A Study to Evaluate the Effects of LCI699 on Cortisol in Participants With Hypertension
Sponsor
Novartis (Industry)
Overall Status
Completed
CT.gov ID
NCT00817414
Collaborator
Great Lakes Drug Development, Inc. (Industry), Integrium (Industry)
63
11
5
6.9
5.7
0.8
Study Details
Study Description
Brief Summary
This study determined the maximum dose of LCI6999 with respect to effect on the ACTH-stimulated cortisol response in participants with hypertension.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
63 participants
Allocation:
Randomized
Intervention Model:
Sequential Assignment
Masking:
Double (Participant, Investigator)
Primary Purpose:
Treatment
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
Actual Study Start Date
:
Jan 14, 2009
Actual Primary Completion Date
:
Aug 12, 2009
Actual Study Completion Date
:
Aug 12, 2009
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: 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. |
Drug: LCI699
LCI699 oral capsules
|
| Experimental: Cohort A: LCI699 1.0 mg QD Participants received LCI699 1.0 mg, capsules, orally, QD, with or without food for up to 6 weeks. |
Drug: LCI699
LCI699 oral capsules
|
| Experimental: Cohort B1: LCI699 1.0 mg BID Participants received LCI699 1.0 mg, capsules, orally, twice daily (BID), with or without food for up to 6 weeks. |
Drug: LCI699
LCI699 oral capsules
|
| Experimental: Cohort B1: LCI699 2.0 mg QD Participants received LCI699 2.0 mg, capsules, orally, QD, with or without food for up to 6 weeks. |
Drug: LCI699
LCI699 oral capsules
|
| Placebo Comparator: Placebo Participants received LCI699-matching placebo, capsules, orally, QD or BID, with or without food for up to 6 weeks. |
Drug: LCI699-matching placebo
LCI699-matching placebo oral capsules
|
Outcome Measures
Primary Outcome Measures
- 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 Outcome Measures
- 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.
- 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]
- 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]
- 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.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
to 75 Years
Sexes Eligible for Study:
All
Accepts 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/exclusion criteria may apply.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Impact Clinical Trials | Beverly Hills | California | United States | 90211 |
| 2 | Associated Pharmaceutical Research Center, Inc | Buena Park | California | United States | 90620 |
| 3 | Innovative Clinical Research, Inc | Harbor City | California | United States | 90710 |
| 4 | Long Beach Center for Clinical Research | Long Beach | California | United States | 90806 |
| 5 | Metro Clinical Research | Littleton | Colorado | United States | 80120 |
| 6 | Clinical Study Center of Asheville, LLC | Asheville | North Carolina | United States | 28801 |
| 7 | Northstate Clinical Research | Lenoir | North Carolina | United States | 28645 |
| 8 | Tipton Medical & Diagnostic Center | Tipton | Pennsylvania | United States | 16684 |
| 9 | Punzi Medical Center | Carrollton | Texas | United States | 75006 |
| 10 | dgd Research, Inc | San Antonio | Texas | United States | 78229 |
| 11 | Encode Clinic | Reykjavik | SA | Iceland |
Sponsors and Collaborators
- Novartis
- Great Lakes Drug Development, Inc.
