John P Bilezikian1, Bart L Clarke2, Michael Mannstadt3, Jeffrey Rothman4, Tamara Vokes5, Hak-Myung Lee6, Alan Krasner6. 1. Division of Endocrinology, College of Physicians and Surgeons, Columbia University, New York, New York. Electronic address: jpb2@cumc.columbia.edu. 2. Division of Endocrinology, Diabetes, Metabolism, and Nutrition, Mayo Clinic, Rochester, Minnesota. 3. Endocrine Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts. 4. University Physicians Group - Research Division and Division of Endocrinology, Staten Island University Hospital, Staten Island, New York. 5. Section of Endocrinology, University of Chicago Medicine, Chicago, Illinois. 6. Shire Human Genetic Therapies Inc, Lexington, Massachusetts.
Abstract
PURPOSE: The present study examined the efficacy and safety of a lower rhPTH(1-84) dose. METHODS: RELAY was a dose-blinded, multicenter, 8-week study of patients with hypoparathyroidism randomized tofixed 25- or 50-μg/d doses of subcutaneous rhPTH(1-84). The primary end point was the percentage of patients at week 8 with supplement reductions in calcium to ≤500 mg/d and in calcitriol to ≤0.25 μg/d, while maintaining serum calcium levels between 1.875 mmol/L and the upper limit of normal. The secondary end point was the percentage of patients at week 8 with a ≥50% reduction in calcium and calcitriol doses, while maintaining serum calcium levels between 1.875 mmol/L and the upper limit of normal. FINDINGS: Forty-two patients were randomized (25-μg group, n = 19; 50-μg group, n = 23). At week 8, the primary end point was achieved by 4 (21%; 95% CI, 6%-46%) and 6 (26%; 95% CI, 10%-48%) of the patients receiving 25 and 50 μg/d of rhPTH(1-84), respectively. The secondary end point was achieved by 2 (11%; 95% CI, 1%-33%) and 6 (26%; 95% CI, 10%-48%) of the patients receiving 25 and 50 μg/d of rhPTH(1-84), respectively. Treatment-emergent adverse events were reported by 11 (58%) patients in the 25-μg group and 17 (74%) patients in the 50-μg group. IMPLICATIONS: Doses as low as 25 µg/d of rhPTH(1-84) are well tolerated and may be effective for a subset of patients. ClinicalTrials.gov identifier: NCT01268098.
RCT Entities:
PURPOSE: The present study examined the efficacy and safety of a lower rhPTH(1-84) dose. METHODS: RELAY was a dose-blinded, multicenter, 8-week study of patients with hypoparathyroidism randomized to fixed 25- or 50-μg/d doses of subcutaneous rhPTH(1-84). The primary end point was the percentage of patients at week 8 with supplement reductions in calcium to ≤500 mg/d and in calcitriol to ≤0.25 μg/d, while maintaining serum calcium levels between 1.875 mmol/L and the upper limit of normal. The secondary end point was the percentage of patients at week 8 with a ≥50% reduction in calcium and calcitriol doses, while maintaining serum calcium levels between 1.875 mmol/L and the upper limit of normal. FINDINGS: Forty-two patients were randomized (25-μg group, n = 19; 50-μg group, n = 23). At week 8, the primary end point was achieved by 4 (21%; 95% CI, 6%-46%) and 6 (26%; 95% CI, 10%-48%) of the patients receiving 25 and 50 μg/d of rhPTH(1-84), respectively. The secondary end point was achieved by 2 (11%; 95% CI, 1%-33%) and 6 (26%; 95% CI, 10%-48%) of the patients receiving 25 and 50 μg/d of rhPTH(1-84), respectively. Treatment-emergent adverse events were reported by 11 (58%) patients in the 25-μg group and 17 (74%) patients in the 50-μg group. IMPLICATIONS: Doses as low as 25 µg/d of rhPTH(1-84) are well tolerated and may be effective for a subset of patients. ClinicalTrials.gov identifier: NCT01268098.
Authors: Michael Mannstadt; Bart L Clarke; John P Bilezikian; Henry Bone; Douglas Denham; Michael A Levine; Munro Peacock; Jeffrey Rothman; Dolores M Shoback; Mark L Warren; Nelson B Watts; Hak-Myung Lee; Nicole Sherry; Tamara J Vokes Journal: J Clin Endocrinol Metab Date: 2019-11-01 Impact factor: 5.958
Authors: Neil Gittoes; Lars Rejnmark; Steven W Ing; Maria Luisa Brandi; Sigridur Björnsdottir; Stefanie Hahner; Lorenz C Hofbauer; Pascal Houillier; Aliya A Khan; Michael A Levine; Michael Mannstadt; Dolores M Shoback; Tamara J Vokes; Pinggao Zhang; Claudio Marelli; John Germak; Bart L Clarke Journal: BMC Endocr Disord Date: 2021-11-20 Impact factor: 2.763