Assessment of GRT6005 in Painful Osteoarthritis of the Knee

A Randomized 4 Week Phase IIa Trial Evaluating the Efficacy, Safety, and Tolerability of GRT6005, a New Centrally Acting Analgesic, in Subjects With Moderate to Severe Pain Due to Osteoarthritis (OA) of the Knee

The purpose of the trial is to determine whether GRT6005 is effective in patients with pain due to osteoarthritis of the knee.

Study Overview

• Status: Completed
• Conditions: Osteoarthritis of the Knee
• Intervention / Treatment: Drug: Matching Placebo; Drug: GRT6005; Drug: GRT6005; Drug: GRT6005

Detailed Description

The purpose of this study is to evaluate the safety, tolerability and efficacy of 3 doses of GRT6005 taken once daily for 4 weeks in outpatients with moderate-to-severe painful osteoarthritis of the knee.

• Study Type: Interventional
• Enrollment (Actual): 207
• Phase: Phase 2

Contacts and Locations

Study Locations

• Austria
  • Linz, Austria, 4021
    • Site 3604
  • Senftenberg, Austria, 3541
    • Site 3605
  • Wien, Austria, 1090
    • Site 3603
  • Wien, Austria, 1100
    • Site 3602
  • Wien, Austria, 1130
    • Site 3601
• Poland
  • Bialystok, Poland, 15-337
    • Site 3203
  • Elblag, Poland, 82-300
    • Site 3202
  • Gdynia, Poland, 81-834
    • Site 3208
  • Krakow, Poland, 30-349
    • Site 3206
  • Lublin, Poland, 20-605
    • Site 3207
  • Szczecin, Poland, 71-252
    • Site 3210
  • Torun, Poland, 87-100
    • Site 3201
  • Warsawa, Poland
    • Site 3204
  • Warszawa, Poland, 02-730
    • Site 3211
  • Wloszczowa, Poland, 29-100
    • Site 3213
  • Wroclaw, Poland, 50-088
    • Site 3205
• Spain
  • Barcelona, Spain, 08028
    • Site 3305
  • Barcelona, Spain, 08034
    • Site 3302
  • Coruna, Spain, 15006
    • Site 3303
  • Málaga, Spain, 29009
    • Site 3312
  • Mérida, Spain, 06800
    • Site 3308
  • Oviedo, Spain, 33009
    • Site 3310
  • Petrel, Spain, 03610
    • Site 3311
  • Santiago de Compostela, Spain, 15705
    • Site 3304
  • Sevilla, Spain, 41009
    • Site 3306
  • Torrelavega, Spain, 39300
    • Site 3313

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• painful Osteoarthritis of the knee based on American College of Rheumatology Criteria
• signed informed consent
• on stable analgesic medications for painful osteoarthritis with regular analgesic intake for at least 3 months
• pain intensity score of 4 or greater on the 11-point numeric rating scale (where 0 indicates "no pain" and 10 indicates "pain as bad as you can imagine").

Exclusion Criteria:

• Substance Abuse
• Significant cardiac disease
• Presence of risk factors for Torsades de Pointes and chronic severe cardiac disease
• History of seizure disorder
• Chronic gastrointestinal disease
• Conditions that contribute and confound to the assessment of pain
• Surgery or painful procedure during or within 3 months of enrollment
• Cancer
• Subjects with impaired renal function
• Subjects with impaired hepatic function
• Female subjects who are breastfeeding
• History of chronic hepatitis B or C or human immunodeficiency virus infection, or presence of acute hepatitis A, B, or C within the past 3 months.
• Clinically relevant history of hypersensitivity or allergy to paracetamol, opioids or the excipients.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Matching Placebo; Once daily oral administration of matching placebo for 4 weeks.	Drug: Matching Placebo; 2 capsules of matching placebo once a day, in the morning, for a total of 28 days
Experimental: 75 µg GRT6005; Once daily oral administration of GRT6005 for 4 weeks.	Drug: GRT6005; 2 capsules containing a total of 75 µg GRT6005 once a day, in the morning, for a total of 28 days; Drug: GRT6005; 2 capsules containing a total of 200 µg GRT6005 once a day, in the morning, for a total of 28 days; Drug: GRT6005; 2 capsules containing a total of 400 µg GRT6005 once a day, in the morning, for a total of 28 days
Experimental: 200 µg GRT6005; Once daily oral administration of GRT6005 for 4 weeks.	Drug: GRT6005; 2 capsules containing a total of 75 µg GRT6005 once a day, in the morning, for a total of 28 days; Drug: GRT6005; 2 capsules containing a total of 200 µg GRT6005 once a day, in the morning, for a total of 28 days; Drug: GRT6005; 2 capsules containing a total of 400 µg GRT6005 once a day, in the morning, for a total of 28 days
Experimental: 400 µg GRT6005; Once daily oral administration of GRT6005 for 4 weeks.	Drug: GRT6005; 2 capsules containing a total of 75 µg GRT6005 once a day, in the morning, for a total of 28 days; Drug: GRT6005; 2 capsules containing a total of 200 µg GRT6005 once a day, in the morning, for a total of 28 days; Drug: GRT6005; 2 capsules containing a total of 400 µg GRT6005 once a day, in the morning, for a total of 28 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change from baseline in the pain intensity scores during the last week of the 4-week treatment period	4 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Change from baseline in the Western Ontario McMaster Questionnaire (WOMAC) Global Score Assessing Pain, Disability and Joint Stiffness of the Knee Over the 4 week treatment period	4 weeks
Change from baseline in quality of health as measured by Short Form-12 Health Survey	4 weeks
Response measured in percentage change of pain intensity since baseline	4 weeks
Leeds Sleep Evaluation Questionnaire to quantify subjective impressions of sleep and waking	4 weeks
Patient's Global Impression of Change (PGIC)	4 weeks
Clinician's Global Impression of Change (CGIC)	4 weeks
Weekly current pain intensity changes from baseline	4 weeks
Rescue medication use	4 weeks
Quality of Life EuroQoL-5 Dimension score, change from baseline	4 weeks
Clinical Opioid Withdrawal Scale	4 weeks
Plasma concentration	4 weeks
Discontinuation from study due to treatment related adverse events	4 weeks
Time to withdrawal from study	4 weeks

Collaborators and Investigators

• Sponsor: Tris Pharma, Inc.
• Collaborators: Forest Laboratories
• Investigators: Principal Investigator: Jacek Olas, MD, Specjalistyczne Centrum Medyczne NZOZ NOWOMED,

Study record dates

Study Major Dates

• Study Start: May 1, 2011
• Primary Completion (Actual): December 1, 2011
• Study Completion (Actual): December 1, 2011

Study Registration Dates

• First Submitted: May 19, 2011
• First Submitted That Met QC Criteria: May 20, 2011
• First Posted (Estimate): May 23, 2011

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: Pain; Analgesia; Painful; Osteoarthritis, knee
• Additional Relevant MeSH Terms: Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Arthritis; Osteoarthritis; Osteoarthritis, Knee
• Other Study ID Numbers: 116918; 2010-022556-23 (EudraCT Number); KF6005/03 (Other Identifier: Sponsor)