A MULTICENTER, RANDOMIZED, DOUBLE-BLIND COMPARISON OF 4 DOSE REGIMENS OF PLA-695, NAPROXEN, AND PLACEBO ADMINISTERED DAILY FOR 6 WEEKS IN SUBJECTS WITH ACTIVE OSTEOARTHRITIS OF THE KNEE

• Register: EUCTR
• Last refreshed on: 19 March 2012
• Main ID: EUCTR2006-002590-44-HU
• Date of registration: 19/09/2006
• Prospective Registration: Yes
• Primary sponsor: Wyeth Research Division of Wyeth Pharmaceuticals Inc, Clinical Research and Development
• Public title: A MULTICENTER, RANDOMIZED, DOUBLE-BLIND COMPARISON OF 4 DOSE REGIMENS OF PLA-695, NAPROXEN, AND PLACEBO ADMINISTERED DAILY FOR 6 WEEKS IN SUBJECTS WITH ACTIVE OSTEOARTHRITIS OF THE KNEE
• Scientific title: A MULTICENTER, RANDOMIZED, DOUBLE-BLIND COMPARISON OF 4 DOSE REGIMENS OF PLA-695, NAPROXEN, AND PLACEBO ADMINISTERED DAILY FOR 6 WEEKS IN SUBJECTS WITH ACTIVE OSTEOARTHRITIS OF THE KNEE
• Date of first enrolment: 25/01/2007
• Target sample size: 560
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2006-002590-44
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: yes Other:

