RSS
Home
Business and Finance
Business News
Round 2: Snow slams Mid-Atlantic, points north- Plows that have been rolling around the clock for days in the nation's capital, Philadelphia and Baltimore won't be heading for the garage any time soon as a second major storm in a week moved into the snowbound region Wednesday.
Obama, Palin trade telling jibes over crib sheets- The jokes about Barack Obama's close relationship with his teleprompter have been constant since he became president.
Doctor says vendor may have been in rubble 27 days- The tale seems dubious: that a rice vendor survived 27 days trapped under the rubble of a flea market following Haiti's devastating earthquake.
Honda adds 437,000 cars to global air bag recall- Honda Motor Co. is adding 437,000 vehicles to its 15-month-old global recall for faulty air bags in the latest quality problem to hit a Japanese automaker.
- Americans backed off from holiday spending in January, but retail sales rose for a third month in a row compared with a year earlier, largely because of gas price hikes, according to figures released Wednesday by a key data service.
Iran rewards Basij militia with political clout- During an Iranian government meeting late last month, a top adviser to President Mahmoud Ahmadinejad brought a proposal to expand the political voice of a group more known for its street muscle: the civilian militia corps called the Basij.
Space shuttle Endeavour pulls in at space station- Shuttle Endeavour arrived to a warm welcome at the International Space Station early Wednesday, delivering a new room and observation deck that will come close to completing construction 200 miles above Earth.
- The Federal Aviation Administration is close to wrapping up a two-year investigation of safety violations at American Airlines that could result in one of the largest fines in the agency's history, according to government and industry officials familiar with the investigation.
Fans delighted by DeGeneres' 'Idol' debut- Ellen DeGeneres hit the right notes with "American Idol" viewers.
Carmelo returns to help Nuggets beat Mavs, 127-91- Carmelo Anthony scored 19 points in his return from an ankle injury and the Denver Nuggets had their biggest win of the season, routing the Dallas Mavericks 127-91 on Tuesday night.
Alexza's AZ-104 (Staccato(R) Loxapine) Phase 2a Trial Meets Primary Endpoint of 2-Hour Pain Relief in Patients with Migraine Headache
MOUNTAIN VIEW, Calif.
(Map)
-
"Loxapine is a potent antagonist at dopamine D2 receptors as well as serotonergic 5-HT2A receptors. While drugs that antagonize the D2 receptor are efficacious in treating migraine, it was proposed that the 5HT2A receptor antagonism might yield an improved adverse effect profile over drugs blocking primarily the D2 receptor. This dual mechanism of pharmacological action provided the scientific rationale to study AZ-104 in this proof-of-concept clinical trial," said James V. Cassella, PhD, Senior Vice President, Research and Development at Alexza and chairman of the Symphony Allegro Development Board. "These promising initial results are exciting. We look forward to working with our colleagues at Symphony Allegro to further analyze the data and determine the next steps in the clinical development of AZ-104."
AZ-104 Phase 2a Clinical Trial Design
The Phase 2a clinical trial was an in-clinic, multi-center, randomized, double blind, placebo-controlled study. The study was designed to evaluate the treatment of a single migraine attack in each of 160 migraine patients, with or without aura. In the trial design, three doses of AZ-104 (Staccato loxapine in 1.25, 2.5 and 5 mg doses) were evaluated against placebo (a Staccato device containing no drug). Patients reported to the clinic when they felt the onset of a migraine and were treated once their headache was considered to be of moderate or severe intensity. Patients stayed in the clinic for 4 hours post-dosing for various assessments and were monitored via patient diary for the remainder of the 24-hour evaluation period. The clinical trial enrolled 168 patients: 43 patients in the 1.25 mg dose group, 43 patients in the 2.5 mg dose group, 43 patients in the 5 mg dose group and 39 patients in the placebo dose group.
Patients rated their headache pain using the International Headache Society (IHS) 4-point rating scale. The primary efficacy endpoint was headache pain relief (headache pain rated as mild or none) at 2-hours post-dose. Secondary efficacy endpoints for the trial included various additional measurements of pain relief, as well as effects on nausea, vomiting, phonophobia and photophobia. All results were considered statistically significant at the p < 0.05 level and all analyses were made on an intent-to-treat basis. Side effects were recorded throughout the clinical trial study period.
Primary Efficacy Endpoint
AZ-104 met the primary efficacy endpoint of the clinical trial for two doses of the drug compared to placebo. Statistically significant improvements in pain response were observed in 76.7% of patients at the 5 mg dose (p = 0.02), 79.1% of patients at the 2.5 mg dose (p = 0.01) and 67.4% of patients at the 1.25 mg dose (p = 0.18), compared to 51.3% of patients receiving placebo. Using survival analysis for pain relief response, all three dose groups were statistically superior (p < 0.05) to placebo during the 4-hour post-treatment time period that the patients remained in the clinic.
Primary Efficacy Endpoint -- Pain Relief at 2-Hours Post-Dose Number of Patients Achieving % p-value Treatment Patients Pain Relief Pain-Relief vs Placebo Placebo 39 20 51.3% na 1.25 mg 43 29 67.4% 0.18 2.5 mg 43 34 79.1% 0.01* 5 mg 43 33 76.7% 0.02* * Statistically significant (p < 0.05)Additional Efficacy Endpoints
Additional measures of efficacy included the achievement of a pain-free response, in which a patient has a post-dose pain score of 0 (or "no") headache pain. In the trial, AZ-104 showed statistically significant differences from placebo in this measure at the 2-hour time point with 30% of patients achieving pain-free status at the 2.5 mg dose (p = 0.01) and 28% at the 1.25 mg dose (p = 0.02). While the 5.0 mg dose was numerically superior to placebo with 21% pain-free, this group did not achieve a statistically significant response, compared to placebo (p = 0.12). The rate of pain-free response at 2 hours in patients receiving placebo was 8%. Using survival analysis for pain free response, all three dose groups were statistically superior (p < 0.05) to placebo during the 4-hour post-treatment time period that the patients remained in the clinic.
