Hypertension Circulatory System
Conditions
Interventions
This is a crossover study in which participants will be randomised via Sealed Envelope. Each participant will receive both the active treatment and a placebo in a randomised sequence over 12 weeks in
Sponsors
Cambridge University Hospitals NHS Foundation Trust
Eligibility
Sex/Gender
All
Age
18 Years to 100 Years
Inclusion criteria
Inclusion criteria: 1. Clinical diagnosis of essential hypertension 2. Age 18 years or older 3. Seated attended office BP =140 and/or =90 mmHg. 4. Standardised home BP readings or daytime ambulatory BP of =130 and/or =80mmHg 5. Currently prescribed and taking at least two antihypertensive drugs at screening 6. eGFR >45ml/min/1.73m2 at screening 7. Capable of providing signed informed consent 8. Female of non-child bearing potential 9. Male being surgically sterile, abstinent or willing to use in conjunction with their female partner, a highly effective method of contraception 10. Willingness to comply with double contraception method (applied to men)
Exclusion criteria
Exclusion criteria: 1. Women of childbearing potential or those who are pregnant, breast-feeding, or women with intent of getting pregnant. 2. Confirmed secondary cause of hypertension (e.g. renal artery stenosis, adrenal adenoma, phaeochromocytoma etc) 3. Seated attended office systolic BP =180 or diastolic BP = 110 mmHg 4. Active planning for pregnancy during the trial (applicable to both men and women) 5. Current or prior medical treatment with an ETA antagonist or SGLT2 inhibitor 6. Known acute coronary syndrome within 3 months of screening visit 7. Unstable heart failure requiring hospitalisation within last 6 months at screening visit 8. Known heart failure with New York Heart Association (NYHA) classification of III or IV 9. Uncontrolled diabetes (HBA1C within last 3 months from screening >12%) 10. Known Type 1 diabetes 11. Known Type 2 diabetes on insulin 12. Participants treated with strong CYP3A4 inhibitor 13. Screening blood pressure indicating hypotension (systolic BP 3 ULN) 17. Positive drugs of abuse test at screening 18. History of alcohol abuse at screening 19. Known clinical diagnosis of hepatitis or HIV 20. Participants with a known hypersensitivity to Dapagliflozin or Zibotentan or any of the excipients of the product 21. Participation in another clinical study involving a study intervention or investigational medicinal device within the past 30 days, or for investigational drugs, within 5 half-lives (whichever is longer) prior to the first dose in this trial
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Unattended seated automated office systolic blood pressure will be measured using a validated device at the end of each treatment period (Visit 5 and Visit 8) | — |
Secondary
| Measure | Time frame |
|---|---|
| The following secondary outcome measures are assessed using an automated sphygmomanometer, unless stated: 1. Unattended seated automated office diastolic blood pressure at the end of each treatment period (Visit 5 and Visit 8) 2. Unattended seated automated office systolic blood pressure after 28 days of each treatment period (Visit 4 and Visit 7) 3. Unattended seated automated office diastolic blood pressure after 28 days of each treatment period (Visit 4 and Visit 7) 4. Attended seated office systolic blood pressure at the end of each treatment period (Visit 5 and Visit 8) 5. Attended seated office diastolic blood pressure at the end of each treatment period (Visit 5 and Visit 8) 6. Attended seated office systolic blood pressure after 28 days of each treatment period (Visit 4 and Visit 7) 7. Attended seated office diastolic blood pressure after 28 days of each treatment period (Visit 4 and Visit 7) 8. Safety as assessed via adverse event and serious adverse event reporting at one timepoint Exploratory outcome measures are assessed using an automated sphygmomanometer, unless stated: 1. Serum creatinine and eGFR using the CKD-EPI formula will be measured from venous blood sample and analysed through standardized laboratory methods at screening (visit 1), baseline (visit 2), week 4 (visit 4), week 6 (visit 5), week 10 (visit 7), week 12 (visit 8), and week 14 (visit 9) 2. HbA1C will be measured from venous blood sample and analysed through standardised laboratory method at screening (visit 1), baseline (visit 2), week 6 (visit 5) and week 12 (visit 8) 3. Serum alanine transaminase (ALT), alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT) will be measured from venous blood sample and analysed through standardised laboratory method at screening (visit 1), baseline (visit 2), week 4 (visit 4), week 6 (visit 5), week 10 (visit 7), week 12 (visit 8), and week 14 (visit 9) 4. Weight will be assessed using standardised scale at screening (visit 1), baseline ( | — |
Countries
England, United Kingdom
Contacts
Public ContactSonakshi Kadyan
Outcome results
None listed