A Safety and Pharmacokinetic Study for Dapivirine and Maraviroc Gel in Belgium
Primary Purpose
HIV Infections
Status
Withdrawn
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
Maraviroc/Dapivirine Gel
Dapivirine Vaginal Gel
Maraviroc Vaginal Gel
Matching Placebo Gel
Sponsored by
About this trial
This is an interventional prevention trial for HIV Infections
Eligibility Criteria
Inclusion Criteria:
- Women 18 to40 years of age who can give written informed consent (illiterate participants may provide a thumbprint or mark witnessed and signed by a person independent from trial staff);
- Available for all visits and consent to follow all procedures scheduled for the trial;
- HIV-negative as determined by an HIV test at time of enrollment;
- Be on a stable form of contraception, defined as:
- A stable oral contraceptive regimen for at least 2 months prior to enrollment, OR,
- Transdermal contraceptive patch for at least 3 months prior to enrollment, OR,
- Long-acting progestins for at least 6 months prior to enrollment, OR,
- An IUD inserted (with no vaginal or gynaecological complaints associated with its use) at least 3 months prior to enrolment, OR,
- Have undergone surgical sterilization at least 3 months prior to enrollment;
- In the absence of the use of exogenous hormone(s), have a self-reported regular menstrual cycle, defined as having a minimum of 21 days and a maximum of 35 days between menses;
- Upon pelvic examination and colposcopy at the time of enrollment, the cervix and vagina appear normal as determined by the Investigator;
- Asymptomatic for genital infections at the time of enrollment (if a woman is diagnosed with any treatable STI, either syndromically or by laboratory test at the time of screening, she must receive treatment at least 2 weeks prior to enrollment and have completed treatment);
- Willing to refrain from the use of vaginal products or objects including, tampons, female condoms, cotton wool, rags, diaphragms, cervical caps (or any other vaginal barrier method), douches, lubricants, vibrators/dildos, and drying agents for 14 days prior to enrollment and for the duration of the trial;
- Willing to use oral contraceptives to avoid menstruation, if necessary, while taking part in this trial;
- Documentation of no abnormality on Pap test, including grossly bloody smear, within 3 months prior to screening;
- Willing to refrain from participation in any other research trial for the duration of this trial;
- Willing to provide adequate locator information for trial retention purposes and be reachable per local standard procedures [e.g., by home visit or telephone; or via family or close neighbour contacts (confidentiality to be maintained)];
- Willing to agree to abstain from oral contact with her genitalia for gel use period, as well as for a total of 3 days (72 hours) after the biopsy procedure:
- Willing to remain sexually abstinent for the gel use period in this trial;
- Hepatitis B and C negative at the time of enrollment.
Exclusion Criteria:
- Currently pregnant or having had their last pregnancy outcome within 3 months prior to screening;
- Currently breast-feeding;
- Currently or within two months of participation in any other clinical research trial involving investigational or marketed products prior to screening;
- Untreated symptomatic urogenital infections, e.g., urinary tract or other sexually transmitted infections, or other gynaecological conditions such as vaginal itching, pain, or discharge, within 2 weeks prior to enrolment;
- Presence of any abnormal clinically significant physical finding on the vulva, vaginal walls or cervix during pelvic examination and/or colposcopy at pre-enrolment;
- History of urogenital or uterine prolapse, undiagnosed vaginal bleeding, urethral obstruction, incontinence or urge incontinence;
- Current vulvar or vaginal symptoms/abnormalities that could influence the trial results;
- Pap test result that requires cryotherapy, biopsy, treatment (other than for infection); or further evaluation [this includes any findings of atypical squamous cells of undetermined significance (ASCUS)];
- Symptomatic genital HSV infection or a history of genital herpetic infection;
- Any Grade 2, 3 or 4 haematology, chemistry or urinalysis laboratory abnormality at baseline (screening) according to the DAIDS Table for Grading Adverse Events (NOTE: This table can be found at: http://rcc.tech-res.com/safetyandpharmacovigilance;and a standardized version will be provided to the research centre in the Study Operations Manual);
- Unexplained, abnormal bleeding per vagina during or following vaginal intercourse, or gynaecologic surgery within 90 days prior to enrollment;
- Any history of anaphylaxis or severe allergy resulting in angioedema; or a history of sensitivity/allergy to latex or silicone;
- Any serious acute, chronic or progressive disease (e.g., any known history of neoplasm, cancer, diabetes, cardiac disease, autoimmune disease, HIV, AIDS, or blood dyscrasias), or signs of cardiac disease, renal failure, or severe malnutrition;
- Have undergone a hysterectomy;
- History of drug abuse within 1 year of enrollment;
- Any condition(s) that, in the opinion of the Investigator, might interfere with adherence to trial requirements or evaluation of the trial objectives.
