None listed
Conditions
Brief summary
This study is assessing the pharmacokinetics, safety and tolerability of single doses of eRapa compared to Rapamune in healthy volunteers. Who is it for? You may be eligible to join this study if you are aged between 18 and 65 years old who are overtly healthy as determined by screening study assessments. People who have been diagnosed with cancer will not be eligible for this study. Study details This healthy volunteer study is designed to compare the absorption of a new formulation of rapamycin called eRapa and a currently available formulation known as Rapamune for the treatment of familial adenomatous polyposis. Familial adenomatous polyposis (FAP) is a rare inherited disease that increases the risk of developing bowel cancer at an earlier age than the general population. Participants in this study are randomly allocated by simple randomisation to eRapa or Rapamune (rapamycin) as a first dose and then vice versa for the second dose 14-20 days after the first dose. Pharmacokinetics, safety and tolerability and will be assessed at regular intervals using clinical examinations and blood tests. The rate and predictability of the absorption of eRapa will be compared to Rapamune. It is hoped this research will contribute to improving clinical outcomes in patients with familial adenomatous polyposis (FAP) by preventing or delaying disease progression.
Interventions
Single oral dose of 0.5 mg eRapa capsules given under fasted conditions.
Intervention period: includes randomisation, pre-treatment procedures, administration of a single dose of eRapa and Rapamune, and various assessments according to the Schedule of Activities as per the protocol. Each participant will complete two treatment periods, one for each trial drug, separated by a washout interval. After the washout, pre-treatment procedures will be repeated starting from Day -1 in preparation for the
Single oral dose of 0.5 mg eRapa capsules given under fasted conditions. Intervention period: includes randomisation, pre-treatment procedures, administration of a single dose of eRapa and Rapamune, and various assessments according to the Schedule of Activities as per the protocol. Each participant will complete two treatment periods, one for each trial drug, separated by a washout interval. After the washout, pre-treatment procedures will be repeated starting from Day -1 in preparation for the second treatment period. • 7 days: Period 1 Study Intervention • 14-20 days: Washout interval between each intervention as required. Patients will be required to fast for atleast 8 hours prior to each intertention and with no food consumed at least 2 hours post dose. Total duration of intervention = approximately 82 days PK blood samples will be collected pre dose and post dose to assess study concentrations in the blood.
Sponsors
Biodexa Australia PTY Ltd
Study design
Allocation
Randomised controlled trial
Intervention model
Crossover
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
1. Male or female participants who are overtly healthy as determined by screening study assessments. 2. Participants must be between 18 and 65 years of age inclusive, at the time of signing the consent form. 3. A body mass index (BMI) within the range 18 and 32 kg/m2 inclusive. 4. Male and/or female assigned at birth, inclusive of all gender identities. Male participants are eligible to participate if they agree to the following prior to the first dose of study intervention, during the study, and for 90 days plus 5 half-lives of eRapa after the last dose of study intervention: • Refrain from donating sperm • Be abstinent from intercourse where pregnancy can occur (abstinent on a long term and persistent basis) and agree to remain abstinent, OR Must agree to use contraception/barrier as detailed below: •. Agree to use an external condom with a partner of childbearing potential, agree to use of an additional highly effective contraceptive method when having sexual intercourse with a partner able to give birth who is not currently pregnant. • Agree to use an external condom when engaging in any activity that allows for passage of ejaculate to another person Female participants are eligible to participate if not pregnant or breastfeeding, and one of the following conditions applies: • Is of non-childbearing potential • Is of childbearing potential and using an established contraceptive method that is highly effective during the study intervention period and for at least 12 weeks after the last dose of study intervention, and agrees not to donate eggs (ova, oocytes) for the purpose of reproduction during this period. • A participant of Childbearing potential in addition to an established contraceptive method must also have a negative highly sensitive pregnancy test (serum at screening, urine at baseline), within 24 hours before the first dose of study intervention, If a urine test cannot be confirmed as negative (e.g., an ambiguous result), a serum pregnancy test is required. In such cases, the participant must be excluded from participation if the serum pregnancy result is positive. 5. Signed informed consent
Exclusion criteria
