Hypertension
Conditions
Brief summary
This is a Phase 2, multicenter, open-label extension (OLE) study to evaluate the long-term safety, tolerability, and effectiveness of CIN-107 for up to 52 weeks in patients with HTN who have completed Part 1 or Part 2 of Study CIN-107-124. The study will be conducted at clinical sites that have participated in the double-blind, Phase 2 Study CIN-107-124.
Interventions
DRUGCIN-107
2 mg of CIN-107, once a day for 52 weeks
Sponsors
AstraZeneca
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Eligible patients from Study CIN-107-124 who elect to participate in this study will continue treatment with 2 mg CIN-107 tablets QD after enrollment, starting at Visit 1 and concluding at EOT (Visit 7)
Eligibility
Sex/Gender
ALL
Age
18 Years to 100 Years
Healthy volunteers
No
Inclusion criteria
1. Have completed Part 1 or Part 2 of Study CIN-107-124; 2. Have had acceptable safety and tolerability during Study CIN-107-124 as determined by the Investigator or Medical Monitor; 3. Have demonstrated ≥70% and ≤120% adherence to their single background antihypertensive agent and the CIN-107 placebo during Study CIN-107-124; 4. Agree to comply with the contraception and reproduction restrictions of the study as follows: * Male patients must agree to abstain from sperm donation from Day 1 through 90 days after the final dose of study drug; * Female patients of childbearing potential (ie, ovulating, pre-menopausal, and not surgically sterile) must have a documented negative serum pregnancy test at enrollment (Visit 1); and * Female patients of childbearing potential must use a highly effective method of contraception (ie, \<1% failure rate) from Day 1 through 30 days after the last administration of study drug. 5. Are able and willing to give informed consent for participation in the clinical study.
Exclusion criteria
1. Have met Protocol-defined stopping criteria, were withdrawn from the study, discontinued CIN-107 at the time of Visits 6 or 9, or were not compliant with the Protocol during Study CIN-107-124; 2. Have received treatment with any investigational agent for disease intervention (ie, other than study drug) during Study CIN-107-124, or since the last administration of study drug in Study CIN-107-124, or plans to participate in another clinical study within 30 days of discontinuation of study drug; 3. Have had any new, significant, or uncontrolled comorbidity since initially enrolling in Study CIN-107-124 that would increase the risk of the patient in Study CIN-107-130, as determined by the Investigator; 4. Have had a mean seated SBP ≥170 mmHg or DBP ≥105 mmHg at the end of Part 1 or Part 2 of Study CIN-107-124; 5. Have an upper arm circumference that does not meet the cuff measurement criteria for the selected BP machine at Visit 1 of Study CIN-107-130; 6. Have any uncontrolled or clinically significant laboratory abnormality that would affect safety, interpretation of study data, or the patient's participation in the study, as determined by the Investigator; 7. Have experienced a de novo or reactivated serious viral infection such as hepatitis B, hepatitis C, or HIV during Study CIN-107-124; 8. Have had any major episode of infection requiring hospitalization or treatment with intravenous antibiotics during Study CIN-107-124; 9. Have developed a malignancy (with the exception of non-serious local and resectable basal or squamous cell carcinoma of the skin) during Study CIN-107-124; 10. Have anticipated initiation of erythropoietin-stimulating agents and/or planned transfusion within 2 months after enrollment (Visit 1); 11. Are expected to receive or are receiving any of the exclusionary drugs (strong cytochrome P450 3A inducers); 12. Have known secondary causes of HTN (eg, renal artery stenosis, uncontrolled or untreated hyperthyroidism, uncontrolled or untreated hypothyroidism, hyperparathyroidism, pheochromocytoma, Cushing's syndrome, or aortic coarctation) except obstructive sleep apnea; 13. Have been diagnosed with New York Heart Association stage III or IV chronic heart failure during Study CIN-107-124; 14. Have had a stroke, transient ischemic attack, hypertensive encephalopathy, acute coronary syndrome, or hospitalization for heart failure during Study CIN-107-124; 15. Have a known current severe left ventricular outflow obstruction, such as obstructive hypertrophic cardiomyopathy and/or severe aortic valvular disease diagnosed from a prior echocardiogram; 16. Have a planned coronary revascularization (percutaneous