A Phase I/II Clinical Study of SK&F-105517-D in Japanese Patients With Chronic Heart Failure

NCT00742508 | Completed Phase 1 Results

• 1 other identifier: CRV110734
• Study Type: interventional
• Target: 41
• Locations: 1 country
• Sites: 23

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.

Conditions

Heart Failure, Congestive

Keywords

carvedilol phosphate; ß-blocker; SK&F-105517-D; Chronic heart failure(CHF)

Outcome Measures

Primary Outcomes (20)

• 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.

  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

• 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.

  Baseline and Week 8

• 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

  Baseline and Week 8

• Mean Change From Baseline in Amylase at Week 8

  Mean change from baseline was calculated as the Week 8 value minus the Baseline value

  Baseline and Week 8

• 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

  Baseline and Week 8

• 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

  Baseline and Week 8

• 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.

  Baseline and Week 8

• 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.

  Baseline and Week 8

• 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.

  Baseline and Week 8

• Mean Change From Baseline in Hematocrit at Week 8

  Mean change from baseline was calculated as the Week 8 value minus the Baseline value.

  Baseline and Week 8

• 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.

  Baseline and Week 8

• 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.

  Baseline and Week 8

• 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.

  Baseline and Week 8

• 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.

  Baseline and Week 8

• 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, -.

  Baseline and Week 8

• 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.

  Baseline and Week 8

• 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.

  Baseline and Week 8

• Mean Change From Baseline in Weight at Week 8

  Mean change from baseline was calculated as the Week 8 value minus the Baseline value.

  Baseline and Week 8

• 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.

  Baseline and Week 8

• 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.

  Baseline and Week 8

Secondary Outcomes (9)

• Maximum Plasma Concentration (Cmax) and Trough Plasma Concentration (Cmin) of S-carvedilol, R-carvedilol, and M4 Active Metabolite (SB-203231) at Week 8

  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) at Week 8

  Week 8

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

  Week 8

• Adjusted Mean Change From Baseline in Systolic Blood Pressure at Week 8

  Baseline and Week 8

• Adjusted Mean Change From Baseline in Diastolic Blood Pressure at Week 8

  Baseline and Week 8

Study Arms (2)

SK&F-105517-D group

EXPERIMENTAL

SK\&F-105517-D 10-80 mg/day

Drug: SK&F-105517-D 10 mg capsule; Drug: SK&F-105517-D 20 mg capsule; Drug: SK&F-105517-D 40 mg capsule

Carvedilol-IR group

OTHER

Carvedilol-IR 5-20 mg/day

Drug: Carvedilol-immediate release (IR) 2.5 mg tablet; Drug: Carvedilol-IR 10 mg tablet

Interventions

SK&F-105517-D 10 mg capsule DRUG

1 capsule once a day

Also known as: carvedilol phosphate

SK&F-105517-D group

Carvedilol-immediate release (IR) 2.5 mg tablet DRUG

1 or 2 tablet(s) twice a day

Carvedilol-IR group

SK&F-105517-D 20 mg capsule DRUG

1 capsule once a day

Also known as: carvedilol phosphate

SK&F-105517-D group

SK&F-105517-D 40 mg capsule DRUG

1 or 2 capsule(s) once a day

Also known as: carvedilol phosphate

SK&F-105517-D group

Carvedilol-IR 10 mg tablet DRUG

1 tablet twice a day

Carvedilol-IR group

Eligibility Criteria

• Age: 20 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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%

You may not qualify if:

• 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

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (23)

GSK Investigational Site

Chiba, 296-8602, Japan

Location

GSK Investigational Site

Ehime, 794-0006, Japan

Location

GSK Investigational Site

Hiroshima, 737-0023, Japan

Location

GSK Investigational Site

Hokkaido, 060-0033, Japan

Location

GSK Investigational Site

Hokkaido, 063-0005, Japan

Location

GSK Investigational Site

Kanagawa, 210-0852, Japan

Location

GSK Investigational Site

Kanagawa, 238-8558, Japan

Location

GSK Investigational Site

Mie, 511-0068, Japan

Location

GSK Investigational Site

Nagano, 397-8555, Japan

Location

GSK Investigational Site

Nagasaki, 859-3615, Japan

Location

GSK Investigational Site

Osaka, 565-8565, Japan

Location

GSK Investigational Site

Ōita, 879-5593, Japan

Location

GSK Investigational Site

Saga, 843-0393, Japan

Location

GSK Investigational Site

Saitama, 364-8501, Japan

Location

GSK Investigational Site

Shizuoka, 410-2295, Japan

Location

GSK Investigational Site

Shizuoka, 411-8611, Japan

Location

GSK Investigational Site

Shizuoka, 427-8502, Japan

Location

GSK Investigational Site

Shizuoka, 430-8502, Japan

Location

GSK Investigational Site

Tokyo, 141-0001, Japan

Location

GSK Investigational Site

Tokyo, 142-8666, Japan

Location

GSK Investigational Site

Tokyo, 153-8515, Japan

Location

GSK Investigational Site

Tokyo, 196-0003, Japan

Location

GSK Investigational Site

Wakayama, 640-8158, Japan

Location

Related Publications (1)

• 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.

  PMID: 22240593 BACKGROUND

Related Links

• Results for study 110734 can be found on the GSK Clinical Study Register.
• Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

MeSH Terms

Conditions

Heart Failure

Interventions

Tablets

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Dosage Forms; Pharmaceutical Preparations

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 26, 2008
• First Posted: August 27, 2008
• Study Start: August 28, 2008
• Primary Completion: August 21, 2009
• Study Completion: August 21, 2009
• Last Updated: August 2, 2017
• Results First Posted: August 19, 2010

Record last verified: 2017-06

Data Sharing

• IPD Sharing: Will share

Locations

JP (23)