Hypertension
Conditions
Keywords
Blood Pressure, Hypertension, Cortisol
Brief summary
This study determined the maximum dose of LCI6999 with respect to effect on the ACTH-stimulated cortisol response in participants with hypertension.
Interventions
LCI699-matching placebo oral capsules
DRUGLCI699
LCI699 oral capsules
Sponsors
Great Lakes Drug Development, Inc.
Integrium
Novartis
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* 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)
Exclusion criteria
* 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/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Tolerated Dose (MTD) of LCI699 With Respect to Effect on the Adrenocorticotropic Hormone (ACTH)-Stimulated Cortisol Response Following ACTH Stimulation in Hypertensive Participants | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| LCI699 Plasma Concentration Post LCI699 Administration at Day 7 | Predose and 3 hours post-dose on Day 7 | — |
| Maximum Plasma Concentration (Cmax) of LCI699 | 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 | 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) | Day 42: Pre-dose and 0.5, 1, 2, 3, 4, and 8-hours post-dose | — |
| LCI699 Exposure-response Relationship on Cortisol Levels Following ACTH Stimulation in Hypertensive Participants | Up to Week 6 | 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. |
| Apparent Terminal Half-life (T1/2) of LCI699 | 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) | Up to 8 weeks | 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. |
| 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) | Week 6 | 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. |
| Percentage of Participants With a Mean Sitting Diastolic Blood Pressure (MSDBP) Response and MSDBP Control at Week 6 LOCF, as Measured by OBP | Week 6 | 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. |
| Area Under the Concentration Time Curve Over the Dosing Interval (AUC0-τ) for LCI699 | 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 | — |
Countries
Iceland, United States
Participant flow
Recruitment details
Participants were enrolled at 10 investigative sites in the United States and Iceland from 14 January 2009 to 12 August 2009.
Pre-assignment details
A total of 63 participants with essential hypertension taking at least one anti-hypertensive treatment were randomized to receive LCI699 in comparison with placebo in an escalated dose design for 6 weeks.
Participants by arm
| Arm | Count |
|---|---|
| Cohort A: LCI699 0.5 mg QD Participants received LCI699 0.5 mg, capsules, orally, once daily (QD), with or without food for up to 6 weeks. | 12 |
| Cohort A: LCI699 1 mg QD Participants received LCI699 1.0 mg, capsules, orally, QD, with or without food for up to 6 weeks. | 12 |
| Cohort B1: LCI699 1 mg BID Participants received LCI699 1.0 mg, capsules, orally, twice daily (BID), with or without food for up to 6 weeks. | 13 |
| Cohort B1: LCI699 2 mg QD Participants received LCI699 2.0 mg, capsules, orally, QD, with or without food for up to 6 weeks. | 13 |
| Placebo Participants received LCI699-matching placebo, capsules, orally, QD or BID with or without food for up to 6 weeks. | 13 |
| Total | 63 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 1 | 1 | 0 | 0 |
| Overall Study | Dose Arm Exceeds Maximum Tolerated Dose (MTD) | 0 | 0 | 0 | 7 | 0 |
| Overall Study | Lost to Follow-up | 0 | 0 | 1 | 1 | 1 |
| Overall Study | Low Adrenocorticotropic Hormone (ACTH)- Stimulated Cortisol | 0 | 1 | 2 | 4 | 0 |
| Overall Study | Protocol Violation | 0 | 0 | 0 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 1 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Cohort A: LCI699 0.5 mg QD | Cohort A: LCI699 1 mg QD | Cohort B1: LCI699 1 mg BID | Cohort B1: LCI699 2 mg QD | Placebo | Total |
|---|---|---|---|---|---|---|
| Age, Continuous | 56.1 years STANDARD_DEVIATION 6.37 | 54.2 years STANDARD_DEVIATION 16.01 | 57.9 years STANDARD_DEVIATION 9.09 | 56.2 years STANDARD_DEVIATION 10.37 | 56.8 years STANDARD_DEVIATION 10.08 | 56.3 years STANDARD_DEVIATION 10.52 |
| Sex: Female, Male Female | 4 Participants | 5 Participants | 3 Participants | 5 Participants | 4 Participants | 21 Participants |
| Sex: Female, Male Male | 8 Participants | 7 Participants | 10 Participants | 8 Participants | 9 Participants | 42 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 12 | 0 / 12 | 0 / 13 | 0 / 13 | 0 / 13 |
| other Total, other adverse events | 6 / 12 | 9 / 12 | 10 / 13 | 10 / 13 | 10 / 13 |
| serious Total, serious adverse events | 0 / 12 | 0 / 12 | 0 / 13 | 0 / 13 | 0 / 13 |
Outcome results
Primary
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.
