2QG1 is a Phase IIa study aiming to assess the blood pressure lowering effect of 4-week administration of QGC001 oral doses in patients with grade I or II essential hypertension compared to placebo, to assess the safety and tolerability, to obtain preliminary PK information for QGC001 given as multiple oral doses and to determine preliminary PD profile of QGC001 multiple oral doses on plasma and urine hormones, which will be compared to that of placebo.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
34
Hôpital Arthur Gardiner
Dinard, France
Hôpital Cardiologique, CHRU de Lille
Lille, France
Hospices Civils de Lyon - Hôpital de la Croix Rousse
Lyon, France
Hôpital Européen Georges Pompidou
Paris, France
Efficacy - 24h ABPM
Measurements will include mean 24h systolic and diastolic pressures, and daytime values (measured every 15 min from 07:00 am to 10:00 pm) and night-time values (measured every 20 min from 10:00 pm to 07:00 am). Only ambulatory BP recordings with a minimum of 24 measurements will be considered as successful.
Time frame: Change from Period 1 to Period 2 up to 16 weeks (end-of-study visit).
Efficacy - Self BP measurements at home
Additional information will be obtained from self-measurement of BP at home (HBP) with an automatic validated device. To be performed for 7 consecutive days just before the planned visit.
Time frame: Change from Period 1 to Period 2 up to 16 weeks.
Efficacy - Office BP measurements
Office SBP, DBP and HR measured after resting in the semi-recumbent position for at least 5 min. Office SBP, DBP and HR measured after 1 min in a standing position will be recorded at each visit, immediately before the administration of the study drug.
Time frame: Change from Period 1 to Period 2 up to 16 weeks.
Efficacy - Hormonal measurements
The pharmacodynamic neurohormonal effects of QGC001 will be assessed by measurements of plasma active renin, aldosterone, cortisol, adrenocorticotropic hormone (ACTH), apelin and copeptin as well as urine aldosterone, cortisol, creatinine, sodium and potassium using commercially available validated assays.
Time frame: Change from Period 1 to Period 2 up to 16 weeks.
Pharmacokinetics - Plasma levels of QGC001
Four (4) PK blood samples will be taken. Plasma levels of QGC001 and its metabolite EC33 will be measured using validated LC/MS/MS methods.
Time frame: Change from Period 1 to Period 2 up to 16 weeks.
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Pharmacokinetics - Plasma levels of EC33
Four (4) PK blood samples will be taken. Plasma levels of QGC001 and its metabolite EC33 will be measured using validated LC/MS/MS methods.
Time frame: Change from Period 1 to Period 2 up to 16 weeks.
Safety - Reported signs and symptoms
Patients will report to the center at approximately 08:00 am, without having taken their morning dose, to undergo safety assessments.
Time frame: Change from Period 1 to Period 2 up to 16 weeks.
Safety - Physical examination
The physical examinations will be performed by the investigator or his/her representatives.
Time frame: Change from Period 1 to Period 2 up to 16 weeks.
Safety - Vital sign measurements
For OBP measurements, three consecutive (2 min interval) SBP/DBP measurements will be done with an adapted cuff after resting in the semi-recumbent position for at least 5 min using a validated oscillometric semi-automatic device. In addition, SBP, DBP and HR will be measured after 1 min in a standing position.
Time frame: Change from Period 1 to Period 2 up to 16 weeks.
Safety - Adverse events
Time frame: Change from Period 1 to Period 2 up to 16 weeks.
Safety - Morisky Medication Adherence Questionnaire
Time frame: Change from Period 1 to Period 2 up to 16 weeks.
Safety - Electrocardiogram
The measurements will consist of a 12-lead digital ECG.
Time frame: Change from Period 1 to Period 2 up to 16 weeks.
Safety - Clinical laboratory tests
These include blood cells count, fasting glucose, sodium, potassium, chlorides, bicarbonates, creatinine, uric acid, total proteins, total cholesterol, high density lipoprotein (HDL) cholesterol, triglycerides, aspartate aminotransferase (ASAT), alanine aminotransferase (ALAT), bilirubin, gamma glutamyl transferase (GammaGT), alkaline phosphatases.
Time frame: Change from Period 1 to Period 2 up to 16 weeks.