Trial Outcomes & Findings for COREG MR Versus TOPROL-XL On The Lipid Profile Of Normolipidemic Or Mildly Dyslipidemic Patients With Hypertension (NCT NCT00273052)

NCT ID: NCT00273052

Last Updated: 2018-06-25

Results Overview

Blood draw for triglyceride levels. Full beta quantification test performed which uses ultracentrifugation to partially separate lipoprotein classes and is the basis for the reference methods. Change = Month 6 value minus Baseline value.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 514 participants
• Primary outcome timeframe: Baseline and Month 6
• Results posted on: 2018-06-25

Participant Flow

Participant milestones

Measure	Coreg CR Carvedilol Phosphate Extended Release 20 mg, 40 mg, and 80 mg Capsules QD (once daily)	Toprol XL Metoprolol Succinate Extended Release 50 mg, 100 mg, and 200 mg Tablets QD (once daily)
Overall Study STARTED	290	278
Overall Study COMPLETED	221	190
Overall Study NOT COMPLETED	69	88

Reasons for withdrawal

Measure	Coreg CR Carvedilol Phosphate Extended Release 20 mg, 40 mg, and 80 mg Capsules QD (once daily)	Toprol XL Metoprolol Succinate Extended Release 50 mg, 100 mg, and 200 mg Tablets QD (once daily)
Overall Study Withdrawal by Subject	16	19
Overall Study Adverse Event	21	19
Overall Study Protocol Violation	14	18
Overall Study Lost to Follow-up	7	25
Overall Study Lack of Efficacy	6	4
Overall Study Non-Compliance	3	1
Overall Study Other	2	0
Overall Study Worsening serum lipid levels	0	2

Baseline Characteristics

COREG MR Versus TOPROL-XL On The Lipid Profile Of Normolipidemic Or Mildly Dyslipidemic Patients With Hypertension

Baseline characteristics by cohort

Measure	Coreg CR n=290 Participants Carvedilol Phosphate Extended Release 20 mg, 40 mg, and 80 mg Capsules QD (once daily)	Toprol XL n=278 Participants Metoprolol Succinate Extended Release 50 mg, 100 mg, and 200 mg Tablets QD (once daily)	Total n=568 Participants Total of all reporting groups
Age, Customized < 65 years	260 participants n=5 Participants	244 participants n=7 Participants	504 participants n=5 Participants
Age, Customized >=65 years	30 participants n=5 Participants	34 participants n=7 Participants	64 participants n=5 Participants
Sex: Female, Male Female	137 Participants n=5 Participants	133 Participants n=7 Participants	270 Participants n=5 Participants
Sex: Female, Male Male	153 Participants n=5 Participants	145 Participants n=7 Participants	298 Participants n=5 Participants
Race/Ethnicity, Customized Black	24 participants n=5 Participants	28 participants n=7 Participants	52 participants n=5 Participants
Race/Ethnicity, Customized White/Caucasian	239 participants n=5 Participants	226 participants n=7 Participants	465 participants n=5 Participants
Race/Ethnicity, Customized Other	27 participants n=5 Participants	24 participants n=7 Participants	51 participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline and Month 6

Population: The Intent to Treat (ITT-E) Population was used for analysis of the efficacy results and consisted of all subjects who randomized, received at least one dose of study medication, and had both a baseline and at least one on-therapy value for an efficacy parameter during the maintenance phase(number of participants will vary between measures).

Blood draw for triglyceride levels. Full beta quantification test performed which uses ultracentrifugation to partially separate lipoprotein classes and is the basis for the reference methods. Change = Month 6 value minus Baseline value.

Outcome measures

Measure	Coreg CR n=235 Participants Carvedilol Phosphate Extended Release 20 mg, 40 mg, and 80 mg Capsules QD (once daily)	Toprol XL n=206 Participants Metoprolol Succinate Extended Release 50 mg, 100 mg, and 200 mg Tablets QD (once daily)
Change From Baseline in Triglycerides Levels by Treatment Group at Maintenance Month 6	2.65 mg/dL	10.39 mg/dL

PRIMARY outcome

Timeframe: Baseline and Month 6

Population: The Intent to Treat (ITT-E) Population was used for analysis of the efficacy results and consisted of all subjects who randomized, received at least one dose of study medication, and had both a baseline and at least one on-therapy value for an efficacy parameter during the maintenance phase(number of participants will vary between measures).

