A Study Of The Effectiveness Of Wafermine Alone And In Combination With Opioids In Subjects Undergoing Bunionectomy

Ketamine

Brief Summary

To evaluate the safety and effectiveness of Wafermine administered with and without an opioid medication for acute pain following bunionectomy surgery.

Intervention / Treatment

  • Wafermine (DRUG)
    35 or 70 mg ketamine in a sublingual wafer
  • Oxycodone (DRUG)
    5 mg oxycodone capsule
  • Placebo (DRUG)
    Placebo capsule or placebo wafer

Condition or Disease

  • Acute Pain

Phase

  • Phase 2

    • Study Design

    Study type: INTERVENTIONAL
    Status: Completed
    Study results: No Results Available
    Age: 18 Years and older   (Adult, Older Adult)
    Enrollment: 72 (ACTUAL)
    Funded by: Other
    Allocation: Randomized
    Primary Purpose: Treatment

    Masking

    QUADRUPLE:
    • Participant
    • Care Provider
    • Investigator
    • Outcomes Assessor

    Clinical Trial Dates

    Start date: Oct 01, 2015
    Primary Completion: Dec 01, 2015 ACTUAL
    Completion Date: Dec 01, 2015 ACTUAL
    Study First Posted: Sep 04, 2015 ESTIMATED
    Results First Posted: Aug 31, 2020
    Last Updated: Feb 22, 2016

    Sponsors / Collaborators

    Lead Sponsor: iX Biopharma Ltd.
    Lead sponsor is responsible party
    Responsible Party: N/A

    Location

    Salt Lake City, Utah, USA

    This is a Phase 2, randomised, double-blind, double-dummy, placebo-controlled evaluation of the analgesic efficacy and safety of WafermineTM alone and in combination with low-dose oxycodone in adult subjects who experience post-operative pain after undergoing primary unilateral bunionectomy. The study will randomise sufficient subjects to have 72 completed subjects at 1 site.

    Study subjects will receive multiple doses of study medication over a 14 hour period and will be asked to complete pain and relief assessments as well as tolerability questionnaires over a 24 hour period.

    Participant Groups

    • Placebo wafers given every 2 hours Placebo capsule given every 4 hours Placebo wafers "top-up" dose given at hour 1

    • Placebo wafers given every 2 hours Oxycodone given every 4 hours Placebo wafers "top-up" dose given at hour 1

    • Wafermine™ 35 mg wafer + placebo wafer given every 2 hours Placebo capsule given every 4 hours Wafermine™ 35 mg wafer + placebo wafer "top-up" dose at hour 1

    • Wafermine™ 35 mg wafer + placebo wafer given every 2 hours Oxycodone 5 mg capsule every 4 hours Wafermine™ 35 mg "wafer + placebo wafer top-up" dose at hour 1

    • Wafermine™ 35 mg + placebo wafer given every 4 hours Placebo wafers given every 2 hours Placebo capsule given every 4 hours Wafermine™ 35 mg wafer + placebo wafer "top-up" dose at hour 1

    • Wafermine™ 35 mg + placebo wafer given every 4 hours Placebo wafers given every 2 hours Oxycodone 5 mg given every 4 hours Wafermine™ 35 mg wafer + placebo wafer "top-up" dose at hour 1

    • Wafermine™ 70 mg given every 4 hours Placebo wafer given every 2 hours Placebo capsule given every 4 hours 2 Placebo wafers "top-up" dose at hour 1

    Eligibility Criteria

    Sex: All
    Minimum Age: 18
    Age Groups: Adult / Older Adult
    Healthy Volunteers: Yes

    Inclusion Criteria:

    * Scheduled for a bunionectomy (with no additional procedures).
    * Healthy, ambulatory subjects able to understand and willing to comply with study procedures, study restrictions and requirements.
    * Body mass index (BMI) ≥19 to ≤33 kg/m2.
    * Females: Not pregnant, not lactating, and not planning to become pregnant during the study.
    * Females: Be abstinent, surgically sterile, at least two years post-menopausal; or medically acceptable contraception.
    * Able to read and understand English.
    * Able to swallow oral capsules whole.