- Integrium
Investigators
- Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.Responsible Party:
Novartis
ClinicalTrials.gov Identifier:
NCT00817414
Other Study ID Numbers:
- CLCI699A2215
- 2008-007337-49
First Posted:
Jan 6, 2009
Last Update Posted:
Jun 2, 2021
Last Verified:
May 1, 2021
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by Novartis
Additional relevant MeSH terms:
Study Results
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 Detail | 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. |
| Arm/Group Title | 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 |
|---|---|---|---|---|---|
| Arm/Group Description | Participants received LCI699 0.5 mg, capsules, orally, once daily (QD), with or without food for up to 6 weeks. | Participants received LCI699 1.0 mg, capsules, orally, QD, with or without food for up to 6 weeks. | Participants received LCI699 1.0 mg, capsules, orally, twice daily (BID), with or without food for up to 6 weeks. | Participants received LCI699 2.0 mg, capsules, orally, QD, with or without food for up to 6 weeks. | Participants received LCI699-matching placebo, capsules, orally, QD or BID with or without food for up to 6 weeks. |
| Period Title: Overall Study | |||||
| STARTED | 12 | 12 | 13 | 13 | 13 |
| COMPLETED | 10 | 9 | 9 | 1 | 11 |
| NOT COMPLETED | 2 | 3 | 4 | 12 | 2 |
Baseline Characteristics
| Arm/Group Title | 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 |
|---|---|---|---|---|---|---|
| Arm/Group Description | Participants received LCI699 0.5 mg, capsules, orally, once daily (QD), with or without food for up to 6 weeks. | Participants received LCI699 1.0 mg, capsules, orally, QD, with or without food for up to 6 weeks. | Participants received LCI699 1.0 mg, capsules, orally, twice daily (BID), with or without food for up to 6 weeks. | Participants received LCI699 2.0 mg, capsules, orally, QD, with or without food for up to 6 weeks. | Participants received LCI699-matching placebo, capsules, orally, QD or BID with or without food for up to 6 weeks. | Total of all reporting groups |
| Overall Participants | 12 | 12 | 13 | 13 | 13 | 63 |
| Age (years) [Mean (Standard Deviation) ] | ||||||
| Mean (Standard Deviation) [years] |
56.1
(6.37)
|
54.2
(16.01)
|
57.9
(9.09)
|
56.2
(10.37)
|
56.8
(10.08)
|
56.3
(10.52)
|
| Sex: Female, Male (Count of Participants) | ||||||
| Female |
4
33.3%
|
5
41.7%
|
3
23.1%
|
5
38.5%
|
4
30.8%
|
21
33.3%
|
| Male |
8
66.7%
|
7
58.3%
|
10
76.9%
|
8
61.5%
|
9
69.2%
|
42
66.7%
|
Outcome Measures
| Title | Maximum Tolerated Dose (MTD) of LCI699 With Respect to Effect on the Adrenocorticotropic Hormone (ACTH)-Stimulated Cortisol Response Following ACTH Stimulation in Hypertensive Participants |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety set population included all participants who were randomized and received at least 1 dose of study drug. |
| Arm/Group Title | LCI699 |
|---|---|
| Arm/Group Description | Participants received LCI699 capsules, orally, QD or BID, with or without food for up to 6 weeks. |
| Measure Participants | 63 |
| Number (90% Confidence Interval) [milligrams (mg)] |
1.30
|
| Title | LCI699 Exposure-response Relationship on Cortisol Levels Following ACTH Stimulation in Hypertensive Participants |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | 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 | Placebo |
|---|---|---|---|---|---|
