A Double-Blind, RandoMised, Placebo-Controlled Study to Assess the

INTERVENTION: ‐ Participants in both the active and placebo group will be provided with oral intervention capsules of Sodium Pentosan Polysulfate (PPS) or Placebo. Every single capsule is 300mg. Participants take the recommended dosage pre‐calculated as per 10mg/kg of their actual body weight. Cycle 1 of the intervention will commence at baseline and completes at week 6 visit, followed by 5 weeks without the medication. Cycle 2 of the intervention will resume at week 11 and completes at week 16. ‐ There is no treatment crossover. This is the standard dosing regime used for the administration of Pentosan. The five‐week cessation period is the same design used in the earlier Ethics approved successful PPS trial (Elmiron) 2019 / ETH11450. The participants take the same capsules as per their group allocation for both cycles. ‐ To measure adherence, each participant will be provided with an e‐diary application installed on their mobile devices (smartphone or iPad) Alternatively, they will be able to use a paper diary. Diary will help participants to stay on track with the medication uptake schedule. Participants will be reminded to take study medication at a scheduled time point by push‐up notifications set up within the e‐diary application. Participants will be instructed to return all unused medication at the next study visit. The remaining capsules will be counted and recorded for the compliance check. Participants will be reminded to commence on the second 5 weeks course at week 11 by an email or a phone call from the study coordinator. Paper diaries or e‐diary will be collected at each time point to ensure compliance is achieved. CONDITION: Musculoskeletal ‐ Osteoarthritis Musculoskeletal Knee Osteoarthritis; ; Musculoskeletal Knee Osteoarthritis PRIMARY OUTCOME: Changes in 24‐hour pain intensity numeric rating scale (NRS) at week 16[Week 16 post‐intervention commencement] SECONDARY OUTCOME: Change in KOOS pain subscale at week 6, 16, and 26. ; [Week 6, 16, and 26 post‐intervention commencement ; ] AEs ‐ assessed by inspection of weekly surveys. Mild effects of swelling, headache, dizziness, nausea, indigestion, or diarrhea may be observed in people taking active pentosan. [Weekly from baseline to Week 26 post‐intervention commencement ; Note: All participants are advised to report any adverse effects experienced by them in the online weekly surveys. Thorough monitoring is also done during the study visits. ] Change in 24‐h Pain Intensity NR scale at week 6 and 26. ; [Week 6, and 26 post‐intervention commencement ; ] Change in fasting HDL/ LDL cholesterol, total cholesterol, and triglyceride levels ; from baseline to week 26.. ; Note: It is a composite secondary outcome[Baseline and week 26 post‐intervention commencement ; ] Change in health‐related quality of life assessed using the Assessment of Quality ; of Life eight dimension (AqoL‐8D) from baseline to week 6, 16 and 26[Week 6, 16, and 26 post‐intervention commencement ; ] Change in MRI MOAKS Semi‐quantitative measures from baseline to week 26.[Baseline and Week 26 post‐intervention commencement ; ] Change in the patient global assessment (PGA) of disease activity from baseline to ; week 6, 16, and 26.[Week 6, 16, and 26 post‐intervention commencement ; .] Changes in consumption of analgesic medications at week 6, 16, and 26.[Week 6,16 and 26 post‐intervention commencement ; ] Safety assessments – physical examination, clinical laboratory; assessments of INCLUSION CRITERIA: (1) Male or female patients with a minimum of 45 years of age; (2) Are able to give written informed consent and to participate fully in the interventions and follow‐up procedures including travel to the Royal North Shore Hospital; (3) Have a history of primary hypercholesterolemia and total fasting cholesterol above 5.0 mmol/L at screening; ; blood and urine;[Baseline to Week 26 post‐intervention commencement. Weekly from baseline to week 26 post‐intervention commencement, all weekly surveys assessed at week 26 post‐intervention commencement, ] (4) Have any symptoms associated with OA of the knee for at least 6 months prior to screening visit and confirmation of OA based on the clinical and radiological criteria of American College of Rheumatology Criteria for OA (Altman et al, 1986) of the knee prior or at screening; (5) Kellgren‐Lawrence (K‐L) Grade 2 or 3 in the index knee based on knee radiograph performed at screening or within six months of the screening visit; (6) Have Index knee pain on most days over the last month. (7) Knee Pain Severity Scale above 4 using an 11‐point (0‐10) numerical severity scale where 0 is no pain at all and 10 is