| Primary | Number of Participants With Adverse Events by Severity From Week 0 Through Week 8 (CRV-IR) or Week 14 (SK&F-105517-D) | Drug-related adverse events (AEs) were defined as AEs that were judged to have a relationship with the investigational product by the investigator (or subinvestigator) with the use of clinical judgment and the Clinical Investigator Brochure to determine the relationship. Refer to adverse event information for type and frequency of adverse events. | Safety Population: all participants who received at least one dose of the investigational product | Posted | | Number | | participants | | 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 | | | | ID | Title | Description |
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| OG000 | 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. | | OG001 | 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. |
| | | Title | Denominators | Categories |
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| Severe | | | | Moderate | | |
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| Secondary | Maximum Plasma Concentration (Cmax) and Trough Plasma Concentration (Cmin) of S-carvedilol, R-carvedilol, and M4 Active Metabolite (SB-203231) at Week 8 | Maximum Plasma Concentration (Cmax) and Trough Plasma Concentration (Cmin) of S-carvedilol, R-carvedilol, and M4 active Metabolite (SB-203231) were measured. Participants in each treatment group were divided into 3 groups by pharmacokinetic sampling timing: Groups A, B, and C in the SK&F-105517-D group and Groups D, E, and F in the CRV-IR group. The analysis was performed on log-transformed data. Carvedilol is a racemic mixture. Non-selective β-blocking activity is shown by S-carvedilol, while α1-blocking activity is shown by both S-carvedilol and R-carvedilol. | PK Parameter Population: total of 13 participants, including 3 who gave samples in group F at Week 8 in CRV-IR group; total of 15 participants, including 4 who gave samples at Week 8 in the SK&F-105517-D group) | Posted | | Geometric Mean | 95% Confidence Interval | nanograms per milliliter (ng/mL) | | Week 8 | | | | ID | Title | Description |
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| OG000 | 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. |
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| 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 | 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) was measured. Participants in each treatment group were divided into 3 groups by pharmacokinetic sampling timing: Groups A, B, and C in the SK&F-105517-D group and Groups D, E, and F in the CRV-IR group. The analysis was performed on log-transformed data. Carvedilol is a racemic mixture. Non-selective β-blocking activity is shown by S-carvedilol, while α1-blocking activity is shown by both S-carvedilol and R-carvedilol. | Pharmacokinetic (PK) Parameter Population: all participants who received the study drug at each dose level and provided sufficient PK concentration data and the data for estimation of PK parameters (total of 13 participants, 3 gave samples at Week 8 in CRV-IR group; total of 15 participants, 4 gave samples at Week 8 in the SK&F-105517-D group) | Posted | | Geometric Mean | 95% Confidence Interval | hours * nanograms per milliliter (ng/mL) | | Week 8 | | | | ID | Title | Description |
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| OG000 | 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. |
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| Secondary | Time of Maximal Plasma Concentration (Tmax) of S-carvedilol, R-carvedilol, and M4 Active Metabolite (SB-203231) at Week 8 | Time of maximal plasma concentration (tmax) of S-carvedilol, R-carvedilol, and M4 active metabolite (SB-203231) was measured. Participants in each treatment group were divided into 3 groups by pharmacokinetic sampling timing: Groups A, B, and C in the SK&F-105517-D group and Groups D, E, and F in the CRV-IR group. Carvedilol is a racemic mixture. Non-selective β-blocking activity is shown by S-carvedilol, while α1-blocking activity is shown by both S-carvedilol and R-carvedilol. | PK Parameter Population: total of 13 participants, including 3 in group F who gave samples at Week 8 in the CRV-IR group; total of 15 participants, including 4 in group C who gave samples at Week 8 in the SK&F-105517-D group | Posted | | Median | Full Range | hours | | Week 8 | | | | ID | Title | Description |
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| OG000 | 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. |
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| Secondary | Adjusted Mean Change From Baseline in Systolic Blood Pressure at Week 8 | Pharmacodynamic (PD) assessment points were 24 hours (h) (from time of first reading to time of last reading), morning (6 am-12 pm), afternoon (12-6 pm), night (6 pm-6 am on following day), waking (8 am-9 pm), sleeping (0-5 am), PDmax (maximal value obtained with each participant during the 0-24 h interval), PDmin (minimal value obtained with each participant during the 0-24 h interval), and PDmax/PDmin. PDmax/PDmim was calculated as the ratio of the PDmax to PDmin, and it showed the degree of change during the 0-24 h interval. The mean was adjusted for Baseline value. | Pharmacodynamic (PD) Population: all participants measurable at the PD endpoints (18 participants at baseline and 3 participants at Week 8 in CRV-IR group, 19 participants at baseline and 4 participants at Week 8 in SK&F-105517-D group) | Posted | | Mean | Standard Error | millimeters of mercury (mmHg) | | Baseline and Week 8 | | | | ID | Title | Description |
