Hypertension, Stage I, Prehypertension
Conditions
Keywords
elevated blood pressure
Brief summary
The purpose of this study is to evaluate and compare the efficacy of B244 in treating patients with hypertension.
Detailed description
This is a Prospective, Vehicle Controlled, Double Blinded, Multicenter, Randomized Phase II trial, comparing the effect of twice daily B244 application for 4 weeks vs vehicle application on BP and inflammatory biomarkers.
Interventions
BIOLOGICALB244
odorless suspension
BIOLOGICALVehicle
odorless suspension
Sponsors
Veristat, Inc.
AOBiome LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male and female subjects ≥18 years of age * In good general health as determined by a thorough medical history and physical examination, and vital signs * Clinical diagnosis of elevated Blood Pressure defined as: * Having systolic prehypertension measurements having systolic BP (mmHg) of 120-139 and Diastolic BP (mmHg) of 90 * OR * Having systolic Stage 1 hypertension measurements having systolic BP (mmHg) of 140-159 and Diastolic BP (mmHg) of 100 * Hypertension treatment naïve patients, defined as those patients who have never been treated with antihypertensive medications or have been off any hypertensive treatment for a period of 12 weeks or longer. * Willing to refrain from using any antihypertensive treatments, other than the investigational product, including herbal supplements, systemic use of steroids, chronic use of NSAIDS, any antihypertensive agents, such as beta-blockers, diuretics, ACE inhibitors, CA channel blockers, Alpha blockers, Central Acting agents and vasodilators. * Ability to comprehend and comply with procedures * Agree to commit to participate in the current protocol * Provide written informed consent prior to any study procedure being performed (all subjects should be able to understand the informed consent form and any other documents that subjects are required to read)
Exclusion criteria
* Pregnant and/or lactating women * Patients on treatment for Benign Prostatic Hyperplasia (BPH) * Clinically significant history of cardiovascular disease (i. e. PCI, CABG MI (if event occurred 12 months), atrial fibrillation, frequent PAC, cardiac rhythm disorder, syncope, valve repair/replacement, heart transplantation, PTA, peripheral bypass surgery, endarterectomy, unstable angina, TIA, stroke and NYHF category II, II and IV heart failure. * Patients with renal failure, significant kidney or renal disease defined as having creatinine level of mg/dL * Presence of any condition (medical, psychological, social, or geographical), actual or anticipated, that the Investigator feels would restrict or limit the patient's successful participation for the duration of the study * History of migraines and/or anxiety, where patient is unable to refrain from the use of beta blockers * History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy that, in the opinion of the Investigator or Medical Monitor, contraindicates their participation. * The participant has been previously randomized in this study * Subjects with clinical diagnosis of Type I Diabetes * Subjects with arm circumference of 42 cm * Any condition that would prevent the subject from participating in the trial in the opinion of the evaluation physician * The participant has received an investigational product within 30 days prior to randomization * Prior use of any product containing B244 or Nitrosomonas eutropha * Unable to lie flat or sit for 15 minutes * Concurrent participation in other trials
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0 | Baseline-6 weeks | Safety and tolerability endpoints will consist of all treatment related adverse events reporting during the study duration. |
| Difference in Mean in Clinic Systolic BP Between the Active and Vehicle Groups | Baseline-Week 4 | Clinical systolic blood pressure (BP) readings were obtained at every visit using a calibrated electronic sphygmomanometer. Three measurements were taken at each visit. The average of the second and third readings was documented. Data was analyzed using mixed-effects model repeated measures (MMRM). Difference was calculated as the change from Baseline to Day 28. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Difference in Mean in Clinic Diastolic BP Between the Active and Vehicle Group | Baseline-Week 4 | Clinical diastolic blood pressure (BP) readings were obtained at every visit using a calibrated electronic sphygmomanometer. Three measurements were taken at each visit. The average of the second and third readings was documented. Data was analyzed using mixed-effects model repeated measures (MMRM). Difference was calculated as the change from Baseline to Day 28. |
| Difference in Mean Ambulatory Systolic and Diastolic Daytime Blood Pressure | Baseline-Week 4 | An ambulatory blood pressure measurement (ABPM) device was placed on a subject's arm during the clinic visit to record 24-hour blood pressure and heart rate measurements. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Microbial Content | Baseline, Day 28, Day 42 | Evaluate if B244 administration on skin twice daily will affect the microbial content on collected skin swab samples. |
| Microbial Composition | Baseline, Day 28, Day 42 | Evaluate if B244 administration on skin twice daily will affect the microbial composition on collected skin samples. |
| Difference in Inflammatory Biomarkers Between Active and Vehicle Groups | Baseline-Week 4 | To evaluate if B244 administration on the skin twice daily will affect the levels of immune biomarkers. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| B244 4 Pumps Applied to the Face 4 pumps total of spray to saturate the entire face. Applications should occur in the morning and at night for 4 weeks.
