Essential HypertensionPhase 22QG1NCT02322450
Phase IIa Study of the Product QGC001 Compared With Placebo in Patients With Essential Hypertension
A Phase 2 study testing QGC001 in people with Essential Hypertension, run by Quantum Genomics SA at 4 sites in France.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Essential Hypertension
- What is being tested?
- QGC001
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 34 participants
- Where
- 4 sitesFrance
- Study dates
- Jan 2015to Apr 2016
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male and female of non-childbearing potential patients (post-menopausal since at least 12 months or surgically sterilized) aged 18 to 75 years;
- Body weight ≥50 kg with a body mass index (BMI) calculated as weight in kg/(height in m2) from 18 to 40 kg/m2 at screening;
- A signed and dated informed consent form before any study-specific screening procedure is performed;
- With a diagnosis of essential grade I or II hypertension defined as:
- a supine office systolic BP (SBP) of 140-159 mmHg or diastolic BP (DBP) of 90-99 mmHg who should have an additional clinical indication according to ESH guidelines for antihypertensive treatment after a 2-week placebo run-in period,
- or a supine office SBP of 160-179 mmHg or DBP of 100-109 mmHg after a 2-week placebo run-in period with a diagnosis of essential grade II hypertension;
- Diagnosis of permanent hypertension confirmed by a mean SBP or DBP higher than135 or 85 mmHg on daytime ambulatory blood pressure monitoring (ABPM) after a 2-week placebo run-in period;
- Estimated glomerular filtration rate (Modification of Diet in Renal Disease (MDRD) formula) ≥ 60 ml/min/1.73 m2.
Who cannot join
- Any significant hepatic, renal, respiratory (e.g., asthma), gastrointestinal, endocrine (e.g., diabetes, dyslipidemia necessitating drug therapy), immunologic, dermatological, hematological, neurologic, psychiatric disease or history of any clinically important drug allergy;
- Acute disease state (e.g., vomiting, fever, diarrhea) within 7 days before study day 1;
- Any history of transient ischemic accident (TIA) or cerebrovascular accident (CVA);
- Any history of acute heart failure or heart failure;
- Any history of myocardial infarction, unstable angina, coronary bypass or percutaneous coronary angioplasty;
- History of malignant tumor during the past 5 years;
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- Any medical or surgical disorder considered by the investigator as increasing the risks of participation in the study, or liable to prevent the patient from complying with the requirements of the study or from continuing the study to completion;
- Any situation which, in the investigator's opinion, might compromise assessment of efficacy or of safety;
- History of non-adherence to treatment;
- History of drug abuse within 1 year before study day 1;
- History of alcoholism within 1 year before day 1;
- Positive serologic findings for human immunodeficiency virus (HIV) antibodies, hepatitis B surface antigen (HBsAg), and/or hepatitis C virus (HCV) antibodies;
- Use of any investigational drug within 30 days before IMP administration;
- Donation of blood (i.e., 500 ml) within 90 days before study day 1;
- Known secondary hypertension;
- Grade III hypertension;
- Estimated glomerular filtration rate (MDRD formula) below 60 ml/min/1.73 m2 ;
- Type I diabetes mellitus or uncontrolled type II diabetes mellitus (HbA1C ≥ 8%);
- Severe obesity (BMI ≥ 40 kg/m2);
- Arm circumference ≥ 42 cm;
- Atrial fibrillation;
- Known hypersensitivity to drugs;
- History of spontaneous or drug induced angioneurotic edema;
- Use of any of the following medications within the four (4) weeks prior to dosing:
- Thyroid medication, statin therapy, oral antidiabetic drugs, estrogen replacement therapy and/or chronic low dose aspirin (75 mg/day) unless the patient has been on a stable maintenance dose for at least 3 months prior to screening.
- Anticoagulant treatments
- Cholestyramine resins.
- Treatment with oral, topical, inhaled, eye drop corticosteroids
- Treatment with class Ia, Ib and Ic or III anti-arrhythmics
- CNS drugs
- P-glycoprotein (P-gp) inhibitors (e.g., verapamil, quinidine, ritonavir),
- known cytochrome P450 inducers or inhibitors (eg, ketoconazole/CYP3A4, quinidine/CYP2D6, gemfibrozil/CYP2C8)
- Chronic use of nonsteroidal anti-inflammatory drugs (NSAIDS) or cyclooxygenase (COX)-2 inhibitors.