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| OG000 | 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. |
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| Primary | Mean Change From Baseline in Albumin and Total Protein at Week 8 | Mean change from baseline was calculated as the Week 8 value minus the Baseline value. | Safety Population: 22 participants at baseline and 11 participants at Week 8 in the CRV-IR group; 19 participants at baseline and 8 participants at Week 8 in the SK&F-105517-D group. Some participants in each treatment arm withdrew prematurely. | Posted | | Mean | Standard Deviation | grams per liter (g/L) | | Baseline and Week 8 | | | | ID | Title | Description |
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| OG000 | 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. | | OG001 | 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. |
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| Primary | Mean Change From Baseline in Alkaline Phosphatase, Alanine Aminotransferase, Aspartate Aminotransferase, Creatine Kinase, and Gamma Glutamyl Transferase at Week 8 | Mean change from baseline was calculated as the Week 8 value minus the Baseline value | Safety Population: 22 participants at baseline and 11 participants at Week 8 in the CRV-IR group; 19 participants at baseline and 8 participants at Week 8 in the SK&F-105517-D group. Some participants in each treatment arm withdrew prematurely. | Posted | | Mean | Standard Deviation | international units per liter (IU/L) | | Baseline and Week 8 | | | | ID | Title | Description |
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| OG000 | 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. | | OG001 | 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. |
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| Primary | Mean Change From Baseline in Amylase at Week 8 | Mean change from baseline was calculated as the Week 8 value minus the Baseline value | Safety Population: 22 participants at baseline and 11 participants at Week 8 in the CRV-IR group; 19 participants at baseline and 8 participants at Week 8 in the SK&F-105517-D group. Some participants in each treatment arm withdrew prematurely. | Posted | | Mean | Standard Deviation | units per liter (U/L) | | Baseline and Week 8 | | | | ID | Title | Description |
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| OG000 | 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. | | OG001 | 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. |
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| Primary | Mean Change From Baseline in Total Bilirubin, Creatinine, and Uric Acid at Week 8 | Mean change from baseline was calculated as the Week 8 value minus the Baseline value | Safety Population: 22 participants at baseline and 11 participants at Week 8 in the CRV-IR group; 19 participants at baseline and 8 participants at Week 8 in the SK&F-105517-D group. Some participants in each treatment arm withdrew prematurely. | Posted | | Mean | Standard Deviation | micromoles per liter (umol/L) | | Baseline and Week 8 | | | | ID | Title | Description |
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| OG000 | 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. | | OG001 | 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. |
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| Primary | Mean Change From Baseline in Calcium, Chloride, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen at Week 8 | Mean change from baseline was calculated as the Week 8 value minus the Baseline value | Safety Population: 22 participants at baseline and 11 participants at Week 8 in the CRV-IR group; 19 participants at baseline and 8 participants at Week 8 in the SK&F-105517-D group. Some participants in each treatment arm withdrew prematurely. | Posted | | Mean | Standard Deviation | millimoles per liter (mmol/L) | | Baseline and Week 8 | | | | ID | Title | Description |
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| OG000 | 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. | | OG001 | 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. |
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| Primary | Mean Change From Baseline in Creatine Kinase BB Percentage, Creatine Kinase MB Percentage, and Creatine Kinase MM Percentage at Week 8 | Mean change from baseline was calculated as the Week 8 value minus the Baseline value. (BB, brain-derived; MB=cardiac muscle-derived; MM=skeletal muscle-derived. | Safety Population: 22 participants at baseline and 11 participants at Week 8 in the CRV-IR group; 19 participants at baseline and 8 participants at Week 8 in the SK&F-105517-D group. Some participants in each treatment arm withdrew prematurely. | Posted | | Mean | Standard Deviation | percentage of Total Creatine Kinase | | Baseline and Week 8 | | | | ID | Title | Description |
