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Trial registered on ANZCTR


Registration number
ACTRN12618000883213
Ethics application status
Approved
Date submitted
21/05/2018
Date registered
25/05/2018
Date last updated
25/05/2018
Type of registration
Retrospectively registered

Titles & IDs
Public title
A single centre, double blind, randomised, parallel group, ascending single and multiple dose, safety and tolerability, pharmacokinetic and pharmacodynamic study of vaginal ointment in healthy women volunteers
Scientific title
Study assessing the single and multiple dose, safety and tolerability of an intravaginal ointment containing R131 in healthy female volunteers.
Secondary ID [1] 294938 0
None
Universal Trial Number (UTN)
U1111-1201-4973
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Cervical neoplasia 307911 0
Condyloma acuminatum 307955 0
Condition category
Condition code
Infection 306955 306955 0 0
Sexually transmitted infections

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
A study to investigate the safety, tolerability, pharmacokinetic, pharmacodynamics of R131 vaginal ointment in healthy women volunteers after multiple doses of 150mg or 300mg.

The study will comprise of two cohorts. Cohort 1 will involve the first period comprising of a single 150mg dose of R131 or placebo vaginal ointment with PK blood sapmling during confinement and then the second period comprising of 21 daily doses of 150mg of R131 or placebo vaginal ointment followed by PK blood sampling. Cohort 2 will be administered a 300mg dose of R131 or placebo vaginal ointment in the same dose regimen as cohort 1.

Cohort 2 will commence following review and approval of DSMB.

The ointment 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 ointment 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 used ointment applicators will be returned and weighed, each participant will be given a diary to complete daily, vaginal swabs will be performed on Day 1, 8, 15 and 21.

Pre and post study laboratory tests will be completed to assess the health of participants. The intervention for this study is the ointment formulation of R131.
Intervention code [1] 301258 0
Treatment: Drugs
Comparator / control treatment
Identical vaginal ointment not containing R131 as Placebo
Control group
Placebo

Outcomes
Primary outcome [1] 305944 0
To compare the bioavailability of Ritonavir (as summarised by Cmax and AUC) for the formulation. All plasma samples will be assayed for Ritonavir using one fully validated LC/MS/MS method. Validation will be conducted to comply with FDA guidelines.
Timepoint [1] 305944 0
Day 1-2: 0, 1, 2, 4, 8, 12, 24. Day 22-23: 0, 1, 2, 4, 8, 12 and 24 hours after dosing
Primary outcome [2] 305945 0
To evaluate the safety (as summarised by adverse events, vital signs and ECG).
Timepoint [2] 305945 0
Adverse events will be assessed continuously from dosing until release from confinement period in each cohort.

Vital signs will be:
Screening
Period 1 - Day 1 baseline and at 12 and 24 hours.
Period 2 - Day 8, Day 15, Day 22 at 12 and 24 hours and on study exit
Primary outcome [3] 305974 0
To compare the bioavailability of Lopinavir (as summarised by Cmax and AUC) for the formulation. All plasma samples will be assayed for Lopinavir using one fully validated LC/MS/MS method. Validation will be conducted to comply with FDA guidelines.
Timepoint [3] 305974 0
Day 1-2: 0, 1, 2, 4, 8, 12, 24. Day 22-23: 0, 1, 2, 4, 8, 12 and 24 hours after dosing
Secondary outcome [1] 347088 0
Time to maximum peak concentration (Tmax) of R131 will be determined by plasma sample analysis. Tmax will be the time where the maximum concentration occurred in the sample points.