- Vasodilators or vascular muscle relaxants prescribed for other conditions
- Unlikely to cooperate in the study and/or poor compliance anticipated by the investigator, e.g., uncooperative attitude, inability to return for follow-up visit, and unlikelihood of completing the study;
- Participation in another interventional study at the same time or within 3 months prior to the beginning of the present study;
- Participant not affiliated with the French social security;
- No written informed consent;
- A marked baseline prolongation of QT/QTc interval (e.g., repeated demonstration of a QTc interval >450 ms);
- A history of additional risk factors for Torsade de Pointes (TdP) (e.g., heart failure, hypokalemia, family history of Long QT Syndrome);
- The use of concomitant medications that prolong the QT/QTc interval.
Trial locations and contacts
4 sites in 1 country.
France4 sites
Hôpital Arthur Gardiner
Dinard, 35800
Hôpital Cardiologique, CHRU de Lille
Lille, 59037
Hospices Civils de Lyon - Hôpital de la Croix Rousse
Lyon, 69317
Hôpital Européen Georges Pompidou
Paris, 75015
About this study
Official title: Multicenter, Randomized, Double-blind, Two-period, Placebo Controlled, Forced-titration Proof of Concept Crossover Study to Compare QGC001 With Placebo in Patients With Grade I or II Essential Hypertension
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.
- Conditions
- Essential Hypertension
- Being tested
- QGC001, Placebo
- Medical subject headings
- Essential Hypertension
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
QGC001Drug
PlaceboDrug
| Study group | Role | What they receive |
|---|---|---|
| A: P1-QGC001 - Washout-placebo - P2-placebo | Experimental | The first period (P1) will correspond either to QGC001 or placebo, the second period (P2) will correspond either to QGC001 or placebo. Receives: Drug: QGC001; Drug: Placebo |
| B: P1-placebo - Washout-placebo - P2-QGC001 | Experimental | The first period (P1) will correspond either to QGC001 or placebo, the second period (P2) will correspond either to QGC001 or placebo. Receives: Drug: QGC001; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Change from Period 1 to Period 2 up to 16 weeks (end-of-study visit).
Secondary outcomes (12)
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Change from Period 1 to Period 2 up to 16 weeks.
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Change from Period 1 to Period 2 up to 16 weeks.
Safety - Adverse events
Measured: Change from Period 1 to Period 2 up to 16 weeks.
Safety - Morisky Medication Adherence Questionnaire
Measured: Change from Period 1 to Period 2 up to 16 weeks.
Safety - Electrocardiogram
The measurements will consist of a 12-lead digital ECG.
Measured: 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.
Measured: Change from Period 1 to Period 2 up to 16 weeks.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Dec 2014 (estimated)
- Study startJan 2015
- Primary completionApr 2016
- Study completionApr 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Essential HypertensionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 34 participants (actual)
Sponsor and investigators
- Lead sponsor
- Quantum Genomics SA
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02322450
- Sponsor's protocol ID
- QGC001/2QG1
- Acronym
- 2QG1
- Status last verified
- Sep 2016
- First submitted
- 11 Dec 2014
- Last updated
- 28 Sep 2016
- Results posted
- No
- Data monitoring committee
- No
Publications
Khosla J, Aronow WS, Frishman WH. Firibastat: An Oral First-in-Class Brain Aminopeptidase A Inhibitor for Systemic Hypertension. Cardiol Rev. 2022 Jan-Feb 01;30(1):50-55. doi: 10.1097/CRD.0000000000000360.
PubMed 33027067Azizi M, Courand PY, Denolle T, Delsart P, Zhygalina V, Amar L, Lantelme P, Mounier-Vehier C, De Mota N, Balavoine F, Llorens-Cortes C. A pilot double-blind randomized placebo-controlled crossover pharmacodynamic study of the centrally active aminopeptidase A inhibitor, firibastat, in hypertension. J Hypertens. 2019 Aug;37(8):1722-1728. doi: 10.1097/HJH.0000000000002092.