1. Have a history of or a current immunosuppressive condition (e.g., human immunodeficiency virus infection). 2. Have any illness, judged by the Principal Investigator (PI) or delegate as clinically significant, in the 3 months prior to the first dose of study intervention. 3. Have PI determined current clinically significant infection or clinically significant infection within 6 months of first dose of study intervention (e.g., opportunistic infections or those requiring hospitalisation or parenteral antimicrobial therapy). 4. Have a history of chronic or recurrent infectious disease within the last 2 years. 5. Have symptomatic herpes zoster or herpes simplex within 12 weeks of first dose of study intervention, or more than 1 episode of local herpes zoster, or a history of disseminated zoster. 6. Have history of malignancy within the past 5 years, except for locally confined malignancies that have been definitively treated and are considered cured, with no evidence of recurrence, such as basal cell carcinoma of the skin. Liver Safety 7. Blood result: Aspartate aminotransferase (AST)/ and alanine aminotransferase (ALT) greater or equal to 1.5 x upper limit of normal (ULN). Total bilirubin greater or equal to 1.5 x ULN. Note: Participants with a history of Gilbert's syndrome may have a direct bilirubin measured and would be eligible for this study provided the direct bilirubin is = ULN. Prior/Concomitant Therapy 8. Participant is taking medications that are considered strong inducers or inhibitors of cytochrome P450 3A4/5 (CYP3A4/5) or strong inducers or inhibitors of P-glycoprotein 1 (P-gp1) that cannot be discontinued at least 1 week prior to first dose of study intervention and for the duration of the study. 9. Have received treatment with any drug known to have a potential for major organ toxicity in the last 3 months before the first dose of this study intervention. 10. Have received treatment with any medication (including over-the-counter and/or prescription medicines [including hormonal replacement therapy for postmenopausal participants], nutraceuticals, Cannabidiol (CBD), herbal supplements such as St. John's Wort (Hypericum perforatum) and recreational drugs), with the exception of hormonal contraception, within the last 2 weeks or 5 half-lives of that drug (whichever is longer) prior to the first dose of this study intervention through to trial completion Note: Occasional paracetamol (maximum dose of 2 g/day) and ibuprofen 400mg/day) is permitted for use at any time during the study. 11. Have, or plan to receive, any live-attenuated vaccine within 4 weeks prior to Day 1 of trial, during intervention and up to 4 weeks following completion. 12. Have had, or plan to have, contact with any household or individuals who have received vaccination with live or attenuated live virus within 4 weeks prior to Day 1 of dosing, during intervention and up to 8 weeks following completion. Prior/Concurrent Clinical Study Experience 13. Have known hypersensitivity to investigational medicinal product (IMP) ingredients (sirolimus, lactose monohydrate, sodium cholate, glycerol and talc) or history of a significant allergic reaction to IMP ingredients as determined by the Investigator, such as anaphylaxis requiring hospitalisation. Or any other significant allergy that the principal investigator or delegate consider clinically significant. 14. Current or previous participation in another investigational research study where the participant has received an investigational drug or drug/device within 30 days or 5 of its half-lives (whichever is longer) prior to the first dose of this study intervention or has received an investigational biologic within 12 weeks or 5 of its half-lives (whichever is longer) prior to the first dose of this study intervention. Note: Participants who have participated in Part 1 of this study are not eligible for enrolment into Part 2 of this study. Safety Laboratory Assessments 15. Positive screen for drugs of abuse (methamphetamine, amphetamines, barbiturates, benzodiazepines, cannabis, cocaine, opiates, methadone, phencyclidine, tricyclic antidepressants) and alcohol at screening and on Day -1. Cotinine testing on Day -1 only. 16. Positive serology for hepatitis B virus surface antigen, hepatitis B virus core antibody, or hepatitis C virus, or history of hepatitis from any cause with the exception of hepatitis A. 17. Presence or sequelae of gastrointestinal, liver, or kidney (estimated creatinine clearance =90 mL/min, using the Cockcroft-Gault formula; if calculated creatinine clearance is =90 mL/min a 24-hour urine collection may be performed to assess renal function) disease, or other conditions known to interfere with the absorption, distribution, metabolism, or excretion of drugs (e.g. small bowel obstruction, pancreatitis, previous major gastrointestinal surgery). Other Exclusion Criteria 18. Clinically significant abnormalities detected on 12-lead ECG of either rhythm or conduction (e.g., corrected QT interval by Fridericia’s formula >450 msec for males or >470 msec for females; known to have long QT syndrome). Mean values per parameter will be considered. A first-degree heart block will not be considered as a significant abnormality. 19. Clinically significant abnormalities detected on vital signs. If an initial vital sign measurement is outside the range required by the protocol or shows a profound/unexpected change, the measurement may be repeated after the participant has rested for approximately 5 to 10 minutes to confirm the value or rule out temporary factors. 20. Significant blood loss (including blood donation [>500 mL]) within 30 days prior to screening, plasma donation within 2 weeks prior to screening or platelet donation 6 weeks prior to dosing and through to end of study. 21. Current use of nicotine-containing products, including but not limited to cigarettes, e-cigarettes/vaping devices, nicotine patches, nicotine gum, or other nicotine replacement therapies. Participants must have discontinued all nicotine-containing products for at least 72 hours prior to cotinine testing on Day -1. Note: casual smoking/vaping, defined as the equivalent of <5 cigarettes per week, is permitted provided the participant agrees to abstain from smoking and the use of nicotine containing products for the entire duration of the intervention period. 22. Active drug or alcohol abuse (sustained use of more than 4 glasses of wine, beer or equivalent/day) within 2 years prior to the first dose of study intervention. 23. Investigator or other site staff or Biodexa employees directly involved in the conduct of the study, and their respective family members. 24. Any condition or circumstances that, in the opinion of the Principal Investigator or delegate, may make a participant unlikely or unable to complete the study or comply with study procedures and requirements.
Outcome results
None listed