| Arm/Group Description | Participants received LCI699 0.5 mg, capsules, orally, once daily (QD), with or without food for up to 6 weeks. | Participants received LCI699 1.0 mg, capsules, orally, QD, with or without food for up to 6 weeks. | Participants received LCI699 1.0 mg, capsules, orally, twice daily (BID), with or without food for up to 6 weeks. | Participants received LCI699 2.0 mg, capsules, orally, QD, with or without food for up to 6 weeks. | Participants received LCI699-matching placebo, capsules, orally, QD or BID, with or without food for up to 6 weeks. |
| Measure Participants | 11 | 12 | 12 | 13 | 12 |
| Day 7 |
690.0
(32.288)
|
669.40
(30.903)
|
625.06
(30.965)
|
562.04
(30.325)
|
799.06
(31.161)
|
| Day 28 |
634.87
(32.181)
|
573.41
(30.642)
|
554.79
(29.466)
|
539.09
(32.826)
|
804.86
(29.786)
|
| Day 42 |
647.51
(45.593)
|
626.08
(45.441)
|
539.68
(37.146)
|
479.91
(48.865)
|
812.91
(39.096)
|
| Title | LCI699 Plasma Concentration Post LCI699 Administration at Day 7 |
|---|---|
| Description | |
| Time Frame | Predose and 3 hours post-dose on Day 7 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacokinetic (PK) set population included all participants with sufficient LCI699 plasma samples at post-baseline visits. |
| Arm/Group Title | 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 |
|---|---|---|---|---|
| Arm/Group Description | Participants received LCI699 0.5 mg, capsules, orally, once daily (QD), with or without food for up to 6 weeks. | Participants received LCI699 1.0 mg, capsules, orally, QD, with or without food for up to 6 weeks. | Participants received LCI699 1.0 mg, capsules, orally, twice daily (BID), with or without food for up to 6 weeks. | Participants received LCI699 2.0 mg, capsules, orally, QD, with or without food for up to 6 weeks. |
| Measure Participants | 11 | 12 | 13 | 13 |
| Geometric Mean (Geometric Coefficient of Variation) [nanogram per milliliter (ng/mL)] |
1.51
(36)
|
2.88
(41)
|
3.92
(31)
|
6.73
(23)
|
| Title | Maximum Plasma Concentration (Cmax) of LCI699 |
|---|---|
| Description | |
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | 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 |
|---|---|---|---|---|
| Arm/Group Description | Participants received LCI699 0.5 mg, capsules, orally, once daily (QD), with or without food for up to 6 weeks. | Participants received LCI699 1.0 mg, capsules, orally, QD, with or without food for up to 6 weeks. | Participants received LCI699 1.0 mg, capsules, orally, twice daily (BID), with or without food for up to 6 weeks. | Participants received LCI699 2.0 mg, capsules, orally, QD, with or without food for up to 6 weeks. |
| Measure Participants | 10 | 7 | 12 | 4 |
| Geometric Mean (Geometric Coefficient of Variation) [ng/mL] |
1.42
(36)
|
2.94
(35)
|
4.62
(35)
|
8.86
(21)
|
| Title | Time of Maximum Plasma Concentration (Tmax) of LCI699 |
|---|---|
| Description | |
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | 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 |
|---|---|---|---|---|
| Arm/Group Description | Participants received LCI699 0.5 mg, capsules, orally, once daily (QD), with or without food for up to 6 weeks. | Participants received LCI699 1.0 mg, capsules, orally, QD, with or without food for up to 6 weeks. | Participants received LCI699 1.0 mg, capsules, orally, twice daily (BID), with or without food for up to 6 weeks. | Participants received LCI699 2.0 mg, capsules, orally, QD, with or without food for up to 6 weeks. |
| Measure Participants | 10 | 7 | 12 | 4 |