coronary intervention \[PCI\] or coronary artery bypass graft \[CABG\]) or any major surgical procedure; 17. Have had a CABG or other major cardiac surgery (eg, valve replacement), peripheral arterial bypass surgery, or PCI during Study CIN-107-124; 18. Have a planned dialysis or kidney transplant during the course of this study; 19. Have a known hypersensitivity to CIN-107 or drugs of the same class, or any of its excipients; 20. Have any clinically relevant medical or surgical conditions (including unstable conditions and/or treatment with systemic immunosuppressants including corticosteroids) that, in the opinion of the Investigator, would put the patient at risk by participating in the study; 21. Are pregnant, breastfeeding, or planning to become pregnant during the study; or 22. Are considered to be unsuitable for any other reason that may either place the patient at increased risk during participation or interfere with the interpretation of the study outcomes by the Investigator, after reviewing medical and psychiatric history, physical examination, and laboratory evaluation.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Temperature | 52 weeks | Change from baseline at 52 weeks in temperature (C) |
| Number of Participants With Any Treatment-emergent Adverse Events of Special Interest (AESIs) | 52 weeks | For this study, AESIs include the following: Events of hypotension that require clinical intervention; Abnormal potassium laboratory values that require clinical intervention; and Abnormal sodium laboratory values that require clinical intervention. |
| Number of Participants With Any Treatment-emergent Serious Adverse Events (TESAEs) | 52 weeks | An AE was or adverse reaction is considered serious if, in the view of either the Investigator or Sponsor, it results in any of the following outcomes: Death, a life-threatening AE, a persistent or significant disability/incapacity or substantial disruption of the ability to conduct normal life functions, a congenital anomaly/birth defect, or an important medical event. |
| Change From Baseline in Serum Potassium | 52 weeks | Mean change from baseline at Week 52 in serum potassium (mmol/L). |
| Change From Baseline in Serum Sodium | 52 weeks | Mean change from baseline at Week 52 in serum sodium (mmol/L). |
| Change From Baseline in Body Weight | 52 weeks | Change from baseline at 52 weeks in body weight (kg) |
| Change From Baseline in Seated Heart Rate | 52 weeks | Change from baseline at 52 weeks in seated heart rate (beats/min) |
| Number of Participants With Any Treatment-emergent Adverse Events (TEAEs) | 52 weeks | An AE was defined as any untoward medical occurrence in a clinical investigation participants administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and/or unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of an investigational medicinal product, whether or not related to the investigational medicinal product. Any medical condition already present at enrollment should be recorded as medical history and not be reported as an AE unless the medical condition or signs or symptoms present at baseline changes in severity, frequency, or seriousness at any time during the study. In this case, it was be reported as an AE. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Mean Seated Diastolic Blood Pressure | 52 weeks | Mean change from baseline at 52 weeks in mean seated diastolic blood pressure (DBP) |
| Achieving Mean Seated Systolic Blood Pressure <130 mmHg | 52 weeks | Number of participants achieved mean seated systolic blood pressure (SBP) \<130 mmHg at 52 week |
| Non-responders in Study CIN-107-124 Achieving a Seated SBP Response <130 mmHg | 52 weeks | Number of non-responders (participants with seated SBP \>=130 mmHg) in Study CIN-107-124 achieving a seated SBP response \<130 mmHg with CIN-107 with/without a single background antihypertensive agent and/or rescue medication and irrespective of Study CIN-107-124 dose strength. |
| Responders in Study CIN-107-124 Achieving a Seated SBP Response <130 mmHg | 52 weeks | Number of responders (participants with \<130 mmHg) in Study CIN-107-124 achieving a seated SBP response \<130 mmHg with CIN-107 with/without a single background antihypertensive agent and/or rescue medication and irrespective of Study CIN-107-124 dose strength. |
