NOT A SQUEEZE PLAY - FDA APPROVAL PLAY - SIMILAR TO $CALT
Aquestive Therapeutics Receives Written Response to Pre-IND Submission for AQST-109 (epinephrine prodrug sublingual film) and Begins Recruitment for its Epinephrine Film Pharmacokinetic and Safety Trial (EPIPHAST)
- FDA confirms 505(b)(2) pathway is acceptable for the development of AQST-109
- FDA indicates AQST-109 has the potential for Fast Track designation
- Health Canada provides clearance to commence the adaptive design crossover study.
WARREN, N.J., Dec. 13, 2021 (GLOBE NEWSWIRE) -- Aquestive Therapeutics, Inc. (NASDAQ: AQST), a pharmaceutical company focused on developing and commercializing differentiated products that address patients’ unmet needs and solve therapeutic problems, today reported that it has received a written response from FDA to its pre-investigational new drug (pre-IND) meeting submission confirming that the development of AQST-109 for the treatment of anaphylaxis under the 505(b)(2) pathway is acceptable.
The FDA’s written response to Aquestive indicates that, pending review, Aquestive has performed sufficient clinical and nonclinical activity to support the opening of an Investigational New Drug (IND) application for AQST-109. In addition, the FDA provided comments on both Aquestive’s toxicology plan and clinical development plan. The FDA confirmed its agreement that (i) the 505(b)2 pathway is appropriate for the development of AQST-109 and (ii) AQST-109 has the potential to meet the regulatory criteria for Fast Track designation. Aquestive plans to file its IND for AQST-109 early in the first quarter 2022.
In addition, Health Canada has provided clearance for Aquestive’s crossover study, known as the EPIPHAST study, of AQST-109. Patient recruitment has begun and the Company expects the first dosing to occur before the end of the year. The EPIPHAST study is a randomized, open-label, three-part adaptive design, crossover study intended to compare the pharmacokinetics and pharmacodynamics of epinephrine fol
... keep reading on reddit ➡7:30a ET 12/14/2021 - Globe Newswire KemPharm, Inc. Announces Top-Line Results from Clinical Trial Evaluating the Safety and Pharmacokinetics of "Higher-Dose SDX" Mentioned: KMPH Data reveal serdexmethylphenidate (SDX) delivered at doses higher than those studied with AZSTARYSis well-tolerated, yields dose-proportional d-MPH exposure, and produces targeted biological effects
KemPharm, Inc. (NASDAQ: KMPH), a specialty pharmaceutical company focused on the discovery and development of proprietary prodrugs, announced today top-line results from its clinical trial exploring the safety and pharmacokinetics of serdexmethylphenidate (SDX) delivered at doses higher than those studied as part of the AZSTARYS development program. AZSTARYS is a once-daily product approved for the treatment of attention deficit hyperactivity disorder (ADHD) in patients ages six years and older which is being commercialized in the U.S. by Corium, Inc., a portfolio company of Gurnet Point Capital (GPC). SDX is KemPharm's proprietary prodrug of d-methylphenidate (d-MPH) and the primary active pharmaceutical ingredient in AZSTARYS. The U.S. Drug Enforcement Agency (DEA) has classified SDX as a Schedule IV controlled substance, which is a lower schedule than all other currently available methylphenidate-based products.
The dose-ascending Phase 1 clinical trial enrolled 14 subjects who were administered up to four increasing single oral doses of SDX, each at least 14 days apart. Doses ranged from 240 mg to 600 mg. Of those individual subjects administered more than one dose of SDX, 10 received 360 mg, seven received 480 mg, and two received 600 mg. Doses greater than 240 mg were above those studied under the AZSTARYS development program. Data from the study indicated that the 240 mg and 360 mg doses of SDX were well-tolerated and produced d-MPH exposure generally proportional to the dose. Consistent with previous studies, after dosing d-MPH plasma concentrations demonstrated a gradual increase followed by a slow decline resulting in prototypical broad d-MPH exposure peak observed after oral administration of SDX. Additionally, data suggested that the higher SDX doses produced targeted biological effects that potentially align with the treatment of idiopathic hypersomnia (IH) and other sleep disorders, as well as stimulant use disorder (SUD). Specifically, increased wakefulness, alertness, excitability and insomnia effects were observed in the study. Modest increases in Drug Liking, which
... keep reading on reddit ➡I'm wondering if anyone can help me figure out the half- life of thebaine. Morphine is 3-7 hours. I can't find much on thebaine except one study saying it was 1.5 hours.
Then I'm also wondering about metabolism. All I am finding are references to buprenorphine and oxycodone since thebaine is a precursor to those drugs. Morphine is primarily catalyzed by UGT2B7. Which enzymes catalyze thebaine?
(Context) I have comorbid ADHD and bipolar spectrum depression and usually take methylphenidate (MPH) in 4 immediate release doses (Ritalin) 10mg that are spaced 4 hours apart. That results in a concentration curve that has this shape: https://imgur.com/a/R0QV74W (nevermind the "bioavailability" that is actually about 0.3, but for easier visualization I set it to 1).
