HypertensionPhase 2NCT00817414

A Study to Evaluate the Effects of LCI699 on Cortisol in Participants With Hypertension

A Phase 2 study testing LCI699 in people with Hypertension, run by Novartis at 11 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Trial summary

This study determined the maximum dose of LCI6999 with respect to effect on the ACTH-stimulated cortisol response in participants with hypertension. Read more about this study

Who is it for?: Ages 18 to 75 years
Conditions the study is for: Hypertension
What is being tested?: LCI699
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 63 participants
Where: 11 sitesin 2 countries
Study dates: 14 Jan 2009to 12 Aug 2009
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

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

Diagnosis of hypertension with blood pressure ≥ 140/90 millimeters of mercury (mmHg) and < 180/110 mmHg on current antihypertensive treatment
Male and female participants 18-75 years of age
Participants must weigh at least 50 kilograms (kg)

Who cannot join

Recent history of myocardial infarction, heart failure, unstable angina, coronary artery bypass graft, percutaneous coronary intervention, hypertensive encephalopathy, cerebral accident or transient ischemic attack
Clinically significant electrocardiography (ECG) findings related to cardiac conduction defects
Type 1 diabetes or uncontrolled type 2 diabetes (haemoglobin A1c [HbA1c] > 9%)
Malignancies within the last 5 years (excluding basal cell skin cancer)
Liver disease
Other protocol-defined inclusion/exclusion criteria may apply.

Trial locations and contacts

11 sites in 2 countries.

Country

City, postcode or hospital

11 sites in 2 countries

United States10 sites

Clinical Study Center of Asheville, LLC
Asheville, North Carolina, 28801
Impact Clinical Trials
Beverly Hills, California, 90211
Associated Pharmaceutical Research Center, Inc
Buena Park, California, 90620
Punzi Medical Center
Carrollton, Texas, 75006
Innovative Clinical Research, Inc
Harbor City, California, 90710
Northstate Clinical Research
Lenoir, North Carolina, 28645
Metro Clinical Research
Littleton, Colorado, 80120
Long Beach Center for Clinical Research
Long Beach, California, 90806
dgd Research, Inc
San Antonio, Texas, 78229
Tipton Medical & Diagnostic Center
Tipton, Pennsylvania, 16684

Other trials in United States

Iceland1 site

Encode Clinic
Reykjavik, SA

Other trials in Iceland

About this study

Official title: A Phase II, Randomized, Double-blind, Placebo Controlled, Multi-center Study to Evaluate the Effects of LCI699 on Cortisol in Patients With Hypertension

This study determined the maximum dose of LCI6999 with respect to effect on the ACTH-stimulated cortisol response in participants with hypertension.

Conditions: Hypertension
Being tested: LCI699-matching placebo, LCI699
Keywords: Blood Pressure, Hypertension, Cortisol
Medical subject headings: Hypertension

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

LCI699-matching placeboDrug
LCI699-matching placebo oral capsules
LCI699Drug
LCI699 oral capsules

Study groups in NCT00817414
Study group	Role	What they receive
Cohort A: LCI699 0.5 mg QD	Experimental	Participants received LCI699 0.5 mg, capsules, orally, once daily (QD), with or without food for up to 6 weeks. Receives: Drug: LCI699
Cohort A: LCI699 1.0 mg QD	Experimental	Participants received LCI699 1.0 mg, capsules, orally, QD, with or without food for up to 6 weeks. Receives: Drug: LCI699
Cohort B1: LCI699 1.0 mg BID	Experimental	Participants received LCI699 1.0 mg, capsules, orally, twice daily (BID), with or without food for up to 6 weeks. Receives: Drug: LCI699
Cohort B1: LCI699 2.0 mg QD	Experimental	Participants received LCI699 2.0 mg, capsules, orally, QD, with or without food for up to 6 weeks. Receives: Drug: LCI699
Placebo	Placebo comparator	Participants received LCI699-matching placebo, capsules, orally, QD or BID, with or without food for up to 6 weeks. Receives: Drug: LCI699-matching placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

Maximum Tolerated Dose (MTD) of LCI699 With Respect to Effect on the Adrenocorticotropic Hormone (ACTH)-Stimulated Cortisol Response Following ACTH Stimulation in Hypertensive Participants
As per the protocol, MTD is the dose at which 4 participants exhibited ACTH-stimulated cortisol results <400 nanomoles per liter (nmol/L). The change in the distribution across the treatments were analyzed using 1- way analysis of variance (ANOVA) for continuous variables.
Measured: Up to Week 6

