January 11, 2016
Ardelyx has issued positive results of an open label clinical study evaluating the pharmacodynamic (PD) activity of RDX022 in healthy adult volunteers. The study consisted of a two-day treatment-free baseline period and a four-day treatment period. The study included four cohorts; in each cohort, 12 subjects received RDX022 and three subjects received a similar dose of sodium polystyrene sulfonate (SPS) for a total of 60 subjects. RDX022 was administered at 4.6g BID (9.2 g/day), 6.9g BID (13.8 g/day), 4.6g TID (13.8g/day) and 9.2g TID (27.5g/day), and resulted in a mean increase of fecal potassium from baseline of 888mg/day, 1,791mg/day, 1,408mg/day, and 1,670mg/day, respectively. RDX022 was generally well-tolerated at all doses and demonstrated comparable results to those observed with sodium polystyrene sulfonate (SPS). Other fecal electrolytes were monitored during the study and no unexpected changes were observed; in particular, fecal magnesium remained unchanged from baseline. The study demonstrated that RDX022, Ardelyx’s proprietary potassium binder for the treatment of hyperkalemia, effectively binds potassium in the gastrointestinal tract supporting plans to proceed with a phase III clinical program currently expected to begin in the second half of 2016. RDX022 was generally well-tolerated at all doses administered (up to 27.5g/day) in the study. Based on discussions with the FDA, the company is pursuing a 505(b)(2) regulatory pathway for RDX022.
September 28, 2015
Trevi Therapeutics has reported results
of a phase II/III trial of Nalbuphine ER for
the treatment of moderate to severe uremic
pruritus. The multicenter, randomized,
double-blind, placebo-controlled, parallel, three-arm study evaluated Nalbuphine
ER tablets dosed twice-daily at 60mg and
120mg in about 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 evaluated. 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 (NRS
considers a score of 7 to be severe), 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. The company
expects the open-label extension study to
be completed by year-end.
December 6, 2010
Keryx issued positive results from a phase III trial of Zerenex for the treatment of hyperphosphatemia in patients with end-stage renal disease on dialysis. This multicenter, randomized, open-label trial enrolled 150 subjects on hemodialysis. Following a two-week washout period, the subjects were randomized to fixed doses of Zerenex 1, 6 or 8 grams per day, for a treatment period of 28 days. The primary endpoint was to demonstrate a dose response in the change of serum phosphorous from baseline (end of washout period) to end of the treatment period (day 28). The study met the primary endpoint, with the regression analysis indicating a highly statistically significant dose response (p<0.0001). In addition, a statistically significant dose response increase in serum bicarbonate was observed and there was no clinically meaningful change in serum calcium. Zerenex appeared to be safe and well-tolerated.
November 21, 2005
CuraGen reported positive results of a phase I trial of CR002, their monoclonal antibody for the treatment of kidney inflammation. Trial data indicated a positive safety profile, with no serious adverse events reported and good overall tolerability. Pharmacokinetic data indicated that meat elimination half-life was 20.1 to 34.2 days, and pharmacodynamic results indicated binding to the antibody's target molecule (platelet derived growth factor-D) for durations exceeding 20 days. This open- label placebo-controlled study enrolled 40 healthy volunteers, who received one of five single doses of the drug (0.3 mg/kg to 30 mg/kg) or placebo, with subsequent 3 month observational follow-up.
October 4, 2004
LAB International has announced positive results of a phase I/II trial of their Growth Hormone Releasing Hormone (GHRH) analog, being developed as an inhalable treatment for growth hormone (GH) deficiency caused by a number of diseases, including HIV, chronic renal failure and lipodystrophy. The drug was found to be safe and well tolerated, with no significant adverse events. Furthermore, the drug produced significant increases in serum GH levels up to 12 hours after treatment at all dosing regimens, and demonstrated a higher-than-expected efficacy for this endpoint. No impact on normal nocturnal GH secretion was observed. The placebo-controlled, single-dose safety and efficacy cross-over study enrolled a total of 10 healthy volunteers, all of whom received randomized sequential dosing regimens of 5-25 ug/kg and placebo. LAB announced plans for both indication-driven phase II trials and another phase I/II dose-ranging trial to establish minimum therapeutic dose.
June 17, 2002
Phase III trial results indicate that Fosrenol (lanthanum carbonate), a phosphate binder for use in dialysis subjects, did not adversely affect bone over 12 months of continuous therapy. Data also showed that there was no evolution towards low bone turnover states in lanthanum-treated subjects. The multicenter trial included 98 subjects beginning renal dialysis for the first time. Subjects were randomized to receive either lanthanum carbonate or calcium carbonate, which was titrated to a well-tolerated dose that gave acceptable control of serum phosphate. Bone biopsies were taken at the beginning and end of the 12-month study, and blood samples were taken at each visit. Fosrenol is being developed by Shire Pharmaceuticals and AnorMED.