A commonly used measure of duration of efficacy is the sustained pain-free response, in which a patient reports a pain-free score at the 2-hour post-dose time point and remains pain-free for the remainder of the study period (up to 24 hours). The 2.5 mg dose of AZ-104 showed a statistically significant difference in sustained pain-free response (26%, p = 0.04) compared to placebo (8%). Sustained pain-free outcomes for the 5 mg (16%) and the 1.25 mg (21%) dose groups were not statistically significant.
Important symptoms to be managed in migraine patients are nausea, photophobia (sensitivity to light) and phonophobia (sensitivity to sound). This proof-of-concept trial was not powered to detect differences in these measurements. AZ-104 did exhibit statistically significant improvement in nausea across all dose levels (survival analysis, p = 0.02). Positive trends were observed in the improvement of the other symptoms, but the changes were not statistically significant.
Safety Evaluations
Side effects were recorded throughout the clinical trial study period. There were no serious adverse events reported during the trial. The most common drug-related side effects (incidence . 5% in at least one drug dose
group) reported across the three drug dose groups and placebo are listed in the table below. Placebo 1.25 mg 2.5 mg 5 mg Side Effects (%) (%) (%) (%) Dysgeusia 13 19 23 37 Somnolence 13 5 23 23 Fatigue 8 0 7 14 Oral discomfort 3 0 2 7 Dizziness 5 2 7 2 Hypoaesthesia, pharyngeal 0 0 0 7 Throat irritation 0 7 0 0 Dry mouth 5 2 5 5 Hypoaesthesia, oral 0 2 5 2 Attention disturbance 0 5 0 2 Hypotension 3 0 2 5About Acute Migraine Headaches
According to the National Headache Foundation, approximately 13 million
people in the
About AZ-104 (Staccato loxapine)
AZ-104 is the combination of Alexza's proprietary Staccato system with loxapine, a drug belonging to the class of compounds known as antipsychotics. The Staccato system technology is a hand-held, chemically-heated, single dose inhaler designed to generate and deliver excipient-free drug aerosol for deep lung delivery that results in IV-like pharmacokinetics. In a Phase 1 dose-escalation clinical trial, doses of Staccato loxapine ranging from 0.625 to 10 mg were generally well tolerated and there were no serious adverse events. Across all doses, pharmacokinetic analyses revealed that peak plasma levels were generally reached within the first few minutes after dosing and the drug exhibited good dose proportionality. Alexza and Symphony Allegro are also developing Staccato loxapine (AZ-004) for the treatment of acute agitation in patients with schizophrenia or bipolar disorder.
About Symphony Allegro
In
About Alexza Pharmaceuticals, Inc.
Alexza Pharmaceuticals is an emerging specialty pharmaceutical company focused on the development and commercialization of novel, proprietary products for the treatment of acute and intermittent conditions. The Company's technology, the Staccato system, vaporizes unformulated drug to form a condensation aerosol that allows rapid systemic drug delivery through deep lung inhalation. The drug is quickly absorbed through the lungs into the bloodstream, providing speed of therapeutic onset that is comparable to intravenous administration, but with greater ease, patient comfort and convenience.
Alexza has six product candidates in clinical development. Alexza's lead
program, AZ-004 (Staccato loxapine) for the treatment of acute agitation in
schizophrenic or bipolar disorder patients, is in Phase 3 testing. AZ-001
(Staccato prochlorperazine) for the acute treatment of migraine headaches has
completed Phase 2 testing. AZ-104 (Staccato loxapine) for the acute treatment
of migraine headaches and AZ-002 (Staccato alprazolam) for the acute treatment
of panic attacks associated with panic disorder are in Phase 2 testing.
Product candidates in Phase 1 testing include AZ-003 (Staccato fentanyl) for
the treatment of breakthrough pain, which is partnered with Endo
Pharmaceuticals in
Safe Harbor Statement
This press release includes forward-looking statements regarding the
development, therapeutic potential and safety of AZ-104, the development of
the Company's product candidates, projected clinical trial enrollment and data
reporting timelines, and safety of the Company's products and technologies.
Any statement describing the Company's expectations or beliefs is a
forward-looking statement, as defined in the Private Securities Litigation
Reform Act of 1995, and should be considered an at-risk statement. Such
statements are subject to certain risks and uncertainties, particularly those
inherent in the process of developing and commercializing drugs. The
Company's forward-looking statements also involve assumptions that, if they
prove incorrect, would cause its results to differ materially from those
expressed or implied by such forward-looking statements. These and other
risks concerning Alexza's business are described in additional detail in the
Company's Annual Report on Form 10-K/A for the year ended
|
|
More Business_and_Finance Releases
(VIA): Paramount Pictures to Make Mission Impossible IV: Tom Cruise & JJ Abrams to Produce; Cruise to Star
(MYL): Mylan Awarded NABP-VAWD Accreditation for Its Primary North American Distribution Facility
