Safety and Efficacy Study of GRT6005 in Patients With Osteoarthritis (OA) Knee Pain

A Randomized, Double-Blind, Placebo- and Active Controlled Study to Evaluate the Safety and Efficacy of GRT6005 in Patients With Moderate to Severe Chronic Pain Due to Osteoarthritis of the Knee

The purpose of this study is to evaluate the safety and efficacy of GRT6005 compared to placebo in patients with moderate to severe chronic pain due to osteoarthritis (OA) of the knee. This study includes a maximum 21 day Screening Period followed by a 15-week Double-blind Treatment Period and a 4-7 day Safety Follow-up period. Patients who are eligible for the Double-blind Treatment Period will be randomized to one of following treatment groups: GRT6005 high-dose range (400, 600 or 800 mcg), GRT6005 low-dose range (200, 300 or 400 mcg), oxycodone controlled release (CR) dose range (10, 20, 30, 40 or 50 mg) or placebo.

Study Overview

• Status: Completed
• Conditions: Moderate to Severe Chronic Pain Due to Osteoarthritis of the Knee
• Intervention / Treatment: Drug: Cebranopadol (GRT6005) Low-Dose Range; Drug: Placebo; Drug: Cebranopadol (GRT6005) High-Dose Range; Drug: Oxycodone CR

• Study Type: Interventional
• Enrollment (Actual): 619
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35209
      • Site 051
    • Birmingham, Alabama, United States, 35216
      • Site 022
    • Huntsville, Alabama, United States, 35801
      • Site 031
  • Arizona
    • Phoenix, Arizona, United States, 85018
      • Site 005
    • Phoenix, Arizona, United States, 85023
      • SITE 018
    • Phoenix, Arizona, United States, 85027
      • Site 070
    • Tucson, Arizona, United States, 85712
      • Site 028
  • California
    • Chino, California, United States, 91710
      • Site 081
    • El Cajon, California, United States, 92020
      • Site 030
    • Fair Oaks, California, United States, 95628
      • Site 039
    • Fresno, California, United States, 93726
      • Site 061
    • North Hollywood, California, United States, 91606
      • Site 084
    • Roseville, California, United States, 95661
      • Site 080
    • Sacramento, California, United States, 95821
      • Site 004
    • San Diego, California, United States, 92117
      • Site 044
    • Tustin, California, United States, 92780
      • Site 043
    • Walnut Creek, California, United States, 94598
      • Site 010
    • Westlake Village, California, United States, 91361
      • Site 027
  • Florida
    • Bradenton, Florida, United States, 34209
      • Site 011
    • Clearwater, Florida, United States, 33761
      • Site 071
    • Edgewater, Florida, United States, 32132
      • Site 090
    • Jacksonville, Florida, United States, 32256
      • Site 060
    • Jupiter, Florida, United States, 33458
      • Site 015
    • Miami, Florida, United States, 33144
      • Site 013
    • New Port Richey, Florida, United States, 34652
      • Site 003
    • Ocala, Florida, United States, 34474
      • Site 012
    • Orlando, Florida, United States, 32806
      • Site 032
    • Ormond Beach, Florida, United States, 32174
      • Site 025
    • Pembroke Pines, Florida, United States, 33028
      • Site 058
    • Pinellas Park, Florida, United States, 33781
      • Site 091
    • Sarasota, Florida, United States, 34238
      • Site 007
  • Georgia
    • Marietta, Georgia, United States, 30066
      • Site 052
    • Perry, Georgia, United States, 31069
      • Site 033
    • Stockbridge, Georgia, United States, 30281
      • Site 073
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Site 086
  • Indiana
    • Indianapolis, Indiana, United States, 46260
      • Site 041
    • Valparaiso, Indiana, United States, 46383
      • Site 085
  • Maryland
    • Towson, Maryland, United States, 21204
      • Site 088
    • Wheaton, Maryland, United States, 20902
      • Site 077
  • Massachusetts
    • New Bedford, Massachusetts, United States, 02740
      • Site 083
    • North Dartmouth, Massachusetts, United States, 02747
      • Site 021
    • Worcester, Massachusetts, United States, 01605
      • Site 020
  • Michigan
    • Bingham Farms, Michigan, United States, 48025
      • Site 016
    • Traverse City, Michigan, United States, 49684
      • Site 042
  • Missouri
    • Saint Louis, Missouri, United States, 63141
      • Site 023
  • Nebraska
    • Grand Island, Nebraska, United States, 68803
      • Site 087
    • Omaha, Nebraska, United States, 68144
      • Site 074
  • Nevada
    • Las Vegas, Nevada, United States, 89130
      • Site 024
    • Las Vegas, Nevada, United States, 89144
      • Site 072
  • New Mexico
    • Albuquerque, New Mexico, United States, 87102
      • Site 009
  • New York
    • Albany, New York, United States, 12208
      • Site 068
    • Hartsdale, New York, United States, 10530
      • SITE 017
  • North Carolina
    • Greensboro, North Carolina, United States, 27410
      • Site 056
    • High Point, North Carolina, United States, 27262
      • Site 006
    • Wilmington, North Carolina, United States, 28401
      • Site 078
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • Site 079
    • Cincinnati, Ohio, United States, 45242
      • Site 008
    • Cleveland, Ohio, United States, 44122
      • Site 069
    • Columbus, Ohio, United States, 43213
      • Site 001
    • Toledo, Ohio, United States, 43623
      • Site 048
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73103
      • Site 075
  • Oregon
    • Bend, Oregon, United States, 97701
      • Site 029
    • Medford, Oregon, United States, 97504
      • Site 067
    • Portland, Oregon, United States, 97239
      • Site 035
  • Pennsylvania
    • Altoona, Pennsylvania, United States, 16602
      • Site 045
    • Duncansville, Pennsylvania, United States, 16635
      • Site 002
  • South Carolina
    • Anderson, South Carolina, United States, 29621
      • Site 034
    • Charleston, South Carolina, United States, 29407
      • Site 076
  • Tennessee
    • Bristol, Tennessee, United States, 37620
      • Site 093
  • Texas
    • Austin, Texas, United States, 78731
      • Site 055
    • Bryan, Texas, United States, 77802
      • Site 049
    • Dallas, Texas, United States, 75203
      • Site 038
    • San Antonio, Texas, United States, 78209
      • Site 089
    • San Antonio, Texas, United States, 78229
      • Site 040
    • Wichita Falls, Texas, United States, 76309
      • Site 082
  • Utah
    • Draper, Utah, United States, 84020
      • Site 019
    • Ogden, Utah, United States, 84405
      • Site 064
    • Salt Lake City, Utah, United States, 84106
      • Site 059
  • Virginia
    • Norfolk, Virginia, United States, 23507
      • Site 092
    • Virginia Beach, Virginia, United States, 23454
      • Site 026
  • Washington
    • Bellevue, Washington, United States, 98007
      • Site 066
    • Renton, Washington, United States, 98057
      • Site 057
    • Seattle, Washington, United States, 98122
      • Site 065

