A randomized, double-blind, parallel-group, placebo-controlled study to assess the clinical benefit of SSR411298 as adjunctive treatment for persistent cancer pain

• Register: EUCTR
• Last refreshed on: 21 August 2017
• Main ID: EUCTR2011-002557-56-BE
• Date of registration: 19/07/2011
• Prospective Registration: Yes
• Primary sponsor: sanofi-aventis
• Public title: A randomized, double-blind, parallel-group, placebo-controlled study to assess the clinical benefit of SSR411298 as adjunctive treatment for persistent cancer pain
• Scientific title: A randomized, double-blind, parallel-group, placebo-controlled study to assess the clinical benefit of SSR411298 as adjunctive treatment for persistent cancer pain
• Date of first enrolment: 24/11/2011
• Target sample size: 180
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2011-002557-56
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Belgium, Czech Republic, France, Hungary, Italy, Netherlands, Russian Federation, United States

Contacts

• Name: Jean Van Rampelbergh
• Affiliation: sanofi-aventis Belgium

• Name: Jean Van Rampelbergh
• Affiliation: sanofi-aventis Belgium

Key inclusion & exclusion criteria

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

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 90
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 60

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 permitted)
• 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



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

cancer pain
MedDRA version: 14.1 Level: LLT Classification code 10069398 Term: Breakthrough cancer pain System Organ Class: 10018065 - General disorders and administration site conditions

Therapeutic area: Diseases [C] - Cancer [C04]

Intervention(s)

Product Code: SSR411298
Pharmaceutical Form: Tablet
INN or Proposed INN: SSR411298
CAS Number: 666860-59-9
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 200-
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Secondary Objective: • 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

Main Objective: • 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)

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

Timepoint(s) of evaluation of this end point: D-7, D-1 and D28

Secondary Outcome(s)

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

Timepoint(s) of evaluation of this end point: From D-7 to D35

Secondary ID(s)

ACT11705