E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Cancer pain not responding to oral opioids in palliative cancer patient, where switching to the parenteral route is indicated. |
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E.1.1.1 | Medical condition in easily understood language |
Pain from cancer disease in patients with incurable cancer. The pain has not responded to treatment with opioid tablets. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Symptoms and general pathology [C23] |
MedDRA Classification |
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 |
The overall objective is to establish whether either the intravenous or subcutaneous route of administration has clinically significant advantages when parenteral administration or morphine is started with a combination of continuous infusion and bolus doses in palliative cancer patients.
Primary research question: • Is there a difference between s.c. and i.v. administration of morphine in how quickly pain control is achieved after initiation of a continuous infusion?
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E.2.2 | Secondary objectives of the trial |
Secondary research questions: • Is there a clinically significant difference between s.c. and i.v. administration of morphine in time from administration of bolus dose to clinically significant pain relief? • How large is the difference in the key pharmacokinetic parameters Tmax, Cmax, and AUC0-60 after s.c. and i.v. administration of morphine bolus doses during morphine infusion in palliative cancer patients?
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
All of the following conditions must apply to the prospective patient at screening prior to receiving study agent: • Unsatisfactory pain control despite titration of oral or transdermal opioids • Planned discharge to home or nursing home • The physician considers the appropriate starting dose to be either morphine 5 mg/ml with infusion rate 0.2 to 0.8 ml/h or morphine 10 mg/ml with infusion rate 0.2 to 0.8 ml/h. • Signed informed consent from the patient • Patient available for admission to Department of Palliative Medicine in time to start infusion between 11 am and 3 pm |
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E.4 | Principal exclusion criteria |
• A clear indication for either intravenous or subcutaneous administration (by consensus of two senior consultants in palliative medicine) • Patient unable to report patient reported outcomes needed in the study due to language barriers, cognitive impairment, or delirium. • Impossible to establish venous access • Allergy or previous serious adverse effects from morphine • Opioid treatments other than oral/parenteral morphine, oral/parenteral oxycodone and transdermal/transmucosal fentanyl. • Contraindications to use of morphine. - Severe renal failure (estimated glomerular filtration rate < 30 based on kreatinin) • Strong indication for start of morphine infusion outside of the time interval of 11 am to 3 pm • Estimated survival time <2 weeks based on clinical judgement (by consensus of two senior consultants in palliative medicine) • Severe cachecia or peripheral edemas which are relative contraindications to the subcutaneous route of administration (clinical judgement by the responsible physician)
Patients with Hb <9 g/dL (7.0 – 9.9 g/dL is considered moderate anemia) will not be included in the pharmacokinetic analyses because it can not be ruled out that the loss of 100-150 ml blood might be harmful in some of these patients.
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E.5 End points |
E.5.1 | Primary end point(s) |
• Time from initiation of infusion until final infusion rate, defined as the time from start of infusion until last change in dosing during double blind double dummy treatment. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
The 48-hours intervention period. |
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E.5.2 | Secondary end point(s) |
• Time from bolus administration to clinically significant pain relief (change of 2 on 0-10 NRS) • Comparision of Tmax, Cmax, and size of AUC0-60 after bolus doses during morphine infusion. • Number of bolus doses first 24 and 48 hours. • The share of patients not reaching acceptable pain relief within 48 hours (assessed by whether physician and patient concludes that further adjustments in pain medication is required after 48 hours). |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
All secondary endpoints will be evaluated within the 48-hour intervention or at the end of the intervention period.
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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 | No |
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) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
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 | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
Compares two different routes of administration for IMP. Placebo for double dummy blinding. |
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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
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
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
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Last visit of last subject |
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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 | 2 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |