Cheers Mozz
Think you nailed it. The original pilot oral study is here.............
https://ibjr.sydney.edu.au/volunteer/pps-study/https://anzctr.org.au/Trial/Registration/TrialReview.aspx?id=376682...and the current Marvel study here.
https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=381498&isReview=trueThese use 10mg/kg, every 4 days according to the first study (ie. ~twice per week). The current study says 10mg/kg but omits to say how often - I'm presuming its every 4 days.
Compared with our 2mg/kg twice per week, the oral is bang on
5 times as much. (we are 4mg/kg/w, oral study is 20mg/kg/w). Matches perfectly with your bioavailability numbers.
We know oral Elmiron has issues with a side effect of blindness/maculopathy with extended use - in fact there are plenty of class actions initiated and some insurers are dropping it as a reimbursable which is huge (
https://www.ichelp.org/insurance-and-elmiron-what-you-need-to-know/). Elmiron is 300mg per day which for a 60kg person is 5mg/kg per day or 35mg/kg/w, so even stronger than the oral OA dose. Nevertheless, given the scrutiny we currently have on the IND over an issue with some preclinical tox data - would FDA approval of oral PPS be 5 times as difficult for 5 times the dose, (esp given the current issues with Elmron)? Then there are the patents which I recall Paul mentioning in some presentation that the PAR patents cover administration of PPS for OA by any route.
It actually seems positive in many ways. The oral trial description states ............
In human patients, a recent pilot open-label study (ACTRN12619000047190) conducted by the University of Sydney aimed to target dyslipidemia in OA participants by oral administration of PPS. Pain and function information from participants were collected to determine if improvements in dyslipidemia would also result in clinical improvements of symptoms associated with knee osteoarthritis. The study outcomes revealed oral PPS significantly improved pain, stiffness, and other functional measures in these patients. The study's secondary outcomes also showed a statistically significant decrease in total and LDL cholesterol and a positive change in self-reported outcomes and severity knee pain score, measured using KOOS and NRS scale together.I know you know we know PPS works....... but always nice to get a statement from a completely independent research body like that!
(20min delay)