DP13 * A Phase II Study in Patients with Primary Aldosteronism to Evaluate the Efficacy, Safety and Tolerability of the Aldosterone Synthase Inhibitor, DP13, over an 8-week Treatment Period

Phase 2

Completed

Conditions: Hormonal diseases
Primary Aldosteronism

Registration Number: NL-OMON54894

Lead Sponsor: DAMIAN Pharma AG

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Completed

Sex: Not specified

Target Recruitment: 15

Inclusion Criteria

Patients will be required to satisfy all of the following eligibility criteria:
1. Patients with a guideline-recommended diagnosis of PA consisting of:
1.1. ARR *40 derived from a PAC *15 ng/dL and a PRA <1.0 ng/mL/h; an ARR *3.7
is derived with PRC <15 mU/L instead of PRA as denominator
and
1.2. PAC >7.0 ng/dL after a 4-hour infusion of 2 litres 0.9% saline (saline
load suppression test) or instead if clinically justified for risk of volume
expansion ARR>30 and PAC >11 ng/dL (respectively ARR>2.4 with PRC in mU/L
instead of PRA as denominator) after 2 hours of an oral intake of 50 mg
captopril
and
1.3. determined within <1 year of study enrolment
2. Patients with PA per above criteria and
2.1. sitting office systolic blood pressure (oSBP) >145 mmHg
and if applicable
2.2. in presence of non-interfering hypertension control therapy consisting of
doxazosin (1 * 8 mg QD) as first-line medication and, if necessary, only
verapamil slow release (40 * 120 mg BID) or diltiazem (slow-release 90 - 360 mg
daily) or amlodipine (2.5 * 10 mg QD) at adjusted and fixed doses
3. Patients with PA per above criteria will have a:
3.1. estimated glomerular filtration rate (eGFR) *45 mL/min/1.73 m2 using the
MDRD-4 GFR equation: GFR <= 175 x [serum creatinine (mg/dL)]-1.154 x (age)-0.203
x f*
*f<=1.000 for men; f<=0.742 for women; the formula is further multiplied by
factor 1.210 for black skinned patients
3.2. body mass index (BMI) between 18 and 34 kg/m2, inclusive
3.3. body weight between 40 and 110 kg, inclusive
4. Patients with PA per above criteria will be:
4.1. female or male patients between 18 and 65 years of age, inclusive
4.2. able to provide voluntary informed written consent to study enrolment

Exclusion Criteria

Patients will be excluded from the study if they satisfy any of the following
criteria:
1. Patients with PA and:
1.1. treated with spironolactone within 2 months of enrolment
1.2. hyperkalaemia of >5.0 mmol/L
1.3. prolonged QT intervals with QTc of >500 msec using Bazett*s formula
2. Patients with PA and:
2.1. sitting office systolic office blood pressure (oSBP) >190 mmHg
and/or
2.2. sitting office diastolic office blood pressure (oDBP) >110 mmHg
and if applicable
2.3. in presence of non-interfering hypertension control therapy consisting of
doxazosin (1 * 8 mg QD) as first-line medication and, if necessary, only
verapamil slow release (40 * 120 mg BID) or diltiazem (slow-release 90 - 360 mg
daily) or amlodipine (2.5 * 10 mg QD) at adjusted and fixed doses
3. Patients with PA who will not consent to special contraception measures
during the entire study period, specifically
3.1. female patients not withdrawing oral contraceptives >2 weeks prior to
enrolment
3.2. female patients not using intrauterine devices (IUD), diaphragm, sponge
with spermicide
3.3. male patients not using condoms and not refraining from sperm donation
4. Patients with PA and a medical history of:
4.1. cerebro- and cardiovascular events (stroke, myocardial infarction,
percutaneous transluminal coronary angioplasty, long QT syndrome, Brugada
syndrome, acute heart failure) within 6 months of study enrolment
4.2. gastrointestinal tract surgeries or malabsorption syndromes
4.3. chronic use of oral or parenteral corticosteroids
4.4. use of drugs prolonging the QT interval (e.g., digoxin, sotalol)
5. Patients with PA who:
5.1. participated in any clinical study within 6 weeks
5.2. suffered a significant blood loss within <2 months
5.3. had a significant illness within <2 weeks
5.4. are pregnant or breastfeeding are unable to follow all study procedures

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>* Change in the plasma aldosterone-to-renin ratio (ARR) from baseline (Day 1)<br /><br>to the end of the 8-week daily oral DP13 treatment period (Day 56) for all dose<br /><br>arms combined<br /><br>* Change in mean 24-hour ambulatory systolic blood pressure (aSBP) from<br /><br>baseline (Day 1) to the end of the 8-week daily oral DP13 treatment period (Day<br /><br>56) for all dose arms combined</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>* Occurrence of treatment-emergent adverse events (TEAE) and serious adverse<br /><br>events (SAE) over the entire study duration<br /><br>* Change in systolic blood pressure (oSBP) from baseline (Day 1) to the end of<br /><br>the 8-week daily oral DP13 treatment period (Day 56) for all dose arms combined<br /><br>* Change in the plasma ARR from baseline (Day 1) to biweekly visits (week 2,<br /><br>week 4, week 6) and to the end of the 8-week daily oral DP13 treatment period<br /><br>(Day 56) in each individual dose arm<br /><br>* Change in 24-hour aSBP from baseline (Day 1) to the end of the 8-week daily<br /><br>oral DP13 treatment period (Day 56) in each individual dose arm<br /><br>* Change in oSBP from baseline (Day 1) to biweekly visits (week 2, week 4, week<br /><br>6) and to the end of the 8-week daily oral DP13 treatment period (Day 56) in<br /><br>each individual dose arm</p><br>