Time frame: Up to Week 6
Population: Safety set population included all participants who were randomized and received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| LCI699 | Maximum Tolerated Dose (MTD) of LCI699 With Respect to Effect on the Adrenocorticotropic Hormone (ACTH)-Stimulated Cortisol Response Following ACTH Stimulation in Hypertensive Participants | 1.30 milligrams (mg) |
Secondary
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
Population: PK set population included all participants with sufficient LCI699 plasma samples at post-baseline visits. Overall number analysed is the number of participants with data available for these analyses.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| LCI699 | Apparent Terminal Half-life (T1/2) of LCI699 | 4.67 hr | Geometric Coefficient of Variation 37 |
| Cohort A: LCI699 1.0 mg QD | Apparent Terminal Half-life (T1/2) of LCI699 | 3.79 hr | Geometric Coefficient of Variation 43 |
| Cohort B1: LCI699 1.0 mg BID | Apparent Terminal Half-life (T1/2) of LCI699 | 5.52 hr | Geometric Coefficient of Variation 33 |
| Cohort B1: LCI699 2.0 mg QD | Apparent Terminal Half-life (T1/2) of LCI699 | 4.90 hr | Geometric Coefficient of Variation 17 |
Secondary
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
Population: PK set population included all participants with sufficient LCI699 plasma samples at post-baseline visits. Overall number analysed is the number of participants with data available for these analyses.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| LCI699 | Area Under the Concentration Time Curve From Time 0 to 8 Hours Post LCI699 Administration (AUC0-8) | 6.60 nanogram*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 42 |
| Cohort A: LCI699 1.0 mg QD | Area Under the Concentration Time Curve From Time 0 to 8 Hours Post LCI699 Administration (AUC0-8) | 14.1 nanogram*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 30 |
| Cohort B1: LCI699 1.0 mg BID | Area Under the Concentration Time Curve From Time 0 to 8 Hours Post LCI699 Administration (AUC0-8) | 24.1 nanogram*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 39 |
| Cohort B1: LCI699 2.0 mg QD | Area Under the Concentration Time Curve From Time 0 to 8 Hours Post LCI699 Administration (AUC0-8) | 46.4 nanogram*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 13 |
Secondary
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
Population: PK set population included all participants with sufficient LCI699 plasma samples at post-baseline visits. Overall number analysed is the number of participants with data available for these analyses.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| LCI699 | Area Under the Concentration Time Curve Over the Dosing Interval (AUC0-τ) for LCI699 | 9.23 ng*hr/mL | Geometric Coefficient of Variation 50 |
| Cohort A: LCI699 1.0 mg QD | Area Under the Concentration Time Curve Over the Dosing Interval (AUC0-τ) for LCI699 | 18.8 ng*hr/mL | Geometric Coefficient of Variation 51 |
| Cohort B1: LCI699 1.0 mg BID | Area Under the Concentration Time Curve Over the Dosing Interval (AUC0-τ) for LCI699 | 30.6 ng*hr/mL | Geometric Coefficient of Variation 41 |
| Cohort B1: LCI699 2.0 mg QD | Area Under the Concentration Time Curve Over the Dosing Interval (AUC0-τ) for LCI699 | 68.9 ng*hr/mL | Geometric Coefficient of Variation 19 |
Secondary
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.
Time frame: Up to Week 6
Population: Safety set population included all participants who were randomized and received at least 1 dose of study drug. Number analyzed is the number of participants with data available for analyses at the given timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| LCI699 | LCI699 Exposure-response Relationship on Cortisol Levels Following ACTH Stimulation in Hypertensive Participants | Day 7 | 690.0 nanomoles per liter (nmol/L) | Standard Error 32.288 |
| LCI699 | LCI699 Exposure-response Relationship on Cortisol Levels Following ACTH Stimulation in Hypertensive Participants | Day 42 | 647.51 nanomoles per liter (nmol/L) | Standard Error 45.593 |
| LCI699 | LCI699 Exposure-response Relationship on Cortisol Levels Following ACTH Stimulation in Hypertensive Participants | Day 28 | 634.87 nanomoles per liter (nmol/L) | Standard Error 32.181 |
| Cohort A: LCI699 1.0 mg QD | LCI699 Exposure-response Relationship on Cortisol Levels Following ACTH Stimulation in Hypertensive Participants | Day 28 | 573.41 nanomoles per liter (nmol/L) | Standard Error 30.642 |
| Cohort A: LCI699 1.0 mg QD | LCI699 Exposure-response Relationship on Cortisol Levels Following ACTH Stimulation in Hypertensive Participants | Day 7 | 669.40 nanomoles per liter (nmol/L) | Standard Error 30.903 |
