Fixed-Dose Combination of Perindopril/Amlodipine (Amlessa®) and Fixed-Dose Combination of Perindopril/Indapamide /Amlodipine (Co-Amlessa®) - Contribution to Management in newly diagnosed and uncontrolled hypertensive patients (PRECIOUS study)

• Register: EUCTR
• Last refreshed on: 16 November 2020
• Main ID: EUCTR2017-001596-23-HR
• Date of registration: 19/04/2018
• Prospective Registration: No
• Primary sponsor: Krka, d.d., Novo mesto
• Public title: Fixed-Dose Combination of Perindopril/Amlodipine (Amlessa®) and Fixed-Dose Combination of Perindopril/Indapamide /Amlodipine (Co-Amlessa®) - Contribution to Management in newly diagnosed and uncontrolled hypertensive patients (PRECIOUS study)
• Scientific title: Fixed-Dose Combination of Perindopril/Amlodipine (Amlessa®) and Fixed-Dose Combination of Perindopril/Indapamide /Amlodipine (Co-Amlessa®) - Contribution to Management in newly diagnosed and uncontrolled hypertensive patients (PRECIOUS study)
• Date of first enrolment: 09/04/2018
• Target sample size: 570
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2017-001596-23
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: no Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: no
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): yes

Countries of recruitment

Armenia, Croatia, Hungary, Poland, Russian Federation, Serbia, Slovenia, Ukraine

Contacts

• Name: Clinical Trials Information
• Affiliation: KRKA-FARMA d.o.o.

• Name: Clinical Trials Information
• Affiliation: KRKA-FARMA d.o.o.

Key inclusion & exclusion criteria

Inclusion criteria:
• Patients with essential arterial hypertension.*
• Men and women aged = 18 years.
• Written informed consent.
• Ability to adhere to study protocol.

*Additional inclusion criteria for Amlessa®:
• Patients with essential arterial hypertension:

o Naïve patients with systolic blood pressure (SBP) from 150 mmHg or higher AND/OR diastolic blood pressure (DBP) from 95 mmHg or higher (SBP = 150 AND/OR DBP = 90 mmHg for patients with type 2 diabetes mellitus)

o Uncontrolled patients on antihypertensive monotherapy with SBP from 140 mmHg or higher AND/OR DBP from 90 mmHg or higher (SBP = 140 AND/OR DBP = 85 mmHg for patients with type 2 diabetes mellitus).

o Uncontrolled patients on dual antihypertensive therapy (either in monoforms or FDC) with SBP from 140 mmHg or higher AND/OR DBP from 90 mmHg or higher (SBP = 140 AND/OR DBP = 85 mmHg for patients with type 2 diabetes mellitus).

*Additional inclusion criteria for Co-Amlessa®:
• Patients with essential arterial hypertension (AH):

o Uncontrolled patients on dual antihypertensive therapy (either in monoforms or FDC, including perindopril+amlodipine combination) with SBP from 140 mmHg or higher AND/OR DBP from 90 mmHg or higher (SBP = 140 AND/OR DBP = 85 mmHg for patients with type 2 diabetes mellitus).

o Uncontrolled patients on triple antihypertensive therapy (either in monoforms or FDC) with SBP from 140 mmHg or higher AND/OR DBP from 90 mmHg or higher (SBP = 140 AND/OR DBP = 85 mmHg for patients with type 2 diabetes mellitus).

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 285
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 285

Exclusion criteria:
• History of adverse reactions or hypersensitivity associated with the use of the active substances, or any other components of the Investigational medicinal products (IMPs) used in the trial.
• Hereditary/idiopathic angioedema.
• Known secondary AH (e.g. pheochromocytoma, primary aldosteronism, renal artery stenosis)
• Office measured Systolic blood pressure =200 mmHg
• Unstable angina pectoris.
• Acute heart failure and heart failure NYHA IV.
• Antihypertensive drugs used for other indication than AH (e.g. tachyarrhythmia, glaucoma) less than 3 months before the study or in changed dosages less than 3 months before the study
• Severe liver impairment OR biliary cirrhosis OR cholestasis OR hepatic encephalopathy
• Renal dysfunction - GFR <60 ml/min (bilateral renal artery stenosis, renal artery stenosis in a solitary kidney, patients with only 1 kidney, or post-renal transplant patients, dialysis patients
• Any of the following clinically relevant laboratory or ECG findings
- significant anaemia with haemoglobin less than 100 g/l,
- serum AST and/or ALT and/or ALP and/or GammaGT of more than 3 x ULN (upper limit of normal)
- hyperkalaemia (serum potassium of more than 5 mmol/l)
- A-V block grade 2 or 3
- ECG signs of acute ischemia
• Concurrent therapy with:
o aliskiren-containing products (in patients with diabetes mellitus or renal impairment)
o Lithium
o Estramustine
o Any “not allowed” medication(s) listed in Study protocol section 6.2
• Bradycardia with heart rate less than 50/min.
• Female patients who are pregnant, planning to become pregnant.
• Breastfeeding female patients.
• Any significant acute condition (severe infection, exacerbation or uncontrolled phase of a chronic disease, major trauma, major surgery) within 30 days prior to screening visit.
• Pathological clinical states (e.g. malignant diseases, excessive alcohol consumption, drug abuse or drug addiction, psychiatric conditions) or any life-threatening illness.
• Patients currently participating in another clinical trial.
• Patient’s refusal to participate with the investigator.
• Normal average 24-hour SBP and DBP obtained by ABPM (<130/80 mmHg at baseline).
• Severe orthostatic hypotension.
• Patients to whom ß-blocker therapy cannot be discountinued in one day.
• Previous or current therapy with perindopril and amlodipine and indapamide taken concomitantly all together as 3 separate tablets or as a fixed-dose combination.
• In Amlessa® arm patients on previous or current therapy with perindopril and amlodipine taken concomitantly all together as 2 separate tablets or as a fixed-dose combination. (this exclusion criterion does not apply to Co-Amlessa® arm).