Blood draw for HDL-C levels. Full beta Quant test performed with HDL subclasses. Change = Month 6 value minus Baseline value.

Outcome measures

Measure	Coreg CR n=235 Participants Carvedilol Phosphate Extended Release 20 mg, 40 mg, and 80 mg Capsules QD (once daily)	Toprol XL n=206 Participants Metoprolol Succinate Extended Release 50 mg, 100 mg, and 200 mg Tablets QD (once daily)
Change From Baseline in High-Density Lipoprotein Cholesterol (HDL-C) Levels by Treatment Group at Maintenance Month 6	-4.4 mg/dL	-5.1 mg/dL

SECONDARY outcome

Timeframe: Baseline and Month 6

Population: The Intent to Treat (ITT-E) Population was used for analysis of the efficacy results and consisted of all subjects who randomized, received at least one dose of study medication, and had both a baseline and at least one on-therapy value for an efficacy parameter during the maintenance phase(number of participants will vary between measures).

Blood draw for hs-CRP. Change = Month 6 value minus Baseline value.

Outcome measures

Measure	Coreg CR n=231 Participants Carvedilol Phosphate Extended Release 20 mg, 40 mg, and 80 mg Capsules QD (once daily)	Toprol XL n=203 Participants Metoprolol Succinate Extended Release 50 mg, 100 mg, and 200 mg Tablets QD (once daily)
Change From Baseline in Log Transformed High Sensitivity C-reactive Protein (Hs-CRP) by Treatment Group at Maintenance Month 6	-1.76 mg/dL	0.49 mg/dL

SECONDARY outcome

Timeframe: Baseline and Month 6

Population: The Intent to Treat (ITT-E) Population was used for analysis of the efficacy results and consisted of all subjects who randomized, received at least one dose of study medication, and had both a baseline and at least one on-therapy value for an efficacy parameter during the maintenance phase(number of participants will vary between measures).

Blood draw for LpPLA2 activity. Change = Month 6 value minus Baseline value.

Outcome measures

Measure	Coreg CR n=222 Participants Carvedilol Phosphate Extended Release 20 mg, 40 mg, and 80 mg Capsules QD (once daily)	Toprol XL n=189 Participants Metoprolol Succinate Extended Release 50 mg, 100 mg, and 200 mg Tablets QD (once daily)
Change From Baseline in Log Transformed Lipoprotein-associated Phospholipase A2 (LpPLA2) by Treatment Group at Maintenance Month 6	-2.38 mcmol/min/L	-2.23 mcmol/min/L

SECONDARY outcome

Timeframe: Baseline and Month 6

Population: The Intent to Treat (ITT-E) Population was used for analysis of the efficacy results and consisted of all subjects who randomized, received at least one dose of study medication, and had both a baseline and at least one on-therapy value for an efficacy parameter during the maintenance phase(number of participants will vary between measures).

Manual physical examination (cuff blood pressure). Change = Month 6 value minus Baseline value.

Outcome measures

Measure	Coreg CR n=280 Participants Carvedilol Phosphate Extended Release 20 mg, 40 mg, and 80 mg Capsules QD (once daily)	Toprol XL n=269 Participants Metoprolol Succinate Extended Release 50 mg, 100 mg, and 200 mg Tablets QD (once daily)
Change From Baseline in Blood Pressure by Treatment Group at Maintenance Month 6 Systolic Blood Pressure	-15.90 mm Hg	-16.23 mm Hg
Change From Baseline in Blood Pressure by Treatment Group at Maintenance Month 6 Diastolic Blood Pressure	-10.89 mm Hg	-11.06 mm Hg

SECONDARY outcome

Timeframe: Baseline and Month 6

Population: The Intent to Treat (ITT-E) Population was used for analysis of the efficacy results and consisted of all subjects who randomized, received at least one dose of study medication, and had both a baseline and at least one on-therapy value for an efficacy parameter during the maintenance phase(number of participants will vary between measures).

Manual physical examination. Change = Month 6 value minus Baseline value. (BPM=beats per minute)

Outcome measures

Measure	Coreg CR n=280 Participants Carvedilol Phosphate Extended Release 20 mg, 40 mg, and 80 mg Capsules QD (once daily)	Toprol XL n=269 Participants Metoprolol Succinate Extended Release 50 mg, 100 mg, and 200 mg Tablets QD (once daily)
Change From Baseline in Heart Rate by Treatment Group at Maintenance Month 6	-5.98 bpm	-6.07 bpm

SECONDARY outcome

Timeframe: Baseline and Month 6

Population: The Intent to Treat (ITT-E) Population was used for analysis of the efficacy results and consisted of all subjects who randomized, received at least one dose of study medication, and had both a baseline and at least one on-therapy value for an efficacy parameter during the maintenance phase(number of participants will vary between measures).

