- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01429051
A Clinical Trial With Intranasal Fentanyl in Cancer Patients With Breakthrough Pain (NOSE-400)
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 Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Actual)
Phase
- Phase 3
Contacts and Locations
Study Locations
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Budapest, Hungary
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Debrecen, Hungary
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Kazincbarcika, Hungary
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Nyíregyháza, Hungary
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Pécs, Hungary
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Drammen, Norway
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Trondheim, Norway
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Moscow, Russian Federation
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Smolensk, Russian Federation
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St. Petersburg, Russian Federation
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Yaroslavl, Russian Federation
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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:
- 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?
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: Double
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: Intranasal Fentanyl Spray (INFS)
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.
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Applied as 1 puff (= 1 dose) in one nostril, or applied as two puffs (= 2 doses, 1 in each nostril) with ten minutes apart.
Other Names:
Matching intranasal placebo spray
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Induction Phase: Pain Intensity Difference at 10 Minutes (PID10) After Treatment
Time Frame: During the efficacy phase (II), at each episode of breakthrough pain, at 0 and 10 minutes after first dose of study drug.
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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.
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During the efficacy phase (II), at each episode of breakthrough pain, at 0 and 10 minutes after first dose of study drug.
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Incidence of Improvement or Worsening in Nasal Mucosa Sign or Abnormality Score
Time Frame: Baseline and at 12 weeks
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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
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Baseline and at 12 weeks
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Efficacy Phase: Pain Intensity Difference (PID) at 5, 30, and 60 Minutes After First Dose of Study Drug
Time Frame: During the efficacy phase (II) each episode of breakthrough pain, at 0, 5, 30 and 60 minutes after study drug.
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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.
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During the efficacy phase (II) each episode of breakthrough pain, at 0, 5, 30 and 60 minutes after study drug.
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Efficacy Phase: Sum of Pain Intensity Differences (SPID0-60 and SPID0-30) Derived From PI Scores
Time Frame: During the efficacy phase (II) each episode of breakthrough pain, at 0, 5, 30 and 60 minutes after study drug
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The SPID30 and SPID60 represent the average improvement in pain intensity over the 30 minute interval and 60 minute interval, respectively. SPIDt was calculated as the area under the curve (AUC) for Pain Intensity Difference over the time interval 0 to t minutes, respectively, divided by the length of the time interval (t minutes). A positive value is a decrease (improvement) of the pain. Pain intensity was assessed at 0, 5, 30 and 60 minutes after study drug 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. |
During the efficacy phase (II) each episode of breakthrough pain, at 0, 5, 30 and 60 minutes after study drug
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Efficacy Phase: Proportion of BTP Episodes With a Positive Response Defined as a ≥ 1, 2 or 3 Point Reduction in Pain Intensity
Time Frame: During the efficacy phase (II) each episode of breakthrough pain, at 0, 5, 30 and 60 minutes after study drug
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Overall responder rate is defined as the proportion of breakthrough pain (BTP) episodes with a positive response to treatment.
The following definitions of a positive response were analyzed: • greater than or equal to 1 point reduction in pain intensity (PI) from time 0, • greater than or equal to 2 point reduction in PI from time 0, and • greater than or equal to 3 point reduction in PI from time 0. Pain intensity was assessed 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".
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During the efficacy phase (II) each episode of breakthrough pain, at 0, 5, 30 and 60 minutes after study drug
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Efficacy Phase: Proportion of BTP Episodes With a Positive Response Defined as a ≥ 33% or 50% Reduction in Pain Intensity
Time Frame: During the efficacy phase (II) each episode of breakthrough pain, at 0, 5, 30 and 60 minutes after study drug
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Overall responder rate is defined as the proportion of breakthrough pain (BTP) episodes with a positive response to treatment.
The following definitions of a positive response were analyzed: • Greater than 33% reduction in PI from time 0; • Greater than or equal to 50% reduction in PI from time 0. Pain intensity was assessed 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".
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During the efficacy phase (II) each episode of breakthrough pain, at 0, 5, 30 and 60 minutes after study drug
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Efficacy Phase: General Impression (GI) Score at 60 Minutes After First Dose
Time Frame: During the efficacy phase (II), at each episode of breakthrough pain, 60 minutes after first dose of study drug.
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Participants assessed their general impression (GI) of treatment efficacy for treated BTP episodes at 60 minutes after first dose of study drug. The validated, categorical 5-point Verbal Rating Scale (VRS) was used for this assessment and scored as follows:
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During the efficacy phase (II), at each episode of breakthrough pain, 60 minutes after first dose of study drug.
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Number of Participants With Adverse Events (AEs)
Time Frame: 12 weeks
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The severity (intensity of each AE was assessed as mild (transient symptoms, no interference with daily activities), moderate (marked symptoms, moderate interference with daily activities), or severe (considerable interference with daily activities) by the investigator.
Serious adverse events are defined as any untoward medical occurrence that at any dose results in death or is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity or is a congenital anomaly/birth defect.
The investigator assessed each AE as either related or not related to study treatment.
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12 weeks
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Collaborators and Investigators
Sponsor
Publications and helpful links
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- FT-1301-032-SP
- 2010-021096-85 (EudraCT Number)
- U1111-1133-6364 (Registry Identifier: WHO)
- 2011/776 (Registry Identifier: REK)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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