scholarly journals PaTH Forward: A randomized, double-blind, placebo-controlled phase 2 trial of TransCon PTH in adult hypoparathyroidism

2021 ◽  
Author(s):  
Aliya A Khan ◽  
Lars Rejnmark ◽  
Mishaela Rubin ◽  
Peter Schwarz ◽  
Tamara Vokes ◽  
...  
Keyword(s):  
Vitamin D ◽  
Hormone Replacement ◽  
Normal Serum ◽  
Phase 2 ◽  
Active Vitamin ◽  
Normal Range ◽  
Open Label ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Active Vitamin D

Abstract Context Hypoparathyroidism is characterized by insufficient levels of parathyroid hormone (PTH). TransCon PTH is an investigational long-acting prodrug of PTH(1-34) for the treatment of hypoparathyroidism. Objective Investigate the safety, tolerability, and efficacy of daily TransCon PTH in adults with hypoparathyroidism. Design Phase 2, randomized, double-blind, placebo-controlled 4-week trial with open-label extension. Patients Enrolled 59 subjects with hypoparathyroidism. Interventions TransCon PTH 15, 18, or 21 µg PTH(1-34)/day or placebo for 4 weeks, followed by a 26-week extension where TransCon PTH dose was titrated (6–60 µg PTH[1-34]/day). Results By Week 26, 91% of subjects treated with TransCon PTH achieved independence from standard of care (SoC, defined as active vitamin D = 0 mcg/day and calcium (Ca) ≤ 500 mg/day). Mean 24-hour urine Ca (uCa) decreased from a baseline mean of 415 mg/24h to 178 mg/24h by Week 26 (n=44) while normal serum Ca (sCa) was maintained and serum phosphate (sP) and Ca x P fell within the normal range. By Week 26, mean scores on SF-36 domains increased from below normal at baseline to within the normal range. The Hypoparathyroidism Patient Experience Scale Symptom and Impact scores improved through 26 weeks. TransCon PTH was well-tolerated with no treatment-related serious or severe adverse events. Conclusions TransCon PTH enabled independence from oral active vitamin D and reduced Ca supplements (≤ 500 mg/day) for most subjects, achieving normal sCa, sP, uCa, CaxP, and demonstrating improved health-related quality of life. These results support TransCon PTH as a potential hormone replacement therapy for adults with hypoparathyroidism.

scholarly journals TransCon PTH as a Hormone Replacement Therapy for Patients with Hypoparathyroidism: 6-Month Update from the PaTH Forward Open-Label Extension

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A253-A253
Author(s):  
Mishaela R Rubin ◽  
Lars Rejnmark ◽  
Peter E Schwarz ◽  
Tamara J Vokes ◽  
Bart Clarke ◽  
...  
Keyword(s):  
Vitamin D ◽  
Replacement Therapy ◽  
Hormone Replacement ◽  
Active Vitamin ◽  
Normal Range ◽  
Open Label ◽  
Active Vitamin D ◽  
Sf 36 ◽  
Open Label Extension