| Cohort A: LCI699 1.0 mg QD | LCI699 Exposure-response Relationship on Cortisol Levels Following ACTH Stimulation in Hypertensive Participants | Day 42 | 626.08 nanomoles per liter (nmol/L) | Standard Error 45.441 |
| Cohort B1: LCI699 1.0 mg BID | LCI699 Exposure-response Relationship on Cortisol Levels Following ACTH Stimulation in Hypertensive Participants | Day 28 | 554.79 nanomoles per liter (nmol/L) | Standard Error 29.466 |
| Cohort B1: LCI699 1.0 mg BID | LCI699 Exposure-response Relationship on Cortisol Levels Following ACTH Stimulation in Hypertensive Participants | Day 7 | 625.06 nanomoles per liter (nmol/L) | Standard Error 30.965 |
| Cohort B1: LCI699 1.0 mg BID | LCI699 Exposure-response Relationship on Cortisol Levels Following ACTH Stimulation in Hypertensive Participants | Day 42 | 539.68 nanomoles per liter (nmol/L) | Standard Error 37.146 |
| Cohort B1: LCI699 2.0 mg QD | LCI699 Exposure-response Relationship on Cortisol Levels Following ACTH Stimulation in Hypertensive Participants | Day 7 | 562.04 nanomoles per liter (nmol/L) | Standard Error 30.325 |
| Cohort B1: LCI699 2.0 mg QD | LCI699 Exposure-response Relationship on Cortisol Levels Following ACTH Stimulation in Hypertensive Participants | Day 42 | 479.91 nanomoles per liter (nmol/L) | Standard Error 48.865 |
| Cohort B1: LCI699 2.0 mg QD | LCI699 Exposure-response Relationship on Cortisol Levels Following ACTH Stimulation in Hypertensive Participants | Day 28 | 539.09 nanomoles per liter (nmol/L) | Standard Error 32.826 |
| Placebo | LCI699 Exposure-response Relationship on Cortisol Levels Following ACTH Stimulation in Hypertensive Participants | Day 28 | 804.86 nanomoles per liter (nmol/L) | Standard Error 29.786 |
| Placebo | LCI699 Exposure-response Relationship on Cortisol Levels Following ACTH Stimulation in Hypertensive Participants | Day 7 | 799.06 nanomoles per liter (nmol/L) | Standard Error 31.161 |
| Placebo | LCI699 Exposure-response Relationship on Cortisol Levels Following ACTH Stimulation in Hypertensive Participants | Day 42 | 812.91 nanomoles per liter (nmol/L) | Standard Error 39.096 |
Secondary
LCI699 Plasma Concentration Post LCI699 Administration at Day 7
Time frame: Predose and 3 hours post-dose on Day 7
Population: Pharmacokinetic (PK) set population included all participants with sufficient LCI699 plasma samples at post-baseline visits.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| LCI699 | LCI699 Plasma Concentration Post LCI699 Administration at Day 7 | 1.51 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 36 |
| Cohort A: LCI699 1.0 mg QD | LCI699 Plasma Concentration Post LCI699 Administration at Day 7 | 2.88 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 41 |
| Cohort B1: LCI699 1.0 mg BID | LCI699 Plasma Concentration Post LCI699 Administration at Day 7 | 3.92 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 31 |
| Cohort B1: LCI699 2.0 mg QD | LCI699 Plasma Concentration Post LCI699 Administration at Day 7 | 6.73 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 23 |
Secondary
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
Population: PK set population included all participants with sufficient LCI699 plasma samples at post-baseline visits. Overall number analysed is the number of participants with data available for these analyses.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| LCI699 | Maximum Plasma Concentration (Cmax) of LCI699 | 1.42 ng/mL | Geometric Coefficient of Variation 36 |
| Cohort A: LCI699 1.0 mg QD | Maximum Plasma Concentration (Cmax) of LCI699 | 2.94 ng/mL | Geometric Coefficient of Variation 35 |
| Cohort B1: LCI699 1.0 mg BID | Maximum Plasma Concentration (Cmax) of LCI699 | 4.62 ng/mL | Geometric Coefficient of Variation 35 |
| Cohort B1: LCI699 2.0 mg QD | Maximum Plasma Concentration (Cmax) of LCI699 | 8.86 ng/mL | Geometric Coefficient of Variation 21 |
Secondary
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.
Time frame: Up to 8 weeks
Population: Safety set population included all participants who were randomized and received at least 1 dose of study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| LCI699 | Number of Participants With Adverse Event (AEs) | 6 Participants |
| Cohort A: LCI699 1.0 mg QD | Number of Participants With Adverse Event (AEs) | 9 Participants |
| Cohort B1: LCI699 1.0 mg BID | Number of Participants With Adverse Event (AEs) | 10 Participants |
| Cohort B1: LCI699 2.0 mg QD | Number of Participants With Adverse Event (AEs) | 10 Participants |
| Placebo | Number of Participants With Adverse Event (AEs) | 10 Participants |
Secondary
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.
