- Email: [email protected]
58
NKF 2007 Spring Clinical Meetings Abstracts
57
58
ERGOCALCIFEROL EFFECTIVELY LOWERS iPTH LEVELS IN CHRONIC KIDNEY DISEASE (CKD) PATIENTS William F. Finn, University of North Carolina Kidney Center, Chapel Hill, NC, USA Vitamin D deficiency (25-hydroxyvitamin D levels <32 ng/ml) is common and likely contributes to the rise in iPTH seen in CKD. While data exist concerning the use of hormonal 1,25-(OH)2 dihydroxyvitamin D (calcitriol) and its analogues in CKD patients, little data are available to compare the effects of standard vitamin D therapy. Patients with CKD, vitamin D deficiency and hyperparathyroidism (HPT) were treated with ergocalciferol 50,000 IU every week for a minimum of 12 weeks. The following results were observed. CKD STAGE 1&2 (n=5) 3 (n=20) 4&5 (n=25) MDRD pre 80±16 47±10 21±4 ml/min post 76±16 49±14 22±7 Calcium pre 9.4±0.8 9.2±0.4 9.3±0.4 mg/dl post 9.7±0.6 9.5±0.4 9.5±0.5 Phosphorus pre 2.9±0.4 3.4±0.6 4.1±0.8 mg/dl post 2.9±0.6 3.5±0.6 4.2±0.6 25-OH D pre 11.2±5.4 15.7±3.9 13.9±4.7 ng/ml post 32.8±6.0 60.2±33.9 48.2±24.6 1,25-(OH)2 D pre 35.0±30.3 27.4±11.6 14.0±9.0 pg/ml post 40.2±25.3 33.2±5.8 20.1±12.6 iPTH pre 200±142 184±157 239±122 pg/ml post 108±53 103±76 186±98 Further analysis of Stage 4&5 patients showed a decline in iPTH of 40% in 17 patients (Group A) with an increase of 31% in 8 patients (Group B). Compared to Group A, Group B post treatment was marked by higher serum phosphorus levels (4.6±0.6 vs. 3.9±0.5; p<0.02) and higher calcium × phosphorus product (43.3±6.0 vs. 37.3±5.3; p<0.03). Ergocalciferol is a safe, effective and inexpensive treatment for CKD patients with vitamin D deficiency and HPT and should be considered as first line treatment. Failure to respond in some CKD 4&5 patients may have been a result of the effects of progressive phosphorus retention and supports the need for early phosphorus management.
C.E.R.A. ONCE MONTHLY MAINTAINS STABLE HB LEVELS IN PATIENTS WITH CKD ON DIALYSIS WITH AND WITHOUT CONGESTIVE HEART FAILURE (CHF) Allen Nissenson, University of California, Los Angeles, CA, USA. Ambrose Kwok, Everest Clinical Research Services, Markham, Ontario, Canada. Richard Beswick, Roche Laboratories, Nutley, NJ, USA. Steven Fishbane, Winthrop University Hospital, Mineola, NY, USA. C.E.R.A., a continuous erythropoietin receptor activator with unique receptor activity and a long half-life, is currently in development to provide correction of anemia and stable Hb levels at intervals up to once monthly. A post-hoc analysis of two Phase III studies assessed the efficacy of C.E.R.A. administered IV or SC up to Q4W for maintaining target Hb in patients on dialysis with or without CHF directly converted from IV or SC epoetin alfa or beta TIW-QW. As with other phase III clinical trials in this therapeutic area, class IV CHF patients were excluded from this study protocol. A total of 413 patients received C.E.R.A. Q2W, 415 received C.E.R.A. Q4W and 417 continued with epoetin TIW-QW. Dose was adjusted to maintain baseline Hb 1.0 g/dL of baseline and 10.0-13.5 g/dL. Mean Hb change between baseline and the evaluation period (weeks 29-36) for patients treated with C.E.R.A. Q4W or epoetin TIW-QW with and without CHF is reported. A total of 20% of patients treated with C.E.R.A. Q4W or epoetin had CHF at baseline. Mean baseline Hb levels were similar for C.E.R.A. and epoetin. During the evaluation period, mean Hb levels were similar in patients with and without CHF (C.E.R.A. Q4W: 11.6 vs 11.7 g/dL; epoetin: 11.7 vs 11.7g/dL). C.E.R.A. Q4W effectively maintained Hb levels from baseline to evaluation in patients with and without CHF: mean changes were –0.14 and –0.03 g/dL, respectively. Mean Hb change was –0.13 and –0.06 g/dL for epoetin-treated patients with and without CHF, respectively. Patients in both study arms with and without CHF had similar AE profiles. These Phase III data indicate that C.E.R.A. is effective for maintaining stable Hb levels in patients on dialysis with and without CHF who convert directly from epoetin TIW-QW.