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 78 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Diagnosis of osteoarthritis (OA) of the knee
• OA knee pain present for at least 3 months
• OA knee pain is the predominant (ie, most painful) pain condition
• Patients require medication on at least 4 of 7 days per week to treat OA knee pain for at least 1 month.
• Dissatisfaction with current OA knee pain treatment and willingness to stop taking all pain medications except for the study drug and allowed rescue medication
• Average daily pain rating of at least 5 on a 0 to 10 point numerical rating scale during the 1 week prior to randomization
• Female patients either postmenopausal, surgically sterile or practicing a medically acceptable method of contraception
• Male patients either status post-bilateral vasectomy or using barrier contraception

Exclusion Criteria:

• Knee pain due to a disorder other than OA
• Other pain that can confound the assessment of, or contribute to, pain at the reference knee
• Surgery at the reference knee within 6 months of Screening or a history of joint replacement surgery at the reference knee
• Trauma to the reference knee within 6 months of Screening with active symptoms
• Steroid injections in the reference knee within 3 months of Screening
• Hyaluronic acid injections in the reference knee within 6 months of Screening
• Body Mass Index > 40 kg/m2
• Patient with any protocol-excluded or clinically significant medical, surgical, or medication history that would limit the patient's ability to complete or participate in this clinical trial or could confound the study assessments

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cebranopadol (GRT6005) Low-Dose Range; Once daily GRT6005, flexible dosing 200, 300 or 400 micrograms, and once daily Placebo; oral administration for 15 weeks	Drug: Cebranopadol (GRT6005) Low-Dose Range; Capsules; Drug: Placebo; Capsules that did not contain active substance but appeared identical to the cebranopadol and oxycodone CR capsules
Experimental: Cebranopadol (GRT6005) High-Dose Range; Once daily GRT6005, flexible dosing 400, 600 or 800 micrograms, and once daily Placebo; oral administration for 15 weeks	Drug: Placebo; Capsules that did not contain active substance but appeared identical to the cebranopadol and oxycodone CR capsules; Drug: Cebranopadol (GRT6005) High-Dose Range; Capsules
Placebo Comparator: Placebo; Twice daily Placebo, oral administration for 15 weeks	Drug: Placebo; Capsules that did not contain active substance but appeared identical to the cebranopadol and oxycodone CR capsules
Active Comparator: Oxycodone CR; Twice daily Oxycodone CR, flexible dosing 10, 20, 30, 40 or 50 milligrams; oral administration for 15 weeks	Drug: Oxycodone CR; Capsules containing oxycodone CR 10 or 20 milligrams

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change from baseline in the weekly average of the daily average pain rating	Baseline to end of treatment (Week 15)

Secondary Outcome Measures

Outcome Measure	Time Frame
Change from baseline in the physical function subscale of the Western Ontario and McMaster University Index of Osteoarthritis Questionnaire (WOMAC)	Baseline to end of treatment (Week 15)

Collaborators and Investigators

• Sponsor: Tris Pharma, Inc.
• Collaborators: Forest Laboratories

Study record dates

Study Major Dates

• Study Start (Actual): December 4, 2012
• Primary Completion (Actual): April 1, 2014
• Study Completion (Actual): April 4, 2014

Study Registration Dates

• First Submitted: October 16, 2012
• First Submitted That Met QC Criteria: October 16, 2012
• First Posted (Estimate): October 18, 2012

Study Record Updates

• Last Update Posted (Actual): July 15, 2021
• Last Update Submitted That Met QC Criteria: July 13, 2021
• Last Verified: July 1, 2021

More Information

Terms related to this study

• Keywords: Arthritis; Osteoarthritis; Pain; Knee; Chronic; OA
• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Arthritis; Osteoarthritis; Osteoarthritis, Knee; Chronic Pain; Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Opioid; Narcotics; Oxycodone
• Other Study ID Numbers: GRT-MD-101

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No