Trial Outcomes & Findings for Open-Label Extension Study of Patients Previously Enrolled in Study CIN-107-124 (NCT NCT05459688)

NCT ID: NCT05459688

Last Updated: 2024-12-16

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 175 participants
• Primary outcome timeframe: 52 weeks
• Results posted on: 2024-12-16

Participant Flow

Participant milestones

Measure	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.
Overall Study STARTED	175
Overall Study COMPLETED	146
Overall Study NOT COMPLETED	29

Reasons for withdrawal

Measure	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.
Overall Study Lost to Follow-up	6
Overall Study Physician Decision	1
Overall Study Withdrawal by Subject	19
Overall Study Noncompliance, Subject unable to complete last visit.	3

Baseline Characteristics

The safety analysis set population

Baseline characteristics by cohort

Measure	2mg CIN-107 n=175 Participants 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.
Age, Continuous	60.6 Years STANDARD_DEVIATION 10.4 • n=5 Participants • The safety analysis set population
Age, Customized > 75 years	11 Participants n=5 Participants • The safety analysis set population
Age, Customized <= 75 years	164 Participants n=5 Participants • The safety analysis set population
Sex: Female, Male Female	78 Participants n=5 Participants • The safety analysis set population
Sex: Female, Male Male	97 Participants n=5 Participants • The safety analysis set population
Ethnicity (NIH/OMB) Hispanic or Latino	99 Participants n=5 Participants • The safety analysis set population
Ethnicity (NIH/OMB) Not Hispanic or Latino	76 Participants n=5 Participants • The safety analysis set population
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants • The safety analysis set population
Race/Ethnicity, Customized American Indian or Alaska Native	0 Participants n=5 Participants • The safety analysis set population
Race/Ethnicity, Customized Asian	4 Participants n=5 Participants • The safety analysis set population
Race/Ethnicity, Customized Black or African American	42 Participants n=5 Participants • The safety analysis set population
Race/Ethnicity, Customized Native Hawaiian or other Pacific Islander	0 Participants n=5 Participants • The safety analysis set population
Race/Ethnicity, Customized Other	1 Participants n=5 Participants • The safety analysis set population
Race/Ethnicity, Customized White	128 Participants n=5 Participants • The safety analysis set population

PRIMARY outcome

Timeframe: 52 weeks

Population: Safety Population includes any participants enrolled in the study who have taken at least 1 dose of any study drug.

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.

Outcome measures

Measure

2mg CIN-107 n=175 Participants 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.

Number of Participants With Any Treatment-emergent Adverse Events (TEAEs)

73 Participants

PRIMARY outcome

Timeframe: 52 weeks

Population: Safety Population includes any participants enrolled in the study who have taken at least 1 dose of any study drug.

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.

Outcome measures

Measure

2mg CIN-107 n=175 Participants 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.

Number of Participants With Any Treatment-emergent Adverse Events of Special Interest (AESIs)

7 Participants

PRIMARY outcome

Timeframe: 52 weeks

Population: Safety Population includes any participants enrolled in the study who have taken at least 1 dose of any study drug.

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.

Outcome measures

Measure

2mg CIN-107 n=175 Participants 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.

Number of Participants With Any Treatment-emergent Serious Adverse Events (TESAEs)

8 Participants

PRIMARY outcome

Timeframe: 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.

Mean change from baseline at Week 52 in serum potassium (mmol/L).

Outcome measures

Measure

2mg CIN-107 n=127 Participants 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.

Change From Baseline in Serum Potassium

0.08 mmol/L Standard Deviation 0.417

PRIMARY outcome

Timeframe: 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.

Mean change from baseline at Week 52 in serum sodium (mmol/L).

Outcome measures

Measure

2mg CIN-107 n=127 Participants 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.

Change From Baseline in Serum Sodium

0.6 mmol/L Standard Deviation 3.02

PRIMARY outcome

Timeframe: 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.

Change from baseline at 52 weeks in body weight (kg)

Outcome measures

Measure

2mg CIN-107 n=138 Participants 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.

