1. 2MD (DP001), a Single Agent in the Management of Hemodialysis Patients: A Randomized Trial
Thadhani et al. Am J Nephrol 2017;45:40-48  (DOI: / )
Fig. 1. a, b Study schema and patient disposition. a Adult patients (≥18 years of age) with ESRD were screened. Patients who met eligibility criteria at the first screening visit were required to discontinue calcitriol, paricalcitol, or doxercalciferol, and cinacalcet (if applicable). Following at least 2 weeks of washout from these agents, patients were eligible for randomization and initiation of the treatment phase if, at the second screening visit, their serum iPTH was ≥300 pg/ml, serum calcium (albumin-corrected) was ≤9.8 mg/dl, and serum phosphorus was ≤6.5 mg/dl. Patients received 4 oral softgel capsules containing blinded study drug after the end of each dialysis session (3 times per week) for 12 weeks. All patients in the DP001 group started at 440 ng per dose. PP dose adjustments were allowed up to 770 ng DP001 and down to 110 ng DP001 per dose every 3 weeks. b A total of 129 patients with ESRD were screened at 16 study sites across the United States. A total of 62 patients were randomized into the DP001 (n = 34) and placebo (n = 28) arms.

2. 2MD (DP001), a Single Agent in the Management of Hemodialysis Patients: A Randomized Trial
Thadhani et al. Am J Nephrol 2017;45:40-48  (DOI: / )
Table 1. Baseline demographic and laboratory data by treatment group

3. 2MD (DP001), a Single Agent in the Management of Hemodialysis Patients: A Randomized Trial
Thadhani et al. Am J Nephrol 2017;45:40-48  (DOI: / )
Table 2. iPTH results after 12 weeks of treatment with DP001 or placebo. Primary and secondary endpoints are shown for the ITT population and PP population

4. 2MD (DP001), a Single Agent in the Management of Hemodialysis Patients: A Randomized Trial
Thadhani et al. Am J Nephrol 2017;45:40-48  (DOI: / )
Fig. 2. Percent change in serum iPTH from baseline (ITT population). DP001 reduced iPTH levels at least 30% by week 4 and this reduction was maintained throughout week 12. In the placebo arm, iPTH levels steadily increased over the course of the study. The dashed line represents averaged baseline. Values are mean ± SEM. SV1 = Screening visit 1; SV2 = screening visit 2; Ave BL = averaged baseline.

5. 2MD (DP001), a Single Agent in the Management of Hemodialysis Patients: A Randomized Trial
Thadhani et al. Am J Nephrol 2017;45:40-48  (DOI: / )
Fig. 3. a, b iPTH in the subgroup of patients previously treated with active vitamin D plus a calcimimetic (PP population). DP001 was effective at lowering iPTH levels relative to placebo in patients previously treated with a combination of active vitamin D plus cinacalcet. a DP001 was similarly effective in patients previously on combination therapy and in patients who were previously receiving active vitamin D alone prior to the study. The placebo-treated patients previously treated with combination therapy had a larger mean increase in iPTH levels than those on active vitamin D alone. Percent PTH change is the average percentage change in iPTH for the last 2 on-treatment values from averaged baseline. b Administration of DP001 reduced serum iPTH down to pre-washout levels (week 12 iPTH levels are no different from SV1 levels) with 12 weeks of treatment, whereas those treated with placebo had a sustained increase in iPTH. The dashed lines represent the target range of iPTH values defined by the protocol ( pg/ml). Values are mean ± SEM.

6. 2MD (DP001), a Single Agent in the Management of Hemodialysis Patients: A Randomized Trial
Thadhani et al. Am J Nephrol 2017;45:40-48  (DOI: / )
Fig. 4. a-c Serum calcium and phosphorus levels (ITT population). Serum calcium (albumin-corrected) (a) and phosphorus (b) levels remained unchanged throughout the 12 weeks of treatment in both groups. The calcium × phosphorus product (c) for the DP001 group remained within the normal range. The dashed lines represent the following: a the reference range for the calcium (albumin-corrected) assay, b the upper limit of the normal range for the phosphorus assay, and c the safety threshold of the calcium × phosphorus product defined by the protocol (70 mg2/dl2). Values are mean ± SEM.

7. 2MD (DP001), a Single Agent in the Management of Hemodialysis Patients: A Randomized Trial
Thadhani et al. Am J Nephrol 2017;45:40-48  (DOI: / )
Tabel 3. Safety results - TEAEs