to 360 minutes post-dose
Population: Subjects who have taken any amount of study drug treatment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment T1 | Vital Signs: Diastolic Blood Pressure (DBP) | 10 min post-dose | 63 mmHg | Standard Deviation 10.1 |
| Treatment T1 | Vital Signs: Diastolic Blood Pressure (DBP) | 120 min post-dose | 61 mmHg | Standard Deviation 9.8 |
| Treatment T1 | Vital Signs: Diastolic Blood Pressure (DBP) | 60 min post-dose | 63 mmHg | Standard Deviation 10.8 |
| Treatment T1 | Vital Signs: Diastolic Blood Pressure (DBP) | Pre-dose (Baseline) | 62 mmHg | Standard Deviation 9.3 |
| Treatment T1 | Vital Signs: Diastolic Blood Pressure (DBP) | 360 min post-dose | 62 mmHg | Standard Deviation 8.8 |
| Treatment T1 | Vital Signs: Diastolic Blood Pressure (DBP) | 180 min post-dose | 62 mmHg | Standard Deviation 8.3 |
| Treatment T1 | Vital Signs: Diastolic Blood Pressure (DBP) | 30 min post-dose | 64 mmHg | Standard Deviation 11.2 |
| Treatment T2 | Vital Signs: Diastolic Blood Pressure (DBP) | 60 min post-dose | 64 mmHg | Standard Deviation 10.4 |
| Treatment T2 | Vital Signs: Diastolic Blood Pressure (DBP) | Pre-dose (Baseline) | 61 mmHg | Standard Deviation 11.2 |
| Treatment T2 | Vital Signs: Diastolic Blood Pressure (DBP) | 10 min post-dose | 64 mmHg | Standard Deviation 10 |
| Treatment T2 | Vital Signs: Diastolic Blood Pressure (DBP) | 30 min post-dose | 64 mmHg | Standard Deviation 9.2 |
| Treatment T2 | Vital Signs: Diastolic Blood Pressure (DBP) | 120 min post-dose | 63 mmHg | Standard Deviation 11.9 |
| Treatment T2 | Vital Signs: Diastolic Blood Pressure (DBP) | 180 min post-dose | 60 mmHg | Standard Deviation 9.5 |
| Treatment T2 | Vital Signs: Diastolic Blood Pressure (DBP) | 360 min post-dose | 62 mmHg | Standard Deviation 10.1 |
| Treatment C | Vital Signs: Diastolic Blood Pressure (DBP) | 120 min post-dose | 62 mmHg | Standard Deviation 10.6 |
| Treatment C | Vital Signs: Diastolic Blood Pressure (DBP) | 10 min post-dose | 65 mmHg | Standard Deviation 10.2 |
| Treatment C | Vital Signs: Diastolic Blood Pressure (DBP) | 360 min post-dose | 62 mmHg | Standard Deviation 8 |
| Treatment C | Vital Signs: Diastolic Blood Pressure (DBP) | 180 min post-dose | 59 mmHg | Standard Deviation 7.5 |
| Treatment C | Vital Signs: Diastolic Blood Pressure (DBP) | 60 min post-dose | 63 mmHg | Standard Deviation 8.8 |
| Treatment C | Vital Signs: Diastolic Blood Pressure (DBP) | 30 min post-dose | 65 mmHg | Standard Deviation 9.5 |
| Treatment C | Vital Signs: Diastolic Blood Pressure (DBP) | Pre-dose (Baseline) | 61 mmHg | Standard Deviation 10.8 |
Secondary
Vital Signs: Heart Rate (HR)
Subject vital signs, i.e., blood pressure and heart rate, were measured prior to study drug dosing (baseline) and up to 360 minutes after dosing during the study visit.
Time frame: Pre-dose (baseline) to 360 minutes post-dose
Population: Subjects who have taken any amount of study drug treatment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment T1 | Vital Signs: Heart Rate (HR) | 10 min post-dose | 67 beats per minute | Standard Deviation 14 |
| Treatment T1 | Vital Signs: Heart Rate (HR) | 120 min post-dose | 60 beats per minute | Standard Deviation 10.1 |
| Treatment T1 | Vital Signs: Heart Rate (HR) | 60 min post-dose | 67 beats per minute | Standard Deviation 12.9 |
| Treatment T1 | Vital Signs: Heart Rate (HR) | Pre-dose (Baseline) | 60 beats per minute | Standard Deviation 10.1 |
| Treatment T1 | Vital Signs: Heart Rate (HR) | 360 min post-dose | 64 beats per minute | Standard Deviation 8.7 |
| Treatment T1 | Vital Signs: Heart Rate (HR) | 180 min post-dose | 66 beats per minute | Standard Deviation 11.1 |
| Treatment T1 | Vital Signs: Heart Rate (HR) | 30 min post-dose | 63 beats per minute | Standard Deviation 14.2 |
| Treatment T2 | Vital Signs: Heart Rate (HR) | 60 min post-dose | 67 beats per minute | Standard Deviation 14.4 |
| Treatment T2 | Vital Signs: Heart Rate (HR) | Pre-dose (Baseline) | 62 beats per minute | Standard Deviation 12.2 |
| Treatment T2 | Vital Signs: Heart Rate (HR) | 10 min post-dose | 69 beats per minute | Standard Deviation 12.2 |