B244: odorless suspension, 8x10E9 cells/mL | 33 |
| B 244 8 Pumps Applied to Face and Torso 8 pumps total - 4 pumps of spray to saturate the entire face and 4 pumps to the torso Applications should occur in the morning and at night for 4 weeks.
B244: odorless suspension, 8x10E9 cells/mL | 33 |
| Vehicle 4 Pumps Applied to the Face 4 pumps total of spray to saturate the entire face. Applications should occur in the morning and at night for 4 weeks.
Vehicle: odorless suspension | 33 |
| Vehicle 8 Pumps Applied to Face and Torso 8 pumps total - 4 pumps of spray to saturate the entire face and 4 pumps to the torso Applications should occur in the morning and at night for 4 weeks.
Vehicle: odorless suspension | 33 |
| Total | 132 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 1 | 1 | 2 | 3 |
| Overall Study | Unplanned travel, family emergency, sponsor request, work schedule | 2 | 1 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 1 | 0 | 1 |
Baseline characteristics
| Characteristic | Total | Vehicle 8 Pumps Applied to Face and Torso | B244 4 Pumps Applied to the Face | Vehicle 4 Pumps Applied to the Face | B 244 8 Pumps Applied to Face and Torso |
|---|---|---|---|---|---|
| Age, Customized <60 years | 100 Participants | 27 Participants | 25 Participants | 25 Participants | 23 Participants |
| Age, Customized ≥60 years | 32 Participants | 6 Participants | 8 Participants | 8 Participants | 10 Participants |
| BMI | 30.044 kg/m^2 STANDARD_DEVIATION 5.7332 | 30.304 kg/m^2 STANDARD_DEVIATION 6.3886 | 30.139 kg/m^2 STANDARD_DEVIATION 6.2438 | 29.306 kg/m^2 STANDARD_DEVIATION 4.3707 | 30.427 kg/m^2 STANDARD_DEVIATION 5.9047 |
| BMI Category <30 kg/m^2 | 77 Participants | 22 Participants | 19 Participants | 20 Participants | 16 Participants |
| BMI Category ≥30 kg/m^2 | 55 Participants | 11 Participants | 14 Participants | 13 Participants | 17 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 38 Participants | 12 Participants | 9 Participants | 11 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 94 Participants | 21 Participants | 24 Participants | 22 Participants | 27 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 2 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 36 Participants | 9 Participants | 8 Participants | 6 Participants | 13 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 90 Participants | 22 Participants | 23 Participants | 26 Participants | 19 Participants |
| Sex: Female, Male Female | 62 Participants | 17 Participants | 15 Participants | 13 Participants | 17 Participants |
| Sex: Female, Male Male | 70 Participants | 16 Participants | 18 Participants | 20 Participants | 16 Participants |
| Smoking History Current | 28 Participants | 11 Participants | 8 Participants | 5 Participants | 4 Participants |
| Smoking History Former | 22 Participants | 3 Participants | 6 Participants | 6 Participants | 7 Participants |
| Smoking History Never | 82 Participants | 19 Participants | 19 Participants | 22 Participants | 22 Participants |
| Weight | 88.38 kg STANDARD_DEVIATION 18.654 | 88.59 kg STANDARD_DEVIATION 18.871 | 89.32 kg STANDARD_DEVIATION 21.084 | 86.56 kg STANDARD_DEVIATION 12.251 | 89.04 kg STANDARD_DEVIATION 21.654 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 33 | 0 / 33 | 0 / 66 |
