A single centre, double blind, randomised, parallel group, single and multiple dose, safety and tolerability, pharmacokinetic study of R131-2 vaginal soft gel capsule in healthy women volunteers
Study assessing the single and multiple dose, safety and tolerability of an intravaginal soft gel capsule containing R131-2 in healthy women volunteers.
Zenith Technology Corporation Limited
12 participants
Nov 6, 2021
Interventional
Conditions
Summary
The purpose of our study is to investigate the absorption, safety and tolerability of R131-2 vaginal soft gel capsule containing 1,3-thiazol-5-ylmethyl N-[(2S,3S,5S)-3-hydroxy-5-[[(2S)-3-methyl-2-[[methyl-[(2-propan-2-yl-1,3-thiazol-4-yl)methyl]carbamoyl]amino]butanoyl]amino]-1,6-diphenylhexan-2-yl]carbamate / (2S)-N-[(2S,4S,5S)-5-[[2-(2,6-dimethylphenoxy)acetyl]amino]-4-hydroxy-1,6-diphenylhexan-2-yl]-3-methyl-2-(2-oxo-1,3-diazinan-1-yl)butanamide. In this study we will measure how much 1,3-thiazol-5-ylmethyl N-[(2S,3S,5S)-3-hydroxy-5-[[(2S)-3-methyl-2-[[methyl-[(2-propan-2-yl-1,3-thiazol-4-yl)methyl]carbamoyl]amino]butanoyl]amino]-1,6-diphenylhexan-2-yl]carbamate / (2S)-N-[(2S,4S,5S)-5-[[2-(2,6-dimethylphenoxy)acetyl]amino]-4-hydroxy-1,6-diphenylhexan-2-yl]-3-methyl-2-(2-oxo-1,3-diazinan-1-yl)butanamide is absorbed into the bloodstream. This is called pharmacokinetics and refers to what happens to a medication from the time it enters the body until the exit of all traces of it. This will be measured from both single and multiple doses of R131-2 vaginal soft gel capsule.
Eligibility
Inclusion Criteria12
- a) Women, 20 to 45 years old, with an intact uterus and vagina.
- b) Generally, in good health with no clinically significant pulmonary, cardiac, gastroenterological, pancreatic, neurologic, renal, musculoskeletal, rheumatologic, metabolic, neoplastic, or endocrine disease.
- c) BMI of greater than or equal to 19 and less than or equal to 30.0
- d) ECG and vital signs within normal ranges
- e) Agree to no Alcohol from 48 hours prior to dosing in period 1 until 7 days after receiving the final dose in period 2.
- f) Abstain from food or beverages containing grapefruit, starfruit, pomegranate, pineapple, or pomelo for the entire study
- g) Able and willing to abstain from sexual intercourse +/– 6 hours around dosing within Periods 1 and 2
- h) Able and willing to use stringent methods of contraception after required abstinence period through to Day 29 (7 days after receiving the final dose in period 2), including the use of a non-latex condom (for partner protection) and a second acceptable contraception method.
- i) Agree to abstain from activities such as vaginal douching or insertion of any vaginal products other than the study drug for at least 48 hours prior to enrolment and throughout the study.
- j) Negative Pap test at screening or within 3 years of enrolment and no history of cervical intraepithelial lesions within the previous 3 years
- k) Able and willing to return to the clinic for all study procedures.
- l) Able and willing to provide informed consent.
Exclusion Criteria14
- a) Women who are pregnant, plan to become pregnant in the next 3 months, or lactating females.
- b) History of genital herpes with >3 outbreaks per year, or active non-HPV vaginal infection
- c) Positive result for Hep B, Hep C or HIV.
- d) Have an active pelvic infection (positive urine screen for gonorrhoea or chlamydial infection, positive test and symptoms for bacterial vaginosis, candida vaginitis or trichomonal vaginitis)
- e) Current or recent abnormal vaginal discharge and /or abnormal vaginal bleeding, within the 3 months prior to randomization as accessed by Investigator.
- f) Had an abortion or miscarriage within the 3 months prior to randomization
- g) Currently taking any of the following medications: oral corticosteroids, inhaled salmeterol and fluticasone; immunomodulatory treatments, over the counter (OTC) intra-vaginal preparation, or any prescription that in the opinion of the Investigator could interfere with the interpretation of the results.
- h) Currently taking any of the medications listed here - Alfuzosin, Amiodarone, dronedarone, Ranolazine, Fusidic Acid, Colchicine, Astemizole, terfenadine, Lurasidone, Pimozide, Quetiapine, Dihydroergotamine, ergonovine, ergotamine, methylergonovine, Cisapride, Lovastatin, simvastatin, Avanafil, Sildenafil, Vardenafil, Oral midazolam, triazolam, St. John's wort.
- i) Recent history (within previous 3 months) of Stevens-Johnson syndrome, erythema multiforme, urticaria, angioedema, deep vein thrombosis, tinnitus, vertigo, blood glucose disorders, pancreatitis, haemophilia.
- j) Hypersensitivity to any component of R131-2 vaginal ointment excipients
- k) Participation in any clinical study with an experimental medication or device within 30 days or 5 half-lives (whichever is longer) of enrolment.
- l) Current alcohol or substance abuse as assessed by the Investigator.
- m) An employee or first degree family member of an employee, the Sponsor, the CRO or study site.
- n) Not having a GP
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Interventions
A study to investigate the safety, tolerability and pharmacokinetics of R131-2 vaginal soft gel capsule in healthy women volunteers after single and multiple doses of 300mg 1,3-thiazol-5-ylmethyl N-[(2S,3S,5S)-3-hydroxy-5-[[(2S)-3-methyl-2-[[methyl-[(2-propan-2-yl-1,3-thiazol-4-yl)methyl]carbamoyl]amino]butanoyl]amino]-1,6-diphenylhexan-2-yl]carbamate / 25mg (2S)-N-[(2S,4S,5S)-5-[[2-(2,6-dimethylphenoxy)acetyl]amino]-4-hydroxy-1,6-diphenylhexan-2-yl]-3-methyl-2-(2-oxo-1,3-diazinan-1-yl)butanamide and observe the rates of side effects reported by women using R131-2 vaginal soft gel capsule compared to placebo. This study comprises of one cohort. It involves a first period comprising a single 300 mg/25 mg dose on Day 1 of R131-2 or placebo vaginal soft gel capsule with Pharmacokinetic blood sampling during confinement up to 48 hours after dosing. Washout of one day and then a multiple dose second period (Day 3-23) comprising 20 daily doses x 300 mg/25 mg of R131-2 or placebo vaginal soft gel capsule administration followed by Pharmacokinetic blood sampling during confinement up to 36 hours post dosing. The confinement days are Days 1-2 (27 hours) and Days 23-24 (27 hours). The soft gel capsule will be self-administered into the vagina. Full instructions will be given as to its application. Participants will also be asked to provide a vaginal swabs at various intervals throughout the study. The capsule will be given to participants to take home along with the study questionnaires. A diary will also be completed by each participant. To monitor adherence to the intervention product each participant will be given a diary to complete daily with vaginal swabs performed on Day 1, 8, 15, 23 and exit. Pre and post study laboratory tests will be completed to assess the health of participants. The intervention for this study is the soft gel capsule formulation of R131.
Locations(1)
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ACTRN12621001487808