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]

Newly diagnosed and uncontrolled patients with essential arterial hypertension.
MedDRA version: 20.0 Level: PT Classification code 10015488 Term: Essential hypertension System Organ Class: 10047065 - Vascular disorders

Intervention(s)

Trade Name: Dalneva®
Pharmaceutical Form: Tablet
INN or Proposed INN: PERINDOPRIL TERT-BUTYLAMINE
Other descriptive name: PERINDOPRIL TERT-BUTYLAMINE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 4-
INN or Proposed INN: AMLODIPINE
Other descriptive name: AMLODIPINE BESILATE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 5-

Trade Name: Dalneva®
Pharmaceutical Form: Tablet
INN or Proposed INN: PERINDOPRIL TERT-BUTYLAMINE
Other descriptive name: PERINDOPRIL TERT-BUTYLAMINE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 8-
INN or Proposed INN: AMLODIPINE
Other descriptive name: AMLODIPINE BESILATE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 5-

Trade Name: Dalneva®
Pharmaceutical Form: Tablet
INN or Proposed INN: PERINDOPRIL TERT-BUTYLAMINE
Other descriptive name: PERINDOPRIL TERT-BUTYLAMINE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 8-
INN or Proposed INN: AMLODIPINE
Other descriptive name: AMLODIPINE BESILATE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 10-

Trade Name: Co-Dalneva®
Pharmaceutical Form: Tablet
INN or Proposed INN: PERINDOPRIL TERT-BUTYLAMINE
Other descriptive name: PERINDOPRIL TERT-BUTYLAMINE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 4-
INN or Proposed INN: INDAPAMIDE
CAS Number: 26807-65-8
Other descriptive name: INDAPAMIDE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 1.25-
INN or Proposed INN: AMLODIPINE
Other descriptive name: AMLODIPINE BESILATE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 5-

Trade Name:

Primary Outcome(s)

Primary end point(s): Responder rate after 16 weeks (visit 5): proportion of patients reaching normal office blood pressure (NBP)*.
* Normal (office) blood pressure (NBP): SBP < 140 mmHg and DBP < 90 mmHg; patients with type 2 diabetes mellitus: SBP < 140 mmHg and DBP < 85 mmHg)

Main Objective: The purpose of the study is to establish the efficacy and safety of fixed-dose combination (FDC) of perindopril/amlodipine (Amlessa®) and fixed-dose combination of perindopril/indapamide/amlodipine (Co-Amlessa®) in wide populations of uncontrolled patients with arterial hypertension (AH) with special focus on effective continuous 24-hour blood pressure (BP) control. The purpose is also to establish the correlation between 24-hour central and peripheral BP.

Secondary Objective: Not applicable

Timepoint(s) of evaluation of this end point: After 16 weeks of treatment

Secondary Outcome(s)

Secondary end point(s): o Responder rate after 4 (visit 2), 8 (visit 3) and 12 weeks (visit 4): proportion of patients reaching office NBP*.
o Mean absolute and relative change from baseline in office SBP and DBP after 4, 8, 12 and 16 weeks (Visit 2, 3, 4, 5).
o Mean absolute and relative changes from baseline to 16 weeks in average 24-hour SBP and DBP, average awake time SBP and DBP, and average sleep time SBP and DBP, all obtained by ABPM.
o Responder rate after 16 weeks (visit 5) in average 24-hour SBP and DBP, average awake time SBP and DBP, and average sleep time SBP and DBP, all obtained by ABPM: proportion of patients reaching normal average 24h ABPM SBP and DBP (<130/80), normal average awake time SBP and DBP (<135/85) and normal average sleep time SBP and DBP (<120/70).
o Proportion of patients reaching a reduction of office SBP by at least 20 mmHg or DBP by at least 10 mmHg from baseline after 16 weeks.
o Proportion of patients reaching a reduction of central (systolic) blood pressure parameters (in 24-hour measurement) below 120 mmHg from baseline after 16 weeks.
o Proportion of patients reaching a reduction of pulse wave velocity (in 24-hour measurement) for at least 0,5 m/s from baseline after 16 weeks.
o Proportion of patients reaching a reduction of SBP and DBP variability expressed as reduction of day-night standard deviation (SDdn) by at least 0.5 and that of average real variability (ARV) by at least 0.5.

Timepoint(s) of evaluation of this end point: After 4, 8, 12 and 16 weeks of treatment

Secondary ID(s)

2017-001596-23-PL

KCT06/2017-PRECIOUS

Source(s) of Monetary Support

Krka, d.d., Novo mesto

Ethics review

Status: Approved
Approval date: 31/01/2018
Contact:

Results

• Results available: Yes
• Date Posted: 01/11/2020
• Date Completed: 27/09/2019
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2017-001596-23/results