Abstract Background: Hypoparathyroidism (HP) is characterized by insufficient levels of parathyroid hormone (PTH), resulting in hypocalcemia, hyperphosphatemia, hypercalciuria, and a reduced quality of life (QoL). PTH replacement therapy should restore physiologic levels of PTH and restore downstream physiologic levels of calcitriol, promoting independence from Ca and active vitamin D supplements and normalization of QoL. TransCon PTH is an investigational long-acting prodrug of PTH(1–34) for the treatment of HP. During the initial 4-week fixed-dose period of the PaTH Forward Trial, TransCon PTH enabled 82% of subjects to achieve independence from standard of care (SoC; no active vitamin D and Ca ≤ 500 mg/day) compared to 15% with placebo. Here, we report 6-month (Week 26) results from the open-label extension (OLE). Methods: PaTH Forward is a phase 2, double-blind, placebo-controlled trial evaluating TransCon PTH in adult HP patients treated with SoC. Subjects received fixed doses of TransCon PTH 15, 18, or 21 µg PTH(1–34)/day or placebo for 4 weeks, followed by an OLE period during which TransCon PTH dose was titrated (6–30 µg PTH[1–34]/day) per individual dosing requirement. Safety and efficacy endpoints were evaluated at predefined timepoints over the OLE. Endpoints were evaluated at Week 26 including 1) sCa, 2) 24-hour uCa, 3) independence from active vitamin D, and 4) independence from therapeutics doses of oral calcium. QoL was assessed by the SF-36 and the Hypoparathyroidism Patient Experience Scales (HPES). Results: All 59 subjects completed the initial 4-week period and continued in the OLE; 58 subjects continue in the OLE beyond 6 months (1 withdrew unrelated to safety or efficacy). TransCon PTH enabled independence from SoC (no active vitamin D and Ca ≤ 500 mg/day) in 91% of subjects and independence from all supplements (no active vitamin D and no Ca) in 76% of subjects by Week 26. Mean 24-hour uCa decreased from a baseline mean of 415 mg/24h to 178 mg/24h by Week 26 (n = 44) while maintaining sCa, and reducing sP and CaxP to fall within the normal range. The mean scores for all SF-36 summary and domains increased from below normal at baseline to within the normal range by Week 26. The HPES Symptom and Impact scores continuously improved through 26 weeks for TransCon PTH and placebo subjects switching to TransCon PTH. TransCon PTH continued to be well-tolerated with no treatment-related serious or severe adverse events. Conclusions: Results from the OLE of the PaTH Forward Trial demonstrated that TransCon PTH continued to enable independence from active vitamin D and Ca supplements for most subjects while maintaining normal sCa, sP, uCa, and demonstrating enhanced quality of life, supporting its potential as a hormone replacement therapy for patients with HP. TransCon PTH will be further evaluated in the phase 3 PaTHway Trial.

scholarly journals Rationale and design of Diabetes Prevention with active Vitamin D (DPVD): a randomised, double-blind, placebo-controlled study

BMJ Open ◽  
2016 ◽  
Vol 6 (7) ◽  
pp. e011183 ◽  
Author(s):  
Tetsuya Kawahara ◽  
Gen Suzuki ◽  
Tetsuya Inazu ◽  
Shoichi Mizuno ◽  
Fumiyoshi Kasagi ◽  
...  
Keyword(s):  
Vitamin D ◽  
Diabetes Prevention ◽  
Controlled Study ◽  
Active Vitamin ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Active Vitamin D

scholarly journals MERIDIAN: A phase 2, randomized, double-blind, placebo-controlled, multicenter study to evaluate the efficacy and safety of pegcetacoplan in patients with amyotrophic lateral sclerosis

2021 ◽  
Author(s):  
Frederico Mennucci de Haidar Jorge ◽  
Angela Genge ◽  
Ammar Al- Chalabi ◽  
Orla Hardiman ◽  
Alice Shen ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Rating Scale ◽  
Phase 2 ◽  
Efficacy And Safety ◽  
Open Label ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Sporadic Als ◽  
The Difference ◽  
Lateral Sclerosis

Introduction: Inflammation underlies the pathogenesis of numerous neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS). In ALS, the complement system has been implicated in the neuropathology of disease and disease progression. Pegcetacoplan, a subcutaneously administered C3 complement inhibitor, is being investigated in hematology, nephrology, and neurology. The current clinical study (NCT04579666) is investigating whether pegcetacoplan can improve survival and function in people diagnosed with apparent sporadic ALS. Objectives and Methodology: Evaluate the efficacy and safety of pegcetacoplan compared to placebo among people diagnosed with ALS in a global, multicenter, randomized, double-blind, placebo-controlled, phase 2 study. Approximately 228 patients diagnosed with apparent sporadic ALS, ≥18 years of age and with an ALS Functional Rating Scale-Revised (ALSFRS-R) score ≥30, slow vital capacity (SVC) ≥60% of the predicted value at screening, and with symptom onset within 72 weeks before screening, are eligible for enrollment. After screening, patients will be randomized 2:1 to treatment groups receiving either subcutaneous pegcetacoplan (1080 mg) or placebo twice weekly for a duration of 52 weeks. The primary efficacy endpoint is the difference in the Combined Assessment of Function and Survival (CAFS) ranked score at 52 weeks after treatment initiation. Additional, secondary functional efficacy (ALSFRS-R, percent SVC, muscle strength, quality of life, and caregiver burden) and safety endpoints will be analyzed at 52 weeks. After the placebo-controlled period, all patients will have the option to receive pegcetacoplan in an open-label period for an additional 52 weeks. Results: This ongoing study is currently enrolling participants. Conclusions: Results of this study will determine the role of complement and C3 inhibition in patients with ALS.

