A Clinical Trial to Assess the Clinical Benefit of SSR411298 as Adjunctive Treatment for Persistent Cancer Pain

Study Overview
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Brief Summary
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The primary objective of this study is to evaluate the efficacy of SSR411298 200 mg daily compared to placebo as adjunctive treatment for persistent cancer pain based on Numeric Rating Scale (NRS). Secondary Objectives are: To evaluate the effect of SSR411298 200 mg daily on pain, breakthrough pain frequency, background therapy utilization, mood, patient satisfaction of pain relief, nausea, constipation, healthcare utilization and quality of life; 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.

Detailed Description
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The total study duration for a participant is 6 weeks (1-week screening, 4-week treatment and 1-week post-treatment follow-up). Participants continue to receive WHO Step 2 or 3 cancer pain treatment as background therapy.

Official Title
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A Randomized, Double-blind, Parallel-group, Placebo-controlled Study to Assess the Clinical Benefit of SSR411298 as Adjunctive Treatment for Persistent Cancer Pain

Conditions
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Pain, Breakthrough Cancer Pain

Intervention / Treatment
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* Drug: SSR411298
* Drug: Placebo (for SSR411298)


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Patient with moderate or severe, persistent cancer pain who is receiving the World Health Organization (WHO) Step 2 or 3 cancer pain treatment: Pain generator (source of pain) must be primarily due to underlying cancer or cancer treatment; Pain generator (source of pain) must be classified as either primarily nociceptive or primarily neuropathic; Pain severity must be moderate or severe with an average NRS score ≥4 during the screening week. Exclusion criteria: Instability of pain during the screening week; Use of prohibited adjuvant pain treatment in the week prior to study entry or plan to use these medications during the study; Current use of medication containing tetrahydrocannabinol (THC); Chemotherapy within 4 weeks before study entry or chemotherapy planned during the study (a stable regiment of hormonal therapy is permitted); Radiotherapy within 4 weeks before study entry or radiotherapy planned during the study (hemostatic palliative radiotherapy is permitted); Cancer related surgery within 4 weeks before study entry or cancer-related surgery planned during the study. The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SSR411298 200 mg<br>SSR411298 200 mg, one tablet once daily for 4 weeks | Drug: SSR411298<br>* Form: tablet Route: oral administration with food<br>|
| Placebo Comparator: Placebo<br>Placebo (for SSR411298), one tablet once daily for 4 weeks | Drug: Placebo (for SSR411298)<br>* Form: tablet Route: oral administration with food<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in average Numeric Rating Scale (NRS) pain intensity score | The NRS is an 11-category descriptive anchor scale that is one of the most frequently employed and accepted scales for pain evaluation. Score ranges from 0 [no pain] to 10 [worst possible pain]. Average NRS score is defined as the average of pain intensity scores measured daily by NRS during a week. | 5 weeks (from D-7 (seven days before randomization) up to D28) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in Brief Pain Inventory Short-Form (BPI-SF) scores | The BPI-SF is a 9-point questionnaire that measures the intensity of pain, interference of pain, pain relief, pain quality, and patient perception of the cause of pain. | 5 weeks (from D-7 (seven days before randomization) up to D28) | 
| Responder rates | Responders are defined as: reduction from baseline ≥30% of pain intensity as measured by NRS; reduction from baseline ≥50% of pain intensity as measured by NRS; composite of decrease in pain intensity or decrease in background therapy utilization. | 5 weeks (from D-7 (seven days before randomization) up to D28) | 
| Breakthrough pain frequency |  | 5 weeks (from D-7 (seven days before randomization) up to D28) | 
| Opioid consumption expressed as the morphine-equivalent dose per day |  | 5 weeks (from D-7 (seven days before randomization) up to D28) | 
| Rescue medication consumption expressed as the number of rescue medication doses per day |  | 5 weeks (from D-7 (seven days before randomization) up to D28) | 
| Mood disorders as measured by the Hospital, Anxiety & Depression Scale (HADS) | The HADS is a self-reported scale that contains 14 items rated on 4-point Likert scales. Two subscales assess depression (7 items) and anxiety (7 items). Each 7-item subscale yields a score of 0 to 21 that is interpreted with the following cut points: 0-7, normal; 8-10, mild mood disturbance; 11-14, moderate mood disturbance; and 12-21, severe mood disturbance. | 5 weeks (from D-7 (seven days before randomization) up to D28) | 
| Change in nausea as measured by Visual Analog Scale (VAS) | The nausea VAS is a patient-centered instrument to measure nausea on a continuous 100-mm scale. | 5 weeks (from D-7 (seven days before randomization) up to D28) | 
| Constipation as measured by the Bowel Function Index (BFI) | The BFI is a 3-item questionnaire to measure constipation from the patient's perspective. The time frame for the questions is during the last 7 days. The answer for each of the 3 items is rated on a scale from 0 (easy or no difficulty) to 100 (severe difficulty). | 5 weeks (from D-7 (seven days before randomization) up to D28) | 
| Healthcare utilization | Healthcare utilization is measured as the number unscheduled hospitalizations, emergency department visits, healthcare provider office visits, and sick leave days. | 5 weeks (from D-7 (seven days before randomization) up to D28) | 
| Patient satisfaction of pain relief | Patient satisfaction of pain relief is a 5-point Likert scale that measures patient satisfaction with treatment. The five categorical responses are: extremely unsatisfied, unsatisfied, neutral, satisfied, extremely satisfied. | 5 weeks (from D-7 (seven days before randomization) up to D28) | 
| Quality of life as measured by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC QLQ-C30) version 3 | The EORTC QLQ-C30 questionnaire contains a total of 30 items, of which 28 items are rated on 4-point Likert-type scale and 2 items are rated on 7-point Likert scale. These include 5 functional scales, 3 symptom scales, a global health status/QoL scale, and 6 single items. A high scale score represents a higher response level. Thus a high score for a functional scale represents a high/healthy level of functioning, a high score for the global health status/QoL represents a high QoL, but a high score for a symptom scale/item represents a high level of symptomatology/problems. | 5 weeks (from D-7 (seven days before randomization) up to D28) | 
| Overview of adverse events (AE) |  | up to 5 weeks (from 1st study drug intake up to 7 days after last study drug intake) | 
| SSR411298 plasma concentration | Plasma concentrations of SSR411298 will be determined by a validated liquid chromatography method coupled with tandem mass spectrometry (LC-MS/MS) with a lower limit of quantification (LLOQ) of 10 ng/mL. | predose and 3-5 hours after study drug intake on Day D14 and Day 28 |