Comparison of Two Dosage Strengths of Transdermal Fentanyl Versus Transdermal Buprenorphine and Placebo in Acute Pain Models in Healthy Volunteers.
Condition: Pain
MeSH terms: Acute Pain
Study type: Interventional
Phase: Phase 1

Summary: 
      The primary objective of this pilot trial is to identify pain model(s) which allow(s) to
      compare and differentiate the analgesic effects between transdermal fentanyl 25Âµg/h,
      transdermal fentanyl 12Âµg/h and placebo in a dose dependent way. The second objective is to
      compare the effects of transdermal buprenorphine 35Âµg/h in these models with the effect of
      the two transdermal fentanyl dosages. Therefore four different treatments are given; all
      treatments will be by means of a patch that is attached to the back for 72 hours.
    

Detailed description: 
      After having read and signed the written informed consent form, patients will participate in
      a screening visit (within 2 weeks before study start, see above selection of study
      participants). Patients will participate in a training session to experience the three pain
      test procedures and to assure whether they are able to perform the tests and they are willing
      to accept these stimuli during the study. They will be hospitalized for 4 treatment cycles (4
      days / 5 nights each during which the 4 treatments mentioned under 'Purpose of the Study' are
      given). Between the hospitalizations they are not required to come to us. The new day -1 for
      the next cycle is at the same day of the week 2 weeks after the previous hospitalization. For
      each treatment cycle they enter the facility in the evening (day -1) before the patch is
      administered and may leave in the morning of day 5. Assessments will be made as follows:

      Evening of Day -1: urine drug and alcohol screen, pregnancy test for females, interview by
      the study physician in charge Days 1, 2, 3, 4, and 5 in the morning: vital signs,
      pulsoximetry (assessment of oxygen saturation by means of a finger clip) From Day 1 in the
      morning to Day 5 in the morning: continuous ECG From Day 1 in the morning to Day 4 in the
      morning: patch administration on the back Days 1, 2, and 4 in the morning: three pain tests*,
      pupillometry (measurement of the pupil size by a photographic device), blood sample for the
      measurement of the drug plasma concentrations prior to patch administration in the morning of
      day 1 they perform three pain tests* (heat, cold pressure test, electric stimulation at the
      forearm) to assess baseline values and the skin will be checked at the designated patch
      locations. Patch adhesion will be checked regularly after administration. Patients will be
      asked regularly during your stay in the unit about concomitant medications and whether any
      adverse event occurred. In the morning of day 5, before dismission, a physical exam will be
      performed. The skin underneath the patch will be assessed after removal. After the fourth
      hospitalisation phase they will leave the facility and they have to return for an ambulant
      follow up visit 6 - 9 days thereafter. Vital signs will be recorded, they will be asked about
      concomitant medications and adverse events, a physical exam, clinical laboratory, vital signs
      and an electrocardiogram will be performed. After this visit the study is terminated. The
      electrical stimulation model uses a commercially available and registered for human use
      constant current device delivering wave pulses of 3-s duration. Two electrodes are applied to
      the lateral lower arm. To determine pain threshold an ascending staircase design is used
      starting with randomly varied stimuli. The intensity of the stimulus is increased until the
      pain threshold is reached and afterwards further increased until the maximally tolerated pain
      is reached. Once pain threshold and the maximally tolerated stimulus are identified, a series
      of stimuli evenly spaced between a stimulus 30% less than the pain threshold and the
      maximally tolerated stimulus is administered in a random fashion and the patient rates the
      pain on a visual analogue scale (VAS).

      Heat test: A thermode will be applied on the forearm. The temperature of the thermode will be
      continuously increased from 30 C to a maximum of 56 C. They will be asked to give a signal
      when perceiving the heat as painful and to press the bottom when feeling the heat as
      intolerable pain and not wanting the heat to be further increased.

      Cold pressor test: The left hand will be immersed in ice-saturated water for a maximum of 2
      min. If pain is felt as intolerable before 2 min have elapsed, they can withdraw the hand.
      Perceived pain intensity will be rated continuously on a 10 mm visual analogue scale and
      recorded. Patients will receive one of four treatments one after another: transdermal
      fentanyl 25 mcg/h, transdermal fentanyl 12 mcg/h, transdermal buprenorphine 35 mcg/h,placebo.
      All of these treatments are administered as patches. Treatment duration per patch is 72
      hours. After this time the patch is removed. Before the next patch of the following treatment
      will be applied, there will be 11 days without any drug administration. Total duration of the
      study is 56 days.
    

Intervention name(s): Fentanyl; Buprenorphine; Naloxone
Intervention type(s): Drug
Intervention MeSH terms: Fentanyl; Buprenorphine; Naloxone
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double
Primary purpose: Treatment
Keywords: Healthy volunteers