| Median (Full Range) [hour (hr)] |
2.21
|
1.00
|
1.00
|
1.00
|
| Title | Area Under the Concentration Time Curve From Time 0 to 8 Hours Post LCI699 Administration (AUC0-8) |
|---|---|
| Description | |
| Time Frame | Day 42: Pre-dose and 0.5, 1, 2, 3, 4, and 8-hours post-dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | 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 |
|---|---|---|---|---|
| Arm/Group Description | Participants received LCI699 0.5 mg, capsules, orally, once daily (QD), with or without food for up to 6 weeks. | Participants received LCI699 1.0 mg, capsules, orally, QD, with or without food for up to 6 weeks. | Participants received LCI699 1.0 mg, capsules, orally, twice daily (BID), with or without food for up to 6 weeks. | Participants received LCI699 2.0 mg, capsules, orally, QD, with or without food for up to 6 weeks. |
| Measure Participants | 10 | 7 | 12 | 4 |
| Geometric Mean (Geometric Coefficient of Variation) [nanogram*hour per milliliter (ng*hr/mL)] |
6.60
(42)
|
14.1
(30)
|
24.1
(39)
|
46.4
(13)
|
| Title | Area Under the Concentration Time Curve Over the Dosing Interval (AUC0-τ) for LCI699 |
|---|---|
| Description | |
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | 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 |
|---|---|---|---|---|
| Arm/Group Description | Participants received LCI699 0.5 mg, capsules, orally, once daily (QD), with or without food for up to 6 weeks. | Participants received LCI699 1.0 mg, capsules, orally, QD, with or without food for up to 6 weeks. | Participants received LCI699 1.0 mg, capsules, orally, twice daily (BID), with or without food for up to 6 weeks. | Participants received LCI699 2.0 mg, capsules, orally, QD, with or without food for up to 6 weeks. |
| Measure Participants | 9 | 6 | 11 | 4 |
| Geometric Mean (Geometric Coefficient of Variation) [ng*hr/mL] |
9.23
(50)
|
18.8
(51)
|
30.6
(41)
|
68.9
(19)
|
| Title | Apparent Terminal Half-life (T1/2) of LCI699 |
|---|---|
| Description | |
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | 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 |
|---|---|---|---|---|
| Arm/Group Description | Participants received LCI699 0.5 mg, capsules, orally, once daily (QD), with or without food for up to 6 weeks. | Participants received LCI699 1.0 mg, capsules, orally, QD, with or without food for up to 6 weeks. | Participants received LCI699 1.0 mg, capsules, orally, twice daily (BID), with or without food for up to 6 weeks. | Participants received LCI699 2.0 mg, capsules, orally, QD, with or without food for up to 6 weeks. |
| Measure Participants | 9 | 6 | 11 | 4 |
| Geometric Mean (Geometric Coefficient of Variation) [hr] |
4.67
(37)
|
3.79
(43)
|
5.52
(33)
|
4.90
(17)
|
| Title | Number of Participants With Adverse Event (AEs) |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety set population included all participants who were randomized and received at least 1 dose of study drug. |
| Arm/Group Title | 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 |
|---|---|---|---|---|---|
| Arm/Group Description | Participants received LCI699 0.5 mg, capsules, orally, once daily (QD), with or without food for up to 6 weeks. | Participants received LCI699 1.0 mg, capsules, orally, QD, with or without food for up to 6 weeks. | Participants received LCI699 1.0 mg, capsules, orally, twice daily (BID), with or without food for up to 6 weeks. | Participants received LCI699 2.0 mg, capsules, orally, QD, with or without food for up to 6 weeks. | Participants received LCI699-matching placebo, capsules, orally, QD or BID with or without food for up to 6 weeks. |
