Wafermine™ contains the non-opioid drug Ketamine
Ketamine has been shown to be effective for the management of moderate to severe pain and provides a useful alternative to opioid analgesia. Ketamine, has also been shown to reduce hyperalgesia (the heightened sensitivity to pain) that occurs in many pain states and also through long-term usage of opioids. When used with opioids, ketamine has also been shown to have a dose-sparing effect on the amount of opioid analgesia required.
The rapidly dissolving wafer once placed under the tongue, causes ketamine to be absorbed through the mucous membrane into the bloodstream, without having to pass through the hostile acidic and enzymatic environment in the gastrointestinal tract or be subjected to the loss of active ketamine by hepatic metabolism (hepatic first pass effect).
With Wafermine™, ketamine can now be delivered sublingually in a rapid and predictable manner to the bloodstream without the potential harmful initial spike in ketamine concentrations seen following intravenous administration.
Study Design & Objective: An open label, two-way crossover Phase 1 study to evaluate the absolute bioavailability and clinical tolerability of a novel sublingual wafer formulation of ketamine in 8 healthy male volunteers (KET-001).
All subjects were administered with Wafermine™ 25mg sublingually (SL) and ketamine solution 10mg intravenously (IV) on two separate occasions.
Absolute bioavailability (F): 29%
Low variability: 90% confidence interval (F), 27-31%
First plasma ketamine detection < 5 mins
(The absolute bioavailability of racemic ketamine from a novel sublingual formulation, British Journal of Clinical Pharmacology, 2013)
Study Design & Objective: A randomised, double-blind, parallel, placebo-controlled dose-ranging study to assess the analgesic efficacy, tolerability, safety and pharmacokinetics profile of Wafermine™ in 120 adults following a third molar extraction, examining a dosing range of 25 mg to 50 mg (KET-003), and a Phase 2 clinical study on Wafermine™ in 80 adults with higher doses of 70 mg and 100 mg (KET-005).
Confirmed rapid ketamine absorption
Mild, short lived side effects
Pain reduction < 10 mins
Results: In both studies, Wafermine™ produced rapid onset of pain relief, usually by 10 minutes post dose, with maximum effects generally at around 20-30 minutes, before subsiding over 1-2 hours.
Study Design & Objective: a randomised, double-blind, placebo-controlled trial in a total of 125 female and male participants who underwent either abdominoplasty or bunionectomy surgery.
Bunionectomy cohort : Wafermine 50mg vs Wafermine 75mg vs Placebo (1:1:1)
Abdominoplasty cohort: Wafermine 25mg vs Wafermine 50mg vs Wafermine 75mg vs Placebo (1:1:1:1)
All Subjects (n=125)
4 treatment arms:
Placebo (n=39), 25mg (n=10), 50mg (n=38), 75mg (n=38)
Effect size 0.13 ; P value 0.71
Effect size 0.65 (moderately strong efficacy); P value 0.009
Results for SL administration of Ketamine
Strong analgesic efficacy observed with 75mg group in both pain models
Dose response observed, limited efficacy observed with both the 25mg and 50mg groups
Wafermine was safe and adequately tolerated. Most adverse events were mild, of short duration and self-limiting
75mg dose identified as dose to move forward with into Phase 3 analgesic clinical trials