Primary Aldosteronism
Conditions
Keywords
Hyperaldosteronism
Brief summary
The purpose of the present phase II study is to determine whether DP13 displays the clinical safety and efficacy profile to support further development in patients with primary aldosteronism.
Detailed description
A phase II, multi-centre, randomized, parallel group, baseline-and withdrawal-controlled study in patients with primary aldosteronism to determine the dose-dependent efficacy, safety and tolerability of DP13 after a 2-week single-blind placebo run-in period followed by a randomized 8-week double-blind treatment period. After an additional single-blind, 2-week DP13 placebo withdrawal period, patients are switched to standard of care.
Interventions
DRUGdexfadrostat phosphate
DP13 systemic administration
Sponsors
Damian Pharma AG
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
Patients with a guideline-recommended diagnosis of primary aldosteronism
Exclusion criteria
Patients with primary aldosteronism and * hyperkalemia * prolonged QT intervals * refusal of special contraception measures
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Aldosterone-to-renin Ratio | 8 weeks | Change from baseline in aldosterone-to-renin ratio (ARR) after 8 weeks of dexfadrostat phosphate treatment by dose group. |
| Change in Ambulatory Systolic Blood Pressure | 8 weeks | All patients receiving at least one dose of dexfadrostat phosphate; analysis of all dose arms combined. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Potassium | 8 weeks | Change from baseline after 8 weeks of treatment with dexfadrostat phosphate |
| Change in Ambulatory Diastolic Blood Pressure | 8 weeks | Change from baseline following 8-weeks of dexfadrostat phosphate treatment |
| Change in 24-hour Urinary Tetrahydroaldosterone Content (uTHA) | 8 weeks | Change from baseline in urinary tetrahydroaldosterone content (uTHA) following 8 weeks of treatment with dexfadrostat phosphate |
Countries
Italy
Participant flow
Recruitment details
Patients were recruited 'de novo' i.e., diagnosed with Primary Aldosteronism within 10 weeks of study entry or as 'recently diagnosed' i.e., diagnosed between 10 weeks and 1 year prior to study entry
Pre-assignment details
Patient screening ARR and BP were reviewed and approved by the Eligibility Review Panel prior to study enrollment. A suppression test was required prior to study entry to confirm PA diagnosis. Patients had a 2-week placebo run-in prior to randomization.
Participants by arm
| Arm | Count |
|---|---|
| 4 mg DP13 Baseline values were determined following 2 weeks of single-blind placebo run-in | 10 |
| 8 mg DP13 Baseline values were determined following 2 weeks of single-blind placebo run-in | 12 |
| 12 mg DP13 Baseline values were determined following 2 weeks of single-blind placebo run-in | 13 |
| Total | 35 |
Baseline characteristics
| Characteristic | 4 mg DP13 | 8 mg DP13 | 12 mg DP13 | Total |
|---|---|---|---|---|
| 24-hour ambulatory diastolic blood pressure (aDBP) | 84 mmHg STANDARD_DEVIATION 9 | 90 mmHg STANDARD_DEVIATION 7 | 89 mmHg STANDARD_DEVIATION 7 | 88 mmHg STANDARD_DEVIATION 8 |
| 24-hour ambulatory systolic blood pressure (aSBP) | 137 mmHg STANDARD_DEVIATION 16 | 145 mmHg STANDARD_DEVIATION 14 | 145 mmHg STANDARD_DEVIATION 13 | 143 mmHg STANDARD_DEVIATION 14 |
| 24-hour Urinary Tetrahydroaldosterone Content (uTHA) | 80.0 ug/24h | 59.5 ug/24h | 69.0 ug/24h | 67.0 ug/24h |
| 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 | 10 Participants | 12 Participants | 13 Participants | 35 Participants |
| Aldosterone-to-renin ratio (ARR) | 21.4 ng*L/dL*mU | 7.2 ng*L/dL*mU | 17.8 ng*L/dL*mU | 15.3 ng*L/dL*mU |
| Office diastolic blood pressure (oDBP) | 90 mmHg STANDARD_DEVIATION 11 | 95 mmHg STANDARD_DEVIATION 9 | 92 mmHg STANDARD_DEVIATION 9 | 92 mmHg STANDARD_DEVIATION 10 |
| Office systolic blood pressure (oSBP) | 147 mmHg STANDARD_DEVIATION 14 | 148 mmHg STANDARD_DEVIATION 6 | 148 mmHg STANDARD_DEVIATION 14 | 148 mmHg STANDARD_DEVIATION 12 |
| Potassium | 3.36 mmol/L STANDARD_DEVIATION 0.45 | 3.55 mmol/L STANDARD_DEVIATION 0.31 | 3.54 mmol/L STANDARD_DEVIATION 0.41 | 3.49 mmol/L STANDARD_DEVIATION 0.39 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 1 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 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 |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 9 Participants | 11 Participants | 13 Participants | 33 Participants |
| Region of Enrollment Italy | 7 participants | 7 participants | 9 participants | 23 participants |
| Region of Enrollment Netherlands | 0 participants | 1 participants | 1 participants | 2 participants |
| Region of Enrollment Switzerland | 3 participants | 4 participants | 3 participants | 10 participants |
| Sex: Female, Male Female | 3 Participants | 3 Participants | 3 Participants | 9 Participants |
| Sex: Female, Male Male | 7 Participants | 9 Participants | 10 Participants | 26 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 10 | 0 / 12 | 0 / 13 |
| other Total, other adverse events | 4 / 10 | 6 / 12 | 7 / 13 |
| serious Total, serious adverse events | 0 / 10 | 0 / 12 | 0 / 13 |
Outcome results
Primary
Change in Aldosterone-to-renin Ratio
Change from baseline in aldosterone-to-renin ratio (ARR) after 8 weeks of dexfadrostat phosphate treatment by dose group.
