| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Treatment of Breakthrough Cancer Pain (BTCP) in Subjects Taking Regular Opioid Therapy |
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| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 8.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10058019 |
| E.1.2 | Term | Cancer pain |
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| 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 superior efficacy of Nasalfent over immediate release morphine sulphate (IRMS) in the treatment of BTCP in opioid tolerant subjects who are receiving regular opioid therapy. |
|
| E.2.2 | Secondary objectives of the trial |
| To demonstrate the safety, tolerability, and acceptability of Nasalfent in the treatment of BTCP in opioid tolerant subjects who are receiving regular opioid therapy. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
Subjects will be included if they meet all the following criteria:
1. Subjects who are able and willing to provide written informed consent.
2. Male or female subjects, 18 years of age and older.
3. If female, and of childbearing potential (not surgically sterile or less than 1 year after the onset of amenorrhea due to menopause), must (a) have a negative urinary pregnancy test, (b) not be lactating and (c) agree to practice a reliable form of contraception or abstinence during the study.
4. Subjects who have histologically documented diagnosis of a malignant solid tumour or a haematological malignancy causing cancer-related pain.
5. Subjects who are taking at least 60 mg oral morphine or equivalent opioid for at least 1 week for cancer-related pain as regular, 24-hour medication for their underlying persistent cancer pain.
6. Subjects who are experiencing, on average, but not necessarily every day, 1 to 4 episodes of BTCP per day that are adequatelly controlled with a stable dose of standard rescue medication, typically a fast acting opioid, of which the subject should have an adequate supply throughout the study. Breakthrough pain is defined as a transitory flare of moderate to severe pain (on a 4-point scale from 0 to 3 [none, mild, moderate, severe] as defined by the Breakthrough Pain Questionnaire in Section 15.2 of the study protocol) that occurs on a background of persistent pain controlled to moderate intensity or less by the opioid regimen. If the subject has more than 1 type of breakthrough pain, or has breakthrough pain in more than 1 location, only 1 of the pains will be identified as a "target" breakthrough pain.
7. Subjects who, in the opinion of the investigator, are willing and able (personally or with the help of a caregiver) to
a. Evaluate and record pain intensity and pain relief.
b. Assess medication performance at specific times after dosing.
c. Record AEs
d. Record each instance of the use of study drug and standard rescue medication in a subject diary for the duration of the study
8. Subjects with an Eastern Cooporeative Oncology Group (ECOG) score of less than or equal to 2 and a life expectancy which, in the opinion of the investigator, will allow them to participate for the duration of the study.
|
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| E.4 | Principal exclusion criteria |
Subjects may be excluded from participating in the study if they meet any of the following criteria:
1. Subjects with an opioid or fentanyl intolerance.
2. Subjects with uncontrolled or rapidly escalating pain.
3. Subjects using intrathecal or epidural opioids.
4. Subjects whose condition is unstable or rapidly deteriorating so that the effective dose found during the Open, Dose-Titration Phase is unlikely to remain so for the duration of the study.
5. Subjects with sleep apnoea or active brain metastases with increased intracranial pressures.
6. Subjects with any respiratory or cardiac condition that, in the opinion of the investigator, may be worsened by opioids.
7. Subjects with any other medical condition that, in the judgment of the investigator, would confound the objectives of the study.
8. Subjects with a recent history of alcohol or substance abuse that would compromise data collection.
9. Subjects with a history of or current neurological or psychiatric impairment, or cognitive dysfunction that, in the opinion of the investigator, would compromise data collection.
10. Subjects with clinically significant renal and hepatic dysfunction test results at Screening outside the following limits:
a. Serum creatinine must be ≤2.0 mg/dL, or creatinine clearance calculated by Cockcroft-Gault formula must be ≥50 ml/min.
b. Serum total bilirubin must be ≤2.0 mg/dL.
c. Serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase must be ≤3 times the upper limit of normal (≤5 times the upper limit of normal if due to liver metastases).
11. Subjects taking any medication likely to affect the physiology of the nasal mucosa.
12. Any abnormal nasal physiology and/or pathology which, in the opinion of the investigator, would not allow the objectives of the study to be accomplished.
13. Subjects with known intolerance to nasal sprays and/or pharmaceutical materials found in the investigational products.
14. Subjects taking monoamine oxidase inhibitors (MAOIs) within 14 days of the screening visit or with an anticipated need for MAOIs during the study.
15. Subjects taking analgesics, if the dose has changed during the 21 days prior to the screening visit (this “no change” criterion does not apply to medication for their underlying, persistent cancer pain or for BTCP).
16. Subjects taking antiepileptic medication (such as gabapentin, topiramate, lamotrigine) for neuropathic pain, if the dose has changed during the 14 days prior to the screening visit.
17. Subjects with uncontrolled infection.
18. Subjects who have received treatment with an investigational drug within 4 weeks of the screening visit.
19. Subjects who have had treatment with any form of radiotherapy within 30 days prior to study entry or who have had any therapy that could alter pain or response to pain medication.
20. Subjects planning to undergo chemotherapy (unless it has been demonstrated in that subject to have no effect on the breakthrough cancer pain), radiotherapy, or surgery during the treatment period.
21. Subjects whose primary source of breakthrough pain is not cancer related.
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|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Pain Intensity Difference 15 minutes after dosing (PID15min) defined as the recorded difference between pain intensity and baseline. Pain intensity will be measured on an 11-point categorical scale where 0=no pain and 10=worst possible pain. |
|
| 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 | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| 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 | Information not present in EudraCT |
| E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
| E.7.1.3 | Other | Information not present in EudraCT |
| 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 | Information not present in EudraCT |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Yes |
| E.8.2.2 | Placebo | Information not present in EudraCT |
| E.8.2.3 | Other | Information not present in EudraCT |
| 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 | 16 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 52 |
| 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 |
|
| 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 | |
| E.8.9.1 | In the Member State concerned months | 12 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial months | 12 |
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