For those participants receiving the placebo, only samples around the expected Tmax i.e. 2-3 hours will be assayed with the pre-dosing samples.
Timepoint [1] 347088 0
Day 1-2: 0, 1, 2, 4, 8, 12, 24. Day 22-23: 0, 1, 2, 4, 8, 12 and 24 hours after dosing
Secondary outcome [2] 347089 0
Additional Primary Outcome: To evaluate tolerability (as summarised by participant questionnaires (vaginal irritation questionnaire))
Timepoint [2] 347089 0
The Daily Diary and vaginal irritation questionnaire will be completed each morning following each previous evening dose. This will occur at each visit to the clinical site (Days 1-2 and 21-22), at each participants home and at each visit to Zenith Technology during the study (Days 8 and 15) for a total of 21 days. In addition to answering specific questions concerning irritation, participants will use a rating scale to evaluate discomfort and severity.
Secondary outcome [3] 347295 0
Additional Primary Outcome: To evaluate pharmacodynamics (as summarised by participant rating scores designed specifically for the study)
Timepoint [3] 347295 0
The Daily Diary and vaginal irritation rating scores will be completed each morning following each previous evening dose. This will occur at each visit to the clinical site (Days 1-2 and 21-22), at each participants home and at each visit to Zenith Technology during the study (Days 8 and 15) for a total of 21 days.

Eligibility
Key inclusion criteria
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.
Minimum age
20 Years
Maximum age
45 Years
Gender
Females
Can healthy volunteers participate?
Yes
Key exclusion criteria
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 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
After obtaining consent and confirming eligibility,the participant will be randomised in the study. Study drug will be prepared for each participant by pharmacy staff, according to the randomisation code. All clinical staff will remain blinded. Individual randomisation envelopes will be provided in case the identity of study drug administered to a participant needs to be known.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomization by computer
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint(s)
Pharmacokinetics
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment outside Australia
Country [1] 10490 0
New Zealand
State/province [1] 10490 0
Otago

Funding & Sponsors
Funding source category [1] 299523 0
Commercial sector/Industry
Name [1] 299523 0
Douglas Pharmaceuticals Limited
Address [1] 299523 0
PO Box 45 027
Auckland 0651
Country [1] 299523 0
New Zealand
Primary sponsor type
Commercial sector/Industry
Name
Zenith Technology Corp Ltd
Address
PO Box 1777
156 Frederick St
Dunedin 9054
Country
New Zealand
Secondary sponsor category [1] 298823 0
None
Name [1] 298823 0
Address [1] 298823 0
Country [1] 298823 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 300420 0
Northern A Health and Disability Ethics Committee
Ethics committee address [1] 300420 0
Ministry of Health
133 Molesworth Street
PO Box 5013
Wellington 6011
Ethics committee country [1] 300420 0
New Zealand
Date submitted for ethics approval [1] 300420 0
31/08/2017
Approval date [1] 300420 0
29/11/2017
Ethics approval number [1] 300420 0
17/NTA/178

Summary
Brief summary
The objective of this study is to evaluate the safety, tolerability, pharmacokinetic and pharmacodynamic of a 21 day treatment of self-administered vaginal ointment containing R131.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 83606 0
Dr Noelyn Hung
Address 83606 0
Zenith Technology Corp Ltd
PO Box 1777
156 Frederick St
Dunedin 9054
Country 83606 0
New Zealand
Phone 83606 0
+6434779669
Fax 83606 0
+6434779605
Email 83606 0
noelyn.hung@otago.ac.nz
Contact person for public queries
Name 83607 0
Mrs Linda Folland
Address 83607 0
Zenith Technology Corp Ltd
PO Box 1777
156 Frederick St
Dunedin 9054
Country 83607 0
New Zealand
Phone 83607 0
+6434779669
Fax 83607 0
+6434779605
Email 83607 0
linda.folland@zenithtechnology.co.nz
Contact person for scientific queries
Name 83608 0
Dr Tak Hung
Address 83608 0
Zenith Technology Corp Ltd
PO Box 1777
156 Frederick St
Dunedin 9054
Country 83608 0
New Zealand
Phone 83608 0
+6434779669
Fax 83608 0
+6434779605
Email 83608 0
tak.hung@zenithtechnology.co.nz

No information has been provided regarding IPD availability
Summary results
No Results