Time frame: 8 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 4 mg DP13 | Change in Aldosterone-to-renin Ratio | -15.0 ng*L/dL*mU |
| 8 mg DP13 | Change in Aldosterone-to-renin Ratio | -7.0 ng*L/dL*mU |
| 12 mg DP13 | Change in Aldosterone-to-renin Ratio | -14.0 ng*L/dL*mU |
| All Dose Arms Combined | Change in Aldosterone-to-renin Ratio | -11.8 ng*L/dL*mU |
p-value: <0.0001Mixed Models Analysis
Primary
Change in Ambulatory Systolic Blood Pressure
All patients receiving at least one dose of dexfadrostat phosphate; analysis of all dose arms combined.
Time frame: 8 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 4 mg DP13 | Change in Ambulatory Systolic Blood Pressure | -8 mm Hg | Standard Deviation 10 |
| 8 mg DP13 | Change in Ambulatory Systolic Blood Pressure | -14 mm Hg | Standard Deviation 8 |
| 12 mg DP13 | Change in Ambulatory Systolic Blood Pressure | -10 mm Hg | Standard Deviation 9 |
| All Dose Arms Combined | Change in Ambulatory Systolic Blood Pressure | -11 mm Hg | Standard Deviation 9 |
p-value: <0.0001Mixed Models Analysis
Secondary
Change in 24-hour Urinary Tetrahydroaldosterone Content (uTHA)
Change from baseline in urinary tetrahydroaldosterone content (uTHA) following 8 weeks of treatment with dexfadrostat phosphate
Time frame: 8 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 4 mg DP13 | Change in 24-hour Urinary Tetrahydroaldosterone Content (uTHA) | -61.0 ug/24 hour urine |
| 8 mg DP13 | Change in 24-hour Urinary Tetrahydroaldosterone Content (uTHA) | -50.0 ug/24 hour urine |
| 12 mg DP13 | Change in 24-hour Urinary Tetrahydroaldosterone Content (uTHA) | -66.0 ug/24 hour urine |
p-value: <0.0001Mixed Models Analysis
Secondary
Change in Ambulatory Diastolic Blood Pressure
Change from baseline following 8-weeks of dexfadrostat phosphate treatment
Time frame: 8 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 4 mg DP13 | Change in Ambulatory Diastolic Blood Pressure | -4.5 mm Hg | Standard Deviation 7 |
| 8 mg DP13 | Change in Ambulatory Diastolic Blood Pressure | -7.9 mm Hg | Standard Deviation 6.4 |
| 12 mg DP13 | Change in Ambulatory Diastolic Blood Pressure | -4.5 mm Hg | Standard Deviation 7 |
p-value: <0.0001Mixed Models Analysis
Secondary
Change in Potassium
Change from baseline after 8 weeks of treatment with dexfadrostat phosphate
Time frame: 8 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 4 mg DP13 | Change in Potassium | 0.74 mmol/L | Standard Deviation 0.51 |
| 8 mg DP13 | Change in Potassium | 0.55 mmol/L | Standard Deviation 0.29 |
| 12 mg DP13 | Change in Potassium | 0.28 mmol/L | Standard Deviation 0.55 |
p-value: <0.0001Mixed Models Analysis