Fostamatinib for the Treatment of Warm Antibody Autoimmune Hemolytic Anemia (wAIHA): A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Global Study

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 1-3
Author(s):  
Nichola Cooper ◽  
Robert P. Numerof ◽  
Sandra Tong ◽  
David J. Kuter
Keyword(s):  
Research Funding ◽  
Rescue Therapy ◽  
Phase 2 ◽  
Publicly Traded ◽  
Open Label ◽  
Phase 3 ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Phase 2 Study ◽  
Syk Inhibitor

Background. Warm antibody autoimmune hemolytic anemia (wAIHA) is a rare disorder that can be potentially serious. In wAIHA, autoantibodies react with protein antigens on red blood cells (RBCs) at body temperature, leading to RBC phagocytosis and destruction by Fcg receptor-bearing macrophages in a spleen tyrosine kinase (SYK) dependent signaling pathway (see figure). Fostamatinib is a potent oral SYK inhibitor, approved for the treatment of chronic immune thrombocytopenia (ITP). Fostamatinib prevents platelet destruction in ITP through inhibition of SYK-dependent platelet phagocytosis by Fcγ receptor-bearing macrophages. Fostamatinib was evaluated in a phase 2, open-label, multicenter study (NCT02612558) for the treatment of wAIHA. Results of the study demonstrated that 11 of 25 (44%) patients had markedly improved hemoglobin (Hgb) levels after fostamatinib treatment. Adverse events (AEs) were consistent with those in the fostamatinib safety database of >4000 patients across multiple diseases. Based on the results of the phase 2 study, a phase 3 randomized, double-blind, placebo-controlled, global study (NCT03764618) was initiated to investigate the safety and efficacy of fostamatinib in patients with wAIHA. The phase 3 study began enrolling patients this year and intends to enroll approximately 90 patients at 103 sites in 22 countries across North America, Europe, and Australia. This is the first randomized, double-blind, placebo-controlled, phase 3 study to evaluate a SYK inhibitor for the treatment of wAIHA (see diagram). Study Design and Methods Inclusion Criteria include: Age ≥18;Diagnosis of primary or secondary wAIHA (documented by an IgG or IgA positive direct antiglobulin test [DAT]);failure of ≥1 prior treatment for wAIHA;Haptoglobin <LLN (lower limit of normal) or total bilirubin >ULN (upper limit of normal) or lactate dehydrogenase (LDH) >ULN;Baseline hemoglobin level ≤9 g/dL or, if hemoglobin is >9 g/dL to <10 g/dL, subject must be on a permitted wAIHA treatment AND have symptoms associated with anemia. Exclusion Criteria include: Presence of other forms of AIHA;Uncontrolled or insufficiently controlled hypertension;Neutrophil count <1,000/µL,Platelet count <30,000/μL (unless patient has Evans syndrome);Transaminase levels >1.5 x ULN. Eligible patients will be randomized 1:1 to fostamatinib or placebo for 24 weeks. Randomization will be stratified by concomitant steroid use and severity of anemia at baseline. The starting dose of fostamatinib is 100 mg BID and will be increased to 150 mg BID at Week 4, based on tolerability. The dose may be reduced in the event of dose-limiting AEs. At screening, patients may continue selected concurrent wAIHA therapies including steroids (maximum of 2 therapies) throughout the 24-week study period. A steroid taper protocol will allow reduced used of steroids in patients who have a hemoglobin response. Rescue therapy will