Change From Baseline in Body Weight

-0.30 kg Standard Deviation 3.839

PRIMARY outcome

Timeframe: 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.

Change from baseline at 52 weeks in temperature (C)

Outcome measures

Measure

2mg CIN-107 n=138 Participants 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.

Change From Baseline in Temperature

-0.03 Celsius Standard Deviation 0.473

PRIMARY outcome

Timeframe: 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.

Change from baseline at 52 weeks in seated heart rate (beats/min)

Outcome measures

Measure

2mg CIN-107 n=138 Participants 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.

Change From Baseline in Seated Heart Rate

0.9 beats/min Standard Deviation 9.49

SECONDARY outcome

Timeframe: 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.

Mean change from baseline at Week 52 in seated systolic blood pressure (SBP)

Outcome measures

Measure

2mg CIN-107 n=138 Participants 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.

Change From Baseline in Mean Seated Systolic Blood Pressure

-5.1 mmHg Standard Deviation 11.51

SECONDARY outcome

Timeframe: 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.

Mean change from baseline at 52 weeks in mean seated diastolic blood pressure (DBP)

Outcome measures

Measure

2mg CIN-107 n=138 Participants 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.

Change From Baseline in Mean Seated Diastolic Blood Pressure

-3.6 mmHg Standard Deviation 8.65

SECONDARY outcome

Timeframe: 52 weeks

Population: Safety Population includes any participants enrolled in the study who have taken at least 1 dose of any study drug.

Number of participants achieved mean seated systolic blood pressure (SBP) <130 mmHg at 52 week

Outcome measures

Measure

2mg CIN-107 n=175 Participants 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.

Achieving Mean Seated Systolic Blood Pressure <130 mmHg

102 Participants

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Measure

2mg CIN-107 n=53 Participants 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.

Non-responders in Study CIN-107-124 Achieving a Seated SBP Response <130 mmHg

20 Participants

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Measure

2mg CIN-107 n=122 Participants 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.

Responders in Study CIN-107-124 Achieving a Seated SBP Response <130 mmHg

82 Participants

Adverse Events

2mg CIN-107

Serious events: 8 serious events

Other events: 20 other events

Deaths: 0 deaths

Serious adverse events

Measure	2mg CIN-107 n=175 participants at risk 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.
Nervous system disorders Lacunar stroke	0.57% 1/175 • Number of events 1 • 52 weeks
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	0.57% 1/175 • Number of events 1 • 52 weeks
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.57% 1/175 • Number of events 1 • 52 weeks
Cardiac disorders Angina pectoris	0.57% 1/175 • Number of events 1 • 52 weeks
Cardiac disorders Bradycardia	0.57% 1/175 • Number of events 1 • 52 weeks
Cardiac disorders Myocardial infarction	0.57% 1/175 • Number of events 1 • 52 weeks
Infections and infestations Diverticulitis	0.57% 1/175 • Number of events 1 • 52 weeks
Injury, poisoning and procedural complications Femoral nerve injury	0.57% 1/175 • Number of events 1 • 52 weeks
Injury, poisoning and procedural complications Joint dislocation	0.57% 1/175 • Number of events 1 • 52 weeks
Metabolism and nutrition disorders Hyperkalaemia	0.57% 1/175 • Number of events 1 • 52 weeks

Other adverse events

Measure	2mg CIN-107 n=175 participants at risk 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.
Infections and infestations Urinary tract infection	7.4% 13/175 • Number of events 16 • 52 weeks
Metabolism and nutrition disorders Hyperkalaemia	5.1% 9/175 • Number of events 13 • 52 weeks

Additional Information

Global Clinical Lead

AstraZeneca

Phone: 1-877-240-9479

Email: information.center@astrazeneca.com

Results disclosure agreements

• Principal investigator is a sponsor employee The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less or equal to 60 days from the time submitted to the sponsor for review. The sponsor can require changes to the communication and can extend the embargo for up to 90 days.
• Publication restrictions are in place

Restriction type: OTHER