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- Being developed for the treatment of acute moderate to severe pain.
- Effective alternative to opioids; has opioid-sparing effect
- Completed end-of-Phase-2 with the US FDA
- Being developed for the treatment of moderate to severe pain
- Buprenorphine is also a suitable substitute drug for opioid addiction
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.
Results for SL administration
- Absolute bioavailability (F): 29%
- Low variability: 90% confidence interval (F), 27-31%
- First plasma ketamine detection < 5 mins
- Rapidly absorbed
(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).
Results for SL administration of Ketamine
- Confirmed rapid ketamine absorption
- Good tolerability
- 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.
Phase 2 Multi-Dose Efficacy Study
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)
- 50mg group:
Effect size 0.13 ; P value 0.71
- 75mg group:
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
BnoX®, is a sublingual buprenorphine oral wafer.
With the spotlight currently on the global opioid epidemic, there is now an increasing recognition that buprenorphine can be a critical and emerging compound and which has been shown to be useful for pain management.
Buprenorphine has also been shown to provide longer lasting pain relief with fewer side effects compared to other opioids. It also exhibits a ceiling effect – higher doses do not result in unwanted additional opioid effects, including euphoria and respiratory depression. Patients are therefore less likely to develop an addiction and/or tolerance, while the risk of death is also greatly reduced.
Buprenorphine is known for its poor bioavailability (reported to be 10% or less) when ingested orally. However, by utilising iX Biopharma’s proprietary sublingual technology WaferiX®, we have demonstrated in a phase 1 pharmacokinetic study (BUP001) that BnoX® facilitates the rapid absorption of buprenorphine (median Tmax 1.0 hour) with greater absolute bioavailability of 45%. These results suggest superior pharmacokinetics to currently marketed sublingual buprenorphine formulations.