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

NCT01429051 | Completed Phase 3 Results

• 4 other identifiers: FT-1301-032-SP2010-021096-85U1111-1133-63642011/776
• Study Type: interventional
• Target: 46
• Locations: 3 countries
• Sites: 11

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.

Conditions

Break Through Pain; Cancer

Keywords

Break through pain; BTP; Cancer; Intranasal Fentanyl Spray; INFS; cancer patients

Outcome Measures

Primary Outcomes (1)

• 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.

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

Secondary Outcomes (7)

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

  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 (II) each episode of breakthrough pain, at 0, 5, 30 and 60 minutes after study drug.

• Efficacy Phase: Sum of Pain Intensity Differences (SPID0-60 and SPID0-30) Derived From PI Scores

  During the efficacy phase (II) each episode of breakthrough pain, at 0, 5, 30 and 60 minutes after study drug

• Efficacy Phase: Proportion of BTP Episodes With a Positive Response Defined as a ≥ 1, 2 or 3 Point Reduction in Pain Intensity

  During the efficacy phase (II) each episode of breakthrough pain, at 0, 5, 30 and 60 minutes after study drug

• Efficacy Phase: Proportion of BTP Episodes With a Positive Response Defined as a ≥ 33% or 50% Reduction in Pain Intensity

  During the efficacy phase (II) each episode of breakthrough pain, at 0, 5, 30 and 60 minutes after study drug

Study Arms (1)

Intranasal Fentanyl Spray (INFS)

EXPERIMENTAL

All participants were step-wise titrated to an effective dose of 50, 100, 200 or 400 μg INFS in the Titration Phase (I). Participants titrated to 200 or 400 μg INFS in the Titration Phase were randomized to an 8-spray sequence in the Efficacy Phase (II); 6 BTP episodes were treated with 400 μg INFS and 2 BTP episodes with placebo in a random sequence. Participants entered the Tolerability Phase (III) either directly from the Titration Phase (with an effective dose of 50 or 100 μg) or from the Efficacy Phase (400 μg) and continued with this specific dose, unless adjustment was needed, for a total treatment time of 12 weeks.

Drug: Intranasal Fentanyl Spray (INFS); Drug: Placebo

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.

Also known as: Instanyl®

Intranasal Fentanyl Spray (INFS)

Placebo DRUG

Matching intranasal placebo spray

Intranasal Fentanyl Spray (INFS)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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?

You may not qualify if:

• Has the patient had an illicit substance abuse within the last year prior to screening?
• Does the patient have severe hepatic impairment? - defined as alanine aminotransferase (ALT or) aspartate aminotransferase (AST) levels \> 3x upper limit of normal (ULN)
• Does the patient have severe renal impairment? - defined as serum creatinine ≥ 3.0 mg/dl (265 micromol/L)
• Has the patient ever had facial radiotherapy or is the patient scheduled to facial radiotherapy?
• Has the patient been treated with any monoamine oxidase (MAO) inhibitors within the last 14 days prior to the screening visit?
• Does the patient have severe impaired respiratory function, which may increase the risk of clinically relevant respiratory depression by BTP fentanyl treatment?
• Is the patient known to be hypersensitive to fentanyl or to other opioids or any of their excipients?
• 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?

Sponsors & Collaborators

• Takeda: lead

Study Sites (11)

Unknown Facility

Budapest, Hungary

Location

Unknown Facility

Debrecen, Hungary

Location

Unknown Facility

Kazincbarcika, Hungary

Location

Unknown Facility

Nyíregyháza, Hungary

Location

Unknown Facility

Pécs, Hungary

Location

Unknown Facility

Drammen, Norway

Location

Unknown Facility

Trondheim, Norway

Location

Unknown Facility

Moscow, Russia

Location

Unknown Facility

Saint Petersburg, Russia

Location

Unknown Facility

Smolensk, Russia

Location

Unknown Facility

Yaroslavl, Russia

Location

Related Publications (1)

• 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.

  PMID: 25641199 DERIVED

MeSH Terms

Conditions

Neoplasms

Results Point of Contact

• Title: Medical Director
• Organization: Takeda

clinicaltrialregistry@tpna.com

+1-800-778-2860

Study Officials

• Medical Director, Clinical Science

  Takeda

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 1, 2011
• First Posted: September 5, 2011
• Study Start: August 1, 2011
• Primary Completion: January 1, 2013
• Study Completion: January 1, 2013
• Last Updated: March 26, 2014
• Results First Posted: March 26, 2014

Record last verified: 2014-02

Locations

NO (2); RU (4); HU (5)