Secondary outcomes (10)

LCI699 Exposure-response Relationship on Cortisol Levels Following ACTH Stimulation in Hypertensive Participants
Exposure-response relationship was assessed using ACTH stimulation test. Tests were done 2 hours after study drug administration (i.e., at peak LCI699 concentrations). An increase in cortisol greater than >500 nmol at 60 minutes after ACTH administration was expected.
Measured: Up to Week 6
LCI699 Plasma Concentration Post LCI699 Administration at Day 7
Measured: Predose and 3 hours post-dose on Day 7
Maximum Plasma Concentration (Cmax) of LCI699
Measured: Days 7, 28: Pre-dose and 3 hours post-dose; Day 30: Pre-dose; Day 42: Pre-dose and 0.5, 1, 2, 3, 4, and 8-hours post-dose
Time of Maximum Plasma Concentration (Tmax) of LCI699
Measured: Days 7, 28: Pre-dose and 3 hours post-dose; Day 30: Pre-dose; Day 42: Pre-dose and 0.5, 1, 2, 3, 4, and 8-hours post-dose
Area Under the Concentration Time Curve From Time 0 to 8 Hours Post LCI699 Administration (AUC0-8)
Measured: Day 42: Pre-dose and 0.5, 1, 2, 3, 4, and 8-hours post-dose
Area Under the Concentration Time Curve Over the Dosing Interval (AUC0-τ) for LCI699
Measured: Days 7, 28: Pre-dose and 3 hours post-dose; Day 30: Pre-dose; Day 42: Pre-dose and 0.5, 1, 2, 3, 4, and 8-hours post-dose
Apparent Terminal Half-life (T1/2) of LCI699
Measured: Days 7, 28: Pre-dose and 3 hours post-dose; Day 30: Pre-dose; Day 42: Pre-dose and 0.5, 1, 2, 3, 4, and 8-hours post-dose
Number of Participants With Adverse Event (AEs)
An AE is an adverse medical event which occurs in a participant of the study and which is not necessarily in a causal relationship with the treatment the participant receives.
Measured: Up to 8 weeks
Percentage of Participants With a Mean Sitting Systolic Blood Pressure (MSSBP) Response and MSSBP Control at Week 6 Last Observation Carried Forward (LOCF), as Measured by Office Blood Pressure (OBP)
Automated arterial BP determinations was made with an automated BP device (such as the Omron BP monitor) in accordance with the Guidelines for management of hypertension: report of the 4th working party of the British Hypertension Society, 2004-BHS IV. Sitting and standing blood pressure (BP) and heart rate (HR) measurements were performed. MSSBP response was defined as the percentage of participants with a MSSBP <140 mmHg or a >=20 mmHg reduction from baseline. MSSBP control was defined as the percentage of participants with a MSSBP <140 mmHg for non-diabetic participants and <130mHg for diabetic participants.
Measured: Week 6
Percentage of Participants With a Mean Sitting Diastolic Blood Pressure (MSDBP) Response and MSDBP Control at Week 6 LOCF, as Measured by OBP
Automated arterial BP determinations was made with an automated BP device (such as the Omron BP monitor) in accordance with the Guidelines for management of hypertension: report of the 4th working party of the British Hypertension Society, 2004-BHS IV. Sitting and standing BP and HR measurements were performed. MSDBP response was defined as the percentage of participants with a MSDBP <90 mmHg or a >= 10 mmHg reduction from baseline. MSDBP control was defined as the percentage of participants with a MSDBP <90 mmHg for non-diabetic participants and <80mHg for diabetic participants.
Measured: Week 6

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

14 Jan 200912 Aug 2009

First posted6 Jan 2009 (estimated)
Study start14 Jan 2009
Primary completion12 Aug 2009
Study completion12 Aug 2009

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for 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: Sequential
Masking: Double blind
Who is masked: Participant, Investigator
Enrolment: 63 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00817414
Sponsor's protocol ID: CLCI699A2215
Other IDs: 2008-007337-49, 2008
Status last verified: May 2021
First submitted: 5 Jan 2009
Last updated: 2 Jun 2021
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No

Publications

Schumacher CD, Steele RE, Brunner HR. Aldosterone synthase inhibition for the treatment of hypertension and the derived mechanistic requirements for a new therapeutic strategy. J Hypertens. 2013 Oct;31(10):2085-93. doi: 10.1097/HJH.0b013e328363570c.
PubMed 24107737

