Essential HypertensionPhase 1NCT01873885
Phase 1, Randomized, Double-Blind, Placebo-Controlled Exploratory Study That Will Assess the Safety, Tolerability, Pharmacokinetics and Hemodynamic Response to a Single 30 Minute Intravenous Infusion of Vasomera™ (PB1046) in Adult Subjects With Stage 1 or 2 Essential Hypertension
A Phase 1 study testing Experimental: Single IV Infusion Vasomera (PB1046) in people with Essential Hypertension, run by PhaseBio Pharmaceuticals Inc. at 1 site in United States.
Trial summary
This study is an exploratory Phase 1 randomized, double-blind (Investigator and study subject and 2-D echo endpoint assessor), placebo-controlled single IV infusion dose escalation study that will enroll up to approximately 32 subjects with stage 1 or 2 essential hypertension. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Essential Hypertension
- What is being tested?
- Experimental: Single IV Infusion Vasomera (PB1046)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 20 participants
- Where
- 1 siteUnited States
- Study dates
- Jun 2013to Mar 2014
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Willing and able to sign a written informed consent and follow all study related procedures.
- Males or females age 18 - 80 years of age inclusive.
- Male and female subjects of childbearing potential must be willing and able to practice effective contraception during the study, and be willing and able to continue contraception for 1 month (30 days) after their last dose of study drug.
- BMI ≥ 20 but ≤ 40 kg/m2
- Diagnosed with essential hypertension and are currently taking one or more antihypertensive medications to control their blood pressure and, who in the opinion of the investigator, could be safely withdrawn from antihypertensive therapy.
Who cannot join
- Known allergy to the study drug or any of its components, or who have previously received Vasomera (PB1046).
- Inadequate "imaging window" by echocardiography as determined by screening echocardiography (core assessment), or cardiac abnormalities that may confound echocardiography readings (i.e., mitral regurgitation, "floppy-valve" syndrome) for evaluation of secondary study endpoints.
- Seated systolic blood pressure <120 mmHg or diastolic blood pressure < 80 mmHg (confirmed in triplicate) at randomization (Day -1) or prior to the first dose of study drug (V3 Day 0) will exclude the subject from participation.
- Evidence of sustained elevation in systolic blood pressure >169 mmHg or diastolic blood pressure >109 mmHg prior to dosing (Day 0) during the washout period which in the opinion of the investigator would place the subject at risk for continued study participation (i.e., can not be safely withdrawn from antihypertensive therapy).
- Clinically significant changes in health status or concomitant prescription medications within 2 weeks prior to dosing (V3 Day 0) that could place the subject at risk for dosing with study drug or confound the primary or secondary outcome measures as assessed by the Investigator.
- Unstable/underlying cardiovascular disease defined as: a. Congestive heart failure (NYHA class III-IV), stroke, transient ischemic attack, unstable angina pectoris, or myocardial infarction within the 6 months prior to screening (V1) b. Mean triplicate 12-lead ECG demonstrating a QT interval (corrected using Fridericia's formula (QTcF)) >450 msec in males and >470 msec in females at Screening, (V1) or a history or evidence of long QT syndrome. c. Sustained heart rate >100 beats per minute (BPM) (at rest) at screening (V1), prior to randomization (V3 Day -1), or prior to dosing (V3 Day 0). d. Any episode of atrial fibrillation, ventricular tachycardia (defined as ten (10) or more beats with heart rate greater than 130 beats per minute), ventricular fibrillation, firing of an implantable cardiac defibrillator (ICD) for documented ventricular ectopy, or other clinically significant documented arrhythmias within 3 months prior to administration of study drug (V3 Day 0).
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- Uncontrolled diabetes defined as a Hemoglobin A1c > 10.0%. Note: only applicable for subjects with a known or suspected history of diabetes.
- Clinically significant renal and/or hepatic dysfunction at Screening (V1) or at baseline (V3 Day -1).
- Pregnant or lactating females.
- Known history of or active drug or alcohol abuse within the 12 months prior to screening (V1) and/or positive drug screen (for illicit drugs) or detection of alcohol at baseline.
- Positive for Human Immunodeficiency Virus (HIV) antibodies, hepatitis B surface antigen (HBsAg) or hepatitis C virus (HCV) antibodies.
- Participation in any other study and have received any other investigational drug or device within 30 days prior to the Screening visit or are taking part in a non-drug study which in the opinion of the Investigator would interfere with the outcome of the study.
- Major surgery, donated or lost > or = 1 unit of blood (approximately 500 mL) within 30 days prior to Screening (V1) or display evidence of volume depletion (i.e., postural hypotension) prior to randomization (V3 Day -1) or dosing (V3 Day 0).
- Other medical or psychiatric condition which in the opinion of the Investigator would place the subject at increased risk, would preclude obtaining voluntary consent, or would confound the results of the study.