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Active Comparator
Active Comparator
Placebo Comparator
Experimental
Arm Label
Maraviroc Vaginal Gel
Dapivirine Vaginal Gel
Matching Placebo Gel
Maraviroc/Dapivirine Gel
Arm Description
Drug: Maraviroc dosage form: vaginal gel dosage: 2.5g frequency: once daily duration: 11 days
Drug: Dapivirine dosage form: vaginal gel dosage: 2.5g dapivirine frequency: once daily duration: 11 days
Drug: placebo dosage form: vaginal gel dosage: 2.5g placebo frequency: once daily duration: 11 days
Drug: Maraviroc/Dapivirine dosage form: combination vaginal gel dosage: 2.5g - Maraviroc 0.1%, Dapivirine 0.05% frequency: once daily duration: 11 days
Outcomes
Primary Outcome Measures
Safety: To assess the safety and tolerability of the combination maraviroc and dapivirine gel, the endpoint was the proportion of women in the four arms experiencing specific, protocol defined safety events during the study (see description).
Mucosal abnormalities (as defined in the WHO/CONRAD manual) visible during naked eye examination and/or colposcopy;
Abnormal vaginal pH and/or abnormal vaginal flora during the course of the trial;
Positive diagnostic tests for trichomonas, gonorrhoea and/or chlamydia;
At least one adverse event during the 2 month trial period;
Any laboratory abnormalities on haematology, electrolytes, liver function, and renal function.
Pharmacokinetics: assessment of local and systemic pharmacokinetics of maraviroc and dapivirine in plasma, vaginal fluid and cervical tissue before, during and after 11 days.
Secondary Outcome Measures
Full Information
NCT ID
NCT01242579
First Posted
November 15, 2010
Last Updated
September 8, 2011
Sponsor
International Partnership for Microbicides, Inc.
1. Study Identification
Unique Protocol Identification Number
NCT01242579
Brief Title
A Safety and Pharmacokinetic Study for Dapivirine and Maraviroc Gel in Belgium
Official Title
A Double-Blind, Randomised, Placebo-Controlled Phase I Trial to Compare the Pharmacokinetics of Maraviroc and Dapivirine Following Application of Maraviroc Vaginal Vaginal Gel, 0.1% 2.5g, Dapivirine Vaginal Gel, 0.05%, 2.5g and Maraviroc 0.1% + Dapivirine 0.05% Vaginal Gel, 2.5g Formulations, and to Assess Their Safety as Compared to the Matching Placebo Vaginal Gel, 2.5g in Healthy, HIV-Negative Women
Study Type
Interventional
2. Study Status
Record Verification Date
September 2011
Overall Recruitment Status
Withdrawn
Why Stopped
In order to focus efforts on the combination ring formulation, IPM decided not to move forward with this trial.
Study Start Date
January 2011 (undefined)
Primary Completion Date
July 2011 (Actual)
Study Completion Date
July 2011 (Actual)
3. Sponsor/Collaborators
Name of the Sponsor
International Partnership for Microbicides, Inc.
