Nortriptyline :: Multiple pharmacies comparison.

CAMBRIDGE, Mass. — CombinatoRx, Incorporated (NASDAQ: CRXX) today announced positive results of its single blind, phase 2, proof-of-concept clinical trial of CRx-170 in patients with asthma. CRx-170 is a novel synergistic combination drug candidate containing low dose budesonide and low dose nortriptyline. In this trial CRx-170 provided clinical benefit on FEV1 and demonstrated activity on immuno-modulatory markers. As measured by FEV1, the standard clinical measure of breathing capacity in asthma and chronic obstructive pulmonary disease (COPD), the novel combination CRx-170 demonstrated a statistically significant improvement from treatment baseline. CRx-170 was generally well tolerated and there were no serious adverse events reported.

Related Results

NortriptylineNortriptyline and smokingNortriptyline and neuropathic painNortriptyline may aid ECT efficacyNortriptyline may beat SSRIs for depression in Parkinson’s

In the study, one week of dosing CRx-170 demonstrated a statistically significant mean percentage improvement (increase) in FEV1 from the treatment baseline of the study of approximately 6% (p=0.045). Neither low dose nortriptyline as a single agent nor low dose budesonide as a single agent showed significant improvement in FEV1 from the separate study baseline used to evaluate the single agents (approximately 2% decrease for low dose nortriptyline, p=0.466; approximately 5% decrease for low dose budesonide, p=0.251). In the wheal and flare skin test, otherwise known as the Late Allergen Response (LAR), CRx-170 decreased the area of LAR by more than 50% (p=0.053). CRx-170 did not show a modulation of the inflammatory marker CD163 from the treatment baseline, although nortriptyline clearly did decrease CD163 on its own. Analysis of additional measurements and the final analysis of these data is ongoing. The most common adverse events related to CRx-170 were dry mouth, drowziness, constipation and headache; known effects of nortriptyline.
“The observed effect of CRx-170 in such a short period of dosing, as measured by FEV1, the most clinically relevant endpoint and generally accepted measure of clinical activity, suggests that CRx-170 may have potential as a novel agent for the treatment of pulmonary diseases such as asthma and COPD,” said Dr. Jan Lessem, Chief Medical Officer of CombinatoRx. “Given these signals of clinical activity and observed immunological activity, CRx-170 certainly merits further clinical studies.”
“This proof of concept trial provides another successful translation of our discovery technology into positive clinical results” commented Alexis Borisy, President and CEO of CombinatoRx. “We are pleased to see the activity of CRx-170 where the low doses of these individual agents have not shown clinical activity, and we look forward to the continuing development of the CombinatoRx pipeline.”
About the Trial Design
This clinical trial was conducted over an approximately 17-week per patient period and was a single center, single blind, dose de-escalation study. The proof-of-concept phase 2 study was primarily descriptive in design, with a change in circulating monocyte CD163, an inflammatory marker, designated as its primary endpoint. Secondary endpoints of the study included clinical measures such as spirometry (i.e., FEV1), evening peak expiratory flow, and the use of rescue medication and reduction in other inflammatory markers including wheal and flare response.
Patients were sequentially treated with decreasing oral doses of nortriptyline and budesonide as single agents, with washout periods between each treatment, followed by 1-week treatment with nortriptyline and 1-week with CRx-170. During the nortriptyline alone and budesonide alone phases, changes in FEV1 were measured versus study baseline, which was set on the first day of dose de-escalation of nortriptyline as a single agent. During the CRx-170 treatment phase, changes in FEV1 were measured from treatment baseline, which was set following the last washout from the single agent dosing period. During the treatment period with CRx-170, patients were given 3 mg of budesonide orally and the lowest dose of nortriptyline from the de-escalation phase.
Patients with mild allergic asthma were enrolled in the trial. To be eligible, patients had to have a history of bronchial asthma for at least 6 months as defined by ATS criteria, a positive wheal and flare skin test response to allergens, and FEV1 greater than or equal to 60% of the predicted FEV1. Of the nineteen patients enrolled, seventeen completed treatment.
About CRx-170
CRx-170 is a novel, orally available syncretic drug candidate in Phase 2 clinical development. A syncretic drug comprises two compounds that are designed to act synergistically through multiple pathways to provide a novel therapeutic effect which neither component alone can achieve. CRx-170 contains a low dose of the steroid budesonide and a low dose of nortriptyline. The target product profile for CRx-170 is to selectively amplify certain elements of budesonide’s anti-inflammatory and immunomodulatory activities, without replicating its side effects. CRx-170 was discovered using the CombinatoRx proprietary combination High Throughput Screening (cHTS(TM)) technology. We plan to develop CRx-170 in a unique formulation for the treatment of pulmonary or additional immuno-inflammatory diseases. CRx-170 is one of a portfolio of six product candidates that CombinatoRx is currently testing in phase 2 clinical trials.