|9 Months Ended|
Sep. 30, 2019
11. Subsequent Events
Healthy Volunteer QT Study
On November 4, 2019, the Company announced the completion of its healthy volunteer QT study for oliceridine and topline results from the study. This was a randomized, single-site, placebo- and positive-controlled three-period crossover study conducted in 68 healthy volunteers, with 59 subjects receiving the maximum daily dose of 27 mg of oliceridine. The protocol and statistical analysis plan were developed based on review and feedback from the FDA. The goal of the study was to collect the additional QT interval data requested by the FDA for the resubmission of the NDA for oliceridine.
Subjects were randomly sequenced through all three study periods: IV oliceridine, placebo, and a single oral 400 mg moxifloxacin dose as a positive control. For the oliceridine and placebo arms, 2 or 3 mg of oliceridine or volume-matched placebo was administered by IV bolus every two hours over a 24-hour period. Electrocardiograms for all subjects were obtained at hourly time points using continuous Holter monitoring.
Oliceridine was well tolerated and adverse events were generally mild to moderate in severity and consistent with adverse events observed in the prior safety database. There were four study discontinuations, including three for lack of venous access and one for a non-serious adverse event, an asymptomatic and transient occurrence of non-sustained ventricular tachycardia, or briefly accelerated heart rate, confounded by hypokalemia, or low potassium levels, with no associated QT prolongation. One subject also completed dosing but was not evaluable due to equipment malfunction. There were no serious adverse events in the study.
The primary endpoint was the placebo-corrected change from baseline in the individual rate-corrected QT interval, measured hourly at each of the 24 time points in the study. On this outcome, the mean increase in the QT interval was less than 10 milliseconds at 22 of the 24 time points. The peak mean increase in QT interval was observed at 9 hours and was 11.7 milliseconds, with a 90% two-sided confidence interval upper bound of 14.7 milliseconds at this time point. At 18 of the 24 measured time points, the upper bound of the 90% confidence intervals for the mean increase in QT interval was less than 10 milliseconds.
Secondary endpoints included the 24-hour time-weighted average increase in QT interval and categorical analyses of clinically significant individual outliers. The 24-hour time-weighted average increase in QT interval for oliceridine was 4.0 milliseconds. There were no individual outliers with a rate-corrected change from baseline greater than 60 milliseconds or an absolute QT interval greater than 500 milliseconds.
TRV250 Acute Migraine Proof-of-Concept Study
On November 4, 2019, the Company announced that it initiated a proof-of-concept study of TRV250 for the treatment of patients with acute migraine. This is a single-dose, double-blind, placebo-controlled study with an enrollment target of approximately 120 patients with acute migraine in a validated nitroglycerin (“NTG”) provocation migraine model. Patients will be randomized before receiving a continuous NTG infusion, followed by administration of a 20 mg subcutaneous dose of TRV250 or placebo.
The primary objective of the study is to determine target engagement, which will be measured as a reduction of sustained NTG-induced headaches. This study will also evaluate the ability of TRV250 to reduce symptomatic anxiety, as well as the safety of TRV250. The Company anticipates reporting topline data from this study in the second half of 2020.
The entire disclosure for significant events or transactions that occurred after the balance sheet date through the date the financial statements were issued or the date the financial statements were available to be issued. Examples include: the sale of a capital stock issue, purchase of a business, settlement of litigation, catastrophic loss, significant foreign exchange rate changes, loans to insiders or affiliates, and transactions not in the ordinary course of business.
Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef