- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00742508
A Phase I/II Clinical Study of SK&F-105517-D in Japanese Patients With Chronic Heart Failure
June 27, 2017 updated by: GlaxoSmithKline
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)
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.
Study Overview
Status
Completed
Conditions
Study Type
Interventional
Enrollment (Actual)
41
Phase
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Chiba, Japan, 296-8602
- GSK Investigational Site
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Ehime, Japan, 794-0006
- GSK Investigational Site
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Hiroshima, Japan, 737-0023
- GSK Investigational Site
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Hokkaido, Japan, 060-0033
- GSK Investigational Site
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Hokkaido, Japan, 063-0005
- GSK Investigational Site
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Kanagawa, Japan, 210-0852
- GSK Investigational Site
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Kanagawa, Japan, 238-8558
- GSK Investigational Site
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Mie, Japan, 511-0068
- GSK Investigational Site
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Nagano, Japan, 397-8555
- GSK Investigational Site
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Nagasaki, Japan, 859-3615
- GSK Investigational Site
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Oita, Japan, 879-5593
- GSK Investigational Site
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Osaka, Japan, 565-8565
- GSK Investigational Site
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Saga, Japan, 843-0393
- GSK Investigational Site
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Saitama, Japan, 364-8501
- GSK Investigational Site
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Shizuoka, Japan, 410-2295
- GSK Investigational Site
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Shizuoka, Japan, 411-8611
- GSK Investigational Site
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Shizuoka, Japan, 427-8502
- GSK Investigational Site
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Shizuoka, Japan, 430-8502
- GSK Investigational Site
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Tokyo, Japan, 142-8666
- GSK Investigational Site
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Tokyo, Japan, 141-0001
- GSK Investigational Site
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Tokyo, Japan, 153-8515
- GSK Investigational Site
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Tokyo, Japan, 196-0003
- GSK Investigational Site
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Wakayama, Japan, 640-8158
- GSK Investigational Site
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
20 years to 80 years (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
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
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: SK&F-105517-D group
SK&F-105517-D 10-80 mg/day
|
1 capsule once a day
Other Names:
1 capsule once a day
Other Names:
1 or 2 capsule(s) once a day
Other Names:
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Other: Carvedilol-IR group
Carvedilol-IR 5-20 mg/day
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1 or 2 tablet(s) twice a day
1 tablet twice a day
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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
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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.
|
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
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Mean Change From Baseline in Albumin and Total Protein at Week 8
Time Frame: Baseline and Week 8
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Mean change from baseline was calculated as the Week 8 value minus the Baseline value.
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Baseline and Week 8
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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
|
Mean change from baseline was calculated as the Week 8 value minus the Baseline value
|
Baseline and Week 8
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Mean Change From Baseline in Amylase at Week 8
Time Frame: Baseline and Week 8
|
Mean change from baseline was calculated as the Week 8 value minus the Baseline value
|
Baseline and Week 8
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Mean Change From Baseline in Total Bilirubin, Creatinine, and Uric Acid at Week 8
Time Frame: Baseline and Week 8
|
Mean change from baseline was calculated as the Week 8 value minus the Baseline value
|
Baseline and Week 8
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Mean Change From Baseline in Calcium, Chloride, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen at Week 8
Time Frame: Baseline and Week 8
|
Mean change from baseline was calculated as the Week 8 value minus the Baseline value
|
Baseline and Week 8
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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
|
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.
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Baseline and Week 8
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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
|
Mean change from baseline was calculated as the Week 8 value minus the Baseline value.
|
Baseline and Week 8
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Mean Change From Baseline in Hemoglobin and Mean Corpuscular Hemoglobin Concentration at Week 8
Time Frame: Baseline and Week 8
|
Mean change from baseline was calculated as the Week 8 value minus the Baseline value.
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Baseline and Week 8
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Mean Change From Baseline in Hematocrit at Week 8
Time Frame: Baseline and Week 8
|
Mean change from baseline was calculated as the Week 8 value minus the Baseline value.
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Baseline and Week 8
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Mean Change From Baseline in Platelet Count and White Blood Cell Count at Week 8
Time Frame: Baseline and Week 8
|
Mean change from baseline was calculated as the Week 8 value minus the Baseline value.
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Baseline and Week 8
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Mean Change From Baseline in Red Blood Cell Count at Week 8
Time Frame: Baseline and Week 8
|
Mean change from baseline was calculated as the Week 8 value minus the Baseline value.
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Baseline and Week 8
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Mean Change From Baseline in Mean Corpuscular Hemoglobin at Week 8
Time Frame: Baseline and Week 8
|
Mean change from baseline was calculated as the Week 8 value minus the Baseline value.