Manual physical examination. Change = Month 6 value minus Baseline value.

Outcome measures

Measure	Coreg CR n=280 Participants Carvedilol Phosphate Extended Release 20 mg, 40 mg, and 80 mg Capsules QD (once daily)	Toprol XL n=269 Participants Metoprolol Succinate Extended Release 50 mg, 100 mg, and 200 mg Tablets QD (once daily)
Change From Baseline in Weight by Treatment Group at Maintenance Month	1.01 kg	0.73 kg

SECONDARY outcome

Timeframe: Baseline and Month 6

Population: The Intent to Treat (ITT-E) Population was used for analysis of the efficacy results and consisted of all subjects who randomized, received at least one dose of study medication, and had both a baseline and at least one on-therapy value for an efficacy parameter during the maintenance phase(number of participants will vary between measures).

Blood draw for lipid levels. Full beta Quant test performed with HDL subclasses and IDL. IDL=Intermediate density lipoproteins, LDL=Low-density lipoprotein, VLDL=Very Low density lipoprotein, HDL=High-density lipoprotein. Change = Month 6 value minus Baseline value.

Outcome measures

Measure	Coreg CR n=280 Participants Carvedilol Phosphate Extended Release 20 mg, 40 mg, and 80 mg Capsules QD (once daily)	Toprol XL n=269 Participants Metoprolol Succinate Extended Release 50 mg, 100 mg, and 200 mg Tablets QD (once daily)
Change From Baseline in Additional Lipid Parameters by Treatment Group With Unit of Measures of mg/dL at Maintenance Month 6 Total Serum Cholesterol	0.1 mg/dL	-0.7 mg/dL
Change From Baseline in Additional Lipid Parameters by Treatment Group With Unit of Measures of mg/dL at Maintenance Month 6 Low-Density Lipoprotein (LDL)	-1.1 mg/dL	-1.7 mg/dL
Change From Baseline in Additional Lipid Parameters by Treatment Group With Unit of Measures of mg/dL at Maintenance Month 6 Low+Very Low Density Lipoprotein	0.9 mg/dL	0.4 mg/dL
Change From Baseline in Additional Lipid Parameters by Treatment Group With Unit of Measures of mg/dL at Maintenance Month 6 High-Density Lipoprotein 2 (HDL2)	-1.45 mg/dL	-6.5 mg/dL
Change From Baseline in Additional Lipid Parameters by Treatment Group With Unit of Measures of mg/dL at Maintenance Month 6 High-Density Lipoprotein 3 (HDL3)	-4.0 mg/dL	-3.5 mg/dL
Change From Baseline in Additional Lipid Parameters by Treatment Group With Unit of Measures of mg/dL at Maintenance Month 6 Low-Density Lipoprotein-Relative Flotation	0.166 mg/dL	-1.360 mg/dL
Change From Baseline in Additional Lipid Parameters by Treatment Group With Unit of Measures of mg/dL at Maintenance Month 6 Intermediate Density Lipoproteins+VLDL	2.0 mg/dL	5.6 mg/dL

SECONDARY outcome

Timeframe: Baseline and Month 6

Population: The Intent to Treat (ITT-E) Population was used for analysis of the efficacy results and consisted of all subjects who randomized, received at least one dose of study medication, and had both a baseline and at least one on-therapy value for an efficacy parameter during the maintenance phase(number of participants will vary between measures).

Blood draw for lipid levels. Full beta Quant test performed. Change = Month 6 value minus Baseline value.