Trial locations and contacts
1 site in 1 country.
United States1 site
New Orleans Center for Clinical Research - Knoxville
Knoxville, Tennessee, 37920
About this study
This study is an exploratory Phase 1 randomized, double-blind (Investigator and study subject and 2-D echo endpoint assessor), placebo-controlled single IV infusion dose escalation study that will enroll up to approximately 32 subjects with stage 1 or 2 essential hypertension.
Read the detailed description
The study will be conducted in two parts.
Part 1: For the initial evaluation of safety, pharmacokinetic exposure and pharmacodynamic response, subjects will be tapered off antihypertensive background therapy.The initial starting dose will be a sub-therapeutic dose. Dose escalation will continue with a maximum of a doubling of the previous dose until either 1) a maximum tolerated dose (MTD) is identified or 2) modeling of the pharmacokinetic (PK) data indicate that maximum exposure (Cmax) at the next planned dose level would exceed a maximum drug concentration (Cmax) which was the maximum observed drug concentration following a single subcutaneous administration in Study PB1046-PT-CL-0001.
Part 2: The dose group which is capable of providing a Cmax exposure which is capable of eliciting a clinically relevant hemodynamic response, will be expanded to enroll an additional 12 subjects (6 active and 6 placebo).
- Conditions
- Essential Hypertension
- Being tested
- Placebo Single IV (Intravenous) Infusion, Experimental: Single IV Infusion Vasomera (PB1046)
- Keywords
- PB1046, VIP, Essential Hypertension, Vasomera
- Medical subject headings
- Essential Hypertension
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Placebo Single IV (Intravenous) InfusionDrug
0.9% Sodium Chloride - 30 minute IV infusion
Experimental: Single IV Infusion Vasomera (PB1046)Drug
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1: Single IV Infusion Vasomera (PB1046) or Placebo | Experimental | Cohort 1 - Single 30 minute infusion Vasomera (PB1046) at 0.01 mg/kg diluted in 0.9% Sodium Chloride or Placebo (0.9% Sodium Chloride) Receives: Drug: Placebo Single IV (Intravenous) Infusion; Drug: Experimental: Single IV Infusion Vasomera (PB1046) |
| Cohort 2: Single IV Infusion Vasomera (PB1046) or Placebo | Experimental | Cohort 2 - Single 30 minute infusion Vasomera (PB1046) at 0.005mg/kg in 0.9% Sodium Chloride or Placebo (0.9% Sodium Chloride) Receives: Drug: Placebo Single IV (Intravenous) Infusion; Drug: Experimental: Single IV Infusion Vasomera (PB1046) |
| Cohort 3: Single IV Infusion Vasomera (PB1046) or Placebo | Experimental | Cohort 3 - Single 30 minute infusion Vasomera (PB1046) at 0.02mg/kg 0.9% Sodium Chloride or Placebo (0.9% Sodium Chloride) Receives: Drug: Placebo Single IV (Intravenous) Infusion; Drug: Experimental: Single IV Infusion Vasomera (PB1046) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety and Tolerability
To evaluate the safety and tolerability of single ascending doses of Vasomera administered as a 30 minute intravenous (IV) infusion to subjects with stage 1 or stage 2 essential hypertension.
- Incidence and severity of adverse events (AEs) and their relationship to Vasomera (including AEs of interest, i.e., incidence and severity of gastrointestinal effects, and infusion site reactions)
- Changes in vital signs, ECGs, safety laboratory parameters, heart rhythm via telemetry monitor from baseline
Measured: Days -45 to 28: Vital signs (Days -45, -14, -1, 0, 1, 2, 3, 4, 7, 14 and 28), ECGs (Days -45, -1, 0, 1 and 2), Safety Labs (Days -45, -1, 1, 7 and 28), and Telemetry (Days -1, 0 and 1)
Pharmacokinetic Profile
To evaluate the pharmacokinetic profile of single ascending doses of Vasomera administered as a 30 minute intravenous (IV) infusion to subjects with stage 1 or stage 2 essential hypertension.
- Elimination Half-life (t½)
- Area under the concentration curve from time 0 to infinity (AUC0-inf)
- Area under the curve to the final sample
- Time to maximum concentration (Tmax)
- Maximum serum concentration (Cmax)
- Elimination rate constant (Lambda-z)
- Clearance (CL)
- Distribution (Vz)
- Compartmental modeling - If the graphical presentations of the individual subject serum concentrations vs. time suggest that a compartmental model may be consistent with the data, then an appropriate compartmental model will be fit to the data.
Measured: Days 0, 1, 2, 3, and 4
Secondary outcomes (2)
Hemodynamic Parameters
Compare changes in hemodynamic parameters as measured by serial systolic and diastolic blood pressure (BP) measurements and echocardiography compared to placebo.