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All Hypertension trials

Study at a glance

From the registry record, last updated by the sponsor on 2 Jun 2021. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase II, Randomized, Double-blind, Placebo Controlled, Multi-center Study to Evaluate the Effects of LCI699 on Cortisol in Patients With Hypertension
ClinicalTrials.gov ID: NCT00817414
Acronym / sponsor ID: CLCI699A2215
Conditions: Hypertension
Keywords: Blood Pressure, Hypertension, Cortisol
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 63 participants (actual)
Lead sponsor: NovartisIndustry (pharma, biotech, devices)
Collaborators: Great Lakes Drug Development, Inc., Integrium
Study start: 14 Jan 2009 (actual)
Primary completion: 12 Aug 2009 (actual)
Study completion: 12 Aug 2009 (actual)
First posted: 6 Jan 2009 (estimated)
Results: Posted 2 Jun 2021

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

This study determined the maximum dose of LCI6999 with respect to effect on the ACTH-stimulated cortisol response in participants with hypertension.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Sequential
Masking: Double blind (participant, investigator)
Number of arms: 5

Arm	Type	Receives
Cohort A: LCI699 0.5 mg QD	Experimental	Drug: LCI699Participants received LCI699 0.5 mg, capsules, orally, once daily (QD), with or without food for up to 6 weeks.
Cohort A: LCI699 1.0 mg QD	Experimental	Drug: LCI699Participants received LCI699 1.0 mg, capsules, orally, QD, with or without food for up to 6 weeks.
Cohort B1: LCI699 1.0 mg BID	Experimental	Drug: LCI699Participants received LCI699 1.0 mg, capsules, orally, twice daily (BID), with or without food for up to 6 weeks.
Cohort B1: LCI699 2.0 mg QD	Experimental	Drug: LCI699Participants received LCI699 2.0 mg, capsules, orally, QD, with or without food for up to 6 weeks.
Placebo	Placebo comparator	Drug: LCI699-matching placeboParticipants received LCI699-matching placebo, capsules, orally, QD or BID, with or without food for up to 6 weeks.

Who may qualify

Ages: 18 to 75 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (3 listed)

Diagnosis of hypertension with blood pressure ≥ 140/90 millimeters of mercury (mmHg) and < 180/110 mmHg on current antihypertensive treatment
Male and female participants 18-75 years of age
Participants must weigh at least 50 kilograms (kg)

Key exclusion criteria (6 listed)

Recent history of myocardial infarction, heart failure, unstable angina, coronary artery bypass graft, percutaneous coronary intervention, hypertensive encephalopathy, cerebral accident or transient ischemic attack
Clinically significant electrocardiography (ECG) findings related to cardiac conduction defects
Type 1 diabetes or uncontrolled type 2 diabetes (haemoglobin A1c [HbA1c] > 9%)
Malignancies within the last 5 years (excluding basal cell skin cancer)
Liver disease

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
LCI699-matching placeboLCI699-matching placebo oral capsules	Drug	Placebo
LCI699LCI699 oral capsules	Drug	Cohort A: LCI699 0.5 mg QD, Cohort A: LCI699 1.0 mg QD, Cohort B1: LCI699 1.0 mg BID, Cohort B1: LCI699 2.0 mg QD

Primary outcome

Maximum Tolerated Dose (MTD) of LCI699 With Respect to Effect on the Adrenocorticotropic Hormone (ACTH)-Stimulated Cortisol Response Following ACTH Stimulation in Hypertensive Participants
Time frame: Up to Week 6
As per the protocol, MTD is the dose at which 4 participants exhibited ACTH-stimulated cortisol results <400 nanomoles per liter (nmol/L). The change in the distribution across the treatments were analyzed using 1- way analysis of variance (ANOVA) for continuous variables.