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| OG000 | 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. | | OG001 | SK&F-105517-D | |
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| Primary | Mean Change From Baseline in Each Type of White Blood Cell (WBC) (Basophils, Eosinophils, Lymphocytes, Monocytes, and Total Neutrophils) at Week 8 | Mean change from baseline was calculated as the Week 8 value minus the Baseline value. | Safety Population: 22 participants at baseline and 11 participants at Week 8 in the CRV-IR group; 19 participants at baseline and 8 participants at Week 8 in the SK&F-105517-D group. Some participants in each treatment arm withdrew prematurely. | Posted | | Mean | Standard Deviation | percentage of each WBC type in WBC count | | Baseline and Week 8 | | | | ID | Title | Description |
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| OG000 | 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. | | OG001 | 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. |
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| Primary | Mean Change From Baseline in Hemoglobin and Mean Corpuscular Hemoglobin Concentration at Week 8 | Mean change from baseline was calculated as the Week 8 value minus the Baseline value. | Safety Population: 22 participants at baseline and 11 participants at Week 8 in the CRV-IR group; 19 participants at baseline and 8 participants at Week 8 in the SK&F-105517-D group. Some participants in each treatment arm withdrew prematurely. | Posted | | Mean | Standard Deviation | grams per liter (g/L) | | Baseline and Week 8 | | | | ID | Title | Description |
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| OG000 | 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. | | OG001 | 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. |
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| Primary | Mean Change From Baseline in Hematocrit at Week 8 | Mean change from baseline was calculated as the Week 8 value minus the Baseline value. | Safety Population: 22 participants at baseline and 11 participants at Week 8 in the CRV-IR group; 19 participants at baseline and 8 participants at Week 8 in the SK&F-105517-D group. Some participants in each treatment arm withdrew prematurely. | Posted | | Mean | Standard Deviation | proportion of 1 (SI) | | Baseline and Week 8 | | | | ID | Title | Description |
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| OG000 | 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. | | OG001 | 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. |
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| Primary | Mean Change From Baseline in Platelet Count and White Blood Cell Count at Week 8 | Mean change from baseline was calculated as the Week 8 value minus the Baseline value. | Safety Population: 22 participants at baseline and 11 participants at Week 8 in the CRV-IR group; 19 participants at baseline and 8 participants at Week 8 in the SK&F-105517-D group. Some participants in each treatment arm withdrew prematurely. | Posted | | Mean | Standard Deviation | gibi (2 to the power of 30)/liter (Gi/L) | | Baseline and Week 8 | | | | ID | Title | Description |
|---|
| OG000 | 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. | | OG001 | 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. |
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| Primary | Mean Change From Baseline in Red Blood Cell Count at Week 8 | Mean change from baseline was calculated as the Week 8 value minus the Baseline value. | Safety Population: 22 participants at baseline and 11 participants at Week 8 in the CRV-IR group; 19 participants at baseline and 8 participants at Week 8 in the SK&F-105517-D group. Some participants in each treatment arm withdrew prematurely. | Posted | | Mean | Standard Deviation | tebi (2 to the power of 40)/liter (Ti/L) | | Baseline and Week 8 | | | | ID | Title | Description |
|---|
| OG000 | 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. | | OG001 | 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. |
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| Primary | Mean Change From Baseline in Mean Corpuscular Hemoglobin at Week 8 | Mean change from baseline was calculated as the Week 8 value minus the Baseline value. | Safety Population: 22 participants at baseline and 11 participants at Week 8 in the CRV-IR group; 19 participants at baseline and 8 participants at Week 8 in the SK&F-105517-D group. Some participants in each treatment arm withdrew prematurely. | Posted | | Mean | Standard Deviation | picograms (pg) | | Baseline and Week 8 | | | | ID | Title | Description |
|---|
| OG000 | 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. | | OG001 | 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. |
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| Primary | Mean Change From Baseline in Mean Corpuscular Volume at Week 8 | Mean change from baseline was calculated as the Week 8 value minus the Baseline value. | Safety Population: 22 participants at baseline and 11 participants at Week 8 in the CRV-IR group; 19 participants at baseline and 8 participants at Week 8 in the SK&F-105517-D group. Some participants in each treatment arm withdrew prematurely. | Posted | | Mean | Standard Deviation | femtoliters (fL) | | Baseline and Week 8 | | | | ID | Title | Description |