Change from baseline in systolic and diastolic BP and heart rate (HR).
Change from baseline in two-dimensional echocardiography parameters which may include:
- BP and HR
- Left ventricular (LV) internal diameter in diastole and in systole, wall thickness in diastole, outflow tract diameter in mid-systole, volumes in end-diastole and end-systole, and outflow tract flow-time velocity integral
- Ascending aorta peak flow velocity
- Transmitral flow velocity pattern
- Doppler tissue imaging of tricuspid, septal and mitral annulus
- Left atrial volume
- Derivation of: LV Ejection Fraction, LV Stroke Volume and Index, LV Cardiac Output and Index, Ejection Time, Systemic Vascular Resistance, Mitral E and A velocities, LV and index, Myocardial tissue velocities S' and e'.
Measured: Days -14, 0, 1, 2, 3, 4, 7, 14 and 28
Immunogenicity Assessment
Evaluate if subjects elicit an immune response to study drug and if that response cross reacts with related endogenous compounds following a single 30 minute IV infusion.
Measured: Days 0, 14 and 28
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Jun 2013 (estimated)
- Study startJun 2013
- Primary completionMar 2014
- Study completionMar 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Essential HypertensionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- PhaseBio Pharmaceuticals Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- William B. Smith, MD, Principal investigator, New Orleans Center for Clinical Research- Knoxville
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01873885
- Sponsor's protocol ID
- PB1046-PT-CL-0002
- Status last verified
- Apr 2014
- First submitted
- 6 Jun 2013
- Last updated
- 10 Apr 2014
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 10 Apr 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 1, Randomized, Double-Blind, Placebo-Controlled Exploratory Study That Will Assess the Safety, Tolerability, Pharmacokinetics and Hemodynamic Response to a Single 30 Minute Intravenous Infusion of Vasomera™ (PB1046) in Adult Subjects With Stage 1 or 2 Essential Hypertension
- ClinicalTrials.gov ID
- NCT01873885
- Acronym / sponsor ID
- PB1046-PT-CL-0002
- Conditions
- Essential Hypertension
- Keywords
- PB1046, VIP, Essential Hypertension, Vasomera
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- PhaseBio Pharmaceuticals Inc.Industry (pharma, biotech, devices)
- Study start
- Jun 2013
- Primary completion
- Mar 2014 (actual)
- Study completion
- Mar 2014 (actual)
- First posted
- 10 Jun 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study is an exploratory Phase 1 randomized, double-blind (Investigator and study subject and 2-D echo endpoint assessor), placebo-controlled single IV infusion dose escalation study that will enroll up to approximately 32 subjects with stage 1 or 2 essential hypertension.
Detailed description
The study will be conducted in two parts.
Part 1: For the initial evaluation of safety, pharmacokinetic exposure and pharmacodynamic response, subjects will be tapered off antihypertensive background therapy.The initial starting dose will be a sub-therapeutic dose. Dose escalation will continue with a maximum of a doubling of the previous dose until either 1) a maximum tolerated dose (MTD) is identified or 2) modeling of the pharmacokinetic (PK) data indicate that maximum exposure (Cmax) at the next planned dose level would exceed a maximum drug concentration (Cmax) which was the maximum observed drug concentration following a single subcutaneous administration in Study PB1046-PT-CL-0001.
Part 2: The dose group which is capable of providing a Cmax exposure which is capable of eliciting a clinically relevant hemodynamic response, will be expanded to enroll an additional 12 subjects (6 active and 6 placebo).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Cohort 1: Single IV Infusion Vasomera (PB1046) or Placebo | Experimental | Drug: Placebo Single IV (Intravenous) Infusion, Drug: Experimental: Single IV Infusion Vasomera (PB1046)Cohort 1 - Single 30 minute infusion Vasomera (PB1046) at 0.01 mg/kg diluted in 0.9% Sodium Chloride or Placebo (0.9% Sodium Chloride) |
| Cohort 2: Single IV Infusion Vasomera (PB1046) or Placebo | Experimental | Drug: Placebo Single IV (Intravenous) Infusion, Drug: Experimental: Single IV Infusion Vasomera (PB1046)Cohort 2 - Single 30 minute infusion Vasomera (PB1046) at 0.005mg/kg in 0.9% Sodium Chloride or Placebo (0.9% Sodium Chloride) |
| Cohort 3: Single IV Infusion Vasomera (PB1046) or Placebo | Experimental | Drug: Placebo Single IV (Intravenous) Infusion, Drug: Experimental: Single IV Infusion Vasomera (PB1046)Cohort 3 - Single 30 minute infusion Vasomera (PB1046) at 0.02mg/kg 0.9% Sodium Chloride or Placebo (0.9% Sodium Chloride) |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Willing and able to sign a written informed consent and follow all study related procedures.
