Hemodialysis

September 21, 2015

Trevi Therapeutics has released results of a phase II/III trial of Nalbuphine ER for severe uremic pruritus. The multicenter, randomized, double-blind, placebo-controlled, parallel, three-arm study evaluated the safety and anti-pruritic efficacy of Nalbuphine ER tablets dosed twice-daily at 60mg and 120mg in approximately 370 patients on hemodialysis in the U.S. and Europe. Patients with a wide range of mean moderate-to-severe itch intensity, ranging from 4.5 to 10 on the 10-point Numerical Rating Score (NRS) scale, were enrolled to evaluate efficacy across a representative patient population for that chronic indication. Patients receiving 120mg of Nalbuphine ER (n=120) experienced a 3.5 point reduction in itch intensity from baseline, resulting in a highly statistically significant mean reduction in itch intensity as compared to placebo (p=0.017). A statistically significant mean reduction for Nalbuphine ER compared to placebo was observed as early as one week following titration to the Nalbuphine ER fixed dose, and there was a statistically significant separation from placebo throughout the remaining blinded period. Sustained duration of drug effect continued to trend away from placebo through the eighth week of the study. On average, patients entered the study with a baseline mean NRS itch score of 6.9 (just under severe NRS score of 7), and at the end of the eight-week dosing period, average itch scores had been reduced to an NRS score of 3.4, which is considered mild on the NRS scale. Severe itch patients (those with NRS scores greater than or equal to 7) experienced on average an NRS score reduction of 4.5 points from baseline, (p=0.007). The 60mg dose showed a numerically favorable reduction over placebo, but did not achieve statistical significance.

Trevi Therapeutics has released results of a phase II/III trial of Nalbuphine ER for severe uremic pruritus. The multicenter, randomized, double-blind, placebo-controlled, parallel, three-arm study evaluated the safety and anti-pruritic efficacy of Nalbuphine ER tablets dosed twice-daily at 60mg and 120mg in approximately 370 patients on hemodialysis in the U.S. and Europe. Patients with a wide range of mean moderate-to-severe itch intensity, ranging from 4.5 to 10 on the 10-point Numerical Rating Score (NRS) scale, were enrolled to evaluate efficacy across a representative patient population for that chronic indication. Patients receiving 120mg of Nalbuphine ER (n=120) experienced a 3.5 point reduction in itch intensity from baseline, resulting in a highly statistically significant mean reduction in itch intensity as compared to placebo (p=0.017). A statistically significant mean reduction for Nalbuphine ER compared to placebo was observed as early as one week following titration to the Nalbuphine ER fixed dose, and there was a statistically significant separation from placebo throughout the remaining blinded period. Sustained duration of drug effect continued to trend away from placebo through the eighth week of the study. On average, patients entered the study with a baseline mean NRS itch score of 6.9 (just under severe NRS score of 7), and at the end of the eight-week dosing period, average itch scores had been reduced to an NRS score of 3.4, which is considered mild on the NRS scale. Severe itch patients (those with NRS scores greater than or equal to 7) experienced on average an NRS score reduction of 4.5 points from baseline, (p=0.007). The 60mg dose showed a numerically favorable reduction over placebo, but did not achieve statistical significance.

July 20, 2015

Rockwell Medical issued results of two phase III studies of Triferic for iron replacement and hemoglobin maintenance in hemodialysis patients. The studies were randomized, single-blind, placebo-controlled studies in chronic hemodialysis patients. Triferic was added to the bicarbonate hemodialysis concentrate while placebo patients received standard hemodialysate without Triferic. A total of 599 patients participated in both studies with 290 randomized to receive Triferic and 295 to placebo. The primary endpoint was the mean change in hemoglobin from baseline to the end-of-treatment (EoT) defined as the average of all hemoglobin values obtained during the last one-sixth of the time spent in the randomized stage of treatment (stage II). Both studies met the primary endpoint with a treatment difference of 0.4g/dL in hemoglobin concentration in favor of Triferic (P=0.011 for individual studies, 95% confidence interval 0.1 to 0.6 g/dL). The most frequent adverse event was procedural hypotension, which was present in 21.6% of Triferic patients and 19.2% of placebo treated patients. No serious adverse events or deaths were attributed to Triferic.

March 9, 2015

Amgen issued results of a head-to-head phase III study comparing AMG 416 with cinacalcet for the treatment of secondary hyperparathyroidism (SHPT) in patients with chronic kidney disease (CKD) receiving hemodialysis. The randomized, active-controlled, double-blind, double-dummy study ran over 26 weeks and enrolled 683 patients. Patients randomized to treatment with AMG 416 received intravenous (IV) doses of AMG 416 three times per week at the end of each dialysis session and daily oral doses of placebo tablets. Subjects randomized to treatment with cinacalcet received daily oral doses of cinacalcet tablets and IV doses of placebo three times per week at the end of each dialysis session. The study met the primary endpoint of non-inferiority of AMG 416 compared to cinacalcet, measured as the achievement of a greater than 30% reduction from baseline in mean pre-dialysis serum intact parathyroid hormone (PTH) levels during the Efficacy Assessment Phase (EAP), defined as the period between weeks 20 and 27. Further, AMG 416 was statistically significantly superior to cinacalcet in the secondary endpoints of the proportion of patients, achieving greater than 50% (52.4% v. 40.2%) and greater than 30% (68.2% v. 57.7%) PTH reduction from baseline during the EAP. Treatment-emergent adverse events (TEAEs) were reported in 92.9% and 90% of patients who received AMG 416 and cinacalcet, respectively. Treatment-emergent events related to cardiac failure were reported in 3% of patients who received AMG 416 v. 0.6% in the cinacalcet group. Serious adverse events were reported in 25.1% and 27.3% of patients who received AMG 416 and cinacalcet, respectively. Fatal adverse events were reported in 2.7% for the AMG 416 arm and 1.8% for the cinacalcet arm.

September 23, 2013

Rockwell Medical issued results of a phase III study of SFP for the treatment of iron deficiency in chronic kidney disease patients receiving hemodialysis. The single-blind, placebo-controlled, parallel-group study comparing SFP (2μM [110μg iron/L] delivered via hemodialysate concentrate) to placebo (standard hemodialysate concentrate) consisted of three stages: run-in, randomization and open-label extension. Patients who continued to meet inclusion criteria during the run-in period were randomized 1:1 to receive either SFP via dialysate or placebo (standard dialysate) in a blinded manner for up to 48 weeks. The study successfully met its pre-defined primary efficacy endpoint. The mean difference between SFP and placebo was 3.6g/L (95% CI 0.8, 6.3) in favor of SFP, and was statistically significant (p=0.011). At baseline the two groups had similar hemoglobin levels (109.6g/L SFP and 109.3g/L placebo). The mean adjusted change from baseline hemoglobin to the end of the randomized treatment period in the SFP group was -0.5g/L (95% CI -2.6, 1.7). In placebo, there was a statistically significant decline of -4.0g/L (95% CI -6.2, -1.9). This study is the second and final of two identical phase III efficacy studies to provide clinical data required to file an NDA.

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