|---|
| OG000 | 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. | | OG001 | 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. |
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| Primary | Number of Participants With the Indicated Urinalysis Dipstick Results at Baseline and Week 8 | Dipstick test values: Negative (-), Traces (+-), +1, +2, +3. +4. Normal ranges (qualitative): protein, - or +-; glucose, - or +-; occult blood, -; ketones, -. | Safety Population: 22 participants at baseline and 11 participants at Week 8 in the CRV-IR group; 19 participants at baseline and 8 participants at Week 8 in the SK&F-105517-D group. Some participants in each treatment arm withdrew prematurely. | Posted | | Number | | participants | | Baseline and Week 8 | | | | ID | Title | Description |
|---|
| OG000 | 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. | | OG001 | 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. |
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| Primary | Mean Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure at Week 8 | Mean change from baseline was calculated as the Week 8 value minus the Baseline value. | Safety Population: 22 participants at baseline and 11 participants at Week 8 in the CRV-IR group; 19 participants at baseline and 8 participants at Week 8 in the SK&F-105517-D group. Some participants in each treatment arm withdrew prematurely. | Posted | | Mean | Standard Deviation | millimeters of mercury (mmHg) | | Baseline and Week 8 | | | | ID | Title | Description |
|---|
| OG000 | 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. | | OG001 | 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. |
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| Primary | Mean Change From Baseline in Heart Rate at Week 8 | Mean change from baseline was calculated as the Week 8 value minus the Baseline value. | Safety Population: 22 participants at baseline and 11 participants at Week 8 in the CRV-IR group; 19 participants at baseline and 8 participants at Week 8 in the SK&F-105517-D group. Some participants in each treatment arm withdrew prematurely. | Posted | | Mean | Standard Deviation | beats per minute | | Baseline and Week 8 | | | | ID | Title | Description |
|---|
| OG000 | 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. | | OG001 | 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. |
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| Primary | Mean Change From Baseline in Weight at Week 8 | Mean change from baseline was calculated as the Week 8 value minus the Baseline value. | Safety Population: 22 participants at baseline and 11 participants at Week 8 in the CRV-IR group; 19 participants at baseline and 8 participants at Week 8 in the SK&F-105517-D group. Some participants in each treatment arm withdrew prematurely. | Posted | | Mean | Standard Deviation | kilograms (kg) | | Baseline and Week 8 | | | | ID | Title | Description |
|---|
| OG000 | 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. | | OG001 | 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. |
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| Primary | Number of Participants With the Indicated Electrocardiogram Findings at Baseline and Week 8 | There are 3 categories for electrocardiogram (ECG) findings: normal; abnormal, not clinically significant; and abnormal, clinically significant. Each of the findings was classified by the investigator according to whether it was normal. Abnormal ECGs were further classified according to whether they were felt to be clinically significant in the medical and scientific judgment of the investigator. | Safety Population: 22 participants at baseline and 11 participants at Week 8 in the CRV-IR group; 19 participants at baseline and 8 participants at Week 8 in the SK&F-105517-D group. Some participants in each treatment arm withdrew prematurely. | Posted | | Number | | participants | | Baseline and Week 8 | | | | ID | Title | Description |
|---|
| OG000 | 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. | | OG001 |
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| Primary | Cardiothoracic Ratio at Baseline and Week 8 | Cardiothoracic ratio is a marker of the degree of heart enlargement and was measured by chest X-ray. It is shown as the ratio of the transverse diameter of the heart to the transverse diameter of the thorax, and is measured as a percentage. | Safety Population: 22 participants at baseline and 11 participants at Week 8 in the CRV-IR group; 19 participants at baseline and 8 participants at Week 8 in the SK&F-105517-D group. Some participants in each treatment arm withdrew prematurely. | Posted | | Mean | Standard Deviation | percentage | | Baseline and Week 8 | | | | ID | Title | Description |
|---|
| OG000 | 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. | | OG001 | 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. |