- Males or females age 18 - 80 years of age inclusive.
- Male and female subjects of childbearing potential must be willing and able to practice effective contraception during the study, and be willing and able to continue contraception for 1 month (30 days) after their last dose of study drug.
- BMI ≥ 20 but ≤ 40 kg/m2
- Diagnosed with essential hypertension and are currently taking one or more antihypertensive medications to control their blood pressure and, who in the opinion of the investigator, could be safely withdrawn from antihypertensive therapy.
Key exclusion criteria (14 listed)
- Known allergy to the study drug or any of its components, or who have previously received Vasomera (PB1046).
- Inadequate "imaging window" by echocardiography as determined by screening echocardiography (core assessment), or cardiac abnormalities that may confound echocardiography readings (i.e., mitral regurgitation, "floppy-valve" syndrome) for evaluation of secondary study endpoints.
- Seated systolic blood pressure <120 mmHg or diastolic blood pressure < 80 mmHg (confirmed in triplicate) at randomization (Day -1) or prior to the first dose of study drug (V3 Day 0) will exclude the subject from participation.
- Evidence of sustained elevation in systolic blood pressure >169 mmHg or diastolic blood pressure >109 mmHg prior to dosing (Day 0) during the washout period which in the opinion of the investigator would place the subject at risk for continued study participation (i.e., can not be safely withdrawn from antihypertensive therapy).
- Clinically significant changes in health status or concomitant prescription medications within 2 weeks prior to dosing (V3 Day 0) that could place the subject at risk for dosing with study drug or confound the primary or secondary outcome measures as assessed by the Investigator.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Placebo Single IV (Intravenous) Infusion0.9% Sodium Chloride - 30 minute IV infusion | Drug | Cohort 1: Single IV Infusion Vasomera (PB1046) or Placebo, Cohort 2: Single IV Infusion Vasomera (PB1046) or Placebo, Cohort 3: Single IV Infusion Vasomera (PB1046) or Placebo |
| Experimental: Single IV Infusion Vasomera (PB1046) | Drug | Cohort 1: Single IV Infusion Vasomera (PB1046) or Placebo, Cohort 2: Single IV Infusion Vasomera (PB1046) or Placebo, Cohort 3: Single IV Infusion Vasomera (PB1046) or Placebo |
Primary outcome
Safety and Tolerability
Time frame: Days -45 to 28: Vital signs (Days -45, -14, -1, 0, 1, 2, 3, 4, 7, 14 and 28), ECGs (Days -45, -1, 0, 1 and 2), Safety Labs (Days -45, -1, 1, 7 and 28), and Telemetry (Days -1, 0 and 1)
To evaluate the safety and tolerability of single ascending doses of Vasomera administered as a 30 minute intravenous (IV) infusion to subjects with stage 1 or stage 2 essential hypertension. * Incidence and severity of adverse events (AEs) and their relationship to Vasomera (including AEs of interest, i.e., incidence and severity of gastrointestinal effects, and infusion site reactions) * Changes in vital signs, ECGs, safety laboratory parameters, heart rhythm via telemetry monitor from baseline
Pharmacokinetic Profile
Time frame: Days 0, 1, 2, 3, and 4
To evaluate the pharmacokinetic profile of single ascending doses of Vasomera administered as a 30 minute intravenous (IV) infusion to subjects with stage 1 or stage 2 essential hypertension. * Elimination Half-life (t½) * Area under the concentration curve from time 0 to infinity (AUC0-inf) * Area under the curve to the final sample * Time to maximum concentration (Tmax) * Maximum serum concentration (Cmax) * Elimination rate constant (Lambda-z) * Clearance (CL) * Distribution (Vz) * Compartmental modeling - If the graphical presentations of the individual subject serum concentrations vs. time suggest that a compartmental model may be consistent with the data, then an appropriate compartmental model will be fit to the data.
2 secondary outcomes
Hemodynamic Parameters
Time frame: Days -14, 0, 1, 2, 3, 4, 7, 14 and 28
Immunogenicity Assessment
Time frame: Days 0, 14 and 28
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Apr 2014.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
William B. Smith, MD principal investigator
New Orleans Center for Clinical Research- Knoxville
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Experimental: Single IV Infusion Vasomera (PB1046) in people with Essential Hypertension, run by PhaseBio Pharmaceuticals Inc. at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 10 Apr 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety and Tolerability (time frame: Days -45 to 28: Vital signs (Days -45, -14, -1, 0, 1, 2, 3, 4, 7, 14 and 28), ECGs (Days -45, -1, 0, 1 and 2), Safety Labs (Days -45, -1, 1, 7 and 28), and Telemetry (Days -1, 0 and 1)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Apr 2014.