Lennham Pharmaceuticals Announces Topline Results from Pharmacokinetic Study of d9-Caffeine Versus Caffeine

Lennham Pharmaceuticals today announced topline results of the first ever human study of d9-caffeine. The study was conducted to compare the single-dose pharmacokinetics of caffeine versus d9-caffeine and their corresponding metabolites in healthy adult volunteers.

“Caffeine is a ubiquitously consumed product with many benefits, but is limited by a short half-life and C_max and metabolite-related side effects,” said Bradford C. Sippy, Founder and CEO of Lennham. “d9-Caffeine potentially addresses these limitations, while retaining the beneficial properties of caffeine. We believe that d9-caffeine has significant potential as a food or energy drink ingredient at low doses, and as a pharmaceutical product at higher doses. We intend to rapidly advance our differentiated version of caffeine for food ingredient, energy drink, and pharmaceutical applications.”

The study was a randomized, controlled, double-blind, two-part, two-period crossover design. Unlabeled caffeine or d9-caffeine at two dose levels were administered with blood samples collected before and up to 48 hours after administration. Plasma levels for caffeine, d9-caffeine and their respective primary metabolites were analyzed.

d9-Caffeine exhibited a similar time to maximum plasma concentration (T_max), a higher peak plasma concentration (C_max) and a 4-fold higher total exposure (AUC) than a similar dose of caffeine. The three active metabolites of d9-caffeine demonstrated a lower C_max and lower exposure relative to their un-deuterated counterparts. Results were consistent in the low and high dose comparison. Slower metabolizers of caffeine demonstrated a lower relative increase in exposure to d9-caffeine than rapid metabolizers. Both products were well tolerated. No adverse events for insomnia were reported during the study.

Lennham plans to present the results of this study at the International Society of Sports Nutrition’s annual meeting in St. Petersburg, FL on June 11, 2021 and to submit the results of the study for publication in a peer-reviewed scientific journal.

Lennham holds two broad United States patents on d9-caffeine as a food ingredient, U.S. Patent Nos. 10,582,716 and 10,765,130, which expire in 2039, and multiple pending applications.

About Caffeine

Caffeine is the most widely consumed psychoactive agent in the world. While caffeine is a safe^1,2 and effective stimulant, it is quickly cleared by the body following a rapid onset, even at high doses, causing what is known colloquially as the “caffeine crash”. Theophylline and theobromine, two active metabolites of caffeine, are associated with safety issues at high doses.^3,4 Caffeine is primarily metabolized by the CYP450 isoenzyme CYP1A2. Genetic polymorphs of CYP1A2 exist that may influence the metabolism of caffeine.⁵

A potent, but under-studied, CNS stimulant, caffeine has been hypothesized to have a beneficial role in the treatment or prevention of numerous conditions including Parkinson's, narcolepsy, ADHD, Alzheimer’s, and weight loss.^6,7,8,9

About d9-Caffeine

Deuterium is a naturally occurring, stable isotope of hydrogen, with an additional neutron in its nucleus. Selectively substituting hydrogen with deuterium, or deuteration, is a way to alter a molecule’s metabolic profile while maintaining the core pharmacodynamic characteristics.

Deuteration strengthens the chemical bond between two elements. Depending on where deuterium is placed, it has the potential to alter the overall metabolism of a molecule, or to reduce conversion to specific, unwanted metabolites.

Deuteration has been successfully leveraged in several approved and/or late-stage pharmaceutical products.

d9-Caffeine is a deuterated form of caffeine that has similar pharmacodynamic characteristics as caffeine. Unlike extended-release caffeine products, which have failed to achieve the T_max and C_max of caffeine, d9-caffeine has demonstrated substantially differentiated pharmacokinetics, including a similar T_max, higher C_max, longer half-life, reduced exposure to certain metabolites of caffeine, and lower relative exposure in slow metabolizers of caffeine.

About Lennham Pharmaceuticals, Inc.

Lennham is a privately held, clinical-stage life sciences company focused on the creative application of deuterium chemistry to improve upon highly utilized and well-characterized compounds. Founded in 2019, Lennham’s unique approach to deuteration has enabled it to rapidly develop a pipeline of product candidates, including deuterium-enriched forms of psilocybin, caffeine, and an androgen-receptor agonist.

For more information, please visit www.lennham.com.

References

1. van Dam RM et al. Coffee, Caffeine, and Health. N Engl J Med. 2020 Jul 23;383(4):369-378.
2. FDA Code of Federal Regulations. 21CFR182.1180. Accessed 03 Jun 2021.
3. Baggot et al., “Psychopharmacology of theobromine in healthy volunteers”, Psychopharmacology (Berl). 2013 Jul; 228(1): 109–118.
4. Journey JD, Bentley TP. Theophylline Toxicity. [Updated 2020 Jun 25]. Treasure Island (FL): StatPearls Publishing; 2021 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK532962/.
5. Nehlig A. Interindividual Differences in Caffeine Metabolism and Factors Driving Caffeine Consumption. Pharmacological Reviews. 2018, 70:384-411.
6. Diepvens K et al. Obesity and thermogenesis related to the consumption of caffeine, ephedrine, capsaicin, and green tea. Am J Physiol Regul Integr Comp Physiol. 2007 Jan;292(1):R77-85.
7. Kolahdouzan M et al. The neuroprotective effects of caffeine in neurodegenerative diseases. CNS Neurosci Ther. 2017 Apr;23(4):272-290.
8. Cipollone G et al. Exploring the Role of Caffeine Use in Adult-ADHD Symptom Severity of US Army Soldiers. J Clin Med. 2020 Nov 23;9(11):3788.
9. Aldosari MS et al. The effects of caffeine on drowsiness in patients with narcolepsy: a double-blind randomized controlled pilot study. Sleep Breath. 2020 Dec;24(4):1675-1684.

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