Clinical trial NCT00742508: A Phase I/II Clinical Study of SK&F-105517-D in Japanese Patients With Chronic Heart Failure
Official title: A Study to Evaluate the Safety and Tolerability of SK&F-105517-D in Patients With Chronic Heart Failure- An Open-label Study to Evaluate the Safety and Tolerability, Pharmacokinetics and Pharmacodynamics of SK&F-105517-D in Patients With Chronic Heart Failure (Phase I/II Study)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Heart Failure, Congestive
Keywords: carvedilol phosphate
ß-blocker
SK&F-105517-D
Chronic heart failure(CHF)
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2008-08-27
Enrollment: 41
Sex: ALL
Minimum age (years): 20
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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

Primary outcomes:
measure: Number of Participants With Adverse Events by Severity From Week 0 Through Week 8 (CRV-IR) or Week 14 (SK&F-105517-D)
timeFrame: 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
measure: Mean Change From Baseline in Albumin and Total Protein at Week 8
timeFrame: Baseline and Week 8
measure: Mean Change From Baseline in Alkaline Phosphatase, Alanine Aminotransferase, Aspartate Aminotransferase, Creatine Kinase, and Gamma Glutamyl Transferase at Week 8
timeFrame: Baseline and Week 8
measure: Mean Change From Baseline in Amylase at Week 8
timeFrame: Baseline and Week 8
measure: Mean Change From Baseline in Total Bilirubin, Creatinine, and Uric Acid at Week 8
timeFrame: Baseline and Week 8
measure: Mean Change From Baseline in Calcium, Chloride, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen at Week 8
timeFrame: Baseline and Week 8
measure: Mean Change From Baseline in Creatine Kinase BB Percentage, Creatine Kinase MB Percentage, and Creatine Kinase MM Percentage at Week 8
timeFrame: Baseline and Week 8
measure: Mean Change From Baseline in Each Type of White Blood Cell (WBC) (Basophils, Eosinophils, Lymphocytes, Monocytes, and Total Neutrophils) at Week 8
timeFrame: Baseline and Week 8
measure: Mean Change From Baseline in Hemoglobin and Mean Corpuscular Hemoglobin Concentration at Week 8
timeFrame: Baseline and Week 8
measure: Mean Change From Baseline in Hematocrit at Week 8
timeFrame: Baseline and Week 8
measure: Mean Change From Baseline in Platelet Count and White Blood Cell Count at Week 8
timeFrame: Baseline and Week 8
measure: Mean Change From Baseline in Red Blood Cell Count at Week 8
timeFrame: Baseline and Week 8
measure: Mean Change From Baseline in Mean Corpuscular Hemoglobin at Week 8
timeFrame: Baseline and Week 8
measure: Mean Change From Baseline in Mean Corpuscular Volume at Week 8
timeFrame: Baseline and Week 8
measure: Number of Participants With the Indicated Urinalysis Dipstick Results at Baseline and Week 8
timeFrame: Baseline and Week 8
measure: Mean Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure at Week 8
timeFrame: Baseline and Week 8
measure: Mean Change From Baseline in Heart Rate at Week 8
timeFrame: Baseline and Week 8
measure: Mean Change From Baseline in Weight at Week 8
timeFrame: Baseline and Week 8
measure: Number of Participants With the Indicated Electrocardiogram Findings at Baseline and Week 8
timeFrame: Baseline and Week 8
measure: Cardiothoracic Ratio at Baseline and Week 8
timeFrame: Baseline and Week 8
Secondary outcomes:
measure: Maximum Plasma Concentration (Cmax) and Trough Plasma Concentration (Cmin) of S-carvedilol, R-carvedilol, and M4 Active Metabolite (SB-203231) at Week 8
timeFrame: Week 8
measure: 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
timeFrame: Week 8
measure: Time of Maximal Plasma Concentration (Tmax) of S-carvedilol, R-carvedilol, and M4 Active Metabolite (SB-203231) at Week 8
timeFrame: Week 8
measure: Adjusted Mean Change From Baseline in Systolic Blood Pressure at Week 8
timeFrame: Baseline and Week 8
measure: Adjusted Mean Change From Baseline in Diastolic Blood Pressure at Week 8
timeFrame: Baseline and Week 8
measure: Adjusted Mean Change From Baseline in Mean Heart Rate at Week 8
timeFrame: Baseline and Week 8
measure: Number of Participants With the Indicated Change From Baseline New York Heart Association (NYHA) Functional Class at Week 8
timeFrame: Baseline and Week 8
measure: Mean Plasma Brain Natriuretic Peptide Concentration at Baseline and Week 8
timeFrame: Baseline and Week 8
measure: Echocardiogram Results: Left Ventricular Ejection Fraction at Baseline and Week 8
timeFrame: Baseline and Week 8
Other outcomes:
Locations:
city: Chiba
country: Japan
facility: GSK Investigational Site
city: Ehime
country: Japan
facility: GSK Investigational Site
city: Hiroshima
country: Japan
facility: GSK Investigational Site
city: Hokkaido
country: Japan
facility: GSK Investigational Site
city: Hokkaido
country: Japan
facility: GSK Investigational Site
city: Kanagawa
country: Japan
facility: GSK Investigational Site
city: Kanagawa
country: Japan
facility: GSK Investigational Site
city: Mie
country: Japan
facility: GSK Investigational Site
city: Nagano
country: Japan
facility: GSK Investigational Site
city: Nagasaki
country: Japan
facility: GSK Investigational Site
city: Oita
country: Japan
facility: GSK Investigational Site
city: Osaka
country: Japan
facility: GSK Investigational Site
city: Saga
country: Japan
facility: GSK Investigational Site
city: Saitama
country: Japan
facility: GSK Investigational Site
city: Shizuoka
country: Japan
facility: GSK Investigational Site
city: Shizuoka
country: Japan
facility: GSK Investigational Site
city: Shizuoka
country: Japan
facility: GSK Investigational Site
city: Shizuoka
country: Japan
facility: GSK Investigational Site
city: Tokyo
country: Japan
facility: GSK Investigational Site
city: Tokyo
country: Japan
facility: GSK Investigational Site
city: Tokyo
country: Japan
facility: GSK Investigational Site
city: Tokyo
country: Japan
facility: GSK Investigational Site
city: Wakayama
country: Japan
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Kitakaze M, Sarai N, Ando H, Sakamoto T, Nakajima H. Safety and tolerability of once-daily controlled-release carvedilol 10-80 mg in Japanese patients with chronic heart failure. Circ J. 2012;76(3):668-74. doi: 10.1253/circj.cj-11-0210. Epub 2012 Jan 12.