Primary Aldosteronism MedDRA version: 20.0 Level: LLT Classification code 10001656 Term: Aldosteronism System Organ Class: 100000004860
Conditions
Interventions
Product Name: DP13
Product Code: DP13
Pharmaceutical Form: Capsule
INN or Proposed INN: FADROZOLE
CAS Number: 102676-47-1
Current Sponsor code: DP13
Other descriptive name: 5R-(+)-Fadrozole-Enantiomer
Sponsors
DAMIAN Pharma AG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion 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 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 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 = 1.75 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 Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 35 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 1
Exclusion criteria
Exclusion 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, or 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 5.5. are unable to follow all study procedures
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: • To determine the efficacy of daily oral DP13 treatment (all dose arms combined) to decrease the plasma aldosterone-to-renin ratio (ARR) from baseline in patients with primary aldosteronism (PA) • To determine the efficacy of daily oral DP13 treatment (all dose arms combined) to reduce 24-hour ambulatory systolic blood pressure (aSBP) from baseline in patients with PA;Secondary Objective: • To determine the safety and tolerability of DP13 treatment in patients with PA • To determine the efficacy of daily oral DP13 treatment (all dose arms combined) to reduce office systolic blood pressure (oSBP) from baseline in patients with PA • To determine the efficacy of daily oral DP13 treatment to decrease the plasma ARR from baseline in each individual dose arm • To determine the efficacy of daily oral DP13 treatment to reduce 24-hour aSBP from baseline in each individual dose arm • To determine the efficacy of daily oral DP13 treatment to reduce oSBP from baseline in each individual dose arm • To determine the dose-dependent efficacy of daily oral DP13 treatment to decrease the ARR from baseline in patients with PA • To determine the dose-dependent efficacy of daily oral DP13 treatment to reduce 24- hour aSBP from baseline in patients with PA • To determine the dose-dependent efficacy of daily oral DP13 treatment to reduce oSBP from baseline in patients with PA;Primary end point(s): • Change in the plasma ARR for all dose arms combined • Change in mean 24-hour aSBP for all dose arms combined;Timepoint(s) of evaluation of this end point: • from baseline (Day 1) to the end of the 8-week daily oral DP13 treatment period (Day 56) • from baseline (Day 1) to the end of the 8-week daily oral DP13 treatment period (Day 56) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Occurrence of treatment-emergent adverse events (TEAE) and serious adverse events (SAE) • Change in oSBP for all dose arms combined • Change in the plasma ARR in each individual dose arm • Change in 24-hour aSBP in each individual dose arm • Change in oSBP from baseline in each individual dose arm;Timepoint(s) of evaluation of this end point: • over the entire study duration • from baseline (Day 1) to the end of the 8-week daily oral DP13 treatment period (Day 56) • from baseline (Day 1) to biweekly visits (week 2, week 4, week 6) and to the end of the 8-week daily oral DP13 treatment period (Day 56) • from baseline (Day 1) to biweekly visits (week 2, week 4, week 6) and to the end of the 8-week daily oral DP13 treatment period (Day 56) • from baseline (Day 1) to biweekly visits (week 2, week 4, week 6) and to the end of the 8-week daily oral DP13 treatment period (Day 56) | — |
Countries
Italy, Netherlands, Switzerland
Contacts
Public ContactChristoph Schumacher
DAMIAN Pharma AG
Outcome results
None listed