A Clinical Trial With Intranasal Fentanyl in Cancer Patients With Breakthrough Pain (NOSE-400)

Takeda

Status and phase: Completed; Phase 3

Conditions: Break Through Pain; Cancer

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

Study type: Interventional

Funder types: Industry

Identifiers

NCT01429051

U1111-1133-6364 (Registry Identifier)

FT-1301-032-SP

2011/776 (Registry Identifier)

2010-021096-85 (EudraCT Number)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 46 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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?

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: Double Blind

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46 participants in 1 patient group

Intranasal Fentanyl Spray (INFS)

Experimental group

Description:

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.

Treatment:

Drug: Placebo

Drug: Intranasal Fentanyl Spray (INFS)