Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
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Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Participants randomized to receive SK&F-105517-D underwent 2 weeks of observation, 8 weeks of Primary Evaluation, 4 weeks of Exploratory Evaluation, 2 weeks of dose-tapering, and 1 week of Follow-up period. Participants randomized to receive CRV-IR underwent 2 weeks of observation, 8 weeks of Primary Evaluation, and 1 week of Follow-up.

Reporting Groups

	Description
CRV-IR	In the 8-week Primary Evaluation Period (including the 2-week Run-in Period [from Week 0 as Baseline]), participants received an initial dose of an immediate-release (IR) formulation of carvedilol (CRV) as a 1.25 milligram (mg) tablet twice daily (BID) (2.5 mg/day) at Week 0, followed by an increased dose of CRV-IR 2.5 mg tablet BID (5 mg/day) at Week 1. The dose was then increased to 5 mg BID (10 mg/day) at Week 4, and finally to 10 mg BID (20 mg/day) at Week 6. The participants on CRV-IR were switched to the marketed CRV-IR in Week 1 of the Follow-up Period; the investigator or subinvestigator determined the dose of the marketed CRV-IR based on the last dose administered during the Primary Evaluation Period after confirming the safety and tolerability of the dose.
SK&F-105517-D	In the 8-week Primary Evaluation Period (including the 2-week Run-in Period [from Week 0 as Baseline]), participants received a CRV-IR 1.25 mg and 2.5 mg tablet BID at Weeks 0 and 1, respectively. They then received a 10 mg extended-release capsule of carvedilol (SK&F-105517-D) once daily (OD) at Week 2; the dose was then increased to 20 mg OD and finally to 40 mg OD at 2-week intervals. The dose was increased from 40 mg to 60 mg and finally to 80 mg at 2-week intervals in the 4-week Exploratory Evaluation Period after confirming that each dose was well tolerated without safety concern and that the participant met all of the dose-escalation criteria. During the 2-week Dose-tapering Period set up to prepare for switch to the marketed CRV-IR, the dose of SK&F-105517-D was reduced to 60 mg OD and then to 40 mg OD at weekly intervals; SK&F-105517-D was then switched to the marketed CRV-IR 10 mg tablet BID in the 1-week Follow-up Period.

Participant Flow for 2 periods

Period 1:   8-Week Primary Evaluation Period

	CRV-IR	SK&F-105517-D
STARTED	22	19
COMPLETED	11	8
NOT COMPLETED	11	11
Adverse Event	2	4
Protocol Violation	1	0
Met Protocol-defined Stopping Criteria	8	5
Withdrawal by Subject	0	2

Period 2:   4-Week Exploratory Evaluation Period

	CRV-IR	SK&F-105517-D
STARTED	0	8
COMPLETED	0	7
NOT COMPLETED	0	1
Met Protocol-defined Stopping Criteria	0	1

Reporting Groups

	Description
CRV-IR	In the 8-week Primary Evaluation Period (including the 2-week Run-in Period [from Week 0 as Baseline]), participants received an initial dose of an immediate-release (IR) formulation of carvedilol (CRV) as a 1.25 milligram (mg) tablet twice daily (BID) (2.5 mg/day) at Week 0, followed by an increased dose of CRV-IR 2.5 mg tablet BID (5 mg/day) at Week 1. The dose was then increased to 5 mg BID (10 mg/day) at Week 4, and finally to 10 mg BID (20 mg/day) at Week 6. The participants on CRV-IR were switched to the marketed CRV-IR in Week 1 of the Follow-up Period; the investigator or subinvestigator determined the dose of the marketed CRV-IR based on the last dose administered during the Primary Evaluation Period after confirming the safety and tolerability of the dose.
SK&F-105517-D	In the 8-week Primary Evaluation Period (including the 2-week Run-in Period [from Week 0 as Baseline]), participants received a CRV-IR 1.25 mg and 2.5 mg tablet BID at Weeks 0 and 1, respectively. They then received a 10 mg extended-release capsule of carvedilol (SK&F-105517-D) once daily (OD) at Week 2; the dose was then increased to 20 mg OD and finally to 40 mg OD at 2-week intervals. The dose was increased from 40 mg to 60 mg and finally to 80 mg at 2-week intervals in the 4-week Exploratory Evaluation Period after confirming that each dose was well tolerated without safety concern and that the participant met all of the dose-escalation criteria. During the 2-week Dose-tapering Period set up to prepare for switch to the marketed CRV-IR, the dose of SK&F-105517-D was reduced to 60 mg OD and then to 40 mg OD at weekly intervals; SK&F-105517-D was then switched to the marketed CRV-IR 10 mg tablet BID in the 1-week Follow-up Period.

