Results demonstrate oral availability, CNS activity, and promising tolerability
KING OF PRUSSIA, PA, USA I June 23, 2014 I Trevena, Inc. (NASDAQ:TRVN) today announced positive results from its Phase 1 trial of TRV734, which Trevena is developing with the goal of providing improved analgesia while avoiding gastrointestinal and respiratory side effects typically associated with opioids. The study tested single ascending doses and the relative bioavailability of oral TRV734 in healthy subjects, and demonstrated that TRV734 is pharmacologically active at a range of safe and well-tolerated doses. The data suggest that TRV734 provides dose-related exposure, speed of onset, and duration of action suitable for treating moderate-to-severe acute pain.
“This trial showed that TRV734 is orally bioavailable and produces central nervous system activity consistent with analgesia, at doses that are safe and generally well-tolerated,” said David Soergel, M.D., senior vice president, clinical development. “We identified an active dose range that was very well tolerated, supporting our belief that TRV734 could present a superior therapeutic profile compared to currently prescribed opioids.”
Highlights of the two-part trial involving a total of 76 healthy subjects include:
- Dose-related increases in plasma concentrations, with peak plasma concentrations reached approximately one hour after dosing and a terminal half life consistent with use for treating acute pain.
- Pupil constriction indicative of analgesia observed at doses of 80 mg and higher, and mild-to-moderate adverse effects reported at the maximum explored dose of 250 mg. This suggests that the analgesic efficacy of TRV734 may be separable from opioid-related adverse effects.
- No clinically significant changes in vital signs, laboratory values or ECG parameters, and no severe or serious adverse events reported.
“These results are highly encouraging and provide a path towards Phase 2 clinical studies of this molecule,” said Maxine Gowen, Ph.D., president and chief executive officer. “In addition, the data further validate the shared mechanism of action of TRV734 and TRV130, and underscore the potential for these agents to provide prescribers and patients with new and differentiated treatment options in both hospital and outpatient settings.”
Phase 1 trial of TRV734
This study was a two-part first-in-human trial and was designed to assess the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of TRV734. Part A assessed single ascending doses of TRV734 in 64 healthy male subjects. The potentially efficacious dose range of TRV734 was evaluated using pupillometry, a validated biomarker for mu-opioid receptor engagement in the central nervous system that correlates with analgesic efficacy. Cohorts of eight subjects were randomized to receive a single dose of up to 250 mg of TRV734 or placebo. Part B of the study was a randomized, open-label, three-period crossover study of single 125 mg doses of TRV734 in 12 healthy male subjects, designed to compare the PK and PD of an oral capsule and oral solution, each administered after a fast, and an oral capsule when administered after a high-fat meal.
About TRV734
The mu-opioid receptor is a well-established target for effective analgesics such as fentanyl and morphine, which are unbiased mu-opioid agonists. TRV734 is a biased ligand at the mu-opioid receptor, activating the G protein pathway, associated with analgesia, without activating the mu-opioid beta-arrestin pathway, associated with respiratory depression and constipation in preclinical studies. TRV734 takes advantage of the same novel biased ligand mechanism at the mu-opioid receptor as TRV130, the company’s Phase 2 intravenous clinical candidate which has shown promising differentiation vs. morphine.
About Trevena
Trevena, Inc. is a clinical stage biopharmaceutical company that discovers, develops and intends to commercialize therapeutics that use a novel approach to target G protein coupled receptors, or GPCRs. Using its proprietary product platform, Trevena has identified and advanced three differentiated biased ligand product candidates into the clinic – TRV027 to treat acute heart failure, TRV130 to treat moderate-to-severe acute pain intravenously, and TRV734 to treat moderate-to-severe acute and chronic pain orally. Trevena also is advancing additional product candidates in its portfolio, including a preclinical program focused on central nervous system indications.
SOURCE: Trevena
Post Views: 146
Results demonstrate oral availability, CNS activity, and promising tolerability
KING OF PRUSSIA, PA, USA I June 23, 2014 I Trevena, Inc. (NASDAQ:TRVN) today announced positive results from its Phase 1 trial of TRV734, which Trevena is developing with the goal of providing improved analgesia while avoiding gastrointestinal and respiratory side effects typically associated with opioids. The study tested single ascending doses and the relative bioavailability of oral TRV734 in healthy subjects, and demonstrated that TRV734 is pharmacologically active at a range of safe and well-tolerated doses. The data suggest that TRV734 provides dose-related exposure, speed of onset, and duration of action suitable for treating moderate-to-severe acute pain.
“This trial showed that TRV734 is orally bioavailable and produces central nervous system activity consistent with analgesia, at doses that are safe and generally well-tolerated,” said David Soergel, M.D., senior vice president, clinical development. “We identified an active dose range that was very well tolerated, supporting our belief that TRV734 could present a superior therapeutic profile compared to currently prescribed opioids.”
Highlights of the two-part trial involving a total of 76 healthy subjects include:
- Dose-related increases in plasma concentrations, with peak plasma concentrations reached approximately one hour after dosing and a terminal half life consistent with use for treating acute pain.
- Pupil constriction indicative of analgesia observed at doses of 80 mg and higher, and mild-to-moderate adverse effects reported at the maximum explored dose of 250 mg. This suggests that the analgesic efficacy of TRV734 may be separable from opioid-related adverse effects.
- No clinically significant changes in vital signs, laboratory values or ECG parameters, and no severe or serious adverse events reported.
“These results are highly encouraging and provide a path towards Phase 2 clinical studies of this molecule,” said Maxine Gowen, Ph.D., president and chief executive officer. “In addition, the data further validate the shared mechanism of action of TRV734 and TRV130, and underscore the potential for these agents to provide prescribers and patients with new and differentiated treatment options in both hospital and outpatient settings.”
Phase 1 trial of TRV734
This study was a two-part first-in-human trial and was designed to assess the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of TRV734. Part A assessed single ascending doses of TRV734 in 64 healthy male subjects. The potentially efficacious dose range of TRV734 was evaluated using pupillometry, a validated biomarker for mu-opioid receptor engagement in the central nervous system that correlates with analgesic efficacy. Cohorts of eight subjects were randomized to receive a single dose of up to 250 mg of TRV734 or placebo. Part B of the study was a randomized, open-label, three-period crossover study of single 125 mg doses of TRV734 in 12 healthy male subjects, designed to compare the PK and PD of an oral capsule and oral solution, each administered after a fast, and an oral capsule when administered after a high-fat meal.
About TRV734
The mu-opioid receptor is a well-established target for effective analgesics such as fentanyl and morphine, which are unbiased mu-opioid agonists. TRV734 is a biased ligand at the mu-opioid receptor, activating the G protein pathway, associated with analgesia, without activating the mu-opioid beta-arrestin pathway, associated with respiratory depression and constipation in preclinical studies. TRV734 takes advantage of the same novel biased ligand mechanism at the mu-opioid receptor as TRV130, the company’s Phase 2 intravenous clinical candidate which has shown promising differentiation vs. morphine.
About Trevena
Trevena, Inc. is a clinical stage biopharmaceutical company that discovers, develops and intends to commercialize therapeutics that use a novel approach to target G protein coupled receptors, or GPCRs. Using its proprietary product platform, Trevena has identified and advanced three differentiated biased ligand product candidates into the clinic – TRV027 to treat acute heart failure, TRV130 to treat moderate-to-severe acute pain intravenously, and TRV734 to treat moderate-to-severe acute and chronic pain orally. Trevena also is advancing additional product candidates in its portfolio, including a preclinical program focused on central nervous system indications.
SOURCE: Trevena
Post Views: 146