be allowed as needed. Patients who complete the phase 3 study can rollover to an open-label extension study. The efficacy endpoints will include hemoglobin response, defined as a hemoglobin level ≥10 g/dL with a ≥2 g/dL increase from baseline (Day 1) in the absence of rescue therapy; duration of hemoglobin response; and the need for wAIHA rescue treatment. The safety endpoints will include the incidence of adverse events. Patients will be evaluated in the clinic, including safety and laboratory assessments, at two-week intervals. Statistics: A sample size of 90 subjects (randomized 1:1) would be required to provide 80% power to detect a difference in the response between the active and placebo groups using the Cochran-Mantel-Haenszel test at a two-sided significance level of 0.05 (based on results of the phase 2 study). The response rate will be compared between groups using a chi-square test adjusted for randomization stratification factors. Current enrollment status: As of July 2, 2020, 83 sites are open to screening (subject to local regulations about the COVID-19 pandemic), and 43 patients have been randomized. Most patients (88%) had primary wAIHA, 12% had secondary disease including chronic lymphocytic leukemia, monoclonal B cell lymphocytosis, scleroderma, smoldering Waldenström's macroglobulinemia, and systemic lupus erythematosus in 1 patient each. The median age at baseline is 61 years (range 28-87), and 63% are female. Figure Disclosures Cooper: Amgen: Honoraria, Speakers Bureau; Novartis: Honoraria, Speakers Bureau. Numerof:Rigel: Current Employment, Current equity holder in publicly-traded company. Tong:Rigel: Current Employment, Current equity holder in publicly-traded company. Kuter:Incyte: Consultancy, Honoraria; Genzyme: Consultancy, Honoraria; Immunovant: Consultancy, Honoraria; Momenta: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Dova: Consultancy, Honoraria; Merck Sharp Dohme: Consultancy, Honoraria; UCB: Consultancy, Honoraria; Up-To-Date: Consultancy, Honoraria, Patents & Royalties; Zafgen: Consultancy, Honoraria; Sanofi (Genzyme): Consultancy, Honoraria; Shionogi: Consultancy, Honoraria; Shire: Consultancy, Honoraria; Principia: Consultancy, Research Funding; Protalix Biotherapeutics: Consultancy; Shionogi: Consultancy; Actelion (Syntimmune): Consultancy, Honoraria, Other: Travel Expenses, Research Funding; Daiichi Sankyo: Consultancy, Honoraria; Agios: Consultancy, Honoraria, Other: Travel Expenses, Research Funding; Alnylam: Consultancy, Honoraria, Other: Travel Expenses, Research Funding; Amgen: Consultancy, Honoraria, Other: Travel Expenses, Research Funding; Argenx: Consultancy, Honoraria, Other: Travel Expenses, Research Funding; Bristol-Myers Squibb: Consultancy, Honoraria, Other: Travel Expenses, Research Funding; Immunovant: Other: Travel Expenses, Research Funding; Caremark: Consultancy, Honoraria; CRICO: Consultancy, Honoraria; Kezar Life Sciences, Inc: Other, Research Funding; Principia Biopharma: Consultancy, Honoraria, Other, Research Funding; Protalex: Consultancy, Honoraria, Other, Research Funding; Rigel: Consultancy, Honoraria, Other, Research Funding; Takeda (Bioverativ): Consultancy, Honoraria, Other, Research Funding; Protalex: Consultancy, Honoraria, Research Funding; Kyowa-Kirin: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Platelet Disorder Support Association: Consultancy, Honoraria.