PubMed 30882604
Study at a glance
From the registry record, last updated by the sponsor on 28 Sep 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Multicenter, Randomized, Double-blind, Two-period, Placebo Controlled, Forced-titration Proof of Concept Crossover Study to Compare QGC001 With Placebo in Patients With Grade I or II Essential Hypertension
- ClinicalTrials.gov ID
- NCT02322450
- Acronym / sponsor ID
- 2QG1 / QGC001/2QG1
- Conditions
- Essential Hypertension
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 34 participants (actual)
- Lead sponsor
- Quantum Genomics SAIndustry (pharma, biotech, devices)
- Study start
- Jan 2015
- Primary completion
- Apr 2016 (actual)
- Study completion
- Apr 2016 (actual)
- First posted
- 23 Dec 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| A: P1-QGC001 - Washout-placebo - P2-placebo | Experimental | Drug: QGC001, Drug: PlaceboThe first period (P1) will correspond either to QGC001 or placebo, the second period (P2) will correspond either to QGC001 or placebo. |
| B: P1-placebo - Washout-placebo - P2-QGC001 | Experimental | Drug: QGC001, Drug: PlaceboThe first period (P1) will correspond either to QGC001 or placebo, the second period (P2) will correspond either to QGC001 or placebo. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Male and female of non-childbearing potential patients (post-menopausal since at least 12 months or surgically sterilized) aged 18 to 75 years;
- Body weight ≥50 kg with a body mass index (BMI) calculated as weight in kg/(height in m2) from 18 to 40 kg/m2 at screening;
- A signed and dated informed consent form before any study-specific screening procedure is performed;
- With a diagnosis of essential grade I or II hypertension defined as:
- Diagnosis of permanent hypertension confirmed by a mean SBP or DBP higher than135 or 85 mmHg on daytime ambulatory blood pressure monitoring (ABPM) after a 2-week placebo run-in period;
Key exclusion criteria (41 listed)
- Any significant hepatic, renal, respiratory (e.g., asthma), gastrointestinal, endocrine (e.g., diabetes, dyslipidemia necessitating drug therapy), immunologic, dermatological, hematological, neurologic, psychiatric disease or history of any clinically important drug allergy;
- Acute disease state (e.g., vomiting, fever, diarrhea) within 7 days before study day 1;
- Any history of transient ischemic accident (TIA) or cerebrovascular accident (CVA);
- Any history of acute heart failure or heart failure;
- Any history of myocardial infarction, unstable angina, coronary bypass or percutaneous coronary angioplasty;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| QGC001 | Drug | A: P1-QGC001 - Washout-placebo - P2-placebo, B: P1-placebo - Washout-placebo - P2-QGC001 |
| Placebo | Drug | A: P1-QGC001 - Washout-placebo - P2-placebo, B: P1-placebo - Washout-placebo - P2-QGC001 |
Primary outcome
Efficacy - 24h ABPM
Time frame: Change from Period 1 to Period 2 up to 16 weeks (end-of-study visit).
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.
12 secondary outcomes
Efficacy - Self BP measurements at home
Time frame: Change from Period 1 to Period 2 up to 16 weeks.
Efficacy - Office BP measurements
Time frame: Change from Period 1 to Period 2 up to 16 weeks.
Efficacy - Hormonal measurements
Time frame: Change from Period 1 to Period 2 up to 16 weeks.
Pharmacokinetics - Plasma levels of QGC001
Time frame: Change from Period 1 to Period 2 up to 16 weeks.
Pharmacokinetics - Plasma levels of EC33
Time frame: Change from Period 1 to Period 2 up to 16 weeks.
Safety - Reported signs and symptoms
Time frame: Change from Period 1 to Period 2 up to 16 weeks.
Safety - Physical examination
Time frame: Change from Period 1 to Period 2 up to 16 weeks.
Safety - Vital sign measurements
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
Time frame: Change from Period 1 to Period 2 up to 16 weeks.
Safety - Clinical laboratory tests
Time frame: Change from Period 1 to Period 2 up to 16 weeks.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Sep 2016.
- Derived from this study: PubMed 33027067Khosla J, Aronow WS, Frishman WH. Firibastat: An Oral First-in-Class Brain Aminopeptidase A Inhibitor for Systemic Hypertension. Cardiol Rev. 2022 Jan-Feb 01;30(1):50-55. doi: 10.1097/CRD.0000000000000360.
- Derived from this study: PubMed 30882604Azizi M, Courand PY, Denolle T, Delsart P, Zhygalina V, Amar L, Lantelme P, Mounier-Vehier C, De Mota N, Balavoine F, Llorens-Cortes C. A pilot double-blind randomized placebo-controlled crossover pharmacodynamic study of the centrally active aminopeptidase A inhibitor, firibastat, in hypertension. J Hypertens. 2019 Aug;37(8):1722-1728. doi: 10.1097/HJH.0000000000002092.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing QGC001 in people with Essential Hypertension, run by Quantum Genomics SA at 4 sites in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 41 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 28 Sep 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Efficacy - 24h ABPM (time frame: Change from Period 1 to Period 2 up to 16 weeks (end-of-study visit).). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02322450, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Sep 2016.