Clinical trial NCT01429051: A Clinical Trial With Intranasal Fentanyl in Cancer Patients With Breakthrough Pain
Official title: A Dose Titrated Clinical Trial With a Placebo-controlled, Double-blind, Randomised, Cross-over Phase to Demonstrate the Efficacy of 400 μg Intranasal Fentanyl (INFS) Dose Strength, and to Evaluate 12 Weeks Safety and Nasal Tolerability of All Dose Strengths Between 50 μg and 400 μg, in Cancer Patients With Breakthrough Pain.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Break Through Pain
Cancer
Keywords: Break through pain
BTP
Cancer
Intranasal Fentanyl Spray
INFS
cancer patients
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2011-09-05
Enrollment: 46
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: 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?

Primary outcomes:
measure: Induction Phase: Pain Intensity Difference at 10 Minutes (PID10) After Treatment
timeFrame: During the efficacy phase (II), at each episode of breakthrough pain, at 0 and 10 minutes after first dose of study drug.
Secondary outcomes:
measure: Incidence of Improvement or Worsening in Nasal Mucosa Sign or Abnormality Score
timeFrame: Baseline and at 12 weeks
measure: Efficacy Phase: Pain Intensity Difference (PID) at 5, 30, and 60 Minutes After First Dose of Study Drug
timeFrame: During the efficacy phase (II) each episode of breakthrough pain, at 0, 5, 30 and 60 minutes after study drug.
measure: Efficacy Phase: Sum of Pain Intensity Differences (SPID0-60 and SPID0-30) Derived From PI Scores
timeFrame: During the efficacy phase (II) each episode of breakthrough pain, at 0, 5, 30 and 60 minutes after study drug
measure: Efficacy Phase: Proportion of BTP Episodes With a Positive Response Defined as a ≥ 1, 2 or 3 Point Reduction in Pain Intensity
timeFrame: During the efficacy phase (II) each episode of breakthrough pain, at 0, 5, 30 and 60 minutes after study drug
measure: Efficacy Phase: Proportion of BTP Episodes With a Positive Response Defined as a ≥ 33% or 50% Reduction in Pain Intensity
timeFrame: During the efficacy phase (II) each episode of breakthrough pain, at 0, 5, 30 and 60 minutes after study drug
measure: Efficacy Phase: General Impression (GI) Score at 60 Minutes After First Dose
timeFrame: During the efficacy phase (II), at each episode of breakthrough pain, 60 minutes after first dose of study drug.
measure: Number of Participants With Adverse Events (AEs)
timeFrame: 12 weeks
Other outcomes:
Locations:
city: Budapest
country: Hungary
city: Debrecen
country: Hungary
city: Kazincbarcika
country: Hungary
city: Nyíregyháza
country: Hungary
city: Pécs
country: Hungary
city: Drammen
country: Norway
city: Trondheim
country: Norway
city: Moscow
country: Russian Federation
city: Smolensk
country: Russian Federation
city: St. Petersburg
country: Russian Federation
city: Yaroslavl
country: Russian Federation
Study officials:
affiliation: Takeda
name: Medical Director, Clinical Science
role: STUDY_DIRECTOR
References:
citation: Thronaes M, Popper L, Eeg M, Jaatun E, Kvitberg M, Kaasa S. Efficacy and tolerability of intranasal fentanyl spray in cancer patients with breakthrough pain. Clin Ther. 2015 Mar 1;37(3):585-96. doi: 10.1016/j.clinthera.2014.12.010. Epub 2015 Jan 30.