| Measure Participants | 12 | 12 | 13 | 13 | 13 |
| Count of Participants [Participants] |
6
50%
|
9
75%
|
10
76.9%
|
10
76.9%
|
10
76.9%
|
| Title | 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) |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| FAS population included all participants who were randomized and received at least 1 dose of study drug. |
| Arm/Group Title | 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 |
|---|---|---|---|---|---|
| Arm/Group Description | Participants received LCI699 0.5 mg, capsules, orally, once daily (QD), with or without food for up to 6 weeks. | Participants received LCI699 1.0 mg, capsules, orally, QD, with or without food for up to 6 weeks. | Participants received LCI699 1.0 mg, capsules, orally, twice daily (BID), with or without food for up to 6 weeks. | Participants received LCI699 2.0 mg, capsules, orally, QD, with or without food for up to 6 weeks. | Participants received LCI699-matching placebo, capsules, orally, QD or BID with or without food for up to 6 weeks. |
| Measure Participants | 12 | 12 | 13 | 13 | 13 |
| MSSBP Response |
58.3
485.8%
|
50.0
416.7%
|
69.2
532.3%
|
76.9
591.5%
|
61.5
473.1%
|
| MSSBP Control |
50.0
416.7%
|
41.7
347.5%
|
61.5
473.1%
|
76.9
591.5%
|
53.8
413.8%
|
| Title | Percentage of Participants With a Mean Sitting Diastolic Blood Pressure (MSDBP) Response and MSDBP Control at Week 6 LOCF, as Measured by OBP |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| FAS population included all participants who were randomized and received at least 1 dose of study drug. |
| Arm/Group Title | 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 |
|---|---|---|---|---|---|
| Arm/Group Description | Participants received LCI699 0.5 mg, capsules, orally, once daily (QD), with or without food for up to 6 weeks. | Participants received LCI699 1.0 mg, capsules, orally, QD, with or without food for up to 6 weeks. | Participants received LCI699 1.0 mg, capsules, orally, twice daily (BID), with or without food for up to 6 weeks. | Participants received LCI699 2.0 mg, capsules, orally, QD, with or without food for up to 6 weeks. | Participants received LCI699-matching placebo, capsules, orally, QD or BID with or without food for up to 6 weeks. |
| Measure Participants | 12 | 12 | 13 | 13 | 13 |
| MSDBP Response |
58.3
485.8%
|
66.7
555.8%
|
100
769.2%
|
76.9
591.5%
|
61.5
473.1%
|
| MSDBP Control |
58.3
485.8%
|
66.7
555.8%
|
76.9
591.5%
|
76.9
591.5%
|
46.2
355.4%
|
Adverse Events
| Time Frame | Up to 8 weeks | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | 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. | |||||||||
| Arm/Group Title | 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 | Placebo | |||||
| Arm/Group Description | Participants received LCI699 0.5 mg, capsules, orally, once daily (QD), with or without food for up to 6 weeks. | Participants received LCI699 1.0 mg, capsules, orally, QD, with or without food for up to 6 weeks. | Participants received LCI699 1.0 mg, capsules, orally, twice daily (BID), with or without food for up to 6 weeks. | Participants received LCI699 2.0 mg, capsules, orally, QD, with or without food for up to 6 weeks. | Participants received LCI699-matching placebo, capsules, orally, QD or BID, with or without food for up to 6 weeks. | |||||