| other Total, other adverse events | 4 / 33 | 6 / 33 | 11 / 66 |
| serious Total, serious adverse events | 0 / 33 | 1 / 33 | 0 / 66 |
Outcome results
Primary
Difference in Mean in Clinic Systolic BP Between the Active and Vehicle Groups
Clinical systolic blood pressure (BP) readings were obtained at every visit using a calibrated electronic sphygmomanometer. Three measurements were taken at each visit. The average of the second and third readings was documented. Data was analyzed using mixed-effects model repeated measures (MMRM). Difference was calculated as the change from Baseline to Day 28.
Time frame: Baseline-Week 4
Population: Subjects from the Intent to Treat (ITT) population (all randomized subjects, analyzed according to treatment assigned) that remained in the study at Week 4.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| B244 4 Pumps Applied to the Face | Difference in Mean in Clinic Systolic BP Between the Active and Vehicle Groups | -2.61 mmHg | Standard Deviation 1.828 |
| B 244 8 Pumps Applied to Face and Torso | Difference in Mean in Clinic Systolic BP Between the Active and Vehicle Groups | -0.66 mmHg | Standard Deviation 1.834 |
| Pooled Vehicle 4 or 8 Pumps Applied to the Face (and Torso for 8 Pumps) | Difference in Mean in Clinic Systolic BP Between the Active and Vehicle Groups | -2.93 mmHg | Standard Deviation 1.296 |
Primary
Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0
Safety and tolerability endpoints will consist of all treatment related adverse events reporting during the study duration.
Time frame: Baseline-6 weeks
Population: Safety Population: All subjects who received at least 1 dose of study medication. Subjects were to be analyzed according to the study drug received.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| B244 4 Pumps Applied to the Face | Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0 | At Least 1 Treatment Related TEAE | 1 Participants |
| B244 4 Pumps Applied to the Face | Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0 | At Least 1 Treatment Related Serious TEAE | 0 Participants |
| B 244 8 Pumps Applied to Face and Torso | Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0 | At Least 1 Treatment Related TEAE | 1 Participants |
| B 244 8 Pumps Applied to Face and Torso | Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0 | At Least 1 Treatment Related Serious TEAE | 0 Participants |
| Pooled Vehicle 4 or 8 Pumps Applied to the Face (and Torso for 8 Pumps) | Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0 | At Least 1 Treatment Related Serious TEAE | 0 Participants |
| Pooled Vehicle 4 or 8 Pumps Applied to the Face (and Torso for 8 Pumps) | Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0 | At Least 1 Treatment Related TEAE | 4 Participants |
Secondary
Difference in Mean Ambulatory Systolic and Diastolic Daytime Blood Pressure
An ambulatory blood pressure measurement (ABPM) device was placed on a subject's arm during the clinic visit to record 24-hour blood pressure and heart rate measurements.
