Phase 1
N=41
A Phase I/II Clinical Study of SK&F-105517-D in Japanese Patients With Chronic Heart Failure
Heart Failure, Congestive
Bottom Line
View on ClinicalTrials.gov: NCT00742508 ↗Enrolled (actual)
41
Serious AEs
9.8%
Results posted
Aug 2010
Primary outcome: Primary: Number of Participants With Adverse Events by Severity From Week 0 Through Week 8 (CRV-IR) or Week 14 (SK&F-105517-D) — 0; 1; 2; 5 participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 1
- Interventions
- SK&F-105517-D 10 mg capsule (Drug); Carvedilol-immediate release (IR) 2.5 mg tablet (Drug); SK&F-105517-D 20 mg capsule (Drug); SK&F-105517-D 40 mg capsule (Drug); Carvedilol-IR 10 mg tablet (Drug)
- Age
- Adult, Older Adult · 20+ yrs
- Sex
- All
- Sponsor
- GlaxoSmithKline
- Primary completion
- Aug 2009
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Participants With Adverse Events by Severity From Week 0 Through Week 8 (CRV-IR) or Week 14 (SK&F-105517-D) |
0; 1; 2; 5; 9; 10 | — |
| PRIMARY Mean Change From Baseline in Albumin and Total Protein at Week 8 |
0.7; -1.9; 0.4; -1.6 | — |
| PRIMARY Mean Change From Baseline in Alkaline Phosphatase, Alanine Aminotransferase, Aspartate Aminotransferase, Creatine Kinase, and Gamma Glutamyl Transferase at Week 8 |
-10.9; -5.0; -0.2; 3.8; 0.8; 1.4 | — |
| PRIMARY Mean Change From Baseline in Amylase at Week 8 |
-10.2; -0.1 | — |
| PRIMARY Mean Change From Baseline in Total Bilirubin, Creatinine, and Uric Acid at Week 8 |
1.555; -4.489; 5.5451; -4.5305; 30.8215; 14.1265 | — |
| PRIMARY Mean Change From Baseline in Calcium, Chloride, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen at Week 8 |
-0.027218; -0.056138; 0.2; 2.4; -0.136252; -1.956728 | — |
| PRIMARY Mean Change From Baseline in Creatine Kinase BB Percentage, Creatine Kinase MB Percentage, and Creatine Kinase MM Percentage at Week 8 |
-0.2; 0.5; -0.3; -0.1; 1.1; 0.8 | — |
| PRIMARY Mean Change From Baseline in Each Type of White Blood Cell (WBC) (Basophils, Eosinophils, Lymphocytes, Monocytes, and Total Neutrophils) at Week 8 |
-0.06; -0.06; 0.15; 0.76; 0.05; 2.21 | — |
| PRIMARY Mean Change From Baseline in Hemoglobin and Mean Corpuscular Hemoglobin Concentration at Week 8 |
-2.3; -3.9; 1.3; -1.9 | — |
| PRIMARY Mean Change From Baseline in Hematocrit at Week 8 |
-0.0085; -0.0095 | — |
| PRIMARY Mean Change From Baseline in Platelet Count and White Blood Cell Count at Week 8 |
-6.9; -11.1; 0.297; -0.498 | — |
| PRIMARY Mean Change From Baseline in Red Blood Cell Count at Week 8 |
-0.091; -0.087 | — |
| PRIMARY Mean Change From Baseline in Mean Corpuscular Hemoglobin at Week 8 |
0.12; -0.21 | — |
| PRIMARY Mean Change From Baseline in Mean Corpuscular Volume at Week 8 |
0.1; -0.1 | — |
| PRIMARY Number of Participants With the Indicated Urinalysis Dipstick Results at Baseline and Week 8 |
20; 19; 1; 0; 0; 0 | — |
| PRIMARY Mean Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure at Week 8 |
-5.7; 10.0; 0.6; 2.8 | — |
| PRIMARY Mean Change From Baseline in Heart Rate at Week 8 |
-10.4; -10.6 | — |
| PRIMARY Mean Change From Baseline in Weight at Week 8 |
0.29; -0.11 | — |
| PRIMARY Number of Participants With the Indicated Electrocardiogram Findings at Baseline and Week 8 |
2; 1; 12; 9; 8; 9 | — |
| PRIMARY Cardiothoracic Ratio at Baseline and Week 8 |
53.70; 53.58; 50.91; 52.35 | — |
| SECONDARY Maximum Plasma Concentration (Cmax) and Trough Plasma Concentration (Cmin) of S-carvedilol, R-carvedilol, and M4 Active Metabolite (SB-203231) at Week 8 |
6.7952; 12.8171; 1.2072; 3.3796; 19.1864; 27.1306 | — |
| 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 |
60.040; 155.109; 170.728; 284.313; 28.113; 64.687 | — |
| SECONDARY Time of Maximal Plasma Concentration (Tmax) of S-carvedilol, R-carvedilol, and M4 Active Metabolite (SB-203231) at Week 8 |
1.983; 5.958; 1.983; 5.958; 1.983; 5.958 | — |
| SECONDARY Adjusted Mean Change From Baseline in Systolic Blood Pressure at Week 8 |
-10.84; -1.45; -12.34; -4.78; -10.14; -12.06 | — |
| SECONDARY Adjusted Mean Change From Baseline in Diastolic Blood Pressure at Week 8 |
-7.10; -4.89; -7.68; -8.24; -5.32; -10.25 | — |
| SECONDARY Adjusted Mean Change From Baseline in Mean Heart Rate at Week 8 |
-11.38; -15.37; -9.59; -14.87; -13.96; -15.93 | — |
| SECONDARY Number of Participants With the Indicated Change From Baseline New York Heart Association (NYHA) Functional Class at Week 8 |
0; 1; 11; 7; 0; 0 | — |
| SECONDARY Mean Plasma Brain Natriuretic Peptide Concentration at Baseline and Week 8 |
108.93; 226.46; 64.88; 111.93 | — |
| SECONDARY Echocardiogram Results: Left Ventricular Ejection Fraction at Baseline and Week 8 |
34.0; 32.2; 42.0; 37.6 | — |
Summary
The primary objective of this study is to evaluate the safety and tolerability of SK&F-105517-D in japanese patients with chronic heart failure.
Eligibility Criteria
Inclusion criteria
- Patients with symptomatically stable chronic heart failure (CHF) based on ischemic heart disease or dilated cardiomyopathy
- Patients who are maintained on basic heart failure therapy with angiotensin converting enzyme (ACE) inhibitors or angiotensin II receptor blocker (ARB) and their dosage/administration is not changed within 2 weeks
- Patients diagnosed with New York Heart Association (NYHA) class I to III
- Patients with a left ventricular ejection fraction (LVEF) between 25% and 45%
Exclusion Criteria
- Patients contraindicated for ß-blockers
- Patients with occurrence of acute myocardial infarction within 2 weeks
- Patients with unstable angina, coronary spastic angina, or angina at rest
- Patients who have collected blood >400 mL within 4 months prior to screening or >200 mL within 1 months
Data sourced from ClinicalTrials.gov (NCT00742508). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.