All Cause Mortality |
||||||||||
| 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 | Placebo | ||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/12 (0%) | 0/12 (0%) | 0/13 (0%) | 0/13 (0%) | 0/13 (0%) | |||||
Serious Adverse Events |
||||||||||
| 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 | Placebo | ||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/12 (0%) | 0/12 (0%) | 0/13 (0%) | 0/13 (0%) | 0/13 (0%) | |||||
Other (Not Including Serious) Adverse Events |
||||||||||
| 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 | Placebo | ||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 6/12 (50%) | 9/12 (75%) | 10/13 (76.9%) | 10/13 (76.9%) | 10/13 (76.9%) | |||||
| Blood and lymphatic system disorders | ||||||||||
| Anaemia | 1/12 (8.3%) | 0/12 (0%) | 0/13 (0%) | 0/13 (0%) | 0/13 (0%) | |||||
| Cardiac disorders | ||||||||||
| Palpitations | 0/12 (0%) | 1/12 (8.3%) | 0/13 (0%) | 0/13 (0%) | 0/13 (0%) | |||||
| Eye disorders | ||||||||||
| Vision blurred | 0/12 (0%) | 0/12 (0%) | 1/13 (7.7%) | 0/13 (0%) | 0/13 (0%) | |||||
| Gastrointestinal disorders | ||||||||||
| Abdominal discomfort | 0/12 (0%) | 0/12 (0%) | 1/13 (7.7%) | 0/13 (0%) | 0/13 (0%) | |||||
| Abdominal pain | 0/12 (0%) | 1/12 (8.3%) | 0/13 (0%) | 0/13 (0%) | 0/13 (0%) | |||||
| Abdominal pain lower | 0/12 (0%) | 0/12 (0%) | 1/13 (7.7%) | 0/13 (0%) | 0/13 (0%) | |||||
| Abdominal pain upper | 0/12 (0%) | 0/12 (0%) | 1/13 (7.7%) | 0/13 (0%) | 0/13 (0%) | |||||
| Constipation | 0/12 (0%) | 0/12 (0%) | 1/13 (7.7%) | 0/13 (0%) | 0/13 (0%) | |||||
| Diarrhoea | 0/12 (0%) | 1/12 (8.3%) | 2/13 (15.4%) | 0/13 (0%) | 3/13 (23.1%) | |||||
| Dry mouth | 1/12 (8.3%) | 0/12 (0%) | 0/13 (0%) | 0/13 (0%) | 0/13 (0%) | |||||
| Dyspepsia | 1/12 (8.3%) | 1/12 (8.3%) | 0/13 (0%) | 1/13 (7.7%) | 1/13 (7.7%) | |||||
| Eructation | 1/12 (8.3%) | 0/12 (0%) | 0/13 (0%) | 0/13 (0%) | 0/13 (0%) | |||||
| Nausea | 1/12 (8.3%) | 1/12 (8.3%) | 1/13 (7.7%) | 0/13 (0%) | 0/13 (0%) | |||||
| Vomiting | 0/12 (0%) | 2/12 (16.7%) | 0/13 (0%) | 0/13 (0%) | 1/13 (7.7%) | |||||
| General disorders | ||||||||||
| Asthenia | 1/12 (8.3%) | 0/12 (0%) | 0/13 (0%) | 0/13 (0%) | 0/13 (0%) | |||||
| Chest discomfort | 0/12 (0%) | 1/12 (8.3%) | 1/13 (7.7%) | 0/13 (0%) | 0/13 (0%) | |||||
| Fatigue | 0/12 (0%) | 1/12 (8.3%) | 1/13 (7.7%) | 0/13 (0%) | 0/13 (0%) | |||||
| Feeling hot | 0/12 (0%) | 0/12 (0%) | 0/13 (0%) | 0/13 (0%) | 1/13 (7.7%) | |||||
| Influenza like illness | 0/12 (0%) | 1/12 (8.3%) | 0/13 (0%) | 0/13 (0%) | 0/13 (0%) | |||||
| Oedema peripheral | 0/12 (0%) | 1/12 (8.3%) | 0/13 (0%) | 0/13 (0%) | 0/13 (0%) | |||||
| Immune system disorders | ||||||||||
| Seasonal allergy | 0/12 (0%) | 1/12 (8.3%) | 0/13 (0%) | 0/13 (0%) | 0/13 (0%) | |||||
| Infections and infestations | ||||||||||
| Cellulitis | 0/12 (0%) | 0/12 (0%) | 1/13 (7.7%) | 0/13 (0%) | 0/13 (0%) | |||||
| Diarrhoea infectious | 0/12 (0%) | 0/12 (0%) | 0/13 (0%) | 1/13 (7.7%) | 0/13 (0%) | |||||
| Fungal skin infection | 0/12 (0%) | 0/12 (0%) | 1/13 (7.7%) | 0/13 (0%) | 0/13 (0%) | |||||
| Nasopharyngitis | 0/12 (0%) | 1/12 (8.3%) | 1/13 (7.7%) | 0/13 (0%) | 1/13 (7.7%) | |||||
| Sinusitis | 0/12 (0%) | 0/12 (0%) | 1/13 (7.7%) | 2/13 (15.4%) | 0/13 (0%) | |||||
| Urinary tract infection | 0/12 (0%) | 0/12 (0%) | 0/13 (0%) | 1/13 (7.7%) | 0/13 (0%) | |||||
| Injury, poisoning and procedural complications | ||||||||||
| Contusion | 0/12 (0%) | 0/12 (0%) | 0/13 (0%) | 1/13 (7.7%) | 0/13 (0%) | |||||