A39
59
60
EFFICACY OF C.E.R.A., A CONTINUOUS ERYTHROPOIETIN RECEPTOR ACTIVATOR, IN TREATMENT OF RENAL ANEMIA: OVERVIEW OF 6 GLOBAL PHASE 3 TRIALS Steven Fishbane1, Cheryl Dalton2, Richard Beswick3, Paula Dutka1, Rebecca Schmidt2 1 Winthrop University Hospital, Mineola, NY; 2School of Medicine, West Virginia University, Morgantown, WV; 3Roche Laboratories, Nutley, NJ C.E.R.A. is a continuous erythropoietin receptor activator with unique receptor activity and a prolonged half-life allowing extended dosing intervals. Six global Phase III studies in >2400 patients compared C.E.R.A. with epoetin alfa or beta (EPO-? or –?) or darbepoetin-? (DAR). All were randomized, open-label, multicenter, parallel-group trials. Two initiation studies enrolled therapy-naïve patients. In AMICUS (N=181), dialysis patients initially received CERA Q2W or EPO-? or -? TIW IV for 24 wks initiation followed by a 28-wk extension in which CERA was dosed Q2W or Q4W. In ARCTOS (n= 324), nondialysis patients received C.E.R.A. Q2W or DAR QW for 18 wks correction and 10 wks evaluation, followed by C.E.R.A. Q2W or Q4W for a 24wk extension. In both studies, C.E.R.A Q2W successfully corrected anemia and maintained Hb levels in naïve patients. Four maintenance studies evaluated switching of dialysis patients from EPO or DAR to C.E.R.A. In MAXIMA (IV, N=673) and PROTOS (SC, N=572), dialysis patients received C.E.R.A. Q2W or Q4W or continued on EPO-? or –? TIW for 28 wks titration, 8 wks evaluation, and an additional 16-wk safety period. In STRIATA (IV, N=313), dialysis patients received C.E.R.A. Q2W or DAR QW or Q2W for 28 wks titration, 8 wks evaluation, and an additional 16-wk safety period. In RUBRA (IV or SC, N=336), dialysis patients received C.E.R.A. in pre-filled syringes Q2W or Q4W or continued on EPO. C.E.R.A. successfully maintained stable Hb levels whether administered SC or IV. C.E.R.A.’s efficacy mirrors that of EPO or DAR but requires less frequent administration.
ADVANCE: THE EFFECT OF CINACALCET + LOW-DOSE VITAMIN D ON VASCULAR CALCIFICATION IN
HEMODIALYSIS PATIENTS – METHODS J Floege1, S Sprague2, J Droge3, A Banos4, G Chertow5 1 RWTH Uni RWTH, Aachen, Germany, 2Evanston Northwestern Healthcare, Northwestern University, Evanston, IL 3 Amgen Inc, Thousand Oaks, CA, 4Amgen Ltd, Uxbridge, UK, 5 UCSF, San Francisco, CA Vascular calcification (VC) in hemodialysis (HD) patients has been associated with elevated serum calcium (Ca) and phosphorus (P) concentrations. Preclinical evidence suggests that the calcimimetic cinacalcet does not induce VC and attenuates vitamin D-associated VC. Clinical studies have shown that cinacalcet + low-dose vitamin D improves control of parathyroid hormone (PTH), Ca, P, and Ca x P in HD patients. However, the effect of cinacalcet on VC has not been examined. In this multicenter, randomized, open-label trial, subjects (projected total n=330) with iPTH ≥300 pg/mL (or 150-300 pg/mL with Ca x P >50 mg2/dL2 and on vitamin D [to capture subjects with secondary HPT with controlled PTH]), a corrected serum Ca ≥8.4 mg/dL, and a coronary artery calcification (CAC) score of ≥30 will be randomly assigned to receive cinacalcet + low-dose vitamin D or flexible vitamin D without cinacalcet for 20-week dose-titration and 32-week follow-up phases. Cinacalcet will be started at 30 mg/day and titrated to 60, 90, 120, and 180 mg/day, as appropriate based on PTH concentrations. In the group not receiving cinacalcet, vitamin D (initiated at a maximum of 2 mcg paricalcitol or equivalent per dialysis session) will be titrated according to clinical practice guidelines. The primary study endpoint is the percent change from baseline to week 52 in CAC.