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Baseline and Week 8
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Mean Change From Baseline in Mean Corpuscular Volume at Week 8
Time Frame: Baseline and Week 8
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Mean change from baseline was calculated as the Week 8 value minus the Baseline value.
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Baseline and Week 8
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Number of Participants With the Indicated Urinalysis Dipstick Results at Baseline and Week 8
Time Frame: Baseline and Week 8
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Dipstick test values: Negative (-), Traces (+-), +1, +2, +3.
+4.
Normal ranges (qualitative): protein, - or +-; glucose, - or +-; occult blood, -; ketones, -.
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Baseline and Week 8
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Mean Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure at Week 8
Time Frame: Baseline and Week 8
|
Mean change from baseline was calculated as the Week 8 value minus the Baseline value.
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Baseline and Week 8
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Mean Change From Baseline in Heart Rate at Week 8
Time Frame: Baseline and Week 8
|
Mean change from baseline was calculated as the Week 8 value minus the Baseline value.
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Baseline and Week 8
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Mean Change From Baseline in Weight at Week 8
Time Frame: Baseline and Week 8
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Mean change from baseline was calculated as the Week 8 value minus the Baseline value.
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Baseline and Week 8
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Number of Participants With the Indicated Electrocardiogram Findings at Baseline and Week 8
Time Frame: Baseline and Week 8
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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.
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Baseline and Week 8
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Cardiothoracic Ratio at Baseline and Week 8
Time Frame: Baseline and Week 8
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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.
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Baseline and Week 8
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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
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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.
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Week 8
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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
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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.
|
Week 8
|
Time of Maximal Plasma Concentration (Tmax) of S-carvedilol, R-carvedilol, and M4 Active Metabolite (SB-203231) at Week 8
Time Frame: 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.
|
Week 8
|
Adjusted Mean Change From Baseline in Systolic Blood Pressure at Week 8
Time Frame: Baseline and 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.
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Baseline and Week 8
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Adjusted Mean Change From Baseline in Diastolic Blood Pressure at Week 8
Time Frame: Baseline and Week 8
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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.
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Baseline and Week 8
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Adjusted Mean Change From Baseline in Mean Heart Rate at Week 8
Time Frame: Baseline and 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.
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Baseline and Week 8
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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
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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.
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Baseline and Week 8
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Mean Plasma Brain Natriuretic Peptide Concentration at Baseline and Week 8
Time Frame: Baseline and Week 8
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Brain natriuretic peptide is a surrogate marker of the severity of heart failure and was measured by a central laboratory.
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Baseline and Week 8
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Echocardiogram Results: Left Ventricular Ejection Fraction at Baseline and Week 8
Time Frame: Baseline and Week 8
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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.
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Baseline and Week 8
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
August 28, 2008
Primary Completion (Actual)
August 21, 2009
Study Completion (Actual)
August 21, 2009
Study Registration Dates
First Submitted
August 26, 2008
First Submitted That Met QC Criteria
August 26, 2008
First Posted (Estimate)
August 27, 2008
Study Record Updates
Last Update Posted (Actual)
August 2, 2017
Last Update Submitted That Met QC Criteria
June 27, 2017
Last Verified
June 1, 2017
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Heart Diseases
- Cardiovascular Diseases
- Heart Failure
- Physiological Effects of Drugs
- Adrenergic beta-Antagonists
- Adrenergic Antagonists
- Adrenergic Agents
- Neurotransmitter Agents
- Molecular Mechanisms of Pharmacological Action
- Antihypertensive Agents
- Vasodilator Agents
- Protective Agents
- Membrane Transport Modulators
- Calcium-Regulating Hormones and Agents
- Calcium Channel Blockers
- Antioxidants
- Adrenergic alpha-1 Receptor Antagonists
- Adrenergic alpha-Antagonists
- Carvedilol
Other Study ID Numbers
- CRV110734
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Yes
IPD Plan Description
Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.
Study Data/Documents
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Dataset Specification
Information identifier: CRV110734Information comments: For additional information about this study please refer to the GSK Clinical Study Register
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Study Protocol
Information identifier: CRV110734Information comments: For additional information about this study please refer to the GSK Clinical Study Register
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Individual Participant Data Set
Information identifier: CRV110734Information comments: For additional information about this study please refer to the GSK Clinical Study Register
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Annotated Case Report Form
Information identifier: CRV110734Information comments: For additional information about this study please refer to the GSK Clinical Study Register
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Statistical Analysis Plan
Information identifier: CRV110734Information comments: For additional information about this study please refer to the GSK Clinical Study Register
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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