| Excoriation | 0/12 (0%) | 0/12 (0%) | 0/13 (0%) | 0/13 (0%) | 1/13 (7.7%) | |||||
| Muscle injury | 0/12 (0%) | 0/12 (0%) | 0/13 (0%) | 1/13 (7.7%) | 0/13 (0%) | |||||
| Investigations | ||||||||||
| ACTH stimulation test abnormal | 0/12 (0%) | 1/12 (8.3%) | 2/13 (15.4%) | 4/13 (30.8%) | 0/13 (0%) | |||||
| Blood creatine phosphokinase increased | 1/12 (8.3%) | 0/12 (0%) | 1/13 (7.7%) | 0/13 (0%) | 0/13 (0%) | |||||
| Occult blood positive | 1/12 (8.3%) | 0/12 (0%) | 0/13 (0%) | 0/13 (0%) | 0/13 (0%) | |||||
| Weight decreased | 0/12 (0%) | 0/12 (0%) | 0/13 (0%) | 1/13 (7.7%) | 0/13 (0%) | |||||
| Metabolism and nutrition disorders | ||||||||||
| Hyperkalaemia | 1/12 (8.3%) | 0/12 (0%) | 0/13 (0%) | 0/13 (0%) | 0/13 (0%) | |||||
| Hypoglycaemia | 0/12 (0%) | 0/12 (0%) | 0/13 (0%) | 0/13 (0%) | 1/13 (7.7%) | |||||
| Hyponatraemia | 1/12 (8.3%) | 1/12 (8.3%) | 1/13 (7.7%) | 0/13 (0%) | 1/13 (7.7%) | |||||
| Musculoskeletal and connective tissue disorders | ||||||||||
| Arthritis | 0/12 (0%) | 0/12 (0%) | 1/13 (7.7%) | 1/13 (7.7%) | 0/13 (0%) | |||||
| Back pain | 0/12 (0%) | 1/12 (8.3%) | 1/13 (7.7%) | 0/13 (0%) | 0/13 (0%) | |||||
| Joint swelling | 0/12 (0%) | 1/12 (8.3%) | 0/13 (0%) | 0/13 (0%) | 0/13 (0%) | |||||
| Muscle spasms | 0/12 (0%) | 0/12 (0%) | 0/13 (0%) | 0/13 (0%) | 1/13 (7.7%) | |||||
| Muscle twitching | 1/12 (8.3%) | 0/12 (0%) | 0/13 (0%) | 0/13 (0%) | 0/13 (0%) | |||||
| Osteoarthritis | 0/12 (0%) | 1/12 (8.3%) | 0/13 (0%) | 0/13 (0%) | 0/13 (0%) | |||||
| Pain in extremity | 0/12 (0%) | 1/12 (8.3%) | 0/13 (0%) | 0/13 (0%) | 1/13 (7.7%) | |||||
| Nervous system disorders | ||||||||||
| Dizziness | 2/12 (16.7%) | 0/12 (0%) | 3/13 (23.1%) | 0/13 (0%) | 1/13 (7.7%) | |||||
| Headache | 1/12 (8.3%) | 4/12 (33.3%) | 2/13 (15.4%) | 2/13 (15.4%) | 3/13 (23.1%) | |||||
| Migraine | 0/12 (0%) | 0/12 (0%) | 1/13 (7.7%) | 0/13 (0%) | 0/13 (0%) | |||||
| Tremor | 0/12 (0%) | 0/12 (0%) | 1/13 (7.7%) | 0/13 (0%) | 0/13 (0%) | |||||
| Psychiatric disorders | ||||||||||
| Anxiety | 1/12 (8.3%) | 0/12 (0%) | 0/13 (0%) | 0/13 (0%) | 0/13 (0%) | |||||
| Insomnia | 0/12 (0%) | 0/12 (0%) | 0/13 (0%) | 0/13 (0%) | 1/13 (7.7%) | |||||
| Sleep disorder | 0/12 (0%) | 1/12 (8.3%) | 0/13 (0%) | 0/13 (0%) | 0/13 (0%) | |||||
| Renal and urinary disorders | ||||||||||
| Pollakiuria | 0/12 (0%) | 1/12 (8.3%) | 0/13 (0%) | 0/13 (0%) | 0/13 (0%) | |||||
| Reproductive system and breast disorders | ||||||||||
| Testicular pain | 1/12 (8.3%) | 0/12 (0%) | 0/13 (0%) | 0/13 (0%) | 0/13 (0%) | |||||
| Respiratory, thoracic and mediastinal disorders | ||||||||||
| Sleep apnoea syndrome | 0/12 (0%) | 1/12 (8.3%) | 0/13 (0%) | 0/13 (0%) | 0/13 (0%) | |||||
| Skin and subcutaneous tissue disorders | ||||||||||
| Skin lesion | 0/12 (0%) | 0/12 (0%) | 0/13 (0%) | 0/13 (0%) | 1/13 (7.7%) | |||||
| Swelling face | 0/12 (0%) | 0/12 (0%) | 1/13 (7.7%) | 0/13 (0%) | 0/13 (0%) | |||||
| Vascular disorders | ||||||||||
| Peripheral coldness | 0/12 (0%) | 0/12 (0%) | 1/13 (7.7%) | 0/13 (0%) | 0/13 (0%) | |||||
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial.
Results Point of Contact
| Name/Title | Study Director |
|---|---|
| Organization | Novartis Pharmaceuticals |
| Phone | 862-778-8300 |
| Novartis.email@novartis.com |
Responsible Party:
Novartis
ClinicalTrials.gov Identifier:
NCT00817414
Other Study ID Numbers:
- CLCI699A2215
- 2008-007337-49
First Posted:
Jan 6, 2009
Last Update Posted:
Jun 2, 2021
Last Verified:
May 1, 2021