Blood Pressure, Human Experimentation
Conditions
Brief summary
Randomized, placebo-controlled double-blind, crossover design study; 116 subjects randomized on Day 1 to obtain 98 completed subjects. Study will be composed of a 7-day period of therapy with randomized active or placebo treatment with a subsequent 6-8 day washout period, followed by a second 7-day period of double-blind therapy with the other agent. Ambulatory blood pressure measurement will be performed beginning on Day 7 of each treatment period following administration of the study drug.
Interventions
DRUGPhenylephrine Hydrochloride (HCl) Extended-Release tablets 30 mg
Phenylephrine HCl Extended-Release tablets 30 mg taken twice daily (12 hours apart) for 7 days.
DRUGPlacebo
Placebo taken twice daily (12 hours apart) for 7 days.
Sponsors
Bayer
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Healthy, male or female volunteers must be 18 years or older, with a Body Mass Index (BMI) between 19-30 inclusive \[BMI = weight (kilograms)/height (meters squared)\]. * Clinical laboratory tests (complete blood count, blood chemistries, urinalysis), Human Immunodeficiency Virus (HIV) antibodies, hepatitis B surface antigen, hepatitis C antibody must be within normal limits or clinically acceptable to the Investigator/Sponsor. * Drug screen for drugs and alcohol with a high potential for abuse must be negative at screening. * Subjects must be free of any clinically significant disease that requires a physician's care and/or would interfere with study evaluations, procedures or participation. * Subjects must agree not to take a monoamine oxidase inhibitor (MAOI) for two weeks (14 days) prior to study participation and for two weeks (14 days) after the end of their study participation. * Subjects must have normal or clinically acceptable physical exam and Electrocardiogram (ECG) intervals (PR, QRS, QT and QTc) on 12-lead ECG (recorded at 25 millimeters/second \[mm/s\]). * Subjects must have a mean after 5 minute of rest sitting systolic/diastolic office blood pressure ≤ 138/88 millimeters of mercury (mmHg). * Subjects with controlled diabetes prior to entry must have a mean sitting after 5 minute of rest systolic/diastolic office blood pressure ≤ 128/78 mmHg from non-dominated arm * Females must have the urine or serum pregnancy test (Human Chorionic Gonadotropin) that is negative at Screening and Day 1 of Period 1. * Female subjects of childbearing potential must be using medically acceptable birth control measures. * Subjects must understand the dosing schedule. * Subjects must be able to read and write in English.
Exclusion criteria
* Subjects must not have any significant medical condition which, in the judgment of the Investigator, is a contraindication to the use of phenylephrine HCl, might interfere with the study or requires treatment expected to affect the blood pressure. These may include hyperthyroidism, hypothyroidism, uncontrolled diabetes mellitus, coronary heart disease, ischemic heart disease, elevated intraocular pressure, prostatic hypertrophy. * Subjects who have a history of any clinically significant local or systemic infectious disease within four weeks prior to initial treatment administration. * Subjects who have received an investigational drug within 30 days prior to study dosing. * Subjects who are, appear to be, or are known, current or former drug addicts or alcoholics. * Subjects who are positive for hepatitis B surface antigen or hepatitis C antibody. * Subjects who are positive for HIV antibodies. * Subjects who have a clinically significant history of food or drug allergy. * Subjects who have a known allergy or intolerance to phenylephrine HCl. * Females who are pregnant, nursing or unwilling to use/practice adequate contraception (hormonal, Intrauterine Device, barrier method, etc.). * Subjects taking topical or oral decongestant products within 7 days of Visit 2. * Subjects taking antihypertensive medication. * Subjects taking monoamine oxidase inhibitors. * Subjects taking tricyclic antidepressants (e.g. amitriptyline, nortriptyline, imipramine) * Subjects taking antithyroid medication (e.g. propylthiouracil, methimazole, iodides).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Average Systolic Blood Pressure (SBP) Readings for a 5-hour Range Around the Time of Maximum Concentration (Tmax). | 24 hours after final dose of each 7-day treatment period. | Five hour (hr) range around the Tmax was defined as approximately 2 hours before to approximately 2 hours after the Tmax, including Tmax. The parameters will be compared between active drug and placebo using analysis of variance (ANOVA). The 95% 2-sided Confidence Interval (CI) on the difference between treatments will also be presented. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Phenylephrine Followed by Placebo Phenylephrine hydrochloride (HCl) Extended Release tablets 30 mg twice daily for 7 days followed by a 6- to 8-day washout period followed by placebo twice daily for 7 days | 58 |
| Placebo Followed by Phenylephrine Placebo twice daily for 7 days followed by a 6- to 8-day washout period followed by Phenylephrine HCl Extended Release tablets 30 mg twice daily for 7 days | 58 |
| Total | 116 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| First Intervention | Adverse Event | 0 | 1 |
| First Intervention | Lost to Follow-up | 0 | 1 |
| First Intervention | positive drug test | 1 | 0 |
| First Intervention | Protocol Violation | 3 | 0 |
| First Intervention | Withdrawal by Subject | 2 | 0 |
| Second Intervention | Protocol Violation | 1 | 0 |
| Second Intervention | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Phenylephrine Followed by Placebo | Placebo Followed by Phenylephrine | Total |
|---|---|---|---|
| Age, Continuous | 29.4 years STANDARD_DEVIATION 10.14 | 29.0 years STANDARD_DEVIATION 10.99 | 29.2 years STANDARD_DEVIATION 10.53 |
| Sex: Female, Male Female | 29 Participants | 26 Participants | 55 Participants |
| Sex: Female, Male Male | 29 Participants | 32 Participants | 61 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 114 | 0 / 111 |
| serious Total, serious adverse events | 0 / 114 | 0 / 111 |
Outcome results
Primary
Average Systolic Blood Pressure (SBP) Readings for a 5-hour Range Around the Time of Maximum Concentration (Tmax).
Five hour (hr) range around the Tmax was defined as approximately 2 hours before to approximately 2 hours after the Tmax, including Tmax. The parameters will be compared between active drug and placebo using analysis of variance (ANOVA). The 95% 2-sided Confidence Interval (CI) on the difference between treatments will also be presented.
Time frame: 24 hours after final dose of each 7-day treatment period.
Population: The per-protocol population included 100 participants who completed both treatment periods and have 24-hour Ambulatory Blood Pressure Monitoring (ABPM) data for SBP measurements for each study drug, 46 participants who received phenylephrine followed by placebo and 54 participants who received placebo followed by phenylephrine.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Phenylephrine | Average Systolic Blood Pressure (SBP) Readings for a 5-hour Range Around the Time of Maximum Concentration (Tmax). | 118.3 mmHg | Standard Deviation 9.24 |
| Placebo | Average Systolic Blood Pressure (SBP) Readings for a 5-hour Range Around the Time of Maximum Concentration (Tmax). | 118.6 mmHg | Standard Deviation 9.38 |
p-value: 0.54895% CI: [-2, 1.1]ANOVA