Time frame: Week 6
Population: FAS population included all participants who were randomized and received at least 1 dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| LCI699 | Percentage of Participants With a Mean Sitting Diastolic Blood Pressure (MSDBP) Response and MSDBP Control at Week 6 LOCF, as Measured by OBP | MSDBP Response | 58.3 percentage of participants |
| LCI699 | Percentage of Participants With a Mean Sitting Diastolic Blood Pressure (MSDBP) Response and MSDBP Control at Week 6 LOCF, as Measured by OBP | MSDBP Control | 58.3 percentage of participants |
| Cohort A: LCI699 1.0 mg QD | Percentage of Participants With a Mean Sitting Diastolic Blood Pressure (MSDBP) Response and MSDBP Control at Week 6 LOCF, as Measured by OBP | MSDBP Response | 66.7 percentage of participants |
| Cohort A: LCI699 1.0 mg QD | Percentage of Participants With a Mean Sitting Diastolic Blood Pressure (MSDBP) Response and MSDBP Control at Week 6 LOCF, as Measured by OBP | MSDBP Control | 66.7 percentage of participants |
| Cohort B1: LCI699 1.0 mg BID | Percentage of Participants With a Mean Sitting Diastolic Blood Pressure (MSDBP) Response and MSDBP Control at Week 6 LOCF, as Measured by OBP | MSDBP Response | 100 percentage of participants |
| Cohort B1: LCI699 1.0 mg BID | Percentage of Participants With a Mean Sitting Diastolic Blood Pressure (MSDBP) Response and MSDBP Control at Week 6 LOCF, as Measured by OBP | MSDBP Control | 76.9 percentage of participants |
| Cohort B1: LCI699 2.0 mg QD | Percentage of Participants With a Mean Sitting Diastolic Blood Pressure (MSDBP) Response and MSDBP Control at Week 6 LOCF, as Measured by OBP | MSDBP Control | 76.9 percentage of participants |
| Cohort B1: LCI699 2.0 mg QD | Percentage of Participants With a Mean Sitting Diastolic Blood Pressure (MSDBP) Response and MSDBP Control at Week 6 LOCF, as Measured by OBP | MSDBP Response | 76.9 percentage of participants |
| Placebo | Percentage of Participants With a Mean Sitting Diastolic Blood Pressure (MSDBP) Response and MSDBP Control at Week 6 LOCF, as Measured by OBP | MSDBP Response | 61.5 percentage of participants |
| Placebo | Percentage of Participants With a Mean Sitting Diastolic Blood Pressure (MSDBP) Response and MSDBP Control at Week 6 LOCF, as Measured by OBP | MSDBP Control | 46.2 percentage of participants |
Secondary
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.
Time frame: Week 6
Population: FAS population included all participants who were randomized and received at least 1 dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| LCI699 | 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) | MSSBP Response | 58.3 percentage of participants |
| LCI699 | 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) | MSSBP Control | 50.0 percentage of participants |
| Cohort A: LCI699 1.0 mg QD | 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) | MSSBP Response | 50.0 percentage of participants |
| Cohort A: LCI699 1.0 mg QD | 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) | MSSBP Control | 41.7 percentage of participants |
| Cohort B1: LCI699 1.0 mg BID | 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) | MSSBP Response | 69.2 percentage of participants |
| Cohort B1: LCI699 1.0 mg BID | 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) | MSSBP Control | 61.5 percentage of participants |
| Cohort B1: LCI699 2.0 mg QD | 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) | MSSBP Control | 76.9 percentage of participants |
| Cohort B1: LCI699 2.0 mg QD | 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) | MSSBP Response | 76.9 percentage of participants |
| Placebo | 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) | MSSBP Response | 61.5 percentage of participants |
| Placebo | 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) | MSSBP Control | 53.8 percentage of participants |
Secondary
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
Population: PK set population included all participants with sufficient LCI699 plasma samples at post-baseline visits. Overall number analysed is the number of participants with data available for these analyses.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| LCI699 | Time of Maximum Plasma Concentration (Tmax) of LCI699 | 2.21 hour (hr) |
| Cohort A: LCI699 1.0 mg QD | Time of Maximum Plasma Concentration (Tmax) of LCI699 | 1.00 hour (hr) |
| Cohort B1: LCI699 1.0 mg BID | Time of Maximum Plasma Concentration (Tmax) of LCI699 | 1.00 hour (hr) |
| Cohort B1: LCI699 2.0 mg QD | Time of Maximum Plasma Concentration (Tmax) of LCI699 | 1.00 hour (hr) |