If you are at least 40 years of age and have osteoarthritis of
the knee for which you must take pain medication, you may be
eligible for a research study of an investigational medication for
osteoarthritis. If you qualify, you will receive study-related
physical exams, knee X-ray, ECGs and lab tests.
1) Men and women ~ 40 with a diagnosis of primary OA of
the knee. The OA must be confirmed by radiographs performed between
Screening and first study drug administration at Baseline at a
selected local radiology center and diagnosed according to American
College of Rheumatology (ACR) guidelines. Subjects must qualify as
ACR global functional stalus I, II, or III (excluding IV) and
Kellgren-Lawrence grade 1, 2 or 3 (excluding grades 0 and 4).
2) Must be a current chronic user of NSAIDs or acetaminophen for
their OA pain and anticipated to benefit from continuous treatment
with NSA10s. A current chronic user is defined as a subject who has
used these treatments for at least 20 days during the last month
prior to Screening.
3) Must discontinue all analgesic therapy at Screening except
the study rescue medication provided and must discontinue this
study rescue medication for at least 24 hours prior to
Baseline.
4) Must experience a flare of pain following discontinuation of
prior NSAIDlanalgesic therapy (discontinuation of at least 5 half
lives - 4 1010 days) at Baseline.
Flare of pain is defined as:
(a) WOMACTM guestion #1 of pain
subscate 2: 50 mm, and
(b) Increase by .?15 mm as compared to Screening.
5) Glucosamine and chondroitin are allowed if administered at
stable dose within the past 3 months before Screening/Baseline.
6) Female SUbjects must be post-menopausal (defined as at least
12 months post cessation of menses), surgically sterile or, if of
childbearing potential, using a reliable method of contraception
for at least 3 months prior to study entry (Screening) and during
the study. In addition, female SUbjects must not be lactating.
7) If of childbearing potential, female subjects must have a
negative urine pregnancy test at both Screening and Baseline.
8) Must be able to understand and comply with study requirements
(e.g. must be able to attend early morning clinic visits).
9) Must provide a written, signed and dated informed consent
prior to any study procedures.
1) Uncontrolled hypertension at Screening or Baseline,
as judged by the Investigator; anti-hypertensive treatment regimens
must be stable within the past 3 months prior to Screening to be
eligible for study entry.
2) Uncontrolled diabetes al Screening, as judged by the
Investigator.
3) Hepatic impairment (ALTor AST > 2 times ULN) at Screening
collection, as judged by the Investigator.
4) A history of renal impairment with a serum creatinine value
> 176 ~lmol/L (2.0 mgldl) at Screening collection
5) Clinically relevant abnormal ECG (12-lead) at Screening, as
Judged by the Investigator.
6) Diagnosis of gastric or duodenal ulceration, or history of
significant gastro-duodenal bleeding during the last 6 months prior
to Screening.
7) A history of hypersensitivity reactions (such as asthma.
rhinitis, or urticaria) to aspirin. naproxen or any other NSAIDs;
or hypersensitivity or contraindications to organk; nitrate drugs
or to acetaminophen at Screening
8) A history of alcohol or drug abuse. or addiction within the
last 2 years prior to Screening
9) Current or expected use of erectile dysfunction
phosphodiesterase type V (PDES) inhibitor, nitrates or any nitric
oxide donating drugs other than (he investigational treatment at
Screening or Baseline.
10) Current or expected use of anticoagulants at Screening or
Baseline.
11) Any use or expected use of concurrent analgesic,
anti-inflammatory therapy. including aspirin (allowed only if
administered daily at a morning dose 5 325 mg per day) at Screening
or Baseline.
12) Oral, intramuscular and lower limbs intra-articular
corticosleroids are not allowed 3 months prior to Screening. Only
stable dose regimens of inhaled and topk:al corticosteroids are
allowed.
13) Hyaluronan injections in lower limb are prohibited 6 months
prior to Screening (and between Screening and Baseline)
14) A current medical or arthritic disease that could confound
or interfere with the evaluation of efficacy, including but not
limited to: rheumatoid arthritis, septic arthritis, systemic lUpus
erythematosus, spondyloarthropathy, Paget's disease affecting
the study joint, osteochondritis dessicans or osteonecrosis of the
study joint, primary osteochondromatosis. Wilson's disease.
gout and fibromvalgia (to be discussed case Der case with the study
SafetyiSAE contact personJ, acromegaly, hemochromatosis, ochronotic
arthn'tis, heritable disorders (e.g. hypermobility) and
collagen gene mutations. and articular fracture.
15) Subjects who are candidates for imminent (i.e. during the 12
upcoming months) joint replacement of any joint.
16) History of any clinically relevant gastrointestinal,
respiratory, psychiatric, kidney, liver, cardiac disease. bleeding
disorder, other disease/condition or abnormal physical finding
which may interfere with the study objectives, as judged by the
Investigator.
17) Current participation or participation within 30 days prior
to Screening in another investigational study.
18) Previous enrollment in a naproxcinod (HCT 3012) clinical
study or previous enrollment in the present study.
19) Any direct involvement with the study conduct at site or any
family link with study site staff.
If you would like to learn more about participating in this study, please send an e-mail message using the form below.
