PPS trials, page-5

Interesting find on the Australian Clinical Trials website. I was not aware of this trial PAR is doing on Healthy Adult Participants.

A Phase 1, Open-label Study to Determine the Safety, Tolerability, and Pharmacokinetics of Multiple Subcutaneous Doses of Pentosan Polysulfate Sodium (PPS) in Healthy Adult Participants

Trial Information

Trial summary

Paradigm Biopharmaceuticals Ltd (Paradigm) is focusing on Pentosan Polysulfate Sodium (PPS) for the treatment of conditions that are associated with inflammation and progress chronically with tissue degeneration, including the treatment of Osteoarthritis Knee pain.   Previous studies demonstrate that PPS is tolerated at the proposed dose (2 mg/kg) and duration (once or twice weekly for 6 weeks).  While most of the clinical data obtained were acquired using a twice weekly regimen, a once weekly SC injection program, if effective and safe, would be ideal for feasibility.This study is will assess safety, tolerability, and pharmacokinetic responses of multiple sub-cutaneous doses of PPS in a healthy western population to support the development program.The clinical and nonclinical evidence demonstrate that PPS is tolerated at the proposed dose (2 mg/kg) and duration (once or twice weekly for 6 weeks). In two studies evaluating dose limiting toxicity, maximum tolerated doses were determined to be 3 mg/kg/day continuous infusion (Pluda et al., 1993) and 22.5 mg/m2 SC injection every 6 hours (Swain et al., 1995). Assuming an average male of 60 kg and 1.9 m, these doses are roughly equivalent to 180 mg/day and 171 mg/day, respectively. These levels are greater than the Sponsor’s current proposed dosing regimen of 2 mg/kg (approximately 120 mg) SC once or twice per week.The PK sampling design in this study will allow comparison with an earlier PK study which evaluated 50 mg to 300 mg PPS administered by SC injection once weekly for 4 weeks. While most of the clinical data obtained were acquired using a twice weekly regimen, a once weekly SC injection program, if effective and safe, would be ideal for feasibility. Therefore, PK data obtained from once and twice weekly dosing regimens will support the development program.

Broad Health ConditionKnee OsteoarthritisBone Marrow Lesion

Specific Health ConditionMusculoskeletalOsteoarthritisMusculoskeletalOther muscular and skeletal disordersInflammatory and Immune SystemOther inflammatory or immune system disorders

Trial FocusTreatment

Recruitment statusRecruiting

Recruitment Details
Recruitment State
SA

Hospital
CMAX Clinical Research Pty Ltd - Adelaide

Postcode
5000 - Adelaide

Anticipated date of first participant enrolment9/09/2020

Anticipated date of last participant enrolment17/09/2020

Phase of TrialPhase 1

Has the study received ethics approval?Approved

Eligibility

Key inclusion criteria

Healthy male or female volunteers, aged grater than or equal to 18 years and less than or equal to 75 years (at the time of informed consent);Participants must be in good general health, with no significant medical history, have no clinically significant abnormalities on physical examination at Screening and/or before administration of the initial dose of study drug;Participants must have a minimum body weight of 50 kg and a Body Mass Index (BMI) greater than or equal to 18.0 and less than or equal to 35.0 kg/m2 at ScreeningParticipants who smoke no more than 10 cigarettes or equivalent per week can be included in the study but must agree to abstain from smoking and all nicotine containing products from 48 hours before each visitMust agree to abstain from alcohol intake from 48 hours before each visitSubjects must be able to provide written informed consent

Minimum age18 Years

Maximum age75 Years

GenderBoth males and females

Can Healthy volunteers participate?Yes

Key exclusion criteria

History of severe allergic or anaphylactic reactionsPregnant or lactating at Screening or planning to become pregnant (self or partner) at any time during the study, including the follow-up periodPrior or ongoing medical conditions, medical history, physical findings, or laboratory abnormality that, in the Investigator’s (or delegate’s) opinion, could adversely affect the safety of the participantPresence of any underlying physical or psychological medical condition that, in the opinion of the Investigator, would make it unlikely that the participant will comply with the protocol or complete the study per protocolAny surgical or medical condition that could interfere with the absorption, distribution, metabolism, or excretion of the study drugBlood donation or significant blood loss within 60 days prior to the first study drug administrationHistory of malignancy except for non-melanoma skin cancer excised more than 2 years ago and cervical intraepithelial neoplasia that has been successfully cured more than 5 years prior to ScreeningHistory of heparin induced thrombocytopeniaParticipants undergoing invasive procedures or having signs/symptoms of underlying coagulopathy or other increased risk of bleeding (due to other therapies such as coumarin anticoagulants, heparin, tissue plasminogen activator (t-PA), streptokinase, high dose aspirin, or nonsteroidal anti-inflammatory drugs [NSAID]). Participants may be enrolled if they satisfy the following criteria with regard to NSAID:•	Participants taking NSAIDs continuously (i.e., daily) agree to a washout period of at least 7 days prior to admission on Day -1;•	Participants taking NSAIDs intermittently (i.e., less than daily) agree to a washout period of at least 24 hours prior to admission on Day -1;•	NSAIDs are not permitted from Day -1 through to the EOS visit