Outcome measures

Measure	Coreg CR n=280 Participants Carvedilol Phosphate Extended Release 20 mg, 40 mg, and 80 mg Capsules QD (once daily)	Toprol XL n=269 Participants Metoprolol Succinate Extended Release 50 mg, 100 mg, and 200 mg Tablets QD (once daily)
Change From Baseline in Additional Lipid Parameters by Treatment Group With Unit of Measures of g/L at Maintenance Month 6 Apolipoprotein A-1 (Apo-A1)	-1.82 g/L	-3.45 g/L
Change From Baseline in Additional Lipid Parameters by Treatment Group With Unit of Measures of g/L at Maintenance Month 6 Apolipoprotein B (Apo-B)	-1.16 g/L	0.81 g/L

SECONDARY outcome

Timeframe: Baseline and Month 6

Population: The Intent to Treat (ITT-E) Population was used for analysis of the efficacy results and consisted of all subjects who randomized, received at least one dose of study medication, and had both a baseline and at least one on-therapy value for an efficacy parameter during the maintenance phase(number of participants will vary between measures).

Blood draw for glycemia levels. Full beta Quant test performed. Test for Fasting plasma glucose, HbA1c, fasting insulin. Homeostasis model Assessment (HOMA) is a computer-generated model consisting of non-linear empirical equations solved numerically to predict glucose, Insulin and C-peptide concentrations in fasting subjects for insulin sensitivity (%S). Change = Month 6 value minus Baseline value.

Outcome measures

Measure	Coreg CR n=280 Participants Carvedilol Phosphate Extended Release 20 mg, 40 mg, and 80 mg Capsules QD (once daily)	Toprol XL n=269 Participants Metoprolol Succinate Extended Release 50 mg, 100 mg, and 200 mg Tablets QD (once daily)
Change From Baseline in Fasting Insulin (Glycemic Parameter) by Treatment Group at Maintenance Month 6	-1.21 uIU/mL	1.35 uIU/mL

SECONDARY outcome

Timeframe: Baseline and Month 6

Population: The Intent to Treat (ITT-E) Population was used for analysis of the efficacy results and consisted of all subjects who randomized, received at least one dose of study medication, and had both a baseline and at least one on-therapy value for an efficacy parameter during the maintenance phase(number of participants will vary between measures).

Blood draw for glycemia levels. Full beta Quant test performed. Test for Fasting plasma glucose, HbA1c, fasting insulin. Homeostasis model Assessment (HOMA) is a computer-generated model consisting of non-linear empirical equations solved numerically to predict glucose, Insulin and C-peptide concentrations in fasting subjects for insulin sensitivity (%S). Change = Month 6 value minus Baseline value.

Outcome measures

Measure	Coreg CR n=280 Participants Carvedilol Phosphate Extended Release 20 mg, 40 mg, and 80 mg Capsules QD (once daily)	Toprol XL n=269 Participants Metoprolol Succinate Extended Release 50 mg, 100 mg, and 200 mg Tablets QD (once daily)
Change From Baseline in Hemoglobin A1c (HbA1c) (Glycemic Parameter) by Treatment Group at Maintenance Month 6	0.01 Percent Change	0.04 Percent Change

SECONDARY outcome

Timeframe: Baseline and Month 6

Population: The Intent to Treat (ITT-E) Population was used for analysis of the efficacy results and consisted of all subjects who randomized, received at least one dose of study medication, and had both a baseline and at least one on-therapy value for an efficacy parameter during the maintenance phase(number of participants will vary between measures).

Blood draw for glycemia levels. Full beta Quant test performed. Test for Fasting plasma glucose, HbA1c, fasting insulin. Homeostasis model Assessment (HOMA) is a computer-generated model consisting of non-linear empirical equations solved numerically to predict glucose, Insulin and C-peptide concentrations in fasting subjects for insulin sensitivity (%S). Change = Month 6 value minus Baseline value.

Outcome measures

Measure	Coreg CR n=280 Participants Carvedilol Phosphate Extended Release 20 mg, 40 mg, and 80 mg Capsules QD (once daily)	Toprol XL n=269 Participants Metoprolol Succinate Extended Release 50 mg, 100 mg, and 200 mg Tablets QD (once daily)
Change From Baseline in c-Peptide (Glycemic Parameter) by Treatment Group at Maintenance Month 6	-0.23 ng/mL	0.20 ng/mL

SECONDARY outcome

Timeframe: Baseline and Month 6

Population: The Intent to Treat (ITT-E) Population was used for analysis of the efficacy results and consisted of all subjects who randomized, received at least one dose of study medication, and had both a baseline and at least one on-therapy value for an efficacy parameter during the maintenance phase(number of participants will vary between measures).

Blood draw for glycemia levels. Full beta Quant test performed. Test for Fasting plasma glucose, HbA1c, fasting insulin. Homeostasis model Assessment (HOMA) is a computer-generated model consisting of non-linear empirical equations solved numerically to predict glucose, Insulin and C-peptide concentrations in fasting subjects for insulin sensitivity (%S). Change = Month 6 value minus Baseline value.