| Change From Baseline in Mean Seated Systolic Blood Pressure | 52 weeks | Mean change from baseline at Week 52 in seated systolic blood pressure (SBP) |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 2mg CIN-107 Participants received 2mg CIN-107 with potential of additional single background antihypertensive agent. Single background antihypertensive (non-CIN-107) agent chosen at Visit 1 or 2 should remain stable until Visit 3 of the study, after which the Investigator was permitted to use his/her medical judgment to up/down titrate or discontinue the background antihypertensive (non-CIN-107) agent. | 175 |
| Total | 175 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Lost to Follow-up | 6 |
| Overall Study | Noncompliance, Subject unable to complete last visit. | 3 |
| Overall Study | Physician Decision | 1 |
| Overall Study | Withdrawal by Subject | 19 |
Baseline characteristics
| Characteristic | 2mg CIN-107 |
|---|---|
| Age, Continuous | 60.6 Years STANDARD_DEVIATION 10.4 |
| Age, Customized <= 75 years | 164 Participants |
| Age, Customized > 75 years | 11 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 99 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 76 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 Participants |
| Race/Ethnicity, Customized Asian | 4 Participants |
| Race/Ethnicity, Customized Black or African American | 42 Participants |
| Race/Ethnicity, Customized Native Hawaiian or other Pacific Islander | 0 Participants |
| Race/Ethnicity, Customized Other | 1 Participants |
| Race/Ethnicity, Customized White | 128 Participants |
| Sex: Female, Male Female | 78 Participants |
| Sex: Female, Male Male | 97 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 175 |
| other Total, other adverse events | 20 / 175 |
| serious Total, serious adverse events | 8 / 175 |
Outcome results
Primary
Change From Baseline in Body Weight
Change from baseline at 52 weeks in body weight (kg)
Time frame: 52 weeks
Population: Safety Population includes any participants enrolled in the study who have taken at least 1 dose of any study drug. In the safety population 37 participants did not have 52 weeks measure for body weight.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 2mg CIN-107 | Change From Baseline in Body Weight | -0.30 kg | Standard Deviation 3.839 |
Primary
Change From Baseline in Seated Heart Rate
Change from baseline at 52 weeks in seated heart rate (beats/min)
Time frame: 52 weeks
Population: Safety Population includes any participants enrolled in the study who have taken at least 1 dose of any study drug. In the safety population 37 participants did not have 52 weeks measure for seated heart rate.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 2mg CIN-107 | Change From Baseline in Seated Heart Rate | 0.9 beats/min | Standard Deviation 9.49 |
Primary
Change From Baseline in Serum Potassium
Mean change from baseline at Week 52 in serum potassium (mmol/L).
Time frame: 52 weeks
Population: Safety Population includes any participants enrolled in the study who have taken at least 1 dose of any study drug. In the safety population 48 participants did not have baseline measure and/or 52 weeks measure for serum potassium.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 2mg CIN-107 | Change From Baseline in Serum Potassium | 0.08 mmol/L | Standard Deviation 0.417 |
Primary
Change From Baseline in Serum Sodium
Mean change from baseline at Week 52 in serum sodium (mmol/L).
Time frame: 52 weeks
Population: Safety Population includes any participants enrolled in the study who have taken at least 1 dose of any study drug. In the safety population 48 participants did not have baseline measure and/or 52 weeks measure for serum sodium.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 2mg CIN-107 | Change From Baseline in Serum Sodium | 0.6 mmol/L | Standard Deviation 3.02 |
Primary
Change From Baseline in Temperature
Change from baseline at 52 weeks in temperature (C)
Time frame: 52 weeks
Population: Safety Population includes any participants enrolled in the study who have taken at least 1 dose of any study drug. In the safety population 37 participants did not have 52 weeks measure for temperature.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 2mg CIN-107 | Change From Baseline in Temperature | -0.03 Celsius | Standard Deviation 0.473 |
Primary
Number of Participants With Any Treatment-emergent Adverse Events of Special Interest (AESIs)
For this study, AESIs include the following: Events of hypotension that require clinical intervention; Abnormal potassium laboratory values that require clinical intervention; and Abnormal sodium laboratory values that require clinical intervention.
