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Successfully Completes Thorough QT Study
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Obtains Special Protocol Assessments (SPAs) From FDA for Phase 3 Trials in Relapsing Multiple Sclerosis
SAN DIEGO, CA, USA I June 5, 2013 I Receptos, Inc. (RCPT), a biopharmaceutical company developing therapeutic candidates for the treatment of immune and metabolic diseases, confirmed today that RPC1063, its selective sphingosine-1- phosphate 1 receptor (S1P1R) modulator, has successfully completed a study of the heart’s electrical conduction system, known as a “thorough QT/QTc” (TQT) study. RPC1063 is currently being studied in randomized Phase 2 trials for the treatment of relapsing multiple sclerosis (RMS) and ulcerative colitis (UC).
The purpose of a TQT study is to rule out the potential for a drug to cause prolongation of the mean corrected QT interval (known as the QTc interval). Prolongation of the QTc interval increases the risk of ventricular arrhythmia, which can lead to palpitations, fainting and sudden death. Drugs that cause QTc prolongation are often contraindicated in certain “at risk” patients or in patients taking select concomitant medications that also cause QTc prolongation.
The completed RPC1063 TQT study enrolled 124 subjects, with 62 subjects randomized to receive RPC1063 at an intended therapeutic dose (1 mg/day) and at a supra-therapeutic dose (2 mg/day), and 62 subjects randomized to receive placebo. The dosage of RPC1063 was titrated in this study from 0.25 mg to 2.0 mg over 14 days of treatment. The primary objective of the TQT study was to assess whether exposure to therapeutic and supra-therapeutic doses of RPC1063 in healthy subjects increased the QTc interval compared to placebo. As previously disclosed, the primary objective of the TQT study was met. Specifically, the study was “negative” in that a relevant QTc effect was ruled out for RPC1063 at both the therapeutic and the supra-therapeutic doses. In addition, the TQT study was validated by reproducing the known effect of a positive control treatment (moxifloxacin) on the QTc interval as part of the study. This study nearly doubled the subject exposure to RPC1063, building on the results of a prior Phase I trial in 88 healthy subjects that demonstrated target reductions in lymphocyte counts as well as a desirable safety and tolerability profile.
The TQT study included additional assessments in order to establish further evidence for a potentially improved cardiac safety profile for RPC1063. In particular, heart rate changes were measured using the dose titration regimen, which is being employed in all ongoing and planned RPC1063 studies. Detailed heart rate data was collected through continuous 24-hour ambulatory ECG monitoring pre-dose and throughout the dose escalation period to assess changes in heart rate and the risk of any cardiac adverse events. The dose titration regimen appeared to attenuate the first dose heart rate effects and was well tolerated. No serious adverse events occurred during the TQT study and a similar proportion of subjects experienced mild or moderate adverse events in both the placebo and RPC1063-treated groups.
Separately, the Company confirmed as previously disclosed that it has obtained two Special Protocol Assessment (SPA) agreements from the FDA for the planned Phase 3 portion of the RPC1063 Phase 2/3 RADIANCE study as well as a second planned Phase 3 study of RPC1063 in RMS. SPA agreements are put in place to document concurrence between the FDA and the study sponsor on both trial design and statistical analysis plans for Phase 3 registration studies to support regulatory approval.
“We are encouraged by the results of the TQT study, which contribute to our understanding of the emerging favorable safety and tolerability profile of RPC1063,” said Sheila Gujrathi, M.D., Chief Medical Officer of Receptos. “In addition, the two SPA agreements for the Phase 3 registration program position RPC1063 as a potential next-to-market S1P1R modulator in RMS. We believe we are building a compelling body of evidence to support a multi-faceted differentiation profile for RPC1063, including a potentially improved cardiovascular profile which may result in safety advantages for patients.”
About RPC1063 and S1P1R Modulators
RPC1063 is a novel, oral, once daily, selective and potent S1P1R modulator in development for autoimmune indications. Previously reported Phase 1 results demonstrated adequate pharmacokinetic, pharmacodynamic and safety features, which provide supportive data for the differentiation strategy for RPC1063 as a potential best-in-class second generation S1P1R modulator. Receptos is currently enrolling patients into the randomized Phase 2 portion of a Phase 2/3 study called RADIANCE examining the efficacy, safety and tolerability of RPC1063 in RMS and a randomized Phase 2 study called TOUCHSTONE examining the efficacy, safety and tolerability of RPC1063 in UC. Top-line results for both studies are expected in mid-2014.
About Receptos
Receptos is a biopharmaceutical company developing therapeutic candidates for the treatment of immune and metabolic diseases. The Company’s lead program, RPC1063, is an S1P1R small molecule modulator candidate for immune indications, including RMS and IBD. The Company is also developing RPC4046, an anti-interleukin-13 (IL-13) antibody for an allergic/immune-mediated Orphan Disease, eosinophilic esophagitis (EoE). Receptos has established expertise in high resolution protein crystal structure determination, biology and drug discovery for G-protein-coupled receptors (GPCRs).