scholarly journals Leukaemic Secretion of Calcitriol: A Novel Mechanism of Hypercalcaemia in AML

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5098-5098
Author(s):  
Joshua Misha Lewis Casan ◽  
Sarah Ghotb ◽  
Sue Morgan ◽  
Stephen B Ting
Keyword(s):  
Vitamin D ◽  
Parathyroid Hormone ◽  
Serum Calcium ◽  
Rare Complication ◽  
Kidney Injury ◽  
Active Vitamin ◽  
Normal Range ◽  
Lymphoid Malignancies ◽  
Active Vitamin D ◽  
Upper Limit

Abstract Introduction: Whilst relatively common in lymphoid malignancies, hypercalcaemia is an extremely rare complication of acute myeloid leukaemia (AML). Previous case reports have described ectopic parathyroid hormone secretion, leukaemic bony invasion and the release of boneresorptivemediators as causes of hypercalcaemia in AML (GewirtzAM et al. Br JHaematology1983;31(12):1590,ZidarBL, et al.NEJM.1976;295:692). We describe a case of severe hypercalcaemia with acute kidney injury (AKI) accompanying a new diagnosis of AML, subsequently demonstrated to be secondary to leukaemic blast production of active vitamin D (calcitriol) with gross over-expression of vitamin D related genes. This represents a novel pathogenic mechanism causing hypercalcaemia in a myeloid malignancy. Case Report: AA, a 68 year old male presenting with fatigue and found to have circulating blasts was subsequently diagnosed with acutemyelomonocyticleukaemia(78% blasts on bone marrow biopsy). Additionally, he had marked hypercalcaemia (calcium 3.3mmol/L, normal range 2.1-2.6mmol/L) and AKI (creatinine 263umol/L, normal range 60-110umol/L). Given the rarity of AML-associated hypercalcaemia, extensive investigations were undertaken to elucidate the cause. In search of a second concurrent malignancy, AA underwent computed tomography and positron emission tomography scanning, with subsequent biopsy of FDG avid vocal cord nodules; but only benign pathology could be demonstrated. Parathyroid hormone (PTH) levels were appropriately suppressed (0.9pmol/L, normal range 1.6-6.9pmol/L) and levels of PTH-related peptide and serum ACE were normal (<2pmol/L, and 37units/L, normal range 20-70units/L, respectively). Inactive vitamin D, (calcidiol or 25(OH)D3) levels were also normal (88nmol/L, normal range 50-250nmol/L). However, the active vitamin D (calcitriol or 1,25(OH)2D3) level was grossly elevated beyond the upper limit of assay (>500pmol/L, upper limit of normal: 190pmol/L). Both the hypercalcaemia and kidney injury proved refractory to multiple therapeutic strategies including aggressive hydration with an average of over 2.5L of crystalloid per day, as well as intravenouspamidronate. However, as depicted in Figure 1, there was a precipitous response following the initiation of chemotherapy (idarubicinandcytarabine, 7+3 regimen). Within several days, AA's serum calcium levels returned to normal levels, and his kidney function followed a similar pattern of improvement shortly thereafter. The rapid resolution of serum calcium levels also mirrored peripheral blast clearance, and repeat testing of calcitriol levels showed progressive improvement towards a normal concentration. AA achieved complete remission following induction chemotherapy and remains leukaemia free after consolidation chemotherapy and current maintenanceazacitidine. His hypercalcaemia has not recurred and his renal function remains normal. Having excluded other causes of hypercalcaemia and given the dramatic response to chemotherapy, we hypothesised that AA's AML blasts were secreting calcitriol. Accordingly, quantitative PCR was performed on AA's stored leukaemic cells for genes essential to vitamin D metabolism: the vitamin-D receptor (VDR), CYP24A1, and CYP27B1 (1-α-hydroxylase). RNA was extracted from AML cells using the QIAGEN RNeasykit. cDNAwas synthesised from 400ng of RNA using the Roche First Strand cDNASynthesis Kit. Gene expression was assessed by quantitative real-time PCR, relative to the housekeeping gene GAPDH. AA's leukaemia cells demonstrated markedly elevated expression of these vitamin-D related genes compared to healthy control CD34+ cells and four other independent primary AML cells (Figure 2, labelled AML 1-4), which were selected for absence of patient hypercalcaemia from our institution's tissue bank (Figure 2). Conclusion: Hypercalcaemia secondary to secretion of calcitriol can be a manifestation of lymphoid malignancies, however our case is the first documented occurrence of this phenomenon in a myeloid cancer. The PCR studies demonstrated striking overexpression of vitamin D related genes in leukaemia cells, resulting in the patient's hypercalcaemia and AKI. This finding represents a novel mechanism for a rare complication in AML. Figure 1 Figure 1. Figure 2 Figure 2. Disclosures No relevant conflicts of interest to declare.

scholarly journals Apararenone in patients with diabetic nephropathy: results of a randomized, double-blind, placebo-controlled phase 2 dose–response study and open-label extension study

2020 ◽  
Author(s):  
Takashi Wada ◽  
Masaya Inagaki ◽  
Toru Yoshinari ◽  
Ryuji Terata ◽  
Naoko Totsuka ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Dose Response ◽  
Serum Potassium ◽  
Extension Study ◽  
Phase 2 ◽  
Open Label ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Remission Rates ◽  
Dose Response Study