Countries of recruitment

Hungary, Netherlands

Key inclusion & exclusion criteria

Inclusion criteria:
- Men or women 50 to 75 years of age.
a) Women must be of non-childbearing potential; women < or = 55 years must have a negative serum ß-HCG pregnancy test.
b)Sexually active men who are not surgically sterile must agree and commit to use of barrier contraception during the study and for at least 12 weeks after the last dose of TA.
- Diagnosed with idiopathic OA of the knee for at least 3 months duration in accordance with [1986] American College of Rheumatology (ACR) clinical and radiographic criteria:
knee pain, the presence of osteophytes, and any one of the following:
age >50 years, crepitus, or morning stiffness <30 minutes.
- Radiographic confirmation of OA at the target joint (weight-bearing anteroposterior and lateral views) within 1 year of screening.
- Must be ambulatory.
- Must be currently treated for OA with a stable daily dose of 1 NSAID, including COX-2 inhibitors, not exceeding the maximum recommended dose in the product label, and taken as prescribed by the physician, starting at least 4 weeks before the screening visit.
- Must be willing to discontinue use of all NSAIDs/COX-2 inhibitors during the study
- At the baseline visit (2 to 14 days after after discontinuation of NSAID therapy), the scores of the following 3 measures must be at least 3 on a 1 to 5 point categorical scale and demonstrate a 1 category worsening (“flare”) in all three measures at the baseline visit as compared with the screening values:
a)Walking pain (5-point categorical scale: none, mild pain, moderate pain, severe pain, very severe pain)
b)Investigator’s overall evaluation of the subject’s condition (5-point categorical scale: very good, good, fair, poor, very poor)
c)Subject’s overall evaluation of his/her condition (5-point categorical scale: very good, good, fair, poor, very poor)
- The subject’s overall assessment of walking pain (Question 1 of the Western Ontario and McMaster Universities Osteoarthritis Index [WOMAC] Visual Analog Scale [VAS]) must be =40 mm (0 as “no pain” to 100 mm as “severe pain”)
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
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
- Subjects who have previously not been able to tolerate NSAIDs/COX-2 inhibitors, or have not had a therapeutic response to NSAIDs for OA.
- History of known hypersensitivity or allergic reaction to any of the components of PLA-695, sulfonamides, 5-lipoxygenase inhibitors, LT receptor antagonists, acetaminophen/paracetamol, or COX-2 inhibitors/NSAIDs, including aspirin.
- History of any surgery at the target knee, including arthroscopic interventional surgical procedure, or anticipated need for any surgery during the study.
- Arthroscopy for diagnostic purposes or lavage at the target knee within 1 year of screening, or any invasive procedures anticipated during the study.
- Orthopedic surgery of the lower extremities other than the target knee within 6 months of screening, or an anticipated need for such surgery during the study.
- History of or suspected current esophageal or gastrointestinal bleeding, ulcers, obstruction, or perforation, or pancreatitis.
- Grade 4 severity on the Kellgren
-Lawrence Scale on the screening target knee radiograph.
- Concomitant inflammatory arthropathy or other diseases or conditions that may affect joints (eg, RA or other auto-immune diseases, metabolic bone disease, psoriatic arthritis, gout, pseudogout, infection of the target knee, chondrocalcinosis in the target knee, Paget’s disease, neuropathic conditions, hemochromatosis).
- History of acute trauma leading to secondary OA of the target knee.
- Cancer, or a history of cancer (other than successfully resected cutaneous basal and squamous cell carcinoma) within 5 years before the screening visit.
- Any significant cardiovascular, hematologic, blood dyscrasia, endocrine, respiratory, neurologic, psychiatric, metabolic, immunologic, infectious, hepatic, or renal condition that the investigator considers detrimental to the subject’s participating in the study or that may prevent the successful completion of the study, including the following:
a)Cardiovascular disease:
i)History of myocardial infarction.
ii)History of angina pectoris.
iii)Cardiac arrhythmia or clinically significant electrocardiogram (ECG) abnormality, such as ischemia.
iv)History of stroke or transient ischemic attack. v)Congestive heart failure (CHF) New York Heart Association classification for CHF: Class III or IV.
vi)Uncontrolled hypertension (systolic blood pressure [SBP] =140 mmHg or diastolic blood pressure [DBP] =90 mmHg).b)Poorly controlled diabetes.
c)Known or suspected untreated infections with Helicobacter pylori infection.
d)History of human immunodeficiency virus (HIV) infection or known risk of HIV disease.
- Any clinically significant laboratory abnormality, including those listed below:
a)Liver function abnormality (total bilirubin >1.5 x the upper limit of normal [ULN], aspartate aminotransferase [AST/SGOT] > 1.2 x ULN, alanine aminotransferase [ALT/SGPT] > 1.2 x ULN).
b)Anemia (hemoglobin or hematocrit below the lower limit of normal).
c)Thrombocytopenia or thrombocytosis (platelets <125,000/mm3 or =1,000,000/mm3 [SI units:<125 x 109/L or = 1,000 x 109/L])
d)Renal function abnormality, including serum creatinine level greater than the upper limit of normal.
e)Positive qualitative serologic findings for hepatitis B surface antigen (HBsAg) or hepatitis C virus (HCV) antibodies.
f)Fasting serum triglyceride levels > 500 mg/dL (SI units:>5.65 mmol/L).
g)Serum amylase or serum lipase = 1.25 x ULN.Screening laboratory tests with abnormal results may be repeated once t

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

ACTIVE OSTEOARTHRITIS OF THE KNEE

Intervention(s)

Product Name: PLA-695 Liquid-Filled Capsules 100 mg
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: PLA-695
CAS Number: 865200-20-0
Current Sponsor code: WAY-198695
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

Product Name: PLA-695 Liquid-Filled Capsules 50 mg
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: PLA-695
CAS Number: 865200-20-0
Current Sponsor code: WAY-198695
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 50-
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

Trade Name: Naprosyn 500 mg Tablets
Product Name: Naproxen 500 mg Tablet-in-Capsule
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Naproxen
CAS Number: 22204-53-1
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 500-
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

Primary Outcome(s)

Secondary Objective: To determine the pharmacokinetics (PK) and pharmacodynamics (PD) of PLA-695 among number of dose levels.
To assess health outcome measures.
To assess the effect of PLA-695 on biomarkers related to clinical responses.
To assess PLA-695 exposure-response relationship on PD, efficacy, and safety measures.
To assess pharmacogenomics (PGX) analysis in OA (not in Europe).

Primary end point(s): WOMAC VAS walking pain (question 1) at week 6

Main Objective: To establish efficacy and safety of PLA-695 in subjects with active OA of the knee.

Secondary ID(s)

3175A1-202-WW