| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Breakthrough Pain (BTP) in adult cancer patients |
|
| E.1.1.1 | Medical condition in easily understood language |
| Breakthrough Pain (BTP) in adult cancer patients |
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| E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 14.0 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10064556 |
| E.1.2 | Term | Breakthrough pain |
| E.1.2 | System Organ Class | 10018065 - General disorders and administration site conditions |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| • To demonstrate the efficacy of 400 μg Intranasal Fentanyl Spray (INFS) in cancer patients with breakthrough pain (BTP) |
|
| E.2.2 | Secondary objectives of the trial |
• To evaluate the nasal tolerability of INFS of all dose strengths between 50 μg and 400 μg in cancer patients with BTP
• To evaluate the safety profile of treatment with all dose strengths between 50 μg and 400 μg INFS in cancer patients with BTP |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
All inclusion criteria must be answered “yes” for a patient to participate in the trial.
1. Has the patient given informed consent according to local requirements before any trial-related activities? Trial-related activities are any procedure that would not have been performed during the routine management of the patient
2. Is the patient a cancer patient with BTP?
3. Is the patient aged ≥ 18 years?
4. Has the patient received either oral opioids or transdermal fentanyl for treatment of BGP within the last month prior to the screening visit?
5. Is the current dose of prescribed opioids (for BGP) equivalent to 60-1000 mg oral morphine/day1?
6. 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 NRS)?
7. 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)?
8. 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?
9. Is the patient able to use intranasal drugs?
10. Is the patient able to adhere to the trial related procedures, e.g. completing the patient diary, adhering to the titration scheme?
11. Is the life expectancy of the patient at least 3 months from the date of the screening visit?
For female patients of childbearing potential (Childbearing potential is considered until menopause has lasted more than 12 months. Surgically hysterectomised and surgically successfully sterilised females may be included on the same conditions as male patients).
12. Will the patient use and continue to use adequate contraception (contraceptive pill, implant or injection or intrauterine device) during the trial period?
13. Does the patient present a negative pregnancy test at the screening visit (including not currently pregnant or nursing)?
Additional inclusion criteria evaluated at visit 2 before proceeding to the titration phase (I): Inclusion criteria 14-16 must evaluated based on the patient’s diary recordings during the screening period.
Within the screening period:
14. Was the BGP controlled to a mild level (defined as ≤ 4 on an 11-point NRS) for at least five days?
15. Did the patient have at least three BTP episodes (per week) and no more than four BTP episodes per day?
16. Were the BTP episodes of such severe pain intensity that the patient took additional analgesia (apart from the usual BGP opioid)? |
|
| E.4 | Principal exclusion criteria |
All exclusion criteria must be answered “no” for a patient to participate in the trial.
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 ALT or AST levels > 3x ULN1 ,2
3.Does the patient have severe renal impairment? – defined as serum creatinine ≥ 3.0 mg/dl (265 micromol/L)2
4.Does the patient have any concomitant conditions resulting in a runny nose (e.g. rhinitis) or any condition that would result in more rapid removal than normal of the non-absorbed drug from the nasal mucosa?
5.Has the patient ever had facial radiotherapy or is the patient scheduled to facial radiotherapy?
6.Has the patient had nasal surgery within the last 30 days prior to the screening visit?
7.Has the patient been treated with any MAO inhibitors within the last 14 days prior to the screening visit?
8.Does the patient have severe impaired respiratory function, which may increase the risk of clinically relevant respiratory depression by BTP fentanyl treatment?
9.Does the patient use any kind of drugs for intranasal administration?
10.Does the patient have a nasopharyngeal probe?
11.Is the patient known to be hypersensitive to fentanyl or to other opioids or any of their excipients?
12.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?
13.Is the patient currently participating or within this trial period intending to participate in another interventional trial with an IMP or device? Current or planned participation in non-interventional study is allowed, unless contradictive with any of the above criteria
14.Does the patient have recurrent episodes of epistaxis?
15.Was the patient included in any of the Nycomed clinical trials with the trial ID: FT-016-IM, FT-017-IM, FT-018-IM or FT-019-IM?
|
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| • Pain intensity difference at 10 minutes (PID10) after treatment with 400µg INFS in the Efficacy Phase (II) |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| The primary endpoint will be analysed based on data collected in the efficacy phase (II). |
|
| E.5.2 | Secondary end point(s) |
•Nasal tolerability of INFS after 12 weeks treatment
•Pain Intensity Difference (PID) at 5, 30, and 60 minutes after first administration of IMP in the Efficacy Phase (II)
• Sum of Pain Intensity Differences (SPID0-60 and SPID0-30) derived from PI scores in the Efficacy Phase (II)
• Responder rates of pain intensity (PI) at all time points in the Efficacy Phase (II)
• General Impression (GI) at 60 minutes after first administration of IMP in all phases (I-III)
• Safety; AEs in all phases (I-III)
|
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| secondary endpoints will be evaluated on data collected in all treatment phases within the trial and the nasal tolerability assessment at baseline (V1 or V2) and EOT. |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | Yes |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | Yes |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | No |
| E.8.1.6 | Cross over | Yes |
| E.8.1.7 | Other | Yes |
| E.8.1.7.1 | Other trial design description |
| The titration phase (I) and tolerability phase (III) is open– labelled |
|
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 2 |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 7 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 12 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
| Hungary |
| Norway |
| Russian Federation |
|
| E.8.7 | Trial has a data monitoring committee | No |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
| |
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 1 |
| E.8.9.1 | In the Member State concerned months | 7 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 1 |
| E.8.9.2 | In all countries concerned by the trial months | 7 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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