Considering how taking separate IR doses of MPH produces peaks in drug concentration throughout the day and how this may adversely affect the bipolar aspect of my mood disorder, my doctors and I are considering switching to a long-term formulation, combined with precisely-calculated doses of IR methylphenidate if needed, to attain smoother concentration curves and hopefully "take the edge off" the fluctuations that these drug peaks may produce in my mood, while keeping the ADHD symptoms in check. (End of context)
Different sustained release MPH formulations are available (e.g. Ritalin LA, Concerta and others) and their delivery profiles can be easily seen by looking that up on Google. One can notice how they also have peaks insteady of a steady release. I have read (e.g. here) that sustained-release formulations that achieve a fast rise and then maintained a flat profile (zero-order delivery) were developed first, and then were found to be not effective, a phenomenon that was attributed to probable acute tolerance.
Now back to my personal context for a bit, I tried Concerta 36mg, which delivery profile looks somewhat like this, but it presents two problems - first, the initial raise during the first hour (which is equal to 22% of the total dosage of 36mg, that is IR) is less effective for me than a dose of 10mg IR that I currently take in the morning. And second, the second peak occurs at a level that appears to be a bit too much for me - I feel somewhat tense and more "perseverative" (i.e. impaired cognitive flexibility) at these higher levels between hours 5 through 9. I'm currently experimenting with a combination of Concerta 18mg and a 7.5mg of IR Ritalin taken together, along with 3 additional (small) doses of IR during the day, to obtain a curve like this, but am finding it to not be working as well as my original regimen of 4x 10mg IR in
... keep reading on reddit ➡Hello I'm studying basic pharmacokinetics and I've come across this statement: ''A faster rate of infusion does not change the time needed to achieve steady state; only the steady state concentration changes''. I mean I don't really get how a faster rate of infusion doesn't let you reach steady state faster. Could someone explain that to me?
So - as a user of modafinil, I often refer to this paper: https://pubmed.ncbi.nlm.nih.gov/19663523/ which features this figure https://i.imgur.com/SAbcEYc.png To my eyes, it shows a relatively predictable curve that could surely be made into a model, with which you could predict the levels of a substance present in the blood at various points since ingestion.
This led me to https://en.wikipedia.org/wiki/Physiologically_based_pharmacokinetic_modelling, which isn't particularly inviting to a newcomer like me, but still is a pretty good pointer for further research.
However, and this is why I'm asking - neither the paper I'm mentioning, nor the Wikipedia article mention the pharmacokinetics of re-dosing - e.g. what happens if a certain dose of something is taken, and while it still significantly present in the blood, taken again (say, in the case of modafinil, 50mg and 3 hours later, 50mg more). Is it simply a sum of the respective curves? Does it prolong the duration, but doesn't change the trend? I imagine it highly depends on the substance - is this described anywhere?
Thanks in advance!
Correction: look at rkm’s comments for updated timelines .
Study is expected to finish by q3. And results are expected early q4. Thanks Rkm.
https://aquestive.com/aquestive-therapeutics-receives-written-response-to-pre-ind-submission-for-aqst-109-epinephrine-prodrug-sublingual-film-and-begins-recruitment-for-its-epinephrine-film-pharmacokinetic-and-safety-tri/
Aquestive Therapeutics Receives Written Response to Pre-IND Submission for AQST-109 (epinephrine prodrug sublingual film) and Begins Recruitment for its Epinephrine Film Pharmacokinetic and Safety Trial (EPIPHAST)
- FDA confirms 505(b)(2) pathway is acceptable for the development of AQST-109
- FDA indicates AQST-109 has the potential for Fast Track designation
- Health Canada provides clearance to commence the adaptive design crossover study.
WARREN, N.J., Dec. 13, 2021 (GLOBE NEWSWIRE) -- Aquestive Therapeutics, Inc. (NASDAQ: AQST), a pharmaceutical company focused on developing and commercializing differentiated products that address patients’ unmet needs and solve therapeutic problems, today reported that it has received a written response from FDA to its pre-investigational new drug (pre-IND) meeting submission confirming that the development of AQST-109 for the treatment of anaphylaxis under the 505(b)(2) pathway is acceptable.
The FDA’s written response to Aquestive indicates that, pending review, Aquestive has performed sufficient clinical and nonclinical activity to support the opening of an Investigational New Drug (IND) application for AQST-109. In addition, the FDA provided comments on both Aquestive’s toxicology plan and clinical development plan. The FDA confirmed its agreement that (i) the 505(b)2 pathway is appropriate for the development of AQST-109 and (ii) AQST-109 has the potential to meet the regulatory criteria for Fast Track designation. Aquestive plans to file its IND for AQST-109 early in the first quarter 2022.
In addition, Health Canada has provided clearance for Aquestive’s crossover study, known as the EPIPHAST study, of AQST-109. Patient recruitment has begun and the Company expects the first dosing to occur before the end of the year. The EPIPHAST study is a randomized, open-label, three-part adaptive design, crossover study intended to compare the pharmacokinetics and pharmacodynamics of epinephrine following administration of AQST-109 and epinephrine administered as intramuscular injection in healthy adult subjects. This study will be used to determine the final product configuration that will be used to manufacture registration batches and conduct pivotal studies planned for the
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