10 secondary outcomes

LCI699 Exposure-response Relationship on Cortisol Levels Following ACTH Stimulation in Hypertensive Participants
Time frame: Up to Week 6
LCI699 Plasma Concentration Post LCI699 Administration at Day 7
Time frame: Predose and 3 hours post-dose on Day 7
Maximum Plasma Concentration (Cmax) of LCI699
Time frame: Days 7, 28: Pre-dose and 3 hours post-dose; Day 30: Pre-dose; Day 42: Pre-dose and 0.5, 1, 2, 3, 4, and 8-hours post-dose
Time of Maximum Plasma Concentration (Tmax) of LCI699
Time frame: Days 7, 28: Pre-dose and 3 hours post-dose; Day 30: Pre-dose; Day 42: Pre-dose and 0.5, 1, 2, 3, 4, and 8-hours post-dose
Area Under the Concentration Time Curve From Time 0 to 8 Hours Post LCI699 Administration (AUC0-8)
Time frame: Day 42: Pre-dose and 0.5, 1, 2, 3, 4, and 8-hours post-dose
Area Under the Concentration Time Curve Over the Dosing Interval (AUC0-τ) for LCI699
Time frame: Days 7, 28: Pre-dose and 3 hours post-dose; Day 30: Pre-dose; Day 42: Pre-dose and 0.5, 1, 2, 3, 4, and 8-hours post-dose
Apparent Terminal Half-life (T1/2) of LCI699
Time frame: Days 7, 28: Pre-dose and 3 hours post-dose; Day 30: Pre-dose; Day 42: Pre-dose and 0.5, 1, 2, 3, 4, and 8-hours post-dose
Number of Participants With Adverse Event (AEs)
Time frame: Up to 8 weeks
Percentage of Participants With a Mean Sitting Systolic Blood Pressure (MSSBP) Response and MSSBP Control at Week 6 Last Observation Carried Forward (LOCF), as Measured by Office Blood Pressure (OBP)
Time frame: Week 6
Percentage of Participants With a Mean Sitting Diastolic Blood Pressure (MSDBP) Response and MSDBP Control at Week 6 LOCF, as Measured by OBP
Time frame: Week 6

Results and safety

Results posted to the registry on 2 Jun 2021, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Cohort A: LCI699 0.5 mg QD	12	10
Cohort A: LCI699 1 mg QD	12	9
Cohort B1: LCI699 1 mg BID	13	9
Cohort B1: LCI699 2 mg QD	13	1
Placebo	13	11

Primary outcome: Maximum Tolerated Dose (MTD) of LCI699 With Respect to Effect on the Adrenocorticotropic Hormone (ACTH)-Stimulated Cortisol Response Following ACTH Stimulation in Hypertensive Participants

Time frame: Up to Week 6. Number (90% Confidence Interval). Unit: milligrams (mg)

Measure	LCI699 n = 63
Value	1.30 (0.88 to 1.81)

Population analysed: Safety set population included all participants who were randomized and received at least 1 dose of study drug.

10 secondary outcomes are reported in the full results.

Adverse events

Time frame: Up to 8 weeks. Other adverse events reported at 2% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Cohort A: LCI699 0.5 mg QD	0 of 12 (0%)	6 of 12 (50%)	0 of 12
Cohort A: LCI699 1.0 mg QD	0 of 12 (0%)	9 of 12 (75%)	0 of 12
Cohort B1: LCI699 1.0 mg BID	0 of 13 (0%)	10 of 13 (76.9%)	0 of 13
Cohort B1: LCI699 2.0 mg QD	0 of 13 (0%)	10 of 13 (76.9%)	0 of 13
Placebo	0 of 13 (0%)	10 of 13 (76.9%)	0 of 13

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 2 Jun 2021.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 24107737Schumacher CD, Steele RE, Brunner HR. Aldosterone synthase inhibition for the treatment of hypertension and the derived mechanistic requirements for a new therapeutic strategy. J Hypertens. 2013 Oct;31(10):2085-93. doi: 10.1097/HJH.0b013e328363570c.

Related trials for Hypertension

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Investigating Vascular Properties of HEMI and SPG Signals in Individuals With or at Risk for Chronic Kidney Disease
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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.

Novartis Pharmaceuticals study director

Novartis Pharmaceuticals

11 sites in 2 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing LCI699 in people with Hypertension, run by Novartis at 11 sites in 2 countries.

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 3 inclusion and 6 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 2 Jun 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 11 sites in United States, Iceland. 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. Some participants in this study may receive a placebo. 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?

Yes. Results are posted in the registry (first posted 2 Jun 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Maximum Tolerated Dose (MTD) of LCI699 With Respect to Effect on the Adrenocorticotropic Hormone (ACTH)-Stimulated Cortisol Response Following ACTH Stimulation in Hypertensive Participants (time frame: Up to Week 6). 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 NCT00817414, which also lists 1 linked publication.

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 2 Jun 2021.