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| Secondary | Adjusted Mean Change From Baseline in Diastolic Blood Pressure at Week 8 | Pharmacodynamic (PD) assessment points were 24 hours (h) (from time of first reading to time of last reading), morning (6 am-12 pm), afternoon (12-6 pm), night (6 pm-6 am on following day), waking (8 am-9 pm), sleeping (0-5 am), PDmax (maximal value obtained with each participant during the 0-24 h interval), PDmin (minimal value obtained with each participant during the 0-24 h interval), and PDmax/PDmin. PDmax/PDmim was calculated as the ratio of the PDmax to PDmin, and it showed the degree of change during the 0-24 h interval. The mean was adjusted for Baseline value. | Pharmacodynamic (PD) Population: all participants measurable at the PD endpoints (18 participants at baseline and 3 participants at Week 8 in CRV-IR group, 19 participants at baseline and 4 participants at Week 8 in SK&F-105517-D group) | Posted | | Mean | Standard Error | millimeters of mercury (mmHg) | | Baseline and Week 8 | | | | ID | Title | Description |
|---|
| OG000 | 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. |
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| Secondary | Adjusted Mean Change From Baseline in Mean Heart Rate at Week 8 | Pharmacodynamic (PD) assessment points were 24 hours (h) (from time of first reading to time of last reading), morning (6 am-12 pm), afternoon (12-6 pm), night (6 pm-6 am on following day), waking (8 am-9 pm), sleeping (0-5 am), PDmax (maximal value obtained with each participant during the 0-24 h interval), PDmin (minimal value obtained with each participant during the 0-24 h interval), and PDmax/PDmin. PDmax/PDmim was calculated as the ratio of the PDmax to PDmin, and it showed the degree of change during the 0-24 h interval. The mean was adjusted for Baseline value. | PD Population: all participants measurable at the PD endpoints (18 participants at baseline and 3 participants at Week 8 in CRV-IR group, 19 participants at baseline and 4 participants at Week 8 in SK&F-105517-D group) | Posted | | Mean | Standard Error | beats per minute | | Baseline and Week 8 | | | | ID | Title | Description |
|---|
| OG000 | 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. |
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| Secondary | Number of Participants With the Indicated Change From Baseline New York Heart Association (NYHA) Functional Class at Week 8 | The NYHA classification assesses the severity of symptoms of heart failure as judged by the investigator and is comprised of. 4 classes: I, no resulting limitations on physical activity (PA); II, slight limitations on PA; III, marked limitations on PA; IV, inability to carry out any PA without discomfort. The number of participants with any change from Baseline in the NYHA Functional Class at Week 8 was calculated. Improved=class at the visit is decreased compared to baseline class, Unchanged=class at the visit is stable, Worsened=class at the visit is increased compared to baseline class. | Efficacy Population: all participants measurable at the efficacy endpoints (20 participants at baseline and 11 participants at Week 8 in the CRV-IR group; 19 participants at baseline and 8 participants at Week 8 in the SK&F-105517-D group. Some participants in each treatment arm withdrew prematurely. | Posted | | Number | | participants | | Baseline and Week 8 | | | | ID | Title | Description |
|---|
| OG000 | 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. |
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| Secondary | Mean Plasma Brain Natriuretic Peptide Concentration at Baseline and Week 8 | Brain natriuretic peptide is a surrogate marker of the severity of heart failure and was measured by a central laboratory. | Efficacy Population: all participants measurable at the efficacy endpoints (20 participants at baseline and 11 participants at Week 8 in the CRV-IR group; 19 participants at baseline and 8 participants at Week 8 in the SK&F-105517-D group). Some participants in each treatment arm withdrew prematurely. | Posted | | Mean | Standard Deviation | ng/L (nanogram per Liter) | | Baseline and Week 8 | | | | ID | Title | Description |
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| OG000 | 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. | | OG001 | 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. |
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| Secondary | Echocardiogram Results: Left Ventricular Ejection Fraction at Baseline and Week 8 | Left ventricular ejection fraction (LVEF) is a marker of left ventricular systolic function and was measured by echocardiogram. It is shown as the ratio of left ventricular stroke volume (LVSV) to left ventricular end-diastolic volume (LVEDV), and is measured as a percentage. | Efficacy Population: all participants measurable at the efficacy endpoints (20 participants at baseline and 11 participants at Week 8 in the CRV-IR group; 19 participants at baseline and 8 participants at Week 8 in the SK&F-105517-D group). Some participants in each treatment arm withdrew prematurely. | Posted | | Mean | Standard Deviation | percentage | | Baseline and Week 8 | | | | ID | Title | Description |
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| OG000 | 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. | | OG001 | SK&F-105517-D |
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