Effects of Multiple Oral Doses of an A1 Adenosine Antagonist, BG9928, in Patients With Heart FailureResults of a Placebo-Controlled, Dose-Escalation Study
Barry Greenberg, MD*,1,*,
Ignatius Thomas, MD ,2,
Dorothy Banish, MD ,
Steven Goldman, MD ,
Edward Havranek, MD||,3,
Barry M. Massie, MD¶,4,
Ying Zhu, PhD#,5,
Barry Ticho, MD, PhD#,5 and
William T. Abraham, MD**,6
* University of California, Advanced Heart Failure Treatment Program, San Diego, California
Medical Research Institute, Slidell, Louisiana
Tchefuncte Cardiovascular Associates, Covington, Louisiana
Tucson VA Medical Center, SAVAHCS, Sarver Heart Center, and University of Arizona, Tucson, Arizona
|| Denver Health Medical Center, Denver, Colorado
¶ University of California and San Francisco VA Medical Center, San Francisco, California
# Biogen Idec Inc., Cambridge, Massachusetts
** The Ohio State University Heart Center, Division of Cardiology, Columbus, Ohio.
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Figure 1 Schematic Illustration of Study Design and Assessments
Timing and hourly intervals for assessments are described in the text. *Inpatient stays until 4 h after second and seventh dose and 32 h after tenth dose. Also collected on day 16. Assessment hourly intervals at baseline: 0 to 4, 4 to 8, 8 to 12, and 12 to 24; on days 1, 6, 10, and 16: 0 to 2, 2 to 4, 4 to 8, 8 to 12, and 12 to 24. Collection hourly intervals at baseline: 0 to 4, 4 to 8, 8 to 12, and 12 to 24; on days 1, 6, 10: 0 to 2, 2 to 4, 4 to 8, 8 to 12, and 12 to 24; on day 11: 28 h to 32 h after last dose. ||Collection hourly intervals at baseline: 0, 4, 8, 12, and 24; on days 1, 6, and 10: 2, 4, 8, and 12; on days 4 and 8: 0; on day 11: 4 and 8. NYHA = New York Heart Association; PGA = Physician’s Global Assessment; PO = per os (by mouth).
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Figure 2 Cumulative Urinary Sodium Excretion During Dosing
Cumulative urinary sodium excretion (mEq) over the interval of 0 to 8 h at baseline and after placebo or BG9928 administration on days 1, 6, and 10. *p < 0.05 versus placebo. p = 0.055 versus placebo. n = 10/group except for 15- and 75-mg dose groups on day 10 (n = 9/group).
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Figure 3 Cumulative Urinary Potassium Excretion During Dosing
Cumulative urinary potassium excretion (mEq) over the interval of 0 to 8 h at baseline and after placebo or BG9928 administration on days 1, 6, and 10. *p < 0.05 versus placebo. n = 10/group except for 15- and 75-mg dose groups on day 10 (n = 9/group).
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Figure 4 Change in Renal Function During Dosing
Absolute change from baseline in adjusted creatinine clearance (CrCl) (ml/min/1.73 m2) for the interval of 2 to 24 h after placebo or BG9928 administration on days 1, 6, and 10. *p < 0.05 versus placebo. n = 7 to 10 per group.
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