Abstract Background We investigated the efficacy and safety of apararenone (MT-3995), a non-steroidal compound with mineralocorticoid receptor agonist activity, in patients with stage 2 diabetic nephropathy (DN). Methods The study had two parts: a dose–response, parallel-group, randomized, double-blind, placebo-controlled, multicenter, phase 2, 24-week study and an open-label, uncontrolled, 28-week extension study. Primary and secondary endpoints were the 24-week percent change from baseline in urine albumin to creatine ratio (UACR) and 24- and 52-week UACR remission rates. Safety parameters were changes from baseline in estimated glomerular filtration rate (eGFR) and serum potassium at 24 and 52 weeks, and incidences of adverse events (AEs) and adverse drug reactions (ADRs). Results In the dose–response period, 73 patients received placebo and 73, 74, and 73 received apararenone 2.5 mg, 5 mg, and 10 mg, respectively. As a percentage of baseline, mean UACR decreased to 62.9%, 50.8%, and 46.5% in the 2.5 mg, 5 mg, and 10 mg apararenone groups, respectively, at week 24 (placebo: 113.7% at week 24; all P < 0.001 vs placebo). UACR remission rates at week 24 were 0.0%, 7.8%, 29.0%, and 28.1% in the placebo and apararenone 2.5 mg, 5 mg, and 10 mg groups, respectively. eGFR tended to decrease and serum potassium tended to increase, but these events were not clinically significant. AE incidence increased with dose while ADR incidence did not. Conclusion The UACR-lowering effect of apararenone administered once daily for 24 weeks in patients with stage 2 DN was confirmed, and the 52-week administration was safe and tolerable. Clinical trial registration NCT02517320 (dose–response study) and NCT02676401 (extension study)

scholarly journals Parathyroid hormone replacement versus oral calcium and active vitamin D supplementation in hypoparathyroidism: A meta-analysis

2020 ◽  
Vol 24 (2) ◽  
pp. 206
Author(s):  
Jayaprakash Sahoo ◽  
Rajan Palui ◽  
RashmiRanjan Das ◽  
Ayan Roy ◽  
Sadishkumar Kamalanathan ◽  
...  
Keyword(s):  
Vitamin D ◽  
Parathyroid Hormone ◽  
Meta Analysis ◽  
Hormone Replacement ◽  
Vitamin D Supplementation ◽  
Active Vitamin ◽  
Oral Calcium ◽  
Active Vitamin D

2MD (DP001), a Single Agent in the Management of Hemodialysis Patients: A Randomized Trial

2016 ◽  
Vol 45 (1) ◽  
pp. 40-48 ◽  
Author(s):  
Ravi Thadhani ◽  
Julia B. Zella ◽  
Danielle C. Knutson ◽  
William J. Blaser ◽  
Lori A. Plum ◽  
...  
Keyword(s):  
Vitamin D ◽  
Single Agent ◽  
Hemodialysis Patients ◽  
Double Blind Study ◽  
Dialysis Patients ◽  
Active Vitamin ◽  
Double Blind ◽  
Active Vitamin D ◽  
Vitamin D Analog ◽  
Calcium Phosphorus

Background: Vitamin D analogs and calcimimetics are used to manage secondary hyperparathyroidism (SHPT) in dialysis patients. DP001 is an oral vitamin D analog that suppresses parathyroid hormone (PTH) in uremic rats, osteopenic women, and hemodialysis patients. The safety and effectiveness of DP001 suppressing PTH in dialysis patients previously managed with active vitamin D with or without a calcimimetic are presented. Methods: A multicenter, randomized, double-blind study compared DP001 to placebo in hemodialysis patients with serum-intact PTH (iPTH) ≥300 pg/ml. The primary efficacy endpoint was the proportion of patients achieving 2 consecutive ≥30% decreases in iPTH levels during the 12 weeks of treatment. Calcium, phosphorus, calcium × phosphorus product and safety were also evaluated. The responses to DP001 were compared in patients previously treated with both active vitamin D and a calcimimetic to those previously on active vitamin D alone. Results: Sixty-two patients were randomized (n = 34 DP001; n = 28 placebo). At week 12, 78% of all DP001-treated patients and 7% of all placebo-treated patients achieved the primary endpoint (p < 0.0001); iPTH fell 45% in the DP001 group and increased 37% in the placebo group. No patient exceeded the safety threshold of 2 consecutively corrected serum calcium levels ≥11.0 mg/dl. Patients previously on cinacalcet plus active vitamin D also responded to DP001 (n = 10) resulting in a 55% decrease in iPTH, while those on placebo (n = 9) increased by 70%. Conclusion: DP001 safely and effectively suppressed iPTH in hemodialysis patients with SHPT that were previously managed with active vitamin D alone or with a calcimimetic (www.clinicaltrials.gov, NCT01922843).

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