| Eligibility |
Inclusion Criteria:
1. Must be able to read and to provide written, personally signed, and dated informed
consent to participate in the study, in accordance with the ICH GCP Guideline E6 and
applicable regulations, before completing any study related procedures.
2. Has an understanding, ability, and willingness to fully comply with study procedures
and restrictions, as determined by the investigator.
3. Must be a male or female between 35 and 85 years of age, inclusive.
4. Must have a body mass index between 18.5 and 40.0 kg/m2, inclusive.
5. Must have a history (documented diagnosis) of clinically symptomatic OA of the lumbar
spine for =3 months at Screening.
6. Must have a Lane Radiographic Grading Scale summary score for lumbar spine OA (levels
L1 through L5) of 1 or 2 as determined by a central radiologist at Screening.
7. Must have had low back pain while standing, walking, and/or on motion for at least 14
days during the month prior to Screening per subject self-report documented by the
investigator.
8. Must have a score =4 and =9 on a 0 to 10 (11 point) NPRS (without analgesic medication
other than rescue medication provided by the Sponsor) over the previous 7 days prior
to Baseline (Day 1).
9. Must have an ODI score =40% and =90 % at Screening Visit and Baseline (Day 1).
10. With the exception of OA of the lumbar spine, must be in good general health with no
clinically significant findings from medical history, vital signs, physical
examination, ECG, and routine laboratory tests that could interfere with subject
safety, pain or functional assessments, as determined by the investigator.
11. Female subjects must either not be of childbearing potential defined as 1)
postmenopausal for at least 1 year; follicle stimulating hormone [FSH] must be in
postmenopausal range for the central lab if used to confirm postmenopausal status in a
woman not using estrogen replacement therapy OR 2) surgically sterile [i.e., bilateral
tubal ligation, bilateral oophorectomy, or hysterectomy]) or be willing to practice
abstinence or at least 1 of the following medically acceptable methods of birth
control:
- Hormonal methods such as oral, implantable, injectable, vaginal ring, or
transdermal contraceptives for a minimum of 1 full cycle (based on the subject's
usual menstrual cycle period) before study drug administration;
- Intrauterine device;
- Double-barrier method (condoms, sponge, or diaphragm with spermicidal jellies or
cream).
Exclusion Criteria:
1. 1. Not willing to avoid unaccustomed, strenuous physical activity (e.g., starting a
new weight lifting routine) for the duration of the study starting at Screening Visit
and through their completion of participation in the study. Normal physical activity
is allowed.
2. Has an active or pending workman's compensation claim or litigation related to back
pain.
3. Has secondary OA of the low back or OA of lower limb joints that, in the opinion of
the investigator, could interfere with pain and functional assessments related to the
low back.
4. Has a history of spinal surgery.
5. Has more than 25% improvement from Numeric Pain Rating Scale (NPRS) score at the
Screening visit to the average NPRS score over the previous 7 days prior to Day 1.
6. Has had significant injury, as judged by the investigator, involving the back within
the 6 months before Screening.
7. Has been diagnosed with or has signs and symptoms of a radiculopathy, e.g., numbness
or tingling in a dermatomal distribution of a lower limb, sciatica, as well as
etiologies of low back pain other than OA.
8. Has skin lesions or wounds on or near the lumbar spine area to be treated at Screening
or on Day 1, which may influence absorption of the medication or confound safety
assessments per the investigator's opinion.
9. Has used gabapentin, pregabalin, antiepileptics, or specific antidepressants (i.e.,
tricyclics, serotonin norepinephrine reuptake inhibitors, or selective serotonin
reuptake inhibitors) to treat pain in the 14 days before Screening. Other uses not
related to the pain treatment may be permitted at the medical monitor's discretion
provided they have been at a stable dose for at least 90 days.
10. Has had injections of corticosteroids, botulinum toxin, or viscosupplements (e.g.,
Synvisc®) to the spine area (eg., intra articular [IA], epidural or paraspinal) within
the 12 weeks before Screening.
11. Has had IA, intradiscal or intravenous (IV) stem cell therapy in the 6 months prior to
Screening.
12. Has received concomitant non-pharmacologic treatments (e.g., physiotherapy,
acupuncture) that per investigator opinion could confound efficacy assessments within
14 days of Day 1.
13. Is not willing to discontinue any NSAIDs or other analgesics (i.e., acetaminophen
other than rescue medication supplied by the Sponsor, and cyclooxygenase-2 [COX-2]
inhibitors), other treatments such as cannabis, and any topical therapies (e.g.,
anesthetics, capsaicin) or potentially confounding concomitant nonpharmacologic
treatments (e.g., physiotherapy, acupuncture) starting at Screening Visit until
completing participation in the study (the use of =325 mg acetylsalicylic acid per day
for cardiac prophylaxis is permitted).