| Treatment T2 | Vital Signs: Heart Rate (HR) | 30 min post-dose | 64 beats per minute | Standard Deviation 9.8 |
| Treatment T2 | Vital Signs: Heart Rate (HR) | 120 min post-dose | 60 beats per minute | Standard Deviation 7.1 |
| Treatment T2 | Vital Signs: Heart Rate (HR) | 180 min post-dose | 66 beats per minute | Standard Deviation 10.5 |
| Treatment T2 | Vital Signs: Heart Rate (HR) | 360 min post-dose | 64 beats per minute | Standard Deviation 10.4 |
| Treatment C | Vital Signs: Heart Rate (HR) | 120 min post-dose | 58 beats per minute | Standard Deviation 9.4 |
| Treatment C | Vital Signs: Heart Rate (HR) | 10 min post-dose | 62 beats per minute | Standard Deviation 12.7 |
| Treatment C | Vital Signs: Heart Rate (HR) | 360 min post-dose | 61 beats per minute | Standard Deviation 8.4 |
| Treatment C | Vital Signs: Heart Rate (HR) | 180 min post-dose | 63 beats per minute | Standard Deviation 9.9 |
| Treatment C | Vital Signs: Heart Rate (HR) | 60 min post-dose | 61 beats per minute | Standard Deviation 10.8 |
| Treatment C | Vital Signs: Heart Rate (HR) | 30 min post-dose | 61 beats per minute | Standard Deviation 13.7 |
| Treatment C | Vital Signs: Heart Rate (HR) | Pre-dose (Baseline) | 58 beats per minute | Standard Deviation 11.7 |
Secondary
Vital Signs: Systolic Blood Pressure (SBP)
Subject vital signs, i.e., blood pressure and heart rate, were measured prior to study drug dosing (baseline) and up to 360 minutes after dosing during the study visit.
Time frame: Pre-dose (baseline) to 360 minutes post-dose
Population: Subjects who have taken any amount of study drug treatment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment T1 | Vital Signs: Systolic Blood Pressure (SBP) | 10 min post-dose | 123 mmHg | Standard Deviation 13.8 |
| Treatment T1 | Vital Signs: Systolic Blood Pressure (SBP) | 120 min post-dose | 112 mmHg | Standard Deviation 10.4 |
| Treatment T1 | Vital Signs: Systolic Blood Pressure (SBP) | 60 min post-dose | 113 mmHg | Standard Deviation 11.2 |
| Treatment T1 | Vital Signs: Systolic Blood Pressure (SBP) | Pre-dose (Baseline) | 110 mmHg | Standard Deviation 10 |
| Treatment T1 | Vital Signs: Systolic Blood Pressure (SBP) | 360 min post-dose | 113 mmHg | Standard Deviation 9.8 |
| Treatment T1 | Vital Signs: Systolic Blood Pressure (SBP) | 180 min post-dose | 114 mmHg | Standard Deviation 10.1 |
| Treatment T1 | Vital Signs: Systolic Blood Pressure (SBP) | 30 min post-dose | 116 mmHg | Standard Deviation 12.3 |
| Treatment T2 | Vital Signs: Systolic Blood Pressure (SBP) | 60 min post-dose | 113 mmHg | Standard Deviation 9.9 |
| Treatment T2 | Vital Signs: Systolic Blood Pressure (SBP) | Pre-dose (Baseline) | 112 mmHg | Standard Deviation 13.2 |
| Treatment T2 | Vital Signs: Systolic Blood Pressure (SBP) | 10 min post-dose | 122 mmHg | Standard Deviation 14.1 |
| Treatment T2 | Vital Signs: Systolic Blood Pressure (SBP) | 30 min post-dose | 117 mmHg | Standard Deviation 11.5 |
| Treatment T2 | Vital Signs: Systolic Blood Pressure (SBP) | 120 min post-dose | 114 mmHg | Standard Deviation 9.6 |
| Treatment T2 | Vital Signs: Systolic Blood Pressure (SBP) | 180 min post-dose | 113 mmHg | Standard Deviation 11.4 |
| Treatment T2 | Vital Signs: Systolic Blood Pressure (SBP) | 360 min post-dose | 113 mmHg | Standard Deviation 9.3 |
| Treatment C | Vital Signs: Systolic Blood Pressure (SBP) | 120 min post-dose | 114 mmHg | Standard Deviation 10.9 |
| Treatment C | Vital Signs: Systolic Blood Pressure (SBP) | 10 min post-dose | 121 mmHg | Standard Deviation 11.3 |
| Treatment C | Vital Signs: Systolic Blood Pressure (SBP) | 360 min post-dose | 113 mmHg | Standard Deviation 9.5 |
| Treatment C | Vital Signs: Systolic Blood Pressure (SBP) | 180 min post-dose | 115 mmHg | Standard Deviation 11 |
| Treatment C | Vital Signs: Systolic Blood Pressure (SBP) | 60 min post-dose | 115 mmHg | Standard Deviation 10 |
| Treatment C | Vital Signs: Systolic Blood Pressure (SBP) | 30 min post-dose | 116 mmHg | Standard Deviation 10.6 |
| Treatment C | Vital Signs: Systolic Blood Pressure (SBP) | Pre-dose (Baseline) | 111 mmHg | Standard Deviation 9.4 |