57
58
ERGOCALCIFEROL EFFECTIVELY LOWERS iPTH LEVELS IN CHRONIC KIDNEY DISEASE (CKD) PATIENTS William F. Finn, University of North Carolina Kidney Center, Chapel Hill, NC, USA Vitamin D deficiency (25-hydroxyvitamin D levels <32 ng/ml) is common and likely contributes to the rise in iPTH seen in CKD. While data exist concerning the use of hormonal 1,25-(OH)2 dihydroxyvitamin D (calcitriol) and its analogues in CKD patients, little data are available to compare the effects of standard vitamin D therapy. Patients with CKD, vitamin D deficiency and hyperparathyroidism (HPT) were treated with ergocalciferol 50,000 IU every week for a minimum of 12 weeks. The following results were observed. CKD STAGE 1&2 (n=5) 3 (n=20) 4&5 (n=25) MDRD pre 80±16 47±10 21±4 ml/min post 76±16 49±14 22±7 Calcium pre 9.4±0.8 9.2±0.4 9.3±0.4 mg/dl post 9.7±0.6 9.5±0.4 9.5±0.5 Phosphorus pre 2.9±0.4 3.4±0.6 4.1±0.8 mg/dl post 2.9±0.6 3.5±0.6 4.2±0.6 25-OH D pre 11.2±5.4 15.7±3.9 13.9±4.7 ng/ml post 32.8±6.0 60.2±33.9 48.2±24.6 1,25-(OH)2 D pre 35.0±30.3 27.4±11.6 14.0±9.0 pg/ml post 40.2±25.3 33.2±5.8 20.1±12.6 iPTH pre 200±142 184±157 239±122 pg/ml post 108±53 103±76 186±98 Further analysis of Stage 4&5 patients showed a decline in iPTH of 40% in 17 patients (Group A) with an increase of 31% in 8 patients (Group B). Compared to Group A, Group B post treatment was marked by higher serum phosphorus levels (4.6±0.6 vs. 3.9±0.5; p<0.02) and higher calcium × phosphorus product (43.3±6.0 vs. 37.3±5.3; p<0.03). Ergocalciferol is a safe, effective and inexpensive treatment for CKD patients with vitamin D deficiency and HPT and should be considered as first line treatment. Failure to respond in some CKD 4&5 patients may have been a result of the effects of progressive phosphorus retention and supports the need for early phosphorus management.
C.E.R.A. ONCE MONTHLY MAINTAINS STABLE HB LEVELS IN PATIENTS WITH CKD ON DIALYSIS WITH AND WITHOUT CONGESTIVE HEART FAILURE (CHF) Allen Nissenson, University of California, Los Angeles, CA, USA. Ambrose Kwok, Everest Clinical Research Services, Markham, Ontario, Canada. Richard Beswick, Roche Laboratories, Nutley, NJ, USA. Steven Fishbane, Winthrop University Hospital, Mineola, NY, USA. C.E.R.A., a continuous erythropoietin receptor activator with unique receptor activity and a long half-life, is currently in development to provide correction of anemia and stable Hb levels at intervals up to once monthly. A post-hoc analysis of two Phase III studies assessed the efficacy of C.E.R.A. administered IV or SC up to Q4W for maintaining target Hb in patients on dialysis with or without CHF directly converted from IV or SC epoetin alfa or beta TIW-QW. As with other phase III clinical trials in this therapeutic area, class IV CHF patients were excluded from this study protocol. A total of 413 patients received C.E.R.A. Q2W, 415 received C.E.R.A. Q4W and 417 continued with epoetin TIW-QW. Dose was adjusted to maintain baseline Hb 1.0 g/dL of baseline and 10.0-13.5 g/dL. Mean Hb change between baseline and the evaluation period (weeks 29-36) for patients treated with C.E.R.A. Q4W or epoetin TIW-QW with and without CHF is reported. A total of 20% of patients treated with C.E.R.A. Q4W or epoetin had CHF at baseline. Mean baseline Hb levels were similar for C.E.R.A. and epoetin. During the evaluation period, mean Hb levels were similar in patients with and without CHF (C.E.R.A. Q4W: 11.6 vs 11.7 g/dL; epoetin: 11.7 vs 11.7g/dL). C.E.R.A. Q4W effectively maintained Hb levels from baseline to evaluation in patients with and without CHF: mean changes were –0.14 and –0.03 g/dL, respectively. Mean Hb change was –0.13 and –0.06 g/dL for epoetin-treated patients with and without CHF, respectively. Patients in both study arms with and without CHF had similar AE profiles. These Phase III data indicate that C.E.R.A. is effective for maintaining stable Hb levels in patients on dialysis with and without CHF who convert directly from epoetin TIW-QW.