14. Is not willing to discontinue applying any topical preparations containing Vitamin A
acids (including all trans retinoic acid [tretinoin], 13 cis retinoic acid
[isotretinoin], 9 cis retinoic acid [alitretinoin], Vitamin A [retinol], retinal, and
their derivatives) to the low back starting at Screening Visit until completing
participation in the study. Topical preparations containing Vitamin A acids or retinol
may be applied to areas of the skin above the shoulders or to the lower extremities.
15. Has a history of significant hypersensitivity, intolerance, or allergy to ibuprofen,
any other NSAIDs, aspirin, or acetaminophen.
16. Has used an anticoagulant or antiplatelet agent (except aspirin up to 325 mg/day for
cardiac prophylaxis) in the 30 days prior to Screening.
17. Has had an active gastrointestinal (GI) ulceration in the 6 months prior to Screening
or a history of GI bleeding within 5 years of Screening.
18. Has uncontrolled depression or other uncontrolled psychiatric disorder (subjects with
controlled depression or other psychiatric disorder, if using medication, must be on a
stable dose of a medication other than an epileptic, tricyclic, serotonin
norepinephrine reuptake inhibitor, or selective reuptake inhibitor for =12 weeks prior
to Screening to participate in the study).
19. Has positive results on fecal occult blood testing at Screening or on Day 1.
20. Has a documented history of chronic inflammatory disease (such as rheumatoid
arthritis, ankylosing spondylitis, axial spondyloarthropathy, psoriatic arthritis,
inflammatory bowel disease or gouty arthritis) or a chronic pain condition (such as
fibromyalgia), or has other conditions that may affect the spine or the functional and
pain assessments (e.g., diffuse idiopathic skeletal hyperostosis, spinal stenosis,
osteoporosis, severe scoliosis [curvature >30 degrees], severe kyphosis or lordosis
[curvature >50 degrees]).
21. Is an asthmatic requiring treatment with systemic corticosteroids in the last year.
Asthmatic subjects using inhaled corticosteroids are eligible.
22. Has uncontrolled hypertension defined as systolic blood pressure >170 mmHg or
diastolic blood pressure >90 mmHg at Baseline (may be repeated 1 additional time after
5 minutes rest to verify). The investigator may, at his discretion, choose to exclude
subjects with blood pressure levels lower than these if he deems it in the best
interest of the subject.
23. Is receiving systemic chemotherapy, has an active malignancy, lymphoproliferative
disorder or blood dyscrasia of any type, or has been diagnosed with cancer within 5
years before Screening. Subjects with completely excised and healed squamous or basal
cell carcinoma of the skin will be allowed.
24. Has had any osteoporosis treatments (e.g., bisphosphonates, denosumab, parathyroid
hormone (PTH), strontium ranelate).
25. Has any other clinically significant unstable cardiovascular, respiratory,
neurological, immunological, hematological, hepatic or renal disease, or any other
condition that, in the investigator's opinion, could compromise the subject's welfare,
ability to communicate with the study staff, or otherwise contraindicate study
participation.
26. Has an abnormal clinical central laboratory assessment at Screening for any of the
following:
- Aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline
phosphatase or lactate dehydrogenase (LDH) =3 × the upper limit of normal [ULN]
- Total bilirubin =1.5 × ULN
- Creatinine =1.5 × ULN
- Hemoglobin <10 g/dL
27. Has any other clinically significant central laboratory finding at Screening that in
the investigator's opinion contraindicates study participation;
28. Has clinically significant abnormality on 12-lead ECG, including a QTcF interval >450
milliseconds for males and 470 msec for females.
29. Is pregnant, planning to become pregnant during the study, or lactating; for women of
childbearing potential, serum and urine pregnancy test must be negative at Screening
Visit and urine pregnancy test must be negative at Baseline (Day 1) for subject to be
eligible to participate.
30. Has participated in a previous clinical study with X0002.
31. Has participated in any other investigational clinical trial within the past 30 days
or 5 half-lives of the investigational drug, whichever is longer, prior to Screening.
32. Has known alcohol or other substance abuse in the investigator's opinion.
33. Is a participating investigator, sub-investigator, study coordinator, or employee of a
participating investigator, or is an immediate family member of the aforementioned.
34. Has any factor, which in the opinion of the investigator would jeopardize the
evaluation or safety or be associated with poor adherence to the protocol.
35. Does not have access to telephone and/or ability to gain technology access.
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