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 |
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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 | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10069398 |
E.1.2 | Term | Breakthrough cancer pain |
E.1.2 | System Organ Class | 10018065 - General disorders and administration site conditions |
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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 evaluate the efficacy of SSR411298 200 mg daily compared to placebo as adjunctive treatment for persistent cancer pain, as measured by the change from baseline (baseline = average pain intensity between Visit 1 (Day 7) and Visit 2 (Day 1) to end of treatment (end of treatment = average pain intensity during Week 4) in the Numeric Rating Scale (NRS) |
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E.2.2 | Secondary objectives of the trial |
• To evaluate the efficacy of SSR411298 200 mg daily compared to placebo as adjunctive treatment for persistent cancer pain, as measured by a variety of secondary efficacy endpoints
• To evaluate the tolerability and safety of SSR411298 as adjunctive treatment for persistent cancer pain
• To characterize patient disease, in terms of cancer, cancer treatment, cancer pain and cancer pain treatment
• To evaluate the pharmacokinetic (PK) exposure of SSR411298 as adjunctive treatment for persistent cancer pain
• To assess endocannabinoid plasma concentrations
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Patients with moderate or severe, persistent cancer pain who are receiving World Health Organization (WHO) Step 2 or 3 cancer pain treatment (2) as Background Therapy (BT)
- Pain generator must be primarily due to underlying cancer or cancer treatment
- Pain generator must be classified as either primarily nociceptive or primarily neuropathic
- Pain severity must be moderate or severe, as defined as an NRS score of ≥4 during the SP [note: average NRS score = average pain intensity (not highest or lowest pain intensity) for each day of the SP, averaged over the SP]
- World Health Organization Step 2 or 3 cancer pain treatment as BT consists of opioids ± non-opioids ± adjuvants ± rescue therapy for breakthrough pain
+ For patients with primarily nociceptive cancer pain (NCCP), examples of permitted adjuvant pain treatments are corticosteroids, bisphosphonates, etc, with planned administration to be stable during the study
+ For patients with primarily neuropathic cancer pain (NPCP), examples of permitted adjuvant pain treatments are antidepressants or antiepileptics, etc, with planned administration to be stable during the study
- Dose adjustment of BT is permitted during the study but any change other than dose adjustment of BT is prohibited
• Signed written informed consent
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E.4 | Principal exclusion criteria |
• Instability of pain between Visit 1 (Day 7) and Visit 2 (Day 1)
• “Satisfied” or “extremely satisfied” response on the 5-point Likert patient satisfaction of pain relief scale at Visit 1 (Day -7) or Visit 2 (Day -1)
• Prohibited adjuvant pain treatments in the week prior to Visit 1 (Day 7) or planned administration during the study
- For patients with primarily NCCP, the prohibited adjuvant pain treatments are antidepressants or antiepileptics
- For patients with primarily NPCP, antidepressants or antiepileptics are permitted but the simultaneous use of both an antidepressant and antiepileptic is prohibited
• Use of tetradydrocannabinol (THC) compounds for the treatment of pain
• Chemotherapy within 4 weeks of Visit 1 (Day -7) or chemotherapy planned during the study (a stable regimen of hormonal therapy is pemitted)
• Radiotherapy within 4 weeks of Visit 1 (Day 7) or radiotherapy planned during the study (hemostatic palliative radiotherapy is permitted)
• Cancer-related surgery within 4 weeks of Visit 1 (Day 7) or cancer-related surgery planned during the study
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E.5 End points |
E.5.1 | Primary end point(s) |
• Change from baseline (baseline = average pain intensity between Visit 1 (Day 7) and Visit 2 (Day 1) to end of treatment (end of treatment = average pain intensity during Week 4) in the NRS
- NRS is a daily assessment performed at the same time each day at the end of the day
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
Efficacy
• Brief Pain Inventory Short-Form (BPISF) (3,4)
• Responder rate: reduction of ≥30% of pain intensity; reduction of ≥50% of pain intensity; pain composite (pain intensity or BT utilization)
• Breakthrough pain frequency
• Background Therapy utilization: morphine-equivalent dose per day; adjuvant agent utilization; number of rescue medication doses per day
• Mood disorders: Hospital Anxiety and Depression Scale (HADS) (5)
• Nausea visual analog scale (VAS)
• Constipation: Bowel Function Index (BFI) score (6); amount of laxative medication use recorded at each assessment visit
• Health care utilization: unscheduled hospitalizations, emergency department visits, healthcare provider office visits and sick leave days
• Patient satisfaction of pain relief: 5point Likert scale
• Quality of life: European Organization for Research and Treatment of Cancer Quality of Life QuestionnaireC30 (EORTC QLQC30) version 3 (7)
Safety
• Adverse events (AEs) and other clinical and para-clinical parameters (eg, vital signs, physical examination, clinical laboratories, electrocardiography)
• Suicidality assessment (Columbia Suicide Severity Rating Scale [CSSRS]) (8)
• Drug Abuse and Liability Assessment (DALA) (9)
• Cognitive function tests: Digit-Symbol Substitution Test (DSST) (10), Rey Auditory Verbal Learning Test (RAVLT) (11), and 2Digit Cancellation Test (2-DCT) (12)
• Pill dysphagia assessment
Other
• SSR411298 plasma concentrations
• Endocannabinoid plasma concentrations
• SAR250960 urine concentration
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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 | No |
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 | Yes |
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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
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 | 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 | 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 | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 42 |
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 | No |
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 |
Belgium |
Czech Republic |
France |
Germany |
Hungary |
Italy |
Netherlands |
Poland |
Portugal |
Russian Federation |
United States |
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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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LPLV |
Poslední návštěva posledního subjektu hodnocení |
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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 | |
E.8.9.1 | In the Member State concerned days | 22 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial days | 22 |