Recent Updates
Recently added Catalysts

Carvedilol

Phase 3

Hypertrophy, Left Ventricular | Small molecule | Cardiovascular |GSK plc|Last Updated: Aug 9, 2017

Target and mechanism

ModalitySmall molecule

Also known as Carvedilol CR capsules, carvedilol MR

Success Probability

Subscribe to view

Market & Valuation

Subscribe to view

Trial Design

RandomizedDouble-BlindCONTROLLED
Total Trials1
Total Enrollment287

FDA Designations

No designations recorded

Clinical trial landscape

Carvedilol · 3 trials · 3 indications

Phase 3 1Phase 1 2
NCT00108082The CLEVER Study - Coreg And Left Ventricular Mass RegressionHypertrophy, Left Ventricular
COMPLETED287 Analytics
PHASE3COMPLETED
The CLEVER Study - Coreg And Left Ventricular Mass Regression
Hypertrophy, Left VentricularUnlock trial analytics

Study Endpoints

Primary Endpoints

Model-adjusted Mean Change From Baseline in Left Ventricular Mass Indexed (LVMI) by Body Surface Area as Measured by Magnetic Resonance Imaging (MRI) at Month 12
Baseline and Month 12 (If Month 12 data were not available, the Last Observation Carried Forward [LOCF] analysis, which includes data collected on or after Month 9 of treatment to Month 12 of treatment, was used)

LVMI was measured by MRI at Baseline and after 12 months of treatment/Month 12. A reduction in left ventricular mass, calculated as LVMI, of 5 g/m\^2 was assumed to be clinically meaningful. Change in Baseline was calculated as Month 12 value (or value after 12 months of treatment) minus the Baseline value.

Absolute Change in Right Ventricular Ejection Fraction
baseline, 6 months

Change in right ventricular ejection fraction is measured by cardiac magnetic resonance imaging, using the method of disks with the reading radiologist being blinded to before and after images. Cardiac magnetic resonance imaging was done at baseline and 6 months only

Assessment of orthostasis 6 hours post dose on day 1, 7, 8, 14 in each dosing session
6 hours post dose on day 1, 7, 8, 14 in each dosing session
To evaluate the incidence of orthostatic hypotension (defined as a decrease in SBP of ≥20 mmHg and/or a decrease in DBP of ≥10 mmHg in changing from the supine to the standing position) following co-administration of COREG CR and lisinopril
Up to Day 14

Secondary Endpoints

Model-adjusted Mean Change From Baseline in Left Ventricular Mass Indexed by Height (LVMIH) as Measured by MRI at Month 12
Baseline and Month 12 (If Month 12 data were not available, the LOCF analysis, which includes data collected on or after Month 9 of treatment to Month 12 of treatment, was used)
Model-adjusted Mean Change From Baseline in Left Ventricular (LV) Mass as Measured by MRI at Month 12
Baseline and Month 12 (If Month 12 data were not available, the LOCF analysis, which includes data collected on or after Month 9 of treatment to Month 12 of treatment, was used)
Model-adjusted Mean Change From Baseline in Left Ventricular Mass Indexed (LVMI) by Body Surface Area as Measured by Echocardiography at Month 12
Baseline and Month 12 (If Month 12 data were not available, the LOCF analysis, which includes data collected on or after Month 9 of treatment to Month 12 of treatment, was used)
Unlock Study Endpoints

Study Design & Arms

AllocationRANDOMIZED
MaskingDOUBLE
ModelPARALLEL
PurposeTREATMENT

Treatment Arms

ArmTypeDescription
Carvedilol CREXPERIMENTALCarvedilol controlled release (CR) 20 to 80 mg once daily (OD) plus lisinopril 20 mg OD. Participants were titrated from the starting dosage to higher dosages until their blood pressure was controlled. Participants continued to receive lisinopril 20 mg OD throughout the study. (In the protocol, carvedilol CR was referred to as carvedilol modified-release \[MR\].)
AtenololEXPERIMENTALAtenolol 50 to 100 mg OD plus lisinopril 20 mg OD. Participants were titrated from the starting dosage to higher dosages until their blood pressure was controlled. Participants continued to receive lisinopril 20 mg OD throughout the study.
LisinoprilEXPERIMENTALLisinopril 10 to 40 mg OD plus lisinopril 20 mg OD. Participants were titrated from the starting dosage to higher dosages until their blood pressure was controlled. Participants continued to receive lisinopril 20 mg OD throughout the study.
carvedilolEXPERIMENTALCarvedilol is titrated from a dose of 3.125mg twice daily to a maximal dose of 25mg twice daily over 24 weeks. Patients are evaluated to their response with 6 minute walk testing, echocardiography, and cardiac MRI
Subjects receiving treatment sequence ABEXPERIMENTALEligible subjects will receive treatment sequence AB; A= Placebo to match COREG CR 20 milligrams once daily plus lisinopril 10 milligrams once daily (Days 1-7). Placebo to match COREG CR 40 milligrams once daily plus lisinopril 10 milligrams once daily (Days 8-14). B=COREG CR 20 milligrams once daily plus lisinopril 10 milligrams once daily (Days 1-7). COREG CR 40 milligrams once daily plus lisinopril 10 milligrams once daily (Days 8-14).
Subjects receiving treatment sequence BAEXPERIMENTALEligible subjects will receive treatment sequence BA; B=COREG CR 20 milligrams once daily plus lisinopril 10 milligrams once daily (Days 1-7). COREG CR 40 milligrams once daily plus lisinopril 10 milligrams once daily (Days 8-14). A= Placebo to match COREG CR 20 milligrams once daily plus lisinopril 10 milligrams once daily (Days 1-7). Placebo to match COREG CR 40 milligrams once daily plus lisinopril 10 milligrams once daily (Days 8-14).

Interventions

NameTypeDescription
carvedilol MRDRUGStudy drug
atenololDRUGComparator
lisinoprilDRUGComparator
CarvedilolDRUGtwice daily oral treatment in escalating dose
Carvedilol CR capsulesDRUGThe carvedilol micropump (COREG) CR cpsules will be available with doses of 20 milligrams and 40 milligrams administered orally once daily.
PlaceboDRUGPlacebo capsules to match each dose level will be provided.
Unlock Study Design Details

Eligibility Criteria

Age Range18 Years to 80 Years
SexALL
Healthy VolunteersNo
Study Sites78

Inclusion criteria: * Stage 1 or Stage 2 hypertension. * Left ventricular hypertrophy. Exclusion criteria: * In atrial fibrillation. * Takes beta-blocker for MI (myocardial infarction) or arrhythmia. * Has uncontrolled diabetes, uncontrollable or symptomatic arrhythmias, unstable angina, second o...

Countries:United States
Unlock Eligibility Criteria