A Study To Evaluate Pregabalin In The Treatment Of Moderate To Severe Chronic Bone Pain Related To Metastatic Cancer

Study Overview
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Brief Summary
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The purpose of this study is to assess the analgesic efficacy of flexibly-dosed pregabalin in the adjunctive treatment of subjects with cancer-induced bone pain.

Detailed Description
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Pfizer decided to discontinue additional enrollment into the study effective Sept 5 2010 after assessing the feasibility of completing this study in a realistic timeframe.The study was not stopped for any safety concerns.

Official Title
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A Randomized Placebo-Controlled Trial Of The Efficacy And Tolerability Of Flexibly Dosed Pregabalin In The Treatment Of Cancer-Induced Bone Pain

Conditions
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Bone Neoplasms, Pain, Intractable, Cancer

Intervention / Treatment
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* Drug: Pregabalin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient must have a malignant, solid tumor that has been diagnosed as having metastasized to bone, and must have moderate to severe pain secondary to the bone metastasis at an identifiable reference site. Exclusion Criteria: The patient who has undergone diagnostic or therapeutic invasive interventions (angiography, biopsy, surgery) less than 15 days prior to study start that would impact their assessment of pain at the reference pain site or area, in the opinion of the investigator.

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: 1<br>flexible dosing | Drug: Pregabalin<br>* Capsule, Flexible-dosing, Double-blind. Treatment duration is 28 days at 100-600 mg/day administered BID+ taper (6 days).<br>|
| Placebo Comparator: 2<br> | Drug: Placebo<br>* Placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration Adjusted Average Change (DAAC) From Baseline in Daily Worst Pain, Fixed Dosing Date to Day 28 | DAAC from baseline based on Numeric Rating Scale (NRS) score for Worst Pain at Reference site from the last day dose adjustment was needed (fixed dosing date) to day 28. DAAC defined as area under the curve (AUC) of change in worst pain divided by pain measurement duration. Pain rated on an 11 point scale ranged from 0 (no pain) to 10 (worst possible pain). Change was week x minus baseline. | Baseline, Fixed Dosing Date to Day 28 or Early Termination (ET) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| DAAC From Baseline in Daily Worst Pain, Days 1 Through 28 | DAAC from baseline in the daily worst pain based on the NRS Worst Pain at Reference Site score collected from participant's daily diary. Pain rated on an 11 point scale ranged from 0 (no pain) to 10 (worst possible pain). DAAC defined as AUC of daily worst pain score divided by pain measurement duration. Change was week x minus baseline. | Baseline, Days 1 through 28 or ET | 
| DAAC From Baseline in Daily Worst Pain, Day 1 to End of Dose Adjustment | DAAC from baseline in the daily worst pain based on the NRS Worst Pain at Reference Site score collected from participant's daily diary. Pain rated on an 11 point scale ranged from 0 (no pain) to 10 (worst possible pain). DAAC defined as AUC of daily worst pain score divided by pain measurement duration. Change was week x minus baseline. | Baseline, Day 1 to End of Dose Adjustment or ET | 
| DAAC From Baseline in Daily Worst Pain 14 Days After Fixed Dosing Date Up to Day 28 | DAAC from baseline in the daily worst pain based on the NRS Worst Pain at Reference Site score collected from participant's daily diary 14 days after dosing stabilized (fixed dosing date) up to Day 28. Pain rated on an 11 point scale ranged from 0 (no pain) to 10 (worst possible pain). DAAC defined as AUC of daily worst pain score divided by pain measurement duration. Change was week x minus baseline. | Baseline, 14 Days After Fixed Dosing Date up to Day 28 or ET | 
| Change From Baseline in Modified Brief Pain Inventory (mBPI-sf) Pain Severity Index Score at Week 4 | m-BPI-sf: participant rated 11-point Likert rating scale ranging from 0 (no pain) to 10 (worst pain possible). Pain severity index was the mean of item scores 1, 2, 3, and 4 (worst, least, average and current pain scores). Change was scores at observation minus scores at baseline. | Baseline, Week 4 or ET | 
| Change From Baseline in mBPI-sf Interference Index Score at Week 4 | m-BPI-sf: participant-rated 11 point Likert rating scale ranging from 0 (does not interfere) to 10 (completely intereres) with functional activities (general activity, mood, walking ability, relations with other people, sleep, normal work, and enjoyment of life) in past 24 hours. Change was score at each observation minus baseline score. | Baseline, Week 4 or ET | 
| Change From Baseline in Average Pain Scores at Weeks 1, 2, 3 and 4 | Change from baseline in daily average pain score NRS 0 (no pain) to 10 (pain as bad as you can imagine) for pain intensity over past 24 hours recorded every evening before bedtime. Change was week x average minus baseline average. | Baseline, Weeks 1, 2, 3 and 4 or ET | 
| Change From Baseline in Total Daily Dose of Opioids Day 0 Through Day 28 | Change from baseline in total daily dose of opioids immediate release (IR), sustained release (SR) formulations separately and combined. | Baseline, Day 0 through Day 28 or ET | 
| Change From Pre-Baseline in Total Daily Dose of Morphine Equivalents Day 0 Through Day 28 | IR and SR formulations separately and combined. Change was day x minus baseline. | Baseline, Day 0 through Day 28 or ET | 
| Change From Baseline in Hospital Anxiety and Depression Scale (HADS) at Week 4 | HADS: participant rated questionnaire with 2 subscales. HADS-Anxiety assessed generalized anxiety (anxious mood/ restlessness/ anxious thoughts/panic attacks); HADS-Depression assessed lost interest/diminished pleasure response (lowering of hedonic tone). Each subscale has 7 items which ranged from 0 (no presence of anxiety or depression) to 3 (severe feeling anxiety/depression). Total 0-21 for each subscale; higher score indicates greater severity of anxiety and depression symptoms. Change was week x minus baseline. | Baseline, Week 4 or ET | 
| Patient Global Impression of Change (PGIC) | PGIC: participant rated instrument to measure participant's change in overall status on a 7-point scale; range from 1 (very much improved) to 7 (very much worse). | Weeks 2 and 4 or ET | 
| Change From Baseline in Opioid-Related Symptoms Distress Scale (OR-SDS) at Day 14 and Day 28 | OR-SDS included OR-SDS individual items by dimension of frequency (rarely to almost constantly), severity (slight to very severe), and degree of bother (not at all to very much), number of episodes of retching/vomiting, OR-SDS dimension composite and overall composite scores. Change was scores at occurance minus score at baseline. | Baseline, Day 14, Day 28 or ET | 
| Change From Baseline in Eastern Cooperative Oncology Group Performance (ECOG) Status Scale at Day 28 | ECOG - assessed disease progression and how disease affected the daily living abilities of the participant and determined appropriate treatment and prognosis. Graded 0 (fully active able to carry on all pre-disease performance without restrictions) to 5 (dead). Change was day 28 minus baseline. | Baseline, Day 28 or ET |