A39
59
60
EFFICACY OF C.E.R.A., A CONTINUOUS ERYTHROPOIETIN RECEPTOR ACTIVATOR, IN TREATMENT OF RENAL ANEMIA: OVERVIEW OF 6 GLOBAL PHASE 3 TRIALS Steven Fishbane1, Cheryl Dalton2, Richard Beswick3, Paula Dutka1, Rebecca Schmidt2 1 Winthrop University Hospital, Mineola, NY; 2School of Medicine, West Virginia University, Morgantown, WV; 3Roche Laboratories, Nutley, NJ C.E.R.A. is a continuous erythropoietin receptor activator with unique receptor activity and a prolonged half-life allowing extended dosing intervals. Six global Phase III studies in >2400 patients compared C.E.R.A. with epoetin alfa or beta (EPO-? or –?) or darbepoetin-? (DAR). All were randomized, open-label, multicenter, parallel-group trials. Two initiation studies enrolled therapy-naïve patients. In AMICUS (N=181), dialysis patients initially received CERA Q2W or EPO-? or -? TIW IV for 24 wks initiation followed by a 28-wk extension in which CERA was dosed Q2W or Q4W. In ARCTOS (n= 324), nondialysis patients received C.E.R.A. Q2W or DAR QW for 18 wks correction and 10 wks evaluation, followed by C.E.R.A. Q2W or Q4W for a 24wk extension. In both studies, C.E.R.A Q2W successfully corrected anemia and maintained Hb levels in naïve patients. Four maintenance studies evaluated switching of dialysis patients from EPO or DAR to C.E.R.A. In MAXIMA (IV, N=673) and PROTOS (SC, N=572), dialysis patients received C.E.R.A. Q2W or Q4W or continued on EPO-? or –? TIW for 28 wks titration, 8 wks evaluation, and an additional 16-wk safety period. In STRIATA (IV, N=313), dialysis patients received C.E.R.A. Q2W or DAR QW or Q2W for 28 wks titration, 8 wks evaluation, and an additional 16-wk safety period. In RUBRA (IV or SC, N=336), dialysis patients received C.E.R.A. in pre-filled syringes Q2W or Q4W or continued on EPO. C.E.R.A. successfully maintained stable Hb levels whether administered SC or IV. C.E.R.A.’s efficacy mirrors that of EPO or DAR but requires less frequent administration.
ADVANCE: THE EFFECT OF CINACALCET + LOW-DOSE VITAMIN D ON VASCULAR CALCIFICATION IN
HEMODIALYSIS PATIENTS – METHODS J Floege1, S Sprague2, J Droge3, A Banos4, G Chertow5 1 RWTH Uni RWTH, Aachen, Germany, 2Evanston Northwestern Healthcare, Northwestern University, Evanston, IL 3 Amgen Inc, Thousand Oaks, CA, 4Amgen Ltd, Uxbridge, UK, 5 UCSF, San Francisco, CA Vascular calcification (VC) in hemodialysis (HD) patients has been associated with elevated serum calcium (Ca) and phosphorus (P) concentrations. Preclinical evidence suggests that the calcimimetic cinacalcet does not induce VC and attenuates vitamin D-associated VC. Clinical studies have shown that cinacalcet + low-dose vitamin D improves control of parathyroid hormone (PTH), Ca, P, and Ca x P in HD patients. However, the effect of cinacalcet on VC has not been examined. In this multicenter, randomized, open-label trial, subjects (projected total n=330) with iPTH ≥300 pg/mL (or 150-300 pg/mL with Ca x P >50 mg2/dL2 and on vitamin D [to capture subjects with secondary HPT with controlled PTH]), a corrected serum Ca ≥8.4 mg/dL, and a coronary artery calcification (CAC) score of ≥30 will be randomly assigned to receive cinacalcet + low-dose vitamin D or flexible vitamin D without cinacalcet for 20-week dose-titration and 32-week follow-up phases. Cinacalcet will be started at 30 mg/day and titrated to 60, 90, 120, and 180 mg/day, as appropriate based on PTH concentrations. In the group not receiving cinacalcet, vitamin D (initiated at a maximum of 2 mcg paricalcitol or equivalent per dialysis session) will be titrated according to clinical practice guidelines. The primary study endpoint is the percent change from baseline to week 52 in CAC.