A Clinical Trial With Intranasal Fentanyl in Cancer Patients With Breakthrough Pain

Takeda46 enrolled

Overview

The aim of this clinical trial was to demonstrate the efficacy of a 400 μg dose strength of intranasal fentanyl spray (INFS, Instanyl®) and to evaluate the safety and to establish long term tolerability of treatment with INFS doses of 50, 100, 200 and 400 μg.

This is a clinical trial with 12 weeks treatment of Intranasal fentanyl (INFS) in cancer patients with breakthrough pain (BTP). It was composed of a dose titrated, placebo-controlled, double-blind, randomised, cross-over efficacy phase, combined with a titration and a tolerability phase assessing the safety and nasal tolerability of INFS. The trial is set up with a screening period and three treatment phases: a titration phase (I), an efficacy phase (II) and a tolerability phase (III). The entire trial period for each completed patient consisted of the one week screening period and 12 weeks treatment with INFS.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

Conditions

Break Through Pain Cancer

Interventions

Intranasal Fentanyl Spray (INFS)DRUG

Applied as 1 puff (= 1 dose) in one nostril, or applied as two puffs (= 2 doses, 1 in each nostril) with ten minutes apart.

PlaceboDRUG

Matching intranasal placebo spray

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: All inclusion criteria were answered 'yes' for a patient to participate in the clinical trial. * Is the patient a cancer patient with breakthrough Pain (BTP)? * Has the patient received either oral opioids or transdermal fentanyl for treatment of background pain (BGP) within the last month prior to the screening visit? * Is the current dose of prescribed opioids (for BGP) equivalent to 60-1000 mg oral morphine/day? * Has the patient's BGP for the last 7 days prior to the screening visit been generally stable, and on average controlled to a mild level (defined as ≤ 4 on the 11-point Numerical Rating Scale \[NRS\])? * Does the patient (at the time of the screening visit) experience his/her current BTP episodes to be of such severe pain intensity, that he/she in general needs additional analgesia (i.e. on top of the background opioid treatment)? * Has the patient on average for the last 7 days prior to the screening visit had at least three BTP episodes per week, but no more than four BTP episodes per day? * Is the patient able to use intranasal drugs? * Is the life expectancy of the patient at least 3 months from the date of the screening visit? Exclusion Criteria: 1. Has the patient had an illicit substance abuse within the last year prior to screening? 2. Does the patient have severe hepatic impairment? - defined as alanine aminotransferase (ALT or) aspartate aminotransferase (AST) levels \> 3x upper limit of normal (ULN) 3. Does the patient have severe renal impairment? - defined as serum creatinine ≥ 3.0 mg/dl (265 micromol/L) 4. Has the patient ever had facial radiotherapy or is the patient scheduled to facial radiotherapy? 5. Has the patient been treated with any monoamine oxidase (MAO) inhibitors within the last 14 days prior to the screening visit? 6. Does the patient have severe impaired respiratory function, which may increase the risk of clinically relevant respiratory depression by BTP fentanyl treatment? 7. Is the patient known to be hypersensitive to fentanyl or to other opioids or any of their excipients? 8. Does the patient have any head injury, primary brain tumor or other pathological conditions, which could significantly increase the risk of increased intracranial pressure or impaired consciousness?

Locations (11)

Unnamed facility

Budapest, Hungary

Unnamed facility

Debrecen, Hungary

Unnamed facility

Kazincbarcika, Hungary

Unnamed facility

Nyíregyháza, Hungary

Outcomes

Primary Outcomes

Induction Phase: Pain Intensity Difference at 10 Minutes (PID10) After Treatment

During the efficacy phase participants assessed their pain intensity at each breakthrough pain (BTP) episode at 0 and 10 minutes after first dose using the 11-point Numerical Rating Scale (NRS) on a scale from 0 to 10, where 0 represents the absence of pain and 10 is "worst possible pain". PID10 is calculated as the difference in pain intensity from time 0 to 10 minutes. A positive value is a decrease (improvement) of the pain; a ≥ 2-point difference is considered as clinically important.

Time frame: During the efficacy phase (II), at each episode of breakthrough pain, at 0 and 10 minutes after first dose of study drug.

Secondary Outcomes

Incidence of Improvement or Worsening in Nasal Mucosa Sign or Abnormality Score

Medical examination of the nasal cavity by rhinoscopy was performed by an oto-rhino-laryngologist before the start of study treatment and at 12 weeks. Signs and any abnormalities were observed for each nostril using the following 4 points assessment scale: • 0 =not present; • 1 =present in a mild degree; • 2 =present in a moderate degree; • 3 =present in a severe degree. A difference in score of 1 or more from Baseline to the end of treatment represented a worsening, while a negative value indicated an improvement of the observed clinical sign. The oto-rhino-laryngologist also assessed whether worsening of a sign was related to study drug. Assessments for both left and right nostrils are presented together. The incidence is calculated as the number of assessments (n) in the improvement or worsening category divided by the number of assessments with a non-missing score for the Nasal Mucosa or Abnormality assessment. Only those signs or abnormalities with n\>0 were included

Time frame: Baseline and at 12 weeks

Efficacy Phase: Pain Intensity Difference (PID) at 5, 30, and 60 Minutes After First Dose of Study Drug

During the efficacy phase participants assessed their pain intensity at each breakthrough pain (BTP) episode at 0, 5, 30 and 60 minutes after first dose using the 11-point Numerical Rating Scale (NRS) on a scale from 0 to 10, where 0 represents the absence of pain and 10 is "worst possible pain". PID is calculated as the difference in pain intensity from time 0 to each time point. A positive value is a decrease (improvement) of the pain; a ≥ 2-point difference is considered as clinically important.

Data from ClinicalTrials.gov

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