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

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

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.

Study Overview

• Status: Terminated
• Conditions: Cancer; Bone Neoplasms; Pain, Intractable
• Intervention / Treatment: Drug: Placebo; Drug: Pregabalin

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 152
• Phase: Phase 4

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Hamilton, Ontario, Canada, L8V 5C2
      • Pfizer Investigational Site
• Czechia
  • Benesov U Prahy, Czechia, 256 30
    • Pfizer Investigational Site
  • Horovice, Czechia, 268 31
    • Pfizer Investigational Site
  • Jablonec nad Nisou, Czechia, 466 60
    • Pfizer Investigational Site
  • Plzen, Czechia, 301 00
    • Pfizer Investigational Site
  • Praha 1 - Nove Mesto, Czechia, 110 00
    • Pfizer Investigational Site
  • Praha 6 - Hradcany, Czechia, 160 00
    • Pfizer Investigational Site
• Egypt
  • Cairo, Egypt, 11796
    • Pfizer Investigational Site
• Finland
  • Helsinki, Finland, 00029
    • Pfizer Investigational Site
  • Joensuu, Finland, 80210
    • Pfizer Investigational Site
• France
  • Bordeaux Cedex, France, 33076
    • Pfizer Investigational Site
  • Villejuif, France, 94805
    • Pfizer Investigational Site
• Hungary
  • Budapest, Hungary, 1125
    • Pfizer Investigational Site
  • Budapest, Hungary, 1106
    • Pfizer Investigational Site
  • Nyiregyhaza, Hungary, 4400
    • Pfizer Investigational Site
  • Szentes, Hungary, 6600
    • Pfizer Investigational Site
  • Tata, Hungary, 2890
    • Pfizer Investigational Site
• Italy
  • Aviano (PN), Italy, 33081
    • Pfizer Investigational Site
  • Milano, Italy, 20133
    • Pfizer Investigational Site
• Korea, Republic of
  • Daegu, Korea, Republic of, 705-717
    • Pfizer Investigational Site
  • Seoul, Korea, Republic of, 110-744
    • Pfizer Investigational Site
  • Seoul, Korea, Republic of, 152-703
    • Pfizer Investigational Site
• Mexico
  • México D.F, Mexico, 14080
    • Pfizer Investigational Site
  • Nuevo Leon
    • Monterrey, Nuevo Leon, Mexico, 064460
      • Pfizer Investigational Site
• Peru
  • Lima, Peru, L13
    • Pfizer Investigational Site
  • Lima, Peru, L-41
    • Pfizer Investigational Site
• Philippines
  • Manila, Philippines, 1015
    • Pfizer Investigational Site
  • Quezon City, Philippines, 1102
    • Pfizer Investigational Site
• Poland
  • Bialystok, Poland, 15-748
    • Pfizer Investigational Site
  • Gdansk, Poland, 80-208
    • Pfizer Investigational Site
  • Kielce, Poland, 25-734
    • Pfizer Investigational Site
  • Lodz, Poland, 90-251
    • Pfizer Investigational Site
  • Warszawa, Poland, 02-781
    • Pfizer Investigational Site
  • Warszawa, Poland, 00-909
    • Pfizer Investigational Site
• Russian Federation
  • Moscow, Russian Federation, 125284
    • Pfizer Investigational Site
  • Saint-Petersburg, Russian Federation, 197089
    • Pfizer Investigational Site
  • Vsevolozhsk District, Leningrad Region
    • Vsevolozhsk, Vsevolozhsk District, Leningrad Region, Russian Federation, 188640
      • Pfizer Investigational Site
• Spain
  • Lleida, Spain, 25198
    • Pfizer Investigational Site
  • Madrid
    • Alcorcon, Madrid, Spain, 28922
      • Pfizer Investigational Site
• Sweden
  • Orebro, Sweden, 701 85
    • Pfizer Investigational Site
  • Stockholm, Sweden, 171 76
    • Pfizer Investigational Site
• Taiwan
  • Kaohsiung Hsien, Taiwan, 833
    • Pfizer Investigational Site
  • Taichung City, Taiwan, 40705
    • Pfizer Investigational Site
  • Taipei, Taiwan, 100
    • Pfizer Investigational Site
• Thailand
  • Bangkok
    • Rachathewi, Bangkok, Thailand, 10400
      • Pfizer Investigational Site
    • Ratchathewi, Bangkok, Thailand, 10400
      • Pfizer Investigational Site
• United States
  • Florida
    • Celebration, Florida, United States, 34747
      • Pfizer Investigational Site
    • Kissimmee, Florida, United States, 34741
      • Pfizer Investigational Site
    • Pensacola, Florida, United States, 32504
      • Pfizer Investigational Site
    • Pensacola, Florida, United States, 32514
      • Pfizer Investigational Site
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • Pfizer Investigational Site
  • Minnesota
    • Edina, Minnesota, United States, 55435
      • Pfizer Investigational Site
  • Ohio
    • Canton, Ohio, United States, 44718
      • Pfizer Investigational Site
    • Dover, Ohio, United States, 44622
      • Pfizer Investigational Site
• Venezuela
  • Distrito Capital
    • Caracas, Distrito Capital, Venezuela, 1010
      • Pfizer Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: 2	Drug: Placebo; Placebo
EXPERIMENTAL: 1; flexible dosing	Drug: Pregabalin; Capsule, Flexible-dosing, Double-blind. Treatment duration is 28 days at 100-600 mg/day administered BID+ taper (6 days).

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Pfizer's Upjohn has merged with Mylan to form Viatris Inc.

Publications and helpful links

General Publications

• Sjolund KF, Yang R, Lee KH, Resnick M. Randomized study of pregabalin in patients with cancer-induced bone pain. Pain Ther. 2013 Jun;2(1):37-48. doi: 10.1007/s40122-013-0009-8. Epub 2013 Feb 26.

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start: December 1, 2006
• Primary Completion (ACTUAL): October 1, 2010
• Study Completion (ACTUAL): October 1, 2010

Study Registration Dates

• First Submitted: September 25, 2006
• First Submitted That Met QC Criteria: September 25, 2006
• First Posted (ESTIMATE): September 27, 2006

Study Record Updates

• Last Update Posted (ACTUAL): January 20, 2021
• Last Update Submitted That Met QC Criteria: January 15, 2021
• Last Verified: April 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Site; Pain; Neurologic Manifestations; Musculoskeletal Diseases; Bone Diseases; Bone Neoplasms; Pain, Intractable; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Tranquilizing Agents; Psychotropic Drugs; Membrane Transport Modulators; Anti-Anxiety Agents; Anticonvulsants; Calcium-Regulating Hormones and Agents; Calcium Channel Blockers; Pregabalin
• Other Study ID Numbers: A0081128