Time frame: Baseline-Week 4
Population: Ambulatory Blood Pressure Monitoring Population (ABPP): Subjects in the Safety Population who had valid baseline and Day 28 ambulatory BP monitoring (ABPM) measurements. Subjects who repeated the ABPM were to be included in the population if the repeated assessment met the device monitor's criteria for passing.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| B244 4 Pumps Applied to the Face | Difference in Mean Ambulatory Systolic and Diastolic Daytime Blood Pressure | Systolic Blood Pressure | -3.06 mmHg | Standard Deviation 9.388 |
| B244 4 Pumps Applied to the Face | Difference in Mean Ambulatory Systolic and Diastolic Daytime Blood Pressure | Diastolic Blood Pressure | -2.17 mmHg | Standard Deviation 5.327 |
| B 244 8 Pumps Applied to Face and Torso | Difference in Mean Ambulatory Systolic and Diastolic Daytime Blood Pressure | Systolic Blood Pressure | -0.21 mmHg | Standard Deviation 12.25 |
| B 244 8 Pumps Applied to Face and Torso | Difference in Mean Ambulatory Systolic and Diastolic Daytime Blood Pressure | Diastolic Blood Pressure | -0.82 mmHg | Standard Deviation 7.325 |
| Pooled Vehicle 4 or 8 Pumps Applied to the Face (and Torso for 8 Pumps) | Difference in Mean Ambulatory Systolic and Diastolic Daytime Blood Pressure | Diastolic Blood Pressure | -0.98 mmHg | Standard Deviation 5.911 |
| Pooled Vehicle 4 or 8 Pumps Applied to the Face (and Torso for 8 Pumps) | Difference in Mean Ambulatory Systolic and Diastolic Daytime Blood Pressure | Systolic Blood Pressure | -0.53 mmHg | Standard Deviation 7.619 |
Secondary
Difference in Mean in Clinic Diastolic BP Between the Active and Vehicle Group
Clinical diastolic blood pressure (BP) readings were obtained at every visit using a calibrated electronic sphygmomanometer. Three measurements were taken at each visit. The average of the second and third readings was documented. Data was analyzed using mixed-effects model repeated measures (MMRM). Difference was calculated as the change from Baseline to Day 28.
Time frame: Baseline-Week 4
Population: Subjects from the Intent to Treat (ITT) population (all randomized subjects, analyzed according to treatment assigned) that remained in the study at Week 4.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| B244 4 Pumps Applied to the Face | Difference in Mean in Clinic Diastolic BP Between the Active and Vehicle Group | -1.65 mmHg | Standard Deviation 1.377 |
| B 244 8 Pumps Applied to Face and Torso | Difference in Mean in Clinic Diastolic BP Between the Active and Vehicle Group | -2.25 mmHg | Standard Deviation 1.358 |
| Pooled Vehicle 4 or 8 Pumps Applied to the Face (and Torso for 8 Pumps) | Difference in Mean in Clinic Diastolic BP Between the Active and Vehicle Group | -1.31 mmHg | Standard Deviation 0.975 |
Other Pre-specified
Difference in Inflammatory Biomarkers Between Active and Vehicle Groups
To evaluate if B244 administration on the skin twice daily will affect the levels of immune biomarkers.
Time frame: Baseline-Week 4
Population: Intent to Treat Population (ITT): All randomized subjects, analyzed according to treatment assigned.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| B244 4 Pumps Applied to the Face | Difference in Inflammatory Biomarkers Between Active and Vehicle Groups | NA units on a scale |
| B 244 8 Pumps Applied to Face and Torso | Difference in Inflammatory Biomarkers Between Active and Vehicle Groups | NA units on a scale |
| Pooled Vehicle 4 or 8 Pumps Applied to the Face (and Torso for 8 Pumps) | Difference in Inflammatory Biomarkers Between Active and Vehicle Groups | NA units on a scale |
Other Pre-specified
Microbial Composition
Evaluate if B244 administration on skin twice daily will affect the microbial composition on collected skin samples.
Time frame: Baseline, Day 28, Day 42
Population: Data was not collected for this exploratory endpoint.
Other Pre-specified
Microbial Content
Evaluate if B244 administration on skin twice daily will affect the microbial content on collected skin swab samples.
Time frame: Baseline, Day 28, Day 42
Population: Data was not collected for this exploratory endpoint.