Hypertension
Conditions
Keywords
hypertension, controlled hypertension, hypertensives
Brief summary
The objective of this study is to evaluate the safety, tolerability, and pharmacokinetics of subcutaneous (SC) PL-3994, relative to placebo in subjects with controlled hypertension. Including in this evaluation is the effect PL3994 has on blood pressure.
Detailed description
Uncontrolled hypertension, including both hypertensive urgency and hypertensive emergency, is commonly seen in emergency rooms and other urgent care settings. Current standards of care include intravenously administered drugs, which can be difficult to titrate and require ongoing monitoring. This study examines the effect of PL-3994 on patients with controlled hypertension who are receiving antihypertensive medications.
Interventions
DRUGPL3994
Study drug
DRUGPlacebo
Placebo
Sponsors
Palatin Technologies, Inc
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Subjects must have had a diagnosis of essential hypertension for at least 1 year, per subject verbal history * Subject must be on a stable dose of at least one, but not more than 3 antihypertensive medications for at least 3 months, per subject verbal history. * Subject must have a systolic blood pressure at screening between 100 and 150 mmHg, and diastolic blood pressure must not exceed 105 mmHg.
Exclusion criteria
* Subject weight greater than 100 kg or less than 50 kg. * Any significant medical condition or abnormal safety laboratory results which, in the judgement of the Investigator would place the subject at significant risk.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics of Subcutaneous (SC) PL-3994 Relative to Placebo in Subjects With Controlled Hypertension. | 24 hours | The pharmacokinetic profile parameters for PL-3994 were calculated using a non compartmental approach. •Maximum concentration (Cmax) The subject numbers below are the evaluable subjects only. The Evaluable Subjects population consisted of subjects who received study drug and who had no major protocol deviations that would have excluded the subject from analysis, and for whom calculations of PK parameters were possible. |
| Pharmacodynamics as Measured by cGMP Levels. | 24 hours | Pharmacodynamic parameters were calculated from the baseline-adjusted plasma cGMP level-time data using WinNonlin® 5.0.1. Actual sample times were used in the calculations. Baseline was the pre-dose levels of plasma cGMP at Visit 2 (Day 1): Emax The patient numbers below represent the evaluable subjects only. The Evaluable Subjects population consisted of subjects who received study drug and who had no major protocol deviations that would have excluded the subject from analysis, and for whom calculations of PD parameters were possible. |
Participant flow
Recruitment details
Initiation Date: 28 April 2008 Completion Date: 21 July 2008 Cohort 1: 6 subjects: PL-3994 0.3 µg/kg; 1 subject Placebo Cohort 2: 6 subjects: PL-3994 0.1 µg/kg; 1 subject Placebo Cohort 3: 6 subjects: PL-3994 0.3 µg/kg; 1 subject Placebo; Study stopped after Cohort 3.
Pre-assignment details
Some results (i.e.Pharmacodynamic results) may include analyses only for the Evaluable Subjects population.The Evaluable Subjects population consisted of subjects who received study drug and who had no major protocol deviations that would have excluded the subject from analysis, and for whom calculations of PK or PD parameters were possible.
Participants by arm
| Arm | Count |
|---|---|
| PL-3994 0.1 µg/kg PL-3994 0.1 µg/kg | 6 |
| PL-3994 0.3 µg/kg PL-3994 0.3 µg/kg | 12 |
| Placebo Placebo | 3 |
| Total | 21 |
Baseline characteristics
| Characteristic | PL-3994 0.3 µg/kg | Placebo | PL-3994 0.1 µg/kg | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 12 Participants | 3 Participants | 6 Participants | 21 Participants |
| Age Continuous | 51.7 years STANDARD_DEVIATION 5.42 | 59.3 years STANDARD_DEVIATION 5.13 | 53.5 years STANDARD_DEVIATION 5.24 | 53.3 years STANDARD_DEVIATION 5.72 |
| Region of Enrollment United States | 12 participants | 3 participants | 6 participants | 21 participants |
| Sex: Female, Male Female | 5 Participants | 2 Participants | 3 Participants | 10 Participants |
| Sex: Female, Male Male | 7 Participants | 1 Participants | 3 Participants | 11 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 / 6 | 6 / 12 | 3 / 3 |
| serious Total, serious adverse events | 0 / 6 | 0 / 12 | 0 / 3 |
Outcome results
Primary
Pharmacodynamics as Measured by cGMP Levels.
Pharmacodynamic parameters were calculated from the baseline-adjusted plasma cGMP level-time data using WinNonlin® 5.0.1. Actual sample times were used in the calculations. Baseline was the pre-dose levels of plasma cGMP at Visit 2 (Day 1): Emax The patient numbers below represent the evaluable subjects only. The Evaluable Subjects population consisted of subjects who received study drug and who had no major protocol deviations that would have excluded the subject from analysis, and for whom calculations of PD parameters were possible.
Time frame: 24 hours
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| PL-3994 0.1 µg/kg | Pharmacodynamics as Measured by cGMP Levels. | 0.996 ng/mL |
| PL-3994 0.3 µg/kg | Pharmacodynamics as Measured by cGMP Levels. | 1.435 ng/mL |
| Placebo | Pharmacodynamics as Measured by cGMP Levels. | 0.676 ng/mL |
Primary
Pharmacokinetics of Subcutaneous (SC) PL-3994 Relative to Placebo in Subjects With Controlled Hypertension.
The pharmacokinetic profile parameters for PL-3994 were calculated using a non compartmental approach. •Maximum concentration (Cmax) The subject numbers below are the evaluable subjects only. The Evaluable Subjects population consisted of subjects who received study drug and who had no major protocol deviations that would have excluded the subject from analysis, and for whom calculations of PK parameters were possible.
Time frame: 24 hours
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PL-3994 0.1 µg/kg | Pharmacokinetics of Subcutaneous (SC) PL-3994 Relative to Placebo in Subjects With Controlled Hypertension. | 0 ng/mL | Standard Deviation 0 |
| PL-3994 0.3 µg/kg | Pharmacokinetics of Subcutaneous (SC) PL-3994 Relative to Placebo in Subjects With Controlled Hypertension. | 0.366 ng/mL | Standard Deviation 0.0656 |
| Placebo | Pharmacokinetics of Subcutaneous (SC) PL-3994 Relative to Placebo in Subjects With Controlled Hypertension. | 0 ng/mL | Standard Deviation 0 |