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 Correction of serum potassium with sodium zirconium cyclosilicate in Japanese patients with hyperkalemia: a randomized, dose–response, phase 2/3 study

2020 ◽  
Vol 24 (12) ◽  
pp. 1144-1153
Author(s):  
Naoki Kashihara ◽  
Toshiki Nishio ◽  
Takeshi Osonoi ◽  
Yosuke Saka ◽  
Toshiyuki Imasawa ◽  
...  
Keyword(s):  
Dose Response ◽  
Serum Potassium ◽  
Japanese Patients ◽  
Rate Of Change ◽  
Exponential Rate ◽  
Phase 2 ◽  
Double Blind ◽  
Sodium Zirconium ◽  
Sodium Zirconium Cyclosilicate ◽  
Dose Response Study

Abstract Background Sodium zirconium cyclosilicate (SZC) is an oral potassium binder approved to treat hyperkalemia in adults in a number of countries, including Japan. Methods This phase 2/3, randomized, double-blind, placebo-controlled, dose–response study (ClinicalTrials.gov: NCT03127644) was designed to determine the efficacy and safety of SZC in Japanese adults with hyperkalemia. Patients with serum potassium (sK+) concentrations ≥ 5.1– ≤ 6.5 mmol/L were randomized 1:1:1 to SZC 5 g, SZC 10 g, or placebo three times daily for 48 h (six doses total). The primary efficacy endpoint was the exponential rate of change in sK+ over 48 h. The proportion of patients with normokalemia (sK+ 3.5–5.0 mmol/L) at 48 h and adverse events (AEs) were also evaluated. Results Overall, 103 patients (mean age, 73.2 years; range 50–89 years) received SZC 5 g (n = 34), SZC 10 g (n = 36), or placebo (n = 33). The exponential rate of sK+ change from 0 to 48 h versus placebo was − 0.00261 (SZC 5 g) and – 0.00496 (SZC 10 g; both P < 0.0001). At 48 h, the proportions of patients with normokalemia were 85.3%, 91.7%, and 15.2% with SZC 5 g, SZC 10 g, and placebo, respectively. No serious AEs were reported. Hypokalemia (sK+  < 3.5 mmol/L) occurred in two patients in the SZC 10 g group; normokalemia was re-established within 6 days and no treatment-related AEs were reported. Conclusion SZC is effective and well tolerated in Japanese patients with hyperkalemia.

scholarly journals A179 CANADIAN INVOLVEMENT IN THE EVALUATION OF NOVEL THERAPY FOR DIABETIC GASTROPARESIS: OVERVIEW OF PLEDGE TRIALS

2020 ◽  
Vol 3 (Supplement_1) ◽  
pp. 45-47
Author(s):  
L W Liu ◽  
M Syrzycka ◽  
P Janiszewski ◽  
L Kemps ◽  
B Degeronimo
Keyword(s):  
Diabetic Gastroparesis ◽  
Extension Study ◽  
Open Label ◽  
Double Blind ◽  
Open Label Study ◽  
Label Study ◽  
Safety And Efficacy ◽  
Double Blind Placebo ◽  
The Third ◽  
Parallel Group

Abstract Background Diabetic gastroparesis(DG) is a serious, chronic complication of type 1 or 2 diabetes mellitus(DM) presenting with a delay in gastric emptying(GE). An estimated 3 million Canadians have been diagnosed with DM; up to 5% of these patients may develop DG. DG can result in poor glycemic control, recurrent nausea and vomiting, often resulting in hospitalization. To date, no effective treatments are available. A phase 2 study showed that relamorelin (RLM), a synthetic ghrelin agonist, was safe and effective in treating DG. Investigators across Canada are participating in a set of phase 3 international trials of RLM in the treatment of DG. Aims To report the Canadian involvement in the international effort to evaluate the safety and efficacy of RLM in the treatment of DG. PLEDGE is a set of 5 trials: two identical 12-week studies, a 46-week extension study, a 52-week exposure study, and an open-label extension study. Collectively, the data from these studies will help to evaluate the safety and efficacy of RLM, a novel treatment for Canadian patients living with DG. Methods Four global, multicenter, randomized, double-blind, placebo-controlled, parallel-group studies compare the efficacy of RLM with placebo in participants with DG using composite endpoints of nausea, abdominal pain, postprandial fullness, bloating. Participants are randomized to RLM 10μg or placebo subcutaneously (SC) twice daily groups. The open-label continuation of treatment will follow participants until RLM becomes commercially available to provide long-term safety information to support the safe use of RLM as a chronic treatment of DG. As seen in Figure 1, participants from the two 12-week studies will rollover into the third study that will continue for 46 weeks. The fourth study will enroll participants that were not randomized in the first two studies because their symptoms were less severe and will also accept new participants. Participants will be randomized 2:1 to RLM 10μg or placebo SC twice daily groups. Participants from the third and fourth studies have the option to enroll in the open-label study. Results Target enrollment is approx. 1800 participants for the 4 global, multicenter, randomized, double-blind, placebo-controlled, parallel-group studies and 1000 participants for the open label study. 700 sites are expected to participate globally; 15 Canadian sites in 6 provinces are participating. Conclusions Canadian centers are actively involved in the PLEDGE trials to help determine the efficacy and safety of RLM, a potential new treatment for DG. This publication increases awareness of the Canadian gastroenterology community, providing an option to refer interested patients to PLEDGE study centers. PLEDGE Studies (NCT03285308, NCT03426345, NCT03420781, NCT03383146, NCT03786380): Placebo-controlled, randomized RLM-MD-01/02/03/04 and open-label study 3071-305-020 to study the safety and efficacy of relamorelin for the treatment of diabetic gastroparesis Funding Agencies None

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