| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
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| E.1.1.1 | Medical condition in easily understood language |
| Patients with chronic cancer pain |
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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 | 13.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10007050 |
| E.1.2 | Term | Cancer |
| E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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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 that once daily administration of Oxycodone HCl XL tablets is at least as effective as twice daily administration of Oxygesic® tablets at the same daily dosage. |
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| E.2.2 | Secondary objectives of the trial |
In case of non-inferiority, to demonstrate that once daily administration of Oxycodone HCl XL tablets is more effective (superior) as twice daily administration of Oxygesic® tablets at the same daily dosage.
To assess the safety and tolerability of once daily administration of Oxycodone HCl XL tablets in comparison with twice daily administration of Oxygesic® tablets.
To investigate the oxycodone plasma concentrations during treatment with once daily administration of Oxycodone HCl XL tablets in comparison with twice daily administration of Oxygesic® tablets (in a subset of maximum 20 patients).
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| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1.Caucasian male and female patients ≥18 years of age with chronic cancer pain.
2.Patients with predominantly non-neuropathic pain
3.Patients requiring continuous oral opioid therapy with at least 40 mg oxycodone per day (or equivalent).
4.Adequate analgesia (mean "current" pain intensity per day ≤40 mm on VAS) prior to randomisation for at least three consecutive days.
5.Stable analgesic requirements prior to randomisation for at least three days (stable maintenance dose of oxycodone; requirement of at least 40 mg oxycodone per day; ≤2 doses of rescue medication per day), tolerable AEs.
6.ECOG (Eastern Cooperative Oncology Group) performance status <3.
7.Life expectancy of at least 3 months
8.Female patients of childbearing potential agree to undergo pregnancy tests.
9.Willingness to undergo a pre-study physical examination and pre- and post-study laboratory investigations.
10.Ability to comprehend and willingness to sign informed consent. |
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| E.4 | Principal exclusion criteria |
1.Hypersensitivity to oxycodone or any of the excipients of the study drugs.
2.Patients requiring more than 120 mg oxycodone per day (or equivalent).
3.Surgery within 1 month prior to study start and/or anticipated or scheduled surgical intervention during the study.
4.Intravenous chemotherapy and/or radiotherapy for pain alleviation and/or neural blockade within 2 weeks prior to study start and/or anticipated and/or scheduled during the course of the study.
5.Known or suspected clinically significant respiratory depression, hypoxia, hypercapnia, or decrease in respiratory reserve.
6.Known or suspected severe obstructive pulmonary disease, acute or severe bronchial asthma, or cor pulmonale.
7.Known or suspected significant hepatic impairment (hepatic transaminases >3 times the upper limit of normal).
8.Known or suspected severe renal impairment (CRCL <30 ml/min) or patients with renal failure who are on any form of dialysis.
9.Known or suspected significant circulatory disturbance, hypotension, or circulatory shock.
10.Known or suspected clinically relevant endocrine disorder, such as myxoedema, not adequately treated hypothyroidism or adrenocortical insufficiency (e.g. Addison's disease)
11.Known or suspected paralytic ileus, significant impairment of bowel motility severe enough to potentially result in ileus.
12.Known or suspected acute or chronic pancreatitis or biliary tract disease.
13.Any gastro-intestinal pathology or surgery or intractable vomiting likely to significantly influence drug absorption.
14.Inability to swallow the study drugs whole (e.g. due to dysphagia).
15.Known or suspected significant prostatic hypertrophy or urethral stricture severe enough to potentially result in urinary retention.
16.Known or suspected CNS depression (signs/symptoms: decreased vital signs, impaired thinking and perception, slurred speech, slowed reflexes, fatigue, decreased consciousness), coma, or convulsive disorder.
17.Known or suspected elevation of intracranial pressure.
18.Known or suspected acute alcoholism, delirium tremens, or toxic psychosis.
19.History of drug addiction or drug seeking behaviour.
20.Concomitant treatment with MAO inhibitors.
21.Pregnancy or breast-feeding. Women of childbearing potential unable or unwilling to practice adequate contraceptive measures. Reliable methods for women are orally administered hormonal contraceptives, surgical intervention (e.g. tubal ligation), intrauterine device (IUD) and sexual abstinence.
22.Any other condition of the patient that in the opinion of the investigator may compromise evaluation of the study treatment or may jeopardize patient’s compliance or adherence to protocol requirements.
23.Previous enrolment in this study or participation in any other drug investigational trial within the past 30 days (or five half-lives whichever is longer) prior to enrolment.
24.Persons suspected to be at risk of suicide.
25.Persons who are not suitable for inclusion in the study in the opinion of the investigator.
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| E.5 End points |
| E.5.1 | Primary end point(s) |
| The primary efficacy end point is the overall “current” pain intensity (PI) on 0 100 mm VAS (mean “current” PI of the last 5 days of each treatment period). |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| Pain intensity (PI) will be assessed five times daily, i.e. at 08:00h, 11:00h, 14:00h, 17:00h, and 20:00h (allowed deviation +/- 20min) on a 0 – 100 mm VAS (“current” pain). PI assessment at 08:00h and 20:00h will also comprise ratings of PI over the past 12 hours (“recalled” pain during day- and night-time). From the PI scores the mean “current” PI over all time points of the last 5 treatment days of period 1 and period 2 (=overall mean “current” PI) will be calculated for each patient as the primary efficacy end point |
|
| E.5.2 | Secondary end point(s) |
Secondary efficacy end points:
- mean “current” Pain intensity (PI) per day
- mean “current” PI per time point
- mean “recalled” PI over the past 12 hours at 08:00h
- mean “recalled” PI oder the past 12 hours at 20:00h
- overall effectiveness on 4-point CAT by patient and investigator (assessed at the end of each treatment period)
- daily dose of rescue medication for each of the last 5 days of period 1 and 2
- mean daily dose of rescue medication over the last 5 treatment days of period 1 and 2
- total amount of rescue medication over the last 5 treatment days of period 1 and 2
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|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
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| 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 | Yes |
| 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 | 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 | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Yes |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| 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 | 4 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 24 |
| 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 |
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| E.8.7 | Trial has a data monitoring committee | Yes |
| 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
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| Definitions are provided in the protocol section 9.3.3 |
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| 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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