Outcome measures

Measure	Coreg CR n=280 Participants Carvedilol Phosphate Extended Release 20 mg, 40 mg, and 80 mg Capsules QD (once daily)	Toprol XL n=269 Participants Metoprolol Succinate Extended Release 50 mg, 100 mg, and 200 mg Tablets QD (once daily)
Change From Baseline in Homeostasis Model Assessment (Glycemic Parameter) by Treatment Group at Maintenance Month 6	2.05 Percent Change	-4.14 Percent Change

SECONDARY outcome

Timeframe: Baseline and Month 6

Population: The Intent to Treat (ITT-E) Population was used for analysis of the efficacy results and consisted of all subjects who randomized, received at least one dose of study medication, and had both a baseline and at least one on-therapy value for an efficacy parameter during the maintenance phase(number of participants will vary between measures).

Blood draw for glycemia levels. Full beta Quant test performed. Test for Fasting plasma glucose, HbA1c, fasting insulin. Homeostasis model Assessment (HOMA) is a computer-generated model consisting of non-linear empirical equations solved numerically to predict glucose, Insulin and C-peptide concentrations in fasting subjects for insulin sensitivity (%S). Change = Month 6 value minus Baseline value.

Outcome measures

Measure	Coreg CR n=280 Participants Carvedilol Phosphate Extended Release 20 mg, 40 mg, and 80 mg Capsules QD (once daily)	Toprol XL n=269 Participants Metoprolol Succinate Extended Release 50 mg, 100 mg, and 200 mg Tablets QD (once daily)
Change From Baseline in Fasting Plasma Glucose (FPG) (Glycemic Parameter) by Treatment Group at Maintenance Month 6	0.94 mg/dL	1.20 mg/dL

Adverse Events

Coreg CR

Serious events: 8 serious events

Other events: 186 other events

Deaths: 0 deaths

Toprol XL

Serious events: 5 serious events

Other events: 160 other events

Deaths: 0 deaths

Serious adverse events

Measure	Coreg CR Results include only treatment emergent events.	Toprol XL Results include only treatment emergent events.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer	0.00% 0/290	0.36% 1/278
General disorders Chest discomfort	0.34% 1/290	0.00% 0/278
Gastrointestinal disorders Colitis ischaemic	0.34% 1/290	0.00% 0/278
Psychiatric disorders Depression suicidal	0.34% 1/290	0.00% 0/278
Gastrointestinal disorders Gastroesophagael reflux disease	0.34% 1/290	0.00% 0/278
Renal and urinary disorders Hydronephrosis	0.00% 0/290	0.36% 1/278
Vascular disorders Hypertension	0.34% 1/290	0.00% 0/278
Cardiac disorders Myocardial Infarction	0.34% 1/290	0.00% 0/278
Nervous system disorders Orthostatic hypotension	0.00% 0/290	0.36% 1/278
Cardiac disorders Palpitations	0.34% 1/290	0.00% 0/278
Infections and infestations Peridiverticular abscess	0.00% 0/290	0.36% 1/278
Nervous system disorders Presyncope	0.00% 0/290	0.36% 1/278
Gastrointestinal disorders Umbilical hernia	0.34% 1/290	0.00% 0/278

Other adverse events

Measure	Coreg CR Results include only treatment emergent events.	Toprol XL Results include only treatment emergent events.
Nervous system disorders Headache	14.5% 42/290	11.9% 33/278
General disorders Edema Peripheral	10.0% 29/290	9.0% 25/278
General disorders Fatigue	7.6% 22/290	10.4% 29/278
Nervous system disorders Dizziness	9.7% 28/290	6.5% 18/278
Infections and infestations Nasopharyngitis	5.5% 16/290	6.1% 17/278
Infections and infestations Upper Respiratory Tract Infection	6.6% 19/290	4.3% 12/278
Gastrointestinal disorders Nausea	6.2% 18/290	4.0% 11/278
Gastrointestinal disorders Diarrhea	4.1% 12/290	5.4% 15/278

Additional Information

GSK Response Center

GlaxoSmithKline

Phone: 866-435-7343

Results disclosure agreements

• Principal investigator is a sponsor employee GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centres of a multi-centre trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
• Publication restrictions are in place

Restriction type: OTHER