Treatment of Osteoarthritis Knee Pain MedDRA version: 14.0 Level: LLT Classification code 10031165 Term: Osteoarthritis knee System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders
Conditions
Sponsors
Allergan Limited
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male or female, 40 to 75 years of age on the day of randomization (day 1). 2. Written informed consent and data protection consent has been obtained prior to initiating any study specific procedures. 3. Primary idiopathic knee OA diagnosed in accordance with the ACR modified clinical classification criteria (Altman et al, 1986; Altman 1991) and verified radiologically as Kellgren-Lawrence grade I, II or III (Kellgren and Lawrence, 1957). 4. For the study knee, the average daily worst pain score over the 14 days prior to day 1 (ie, days -14 to day -1) must be 4.0 to 9.0. The 14-day average score will be derived from daily worst pain scores recorded in a diary for the study knee. 5. Stable knee pain in the study knee for = 6 consecutive months prior to visit 1. No evidence of abnormal mechanical symptoms such as locking or catching of the study knee per medical history or physical examination. 6. Body weight = 40 kg and = 150 kg with a body mass index (BMI) of 19 to = 40 kg/m2 inclusive. 7. For females of childbearing potential, a negative urine pregnancy test at screening, baseline, and on the day of the treatment (prior to the administration of the study medication) is required. 8. Must be ambulatory without assistive walking devices, able to perform usual daily activities, and agree to maintain the similar activity level throughout the course of the study. 9. Ability to follow study instructions and likely to complete all required visits. 10. Stable medical condition, in the investigator’s opinion. 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 70 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 50
Exclusion criteria
Exclusion criteria: 1. Patient diagnosed with any condition suggestive of a secondary cause of knee OA including but not limited to knee trauma, articular fracture, major dysplasias or congenital abnormality, acromegaly, ochronosis, hemochromatosis, Wilson’s disease,or primary osteochondromatosis. 2. History of or current evidence of rheumatoid arthritis as diagnosed by ACR criteria, or history of prior synovial fluid analysis of the study knee showing a white blood cell count =2000 mm3 that is indicative of a diagnosis other than OA. 3. Presence of bursitis or tear of meniscus or ligament of the study knee, or history of significant knee injury to the study knee within 1 year of visit 1. 4. History of surgery in the study knee within 24 weeks prior to visit 1, or already planned surgery of the study knee such as, arthroplasty, arthroscopy inspection, or repair of knee ligaments. 5. Treatment with IA hyaluronic acid in the study knee within 24 weeks prior to visit 1. 6. Treatment with IA corticosteroid in any joint or intramuscular corticosteroid administration within 12 weeks prior to visit 1. 7. Concurrent chronic pain conditions such as back pain, hip pain (eg, disc herniation, peripheral nerve entrapment, multiple sclerosis), fibromyalgia that may interfere with assessment of the study knee. The study knee pain should be the predominant pain. 8. History or current diagnosis of gout or pseudogout with knee involvement. 9. History or current diagnosis of Reiter’s, Sjögren’s syndrome, psoriasis or systemic lupus erythematosus or other autoimmune diseases with joint involvement. 10. Patients at a high risk of joint infection complication (eg, infection of local skin, soft tissue and joint in the study knee, indwelling urinary catheter) or have immunocompromised conditions (eg, known HIV or organ transplant). 11. Evidence of abnormal coagulation status (eg, excessive tooth bleeding with brushing, abnormal bleeding time, partial thromboplastin time or prothrombin time) or patients with hemophilia or other blood diseases affecting coagulation (eg, aplastic anemia, leukemia, or under chemo-/radio-therapy). 12. Patients continue to take excluded analgesic medications after visit 2. 13. Patients with contraindications to the use of paracetamol (ie, rescue medication for this study). 14. History of severe, progressive, or current unstable medical conditions other than OA such as renal, hepatic, gastrointestinal, neurological, endocrine, metabolic, degenerative bone disorders, respiratory, and/or psychiatric disorder as determined by medical history, physical examination and /or laboratory tests. 15. History of severe cardiovascular diseases, stroke, recurrent seizures, frequent or severe allergic reactions to multiple medications. 16. Electrocardiogram (ECG) abnormality at screening that in the opinion of the investigator could increase risk associated with participation in the study. 17. Patients with an active malignancy of any type or a history of malignancy within the last 5 years (except basal cell carcinoma of the skin that has been excised at least 12 weeks prior to study start). 18. Have a history of substance abuse or dependence within the past year, excluding nicotine and caffeine. 19. Patient Health Questionnaire-9 (PHQ-9) score of >15 or a score of > 0 on item #9 of the PHQ-9 at week -4. 20. Known allergy or sensitivity to the study medication(s) or its components. 21. Females who are pregnant, nursing, or planning a pregnancy dur
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of this study is to evaluate the efficacy and safety of a single IA injection of BOTOX (200 U) compared with placebo as treatment for OA knee pain.;Secondary Objective: Secondary objectives are to explore the efficacy of a single IA injection of BOTOX (200 U) compared with placebo on OA knee pain in patients with different pain phenotypes and/or different knee synovial effusion neurotransmitter/biomarker concentration profiles.;Primary end point(s): Change from baseline: Daily worst pain score (11-point [0 to 10] NRS; 0 = no pain, 10 = worst pain possible) for the study knee;Timepoint(s) of evaluation of this end point: 4, 8 and 12 weeks post injection | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Change from baseline: • WOMAC Osteoarthritis Index NRS3.1: o WOMAC Total Index Score (0-240 scale) o WOMAC Pain Score (0-50 scale) o WOMAC Physical Function (difficulty performing daily activities) Score (0-170 scale) • Patient Global Impression of Change (Patient-GIC) The Patient-GIC is a questionnaire used by the patient to provide a global impression of change in their health status since enrollment, whether or not in the patient’s judgment a change is related to the study treatment. The Patient-GIC is useful in assessing whether the impact of the study treatment is meaningful enough to have value to the patient (Turk et al, 2003). A 7-point scale with +3 equaling very much improved and -3 equaling very much worse will be used for scoring purposes (Guy and Bonato, 1976). The Patient-GIC and other global impression questionnaires have a long history of use across a number of therapeutic areas and chronic pain indications (Farrar et al, 2001). Patient-GIC instructions: Since you enrolled into this study, how much have you changed? Please rate your total change whether or not, in your judgment, it is entirely due to the study treatment. Very much improved, Much improved, Minimally improved, No change, Minimally worse, Much worse, Very much worse ;Timepoint(s) of evaluation of this end point: 1, 4, 8 and 12 weeks post injection | — |
Countries
Denmark
Contacts
Public ContactAllergan Ltd, EU Regulatory Affairs
Allergan Limited
Outcome results
None listed