    Exclusion Criteria:

    * Allergy, intolerance, or contraindication to ketamine, oxycodone, morphine, ibuprofen or surgical medications.
    * Clinically significant medical condition.
    * History of illicit drug use or alcohol abuse and not in full remission.
    * Positive test for human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV) at the screening visit.
    * Clinically significant 12 lead ECG abnormalities at screening.
    * Smokers who are unwilling to abstain during the inpatient stay.

    Primary Outcomes

    • Subjects will use an 11 point numerical pain rating scale (NPRS) where 0=No Pain and 10= Worst Possible pain to rate their pain at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, 8, 8.5, 9, 9.5, 10, 10.5, 11, 11.5, 12, 12.5, 13, 13.5, 14, 14.5, 15, 15.5, 16 and 24 hours. TOTPAR is computed as follows at the specified time points: TOTPAR-t = ∑ \[T(i) - T(i-1) \* \[(PR(i-1) + PR(i))/2\]

    Secondary Outcomes

    • The percent of maximum pain relief is defined as the proportion of subjects reporting "Complete Relief" (score of 4) on a 4 point categorical scale (no relief, a little relief, some relief, a lot of relief and complete relief) at each time point over the sampling interval.

    • Calculation of the proportion of subjects requiring "Rescue Medication" at each time point over the sampling interval.

    • Calculated using the double stopwatch technique. Subjects stop the first stopwatch when they experience perceptible relief and the second stopwatch when they experience meaningful relief.

    • Measurement of the time it takes subjects to report their maximum pain relief on a 5 point categorical relief scale (0=no relief, 1=a little relief, 2=some relief, 3=a lot of relief, 4=complete relief)

    • Measurement of the time it takes subjects to reach their maximum reduction in pain on the 11 point NPRS where 0=No pain and 10=Worst Possible pain.

    • Measurement of the time for pain intensity to return to baseline using scores from the NPRS assessments where 0=No pain and 10=Worst possible pain.

    • Measurement of the time elapsed from initial dose of study medication to time of first dose of rescue medication.

    • Subjects will use an 11 point numerical pain rating scale (NPRS) where 0=No Pain and 10= Worst Possible pain to rate their pain at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, 8, 8.5, 9, 9.5, 10, 10.5, 11, 11.5, 12, 12.5, 13, 13.5, 14, 14.5, 15, 15.5, 16 and 24 hours. Percentage of Maximum Total Pain Relief is computed at each time-point using: %maxTOTPAR= 〖TOTPAR〗_t/〖maxTOTPAR〗_t x100

    • Subjects will use an 11 point numerical pain rating scale (NPRS) where 0-No Pain and 10= Worst Possible pain to rate their pain at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, 8, 8.5, 9, 9.5, 10, 10.5, 11, 11.5, 12, 12.5, 13, 13.5, 14, 14.5, 15, 15.5, 16 and 24 hours. Sum of Pain Intensity Differences is computed at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, 8, 8.5, 9, 9.5, 10, 10.5, 11, 11.5, 12, 12.5, 13, 13.5, 14, 14.5, 15, 15.5, 16 and 24 hours. SPIDx is a time weighted sum of pain intensity difference score from baseline over the time interval in hours.

    • The responder rate is defined as the proportion of subjects with a value of percentage change greater than or equal to 30% (and 50%) from baseline in pain intensity (using scores from the 11 point NPRS where 0=no pain and 10=worst possible pain) at each time point over the sampling interval.

    • Measurement of treatment emergent adverse events reported during the study. Measurement of significant changes in physical examination findings as well as vital sign measurements (heart rate, blood pressure, breathing rate and pulse oximetry readings).

    • Measurement of tolerability as judged by subject answers on oral symptoms questionnaire measuring irritation, burning and bitterness, as well as physical examination of oral cavity. Also measuring the number of subjects who discontinue the study due to intolerable side effects.

    More Details

    NCT Number: NCT02541396
    Other IDs: KET009
    Study URL: https://clinicaltrials.gov/study/NCT02541396
    Last updated: Sep 29, 2023