Baseline Measures

	CRV-IR	SK&F-105517-D	Total
Number of Participants   [units: participants]	22	19	41
Age   [units: years] Mean ± Standard Deviation	62.7  ± 8.17	66.7  ± 12.00	64.6  ± 10.20
Gender   [units: participants]
Female	2	1	3
Male	20	18	38
Race/Ethnicity, Customized   [units: participants]
Asian-Japanese Heritage	22	19	41

1.  Primary:

Number of Participants With Adverse Events by Severity From Week 0 Through Week 8 (CRV-IR) or Week 14 (SK&F-105517-D)   [ Time Frame: Treatment Period from Week 0 (Baseline) to Week 8 and 1-week Follow-up Period (Week 9) for CRV-IR; Treatment Period from Week 0 (Baseline) to Week 14 and 1-week Follow-up Period (Week 15) for SK&F-105517-D ]

2.  Primary:

Mean Change From Baseline in Albumin and Total Protein at Week 8   [ Time Frame: Baseline and Week 8 ]

3.  Primary:

Mean Change From Baseline in Alkaline Phosphatase, Alanine Aminotransferase, Aspartate Aminotransferase, Creatine Kinase, and Gamma Glutamyl Transferase at Week 8   [ Time Frame: Baseline and Week 8 ]

4.  Primary:

Mean Change From Baseline in Amylase at Week 8   [ Time Frame: Baseline and Week 8 ]

5.  Primary:

Mean Change From Baseline in Total Bilirubin, Creatinine, and Uric Acid at Week 8   [ Time Frame: Baseline and Week 8 ]

6.  Primary:

Mean Change From Baseline in Calcium, Chloride, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen at Week 8   [ Time Frame: Baseline and Week 8 ]

7.  Primary:

Mean Change From Baseline in Creatine Kinase BB Percentage, Creatine Kinase MB Percentage, and Creatine Kinase MM Percentage at Week 8   [ Time Frame: Baseline and Week 8 ]

8.  Primary:

Mean Change From Baseline in Each Type of White Blood Cell (WBC) (Basophils, Eosinophils, Lymphocytes, Monocytes, and Total Neutrophils) at Week 8   [ Time Frame: Baseline and Week 8 ]

9.  Primary:

Mean Change From Baseline in Hemoglobin and Mean Corpuscular Hemoglobin Concentration at Week 8   [ Time Frame: Baseline and Week 8 ]

10.  Primary:

Mean Change From Baseline in Hematocrit at Week 8   [ Time Frame: Baseline and Week 8 ]

11.  Primary:

Mean Change From Baseline in Platelet Count and White Blood Cell Count at Week 8   [ Time Frame: Baseline and Week 8 ]

12.  Primary:

Mean Change From Baseline in Red Blood Cell Count at Week 8   [ Time Frame: Baseline and Week 8 ]

13.  Primary:

Mean Change From Baseline in Mean Corpuscular Hemoglobin at Week 8   [ Time Frame: Baseline and Week 8 ]

14.  Primary:

Mean Change From Baseline in Mean Corpuscular Volume at Week 8   [ Time Frame: Baseline and Week 8 ]

15.  Primary:

Number of Participants With the Indicated Urinalysis Dipstick Results at Baseline and Week 8   [ Time Frame: Baseline and Week 8 ]

16.  Primary:

Mean Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure at Week 8   [ Time Frame: Baseline and Week 8 ]

17.  Primary:

Mean Change From Baseline in Heart Rate at Week 8   [ Time Frame: Baseline and Week 8 ]

18.  Primary:

Mean Change From Baseline in Weight at Week 8   [ Time Frame: Baseline and Week 8 ]

19.  Primary:

Number of Participants With the Indicated Electrocardiogram Findings at Baseline and Week 8   [ Time Frame: Baseline and Week 8 ]

20.  Primary:

Cardiothoracic Ratio at Baseline and Week 8   [ Time Frame: Baseline and Week 8 ]

21.  Secondary:

Maximum Plasma Concentration (Cmax) and Trough Plasma Concentration (Cmin) of S-carvedilol, R-carvedilol, and M4 Active Metabolite (SB-203231) at Week 8   [ Time Frame: Week 8 ]

22.  Secondary:

Area Under the Plasma Concentration Versus Time Curve From Time Zero to 24 Hours (AUC0-24) of S-carvedilol, R-carvedilol, and M4 Active Metabolite (SB-203231) at Week 8   [ Time Frame: Week 8 ]

23.  Secondary:

Time of Maximal Plasma Concentration (Tmax) of S-carvedilol, R-carvedilol, and M4 Active Metabolite (SB-203231) at Week 8   [ Time Frame: Week 8 ]

24.  Secondary:

Adjusted Mean Change From Baseline in Systolic Blood Pressure at Week 8   [ Time Frame: Baseline and Week 8 ]

25.  Secondary:

Adjusted Mean Change From Baseline in Diastolic Blood Pressure at Week 8   [ Time Frame: Baseline and Week 8 ]

26.  Secondary:

Adjusted Mean Change From Baseline in Mean Heart Rate at Week 8   [ Time Frame: Baseline and Week 8 ]

27.  Secondary:

Number of Participants With the Indicated Change From Baseline New York Heart Association (NYHA) Functional Class at Week 8   [ Time Frame: Baseline and Week 8 ]

28.  Secondary:

Mean Plasma Brain Natriuretic Peptide Concentration at Baseline and Week 8   [ Time Frame: Baseline and Week 8 ]

29.  Secondary:

Echocardiogram Results: Left Ventricular Ejection Fraction at Baseline and Week 8   [ Time Frame: Baseline and Week 8 ]