A 4-week trial evaluating the efficacy, safety, and tolerability of GRT6005, a new centrally acting analgesic, in subjects with moderate to severe pain due to osteoarthritis of the knee.

• Conditions: Pain due to Osteoarthritis of the knee; MedDRA version: 14.0Level: LLTClassification code 10023476Term: Knee osteoarthritisSystem Organ Class: 10028395 - Musculoskeletal and connective tissue disorders; MedDRA version: 14.0Level: PTClassification code 10031161Term: OsteoarthritisSystem Organ Class: 10028395 - Musculoskeletal and connective tissue disorders; Therapeutic area: Diseases [C] - Musculoskeletal Diseases [C05]

• Registration Number: EUCTR2010-022556-23-AT
• Lead Sponsor: Grünenthal GmbH

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2011-06-29
• Last Update Posted: 19 March 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 170

Inclusion Criteria

1. Subjects must have signed an informed consent form.
2. Male or female subjects aged 40 years to 75 years inclusive at the Enrollment Visit.
3. Diagnosis of OA of the knee based on American College of Rheumatology criteria and functional capacity class of I-III. Pain must be present for at least 3 months.
4. Subjects must be using medically acceptable and highly effective methods of birth control:
For women of childbearing potential:
A medically acceptable and highly effective method of birth control is defined as any form of contraception with a low failure rate defined as <1% per year. For example:
- Hormonal contraceptives for at least 2 months prior to the Enrollment Visit and at least until 4 weeks after the Final Visit.
- An intra-uterine device.
Additional barrier contraception must be used by the partner for the duration of the trial, defined as from the time of the Enrollment Visit until 4 weeks after the Final Visit. Women of non-childbearing potential may be included if surgically sterile (i.e., after hysterectomy) or post-menopausal for at least 2 years.
For men: Males have to use barrier contraception (condom) during sexual intercourse and not have sex with women who are pregnant or lactating from the first administration of IMP until 4 weeks after the Final Visit. The male subject has to take care that the female sexual partner uses at least 1 additional method of contraception with a low failure rate defined as <1% per year (e.g., oral contraceptives for at least 2 months prior to the Enrollment Visit) during this time frame. A double-barrier method should be supplemented by the use of spermicidal agents.
5. Women of childbearing potential must have a negative urine ß human chorionic gonadotropin (ß-hCG) pregnancy test at the Enrollment Visit and at the Baseline Visit.
6. Subjects must be on stable analgesic medications for their condition with regular intake for at least 3 months prior to the Enrollment Visit according to their medical history and must be dissatisfied with their current analgesic treatment in terms of efficacy and/or tolerability.
7. A daily average pain intensity score =4 on the 11 point numeric rating scale (NRS) during the last 3 days prior to the Baseline Visit without intake of rescue medication, during which a subject completed at least 5 of 6 possible pain intensity assessments of these 3 days.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 170
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 170

Exclusion Criteria

1. Concurrent participation in another trial, or within 30 days before the Enrollment Visit of this trial.
2. Previous participation in this or other trials with GRT6005 (unless enrollment failure due to technical reason).
3. Previous or current alcohol or drug abuse according to the investigator’s judgment, based on subject’s history, physical examination, or the result of the drug test at the Enrollment Visit or at the Baseline Visit.
4. Previous or current opioid dependency, based on subject’s history, physical examination, or the result of the drug test at the Enrollment Visit or at the Baseline Visit.
5. Female subjects who are breastfeeding.
6. Known or suspected of not being able to comply with the protocol and with the use of the IMP.
7. Any clinically significant disease that in the investigator's opinion may affect efficacy or safety assessments or may compromise the subject’s safety during trial participation, e.g., significant pulmonary, gastrointestinal, endocrine, metabolic, neurological, or psychiatric disorders.
8. Employees of the investigator, trial site, or sponsor, with direct involvement in the proposed trial or other trials under the direction of that investigator, trial site, or sponsor, as well as family members of employees or the investigator.
9. Subjects with impaired hepatic functionality/cellular integrity determined by bilirubin greater than 2.0 mg/dL and albumin lower than 2.8 g/dL or increased transaminases with alanine aminotransferase or aspartate aminotransferase greater than 3 times the upper limit of normal at the Enrollment Visit or at the Pre baseline Visit.
10. 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.
11. Subjects with impaired renal function. Creatinine clearance less than 60 mL/min at the Enrollment Visit or the Pre-baseline Visit (calculated from the Cockcroft-Gault formula).
12. Any chronic gastrointestinal disease (e.g., celiac disease or colitis ulcerosa) or previous major abdominal surgery (e.g., Billroth procedure or enteroanastomosis) that might affect drug absorption or excretion.
13. Significant cardiac disease (e.g., unstable angina pectoris, angina pectoris Canadian Cardiovascular Society Class III-IV, acute myocardial infarction within the last 3 months, cardiac insufficiency New York Heart Association Class III-IV).
14. Presence of risk factors for Torsade de Pointes (e.g., heart failure, hypokalemia, bradycardia).
15. Marked prolongation of QTc >450 ms at the Enrollment Visit or at the Pre baseline Visit.
16. History of seizure disorder and/or epilepsy or any condition associated with a significant risk for seizure disorder or epilepsy at the Enrollment Visit at the discretion of the investigator.
17. History or presence of malignancy, with the exception of curative treated subjects or subjects being in remission of cancer for at least 2 years and not requiring treatment.
Trial specific:
18. Surgery of any joint within 3 months of the Enrollment Visit or any scheduled surgery or painful procedure during the course of the trial.
19. Clinically relevant history of hypersensitivity, allergy, or contraindications to any of the IMP’s excipients as well as to opioids or paracetamol.
20. Presence of conditions other than pain due to OA that could contribute to pain or confound the assessment of self-evaluation of pain,

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified