Osteoarthritis MedDRA version: 16.1 Level: LLT Classification code 10019115 Term: Hand osteoarthritis System Organ Class: 100000004859 MedDRA version: 16.1 Level: LLT Classification code 10023476 Term: Knee osteoarthritis System Organ Class: 100000004859
Conditions
Interventions
Product Code: AMAP102
Pharmaceutical Form: Capsule
INN or Proposed INN: AMAP102
Current Sponsor code: AMAP102
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 25-
Ph
Sponsors
AnaMar AB
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male or female outpatients aged = 50 years. 2. Male or female outpatients with a body mass index of 18 to 30 kg/m2 and a minimum weight of 50 kg. 3. Patients with a clinical diagnosis of unilateral or bilateral knee OA based on clinical and radiographic criteria. Patients should fulfill the validated criteria for the classification of primary OA, published by the American College of Rheumatology (ACR): • The ACR Classification Criteria (1986) for clinical and radiographic OA of the knee are: - Knee pain. - Osteophytes - And one of the following: o Age = 50 years. o Stiffness of =65 years) yes F.1.3.1 Number of subjects for this age range 30
Exclusion criteria
Exclusion criteria: 1.The patient has primary inflammatory diseases of the joint (e.g.rheumatoid arthritis,psoriatic arthritis,Reiter’s syndrome,arthritis of inflammatory spondyloarthropathy or inflammatory bowel disease, or infectious arthritis). 2.The patient has unstable knees including a history of the knee catching or giving way and/or physical examination evidence of instability (e.g.positive posterior drawer sign,positive Lachman,positive anterior drawer sign,medial or lateral collateral ligament instability,etc). 3.The patient has arthropathies that occur in conjunction with systemic diseases such as chondrocalcinosis,chondromatosis,gout,pseudo gout,haemophilia,or collagen vascular disease. 4.The patient has a chronic pain condition (e.g.somatisation disorders,chronic headache,fibromyalgia,etc).The patient has chronic lower back pain (individual cases should be discussed with the Medical Monitor) that could confound the analgesic response of the study medication. 5.The patient has a history of knee surgery within the past 12 months,arthroscopy within the past 6 months,or is anticipated to undergo knee surgery in next 3 months or general surgery during the time of participation in the study. 6.The patient has advanced joint damage (Kellgren-Lawrence grade 4); or,in the opinion of the investigator,the patient has advanced joint damage assessed without an X-ray. 7.The patient has a history of osteotomies. 8.The patient is using any of the prohibited medications that are listed in Table 3 of the protocol. 9.The patient used opioids (e.g.codeine,propoxyphene,or combinations of these drugs with NSAIDs or paracetamol) for OA pain within 1 month or 5 half-lives of the drug (whichever is longer) prior to the screening visit (Visit 1). 10.The patient received intra-articular injections of sodium hyaluronate agents within 6 months or 5 half lives of the drug (whichever is longer) before the screening visit (Visit 1) or steroids in joints other than the knee or intravenous or intramuscular steroids within 2 months or 5 half-lives of the drug (whichever is longer) before the screening visit (Visit 1). 11.The patient used oral steroids,intra-articular steroids in the knee, or other immunosuppressant medications within 2 months or 5 half-lives of the drug (whichever is longer) before the screening visit (Visit 1). 12.The patient received methotrexate within 30 days before the screening visit (Visit 1). 13.The patient must agree not to take rescue medication (paracetamol) between the screening visit and baseline, and for 24 hours before any clinic visit. 14.The patient has significant renal impairment (defined as a serum creatinine > 2 x upper limit of normal [ULN] or creatinine clearance 3 x ULN, positive class III/IV angina or uncontrolled congestive heart failure in the opinion of the investigator, significant active hepatic disease, history of malignant neoplastic disease (other than basal cell carcinoma of the skin) within the past 5 years, or a current severe infectious disease with or without fever. 15.The patient is a woman of childbearing potential who has a positive serum pregnancy test or is a nursing mother. The patient is not surgically sterile (by tubal ligation or hysterectomy) or at least 2 years postmenopausal and has not practiced an acceptable form of birth control (defined as the use of an intrauterine device with spermicide, a barrier method with spermicide, condoms with spermicide, subdermal implant,
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the efficacy of AMAP102 in patients with pain secondary to osteoarthritis (OA) over 28 days of dosing;Secondary Objective: • To assess the efficacy of AMAP102 in OA patients. • To assess the safety and tolerability of AMAP102 in OA patients. • To measure the plasma concentrations of AMAP102 in OA patients. • To explore the effects of AMAP102 on interleukin-6 (IL-6), tumour necrosis factor-alpha (TNF a), cartilage oligomeric matrix protein (COMP), and serotonin (5-HT) in OA patients ;Primary end point(s): Primary Efficacy Endpoint: WOMAC Pain subscale for the target knee. ;Timepoint(s) of evaluation of this end point: Primary Efficacy Endpoint: at Visit 2 (Day 1) Visit 3 (Day 7), Visit 4 (Day 14) and Visit 5 (Day 28) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Daily 24-hour average pain during activity score in the target knee measured with the NRS from the patient’s daily diary. • Daily 24-hour average pain score in the target knee measured with the NRS from the patient’s daily diary. • Daily 24-hour average worst pain score in the target knee measured with the NRS from the patient’s daily diary. • Daily cumulative proportion of responders from baseline to on average 24-hour pain during activity scores in the target knee assessed with the NRS from the patient’s daily diaries. A responder is defined as a patient who achieves and maintains a 30% improvement in the average 24-hour pain during activity scores over baseline until the end of the study. • Number of responders, defined as patients who achieve and maintain a 30% improvement in the average 24-hour pain during activity scores in the target knee over baseline until the end of the study. • Average daily and weekly use and total use of rescue medication (paracetamol). • Daily quality of sleep rating assessed by the Modified Pittsburgh Sleep Quality Index. • WOMAC Stiffness subscale for the target knee. • WOMAC Physical Functioning subscale for the target knee. • WOMAC total score for the target knee. • Patient global assessment of study drug satisfaction. • Investigator global assessment of study drug satisfaction. • EQ-5D-5L™. • Serum hsCRP levels. Safety Endpoints: Safety will be assessed using incidence of all adverse events, serious adverse events and those leading to withdrawal of study medication, review of clinical laboratory assessments (haematology, clinical chemistry and urinalysis), concomitant medications, ECG monitoring, physical examinations, vital signs, body weight and C-SSRS. Pharmacokinetic Endpoints: • Plasma AMAP102 concentrations at Visit 3 (Day 7), Visit 4 (Day 14), Visit 5 (Day 28) and Visit 6 (Day 35) after b.i.d. dosing in each treatment group. • The proportion of patients in each treatment group showing measurable | — |
Countries
Germany, Sweden
Contacts
Public ContactAnna-Carin Ryde
AnaMar AB
Outcome results
None listed