Time frame: 52 weeks
Population: Safety Population includes any participants enrolled in the study who have taken at least 1 dose of any study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 2mg CIN-107 | Number of Participants With Any Treatment-emergent Adverse Events of Special Interest (AESIs) | 7 Participants |
Primary
Number of Participants With Any Treatment-emergent Adverse Events (TEAEs)
An AE was defined as any untoward medical occurrence in a clinical investigation participants administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and/or unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of an investigational medicinal product, whether or not related to the investigational medicinal product. Any medical condition already present at enrollment should be recorded as medical history and not be reported as an AE unless the medical condition or signs or symptoms present at baseline changes in severity, frequency, or seriousness at any time during the study. In this case, it was be reported as an AE.
Time frame: 52 weeks
Population: Safety Population includes any participants enrolled in the study who have taken at least 1 dose of any study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 2mg CIN-107 | Number of Participants With Any Treatment-emergent Adverse Events (TEAEs) | 73 Participants |
Primary
Number of Participants With Any Treatment-emergent Serious Adverse Events (TESAEs)
An AE was or adverse reaction is considered serious if, in the view of either the Investigator or Sponsor, it results in any of the following outcomes: Death, a life-threatening AE, a persistent or significant disability/incapacity or substantial disruption of the ability to conduct normal life functions, a congenital anomaly/birth defect, or an important medical event.
Time frame: 52 weeks
Population: Safety Population includes any participants enrolled in the study who have taken at least 1 dose of any study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 2mg CIN-107 | Number of Participants With Any Treatment-emergent Serious Adverse Events (TESAEs) | 8 Participants |
Secondary
Achieving Mean Seated Systolic Blood Pressure <130 mmHg
Number of participants achieved mean seated systolic blood pressure (SBP) \<130 mmHg at 52 week
Time frame: 52 weeks
Population: Safety Population includes any participants enrolled in the study who have taken at least 1 dose of any study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 2mg CIN-107 | Achieving Mean Seated Systolic Blood Pressure <130 mmHg | 102 Participants |
Secondary
Change From Baseline in Mean Seated Diastolic Blood Pressure
Mean change from baseline at 52 weeks in mean seated diastolic blood pressure (DBP)
Time frame: 52 weeks
Population: Safety Population includes any participants enrolled in the study who have taken at least 1 dose of any study drug. In the safety population 37 participants did not have 52 weeks measure for seated DBP.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 2mg CIN-107 | Change From Baseline in Mean Seated Diastolic Blood Pressure | -3.6 mmHg | Standard Deviation 8.65 |
Secondary
Change From Baseline in Mean Seated Systolic Blood Pressure
Mean change from baseline at Week 52 in seated systolic blood pressure (SBP)
Time frame: 52 weeks
Population: Safety Population includes any participants enrolled in the study who have taken at least 1 dose of any study drug. In the safety population 37 participants did not have 52 weeks measure for seated SBP.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 2mg CIN-107 | Change From Baseline in Mean Seated Systolic Blood Pressure | -5.1 mmHg | Standard Deviation 11.51 |
Secondary
Non-responders in Study CIN-107-124 Achieving a Seated SBP Response <130 mmHg
Number of non-responders (participants with seated SBP \>=130 mmHg) in Study CIN-107-124 achieving a seated SBP response \<130 mmHg with CIN-107 with/without a single background antihypertensive agent and/or rescue medication and irrespective of Study CIN-107-124 dose strength.
Time frame: 52 weeks
Population: Subpopulation of the safety population (any participants enrolled in the study who have taken at least 1 dose of any study drug) who were non-responders (participants with seated SBP \>=130 mmHg) in Study CIN-107-124.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 2mg CIN-107 | Non-responders in Study CIN-107-124 Achieving a Seated SBP Response <130 mmHg | 20 Participants |
Secondary
Responders in Study CIN-107-124 Achieving a Seated SBP Response <130 mmHg
Number of responders (participants with \<130 mmHg) in Study CIN-107-124 achieving a seated SBP response \<130 mmHg with CIN-107 with/without a single background antihypertensive agent and/or rescue medication and irrespective of Study CIN-107-124 dose strength.
Time frame: 52 weeks
Population: Subpopulation of the safety population (any participants enrolled in the study who have taken at least 1 dose of any study drug) who were responders (participants with seated SBP \<130 mmHg) in Study CIN-107-124.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 2mg CIN-107 | Responders in Study CIN-107-124 Achieving a Seated SBP Response <130 mmHg | 82 Participants |