SOURCE: Receptos
Post Views: 230
-
Successfully Completes Thorough QT Study
-
Obtains Special Protocol Assessments (SPAs) From FDA for Phase 3 Trials in Relapsing Multiple Sclerosis
SAN DIEGO, CA, USA I June 5, 2013 I Receptos, Inc. (RCPT), a biopharmaceutical company developing therapeutic candidates for the treatment of immune and metabolic diseases, confirmed today that RPC1063, its selective sphingosine-1- phosphate 1 receptor (S1P1R) modulator, has successfully completed a study of the heart’s electrical conduction system, known as a “thorough QT/QTc” (TQT) study. RPC1063 is currently being studied in randomized Phase 2 trials for the treatment of relapsing multiple sclerosis (RMS) and ulcerative colitis (UC).
The purpose of a TQT study is to rule out the potential for a drug to cause prolongation of the mean corrected QT interval (known as the QTc interval). Prolongation of the QTc interval increases the risk of ventricular arrhythmia, which can lead to palpitations, fainting and sudden death. Drugs that cause QTc prolongation are often contraindicated in certain “at risk” patients or in patients taking select concomitant medications that also cause QTc prolongation.
The completed RPC1063 TQT study enrolled 124 subjects, with 62 subjects randomized to receive RPC1063 at an intended therapeutic dose (1 mg/day) and at a supra-therapeutic dose (2 mg/day), and 62 subjects randomized to receive placebo. The dosage of RPC1063 was titrated in this study from 0.25 mg to 2.0 mg over 14 days of treatment. The primary objective of the TQT study was to assess whether exposure to therapeutic and supra-therapeutic doses of RPC1063 in healthy subjects increased the QTc interval compared to placebo. As previously disclosed, the primary objective of the TQT study was met. Specifically, the study was “negative” in that a relevant QTc effect was ruled out for RPC1063 at both the therapeutic and the supra-therapeutic doses. In addition, the TQT study was validated by reproducing the known effect of a positive control treatment (moxifloxacin) on the QTc interval as part of the study. This study nearly doubled the subject exposure to RPC1063, building on the results of a prior Phase I trial in 88 healthy subjects that demonstrated target reductions in lymphocyte counts as well as a desirable safety and tolerability profile.
The TQT study included additional assessments in order to establish further evidence for a potentially improved cardiac safety profile for RPC1063. In particular, heart rate changes were measured using the dose titration regimen, which is being employed in all ongoing and planned RPC1063 studies. Detailed heart rate data was collected through continuous 24-hour ambulatory ECG monitoring pre-dose and throughout the dose escalation period to assess changes in heart rate and the risk of any cardiac adverse events. The dose titration regimen appeared to attenuate the first dose heart rate effects and was well tolerated. No serious adverse events occurred during the TQT study and a similar proportion of subjects experienced mild or moderate adverse events in both the placebo and RPC1063-treated groups.
Separately, the Company confirmed as previously disclosed that it has obtained two Special Protocol Assessment (SPA) agreements from the FDA for the planned Phase 3 portion of the RPC1063 Phase 2/3 RADIANCE study as well as a second planned Phase 3 study of RPC1063 in RMS. SPA agreements are put in place to document concurrence between the FDA and the study sponsor on both trial design and statistical analysis plans for Phase 3 registration studies to support regulatory approval.
“We are encouraged by the results of the TQT study, which contribute to our understanding of the emerging favorable safety and tolerability profile of RPC1063,” said Sheila Gujrathi, M.D., Chief Medical Officer of Receptos. “In addition, the two SPA agreements for the Phase 3 registration program position RPC1063 as a potential next-to-market S1P1R modulator in RMS. We believe we are building a compelling body of evidence to support a multi-faceted differentiation profile for RPC1063, including a potentially improved cardiovascular profile which may result in safety advantages for patients.”
About RPC1063 and S1P1R Modulators
RPC1063 is a novel, oral, once daily, selective and potent S1P1R modulator in development for autoimmune indications. Previously reported Phase 1 results demonstrated adequate pharmacokinetic, pharmacodynamic and safety features, which provide supportive data for the differentiation strategy for RPC1063 as a potential best-in-class second generation S1P1R modulator. Receptos is currently enrolling patients into the randomized Phase 2 portion of a Phase 2/3 study called RADIANCE examining the efficacy, safety and tolerability of RPC1063 in RMS and a randomized Phase 2 study called TOUCHSTONE examining the efficacy, safety and tolerability of RPC1063 in UC. Top-line results for both studies are expected in mid-2014.
About Receptos
Receptos is a biopharmaceutical company developing therapeutic candidates for the treatment of immune and metabolic diseases. The Company’s lead program, RPC1063, is an S1P1R small molecule modulator candidate for immune indications, including RMS and IBD. The Company is also developing RPC4046, an anti-interleukin-13 (IL-13) antibody for an allergic/immune-mediated Orphan Disease, eosinophilic esophagitis (EoE). Receptos has established expertise in high resolution protein crystal structure determination, biology and drug discovery for G-protein-coupled receptors (GPCRs).
SOURCE: Receptos
Post Views: 230
