Wafermine™ is intended for the management of moderate to severe pain and provides a useful alternative to opioid analgesia. Ketamine, the active ingredient in Wafermine™, has 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 be delivered rapidly and predictably to the bloodstream providing rapid pain relief without the potentially harmful initial spike in ketamine concentrations seen following intravenous administration.
Wafermine is currently supplied to hospitals and pharmacies in Australia under Schedule 5A of the Therapeutic Goods Regulations 1990 of Australia (TGR).
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 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 30 minutes, before subsiding over 1-2 hours.
Phase 2 Multi-Dose Clinical Study
Study Design & Objective: A multi-dose, placebo-controlled study of Wafermine™, alone and in combination with opioids in participants undergoing bunionectomy to evaluate the safety, tolerability and efficacy of three different dosing regimens of Wafermine™ (KET-009).
A total of 72 participants were enrolled. A summary of the dosing allocation was as follows:
The maximum dose administered was 315 mg over a 14-hour period.
Safe and well-tolerated
No serious adverse events
Common adverse events occured in all treatment groups
Evidence of pain reduction in participants who absorbed the drug well