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The purpose of this study is to assess the pharmacokinetics of the combination dapivirine and maraviroc gel and determine whether it is safe for daily use by healthy women in the United Kingdom
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
HIV Infections
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
0 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Maraviroc Vaginal Gel
Arm Type
Active Comparator
Arm Description
Drug: Maraviroc dosage form: vaginal gel dosage: 2.5g frequency: once daily duration: 11 days
Arm Title
Dapivirine Vaginal Gel
Arm Type
Active Comparator
Arm Description
Drug: Dapivirine dosage form: vaginal gel dosage: 2.5g dapivirine frequency: once daily duration: 11 days
Arm Title
Matching Placebo Gel
Arm Type
Placebo Comparator
Arm Description
Drug: placebo dosage form: vaginal gel dosage: 2.5g placebo frequency: once daily duration: 11 days
Arm Title
Maraviroc/Dapivirine Gel
Arm Type
Experimental
Arm Description
Drug: Maraviroc/Dapivirine dosage form: combination vaginal gel dosage: 2.5g - Maraviroc 0.1%, Dapivirine 0.05% frequency: once daily duration: 11 days
Intervention Type
Drug
Intervention Name(s)
Maraviroc/Dapivirine Gel
Intervention Description
Vaginal gel containing 2.5g - Maraviroc 0.1%, Dapivirine 0.05%
Intervention Type
Drug
Intervention Name(s)
Dapivirine Vaginal Gel
Intervention Description
Dapivirine vaginal gel containing 2.5g
Intervention Type
Drug
Intervention Name(s)
Maraviroc Vaginal Gel
Intervention Description
Maraviroc vaginal gel containing 2.5g
Intervention Type
Drug
Intervention Name(s)
Matching Placebo Gel
Intervention Description
Matching placebo gel containing 2.5g
Primary Outcome Measure Information:
Title
Safety: To assess the safety and tolerability of the combination maraviroc and dapivirine gel, the endpoint was the proportion of women in the four arms experiencing specific, protocol defined safety events during the study (see description).
Description
Mucosal abnormalities (as defined in the WHO/CONRAD manual) visible during naked eye examination and/or colposcopy;
Abnormal vaginal pH and/or abnormal vaginal flora during the course of the trial;
Positive diagnostic tests for trichomonas, gonorrhoea and/or chlamydia;
At least one adverse event during the 2 month trial period;
Any laboratory abnormalities on haematology, electrolytes, liver function, and renal function.
Time Frame
8 weeks
Title
Pharmacokinetics: assessment of local and systemic pharmacokinetics of maraviroc and dapivirine in plasma, vaginal fluid and cervical tissue before, during and after 11 days.
Time Frame
8 weeks
10. Eligibility
Sex
Female
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
40 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
Women 18 to40 years of age who can give written informed consent (illiterate participants may provide a thumbprint or mark witnessed and signed by a person independent from trial staff);
Available for all visits and consent to follow all procedures scheduled for the trial;
HIV-negative as determined by an HIV test at time of enrollment;
Be on a stable form of contraception, defined as:
A stable oral contraceptive regimen for at least 2 months prior to enrollment, OR,
Transdermal contraceptive patch for at least 3 months prior to enrollment, OR,
Long-acting progestins for at least 6 months prior to enrollment, OR,
An IUD inserted (with no vaginal or gynaecological complaints associated with its use) at least 3 months prior to enrolment, OR,
Have undergone surgical sterilization at least 3 months prior to enrollment;
In the absence of the use of exogenous hormone(s), have a self-reported regular menstrual cycle, defined as having a minimum of 21 days and a maximum of 35 days between menses;
Upon pelvic examination and colposcopy at the time of enrollment, the cervix and vagina appear normal as determined by the Investigator;
Asymptomatic for genital infections at the time of enrollment (if a woman is diagnosed with any treatable STI, either syndromically or by laboratory test at the time of screening, she must receive treatment at least 2 weeks prior to enrollment and have completed treatment);
Willing to refrain from the use of vaginal products or objects including, tampons, female condoms, cotton wool, rags, diaphragms, cervical caps (or any other vaginal barrier method), douches, lubricants, vibrators/dildos, and drying agents for 14 days prior to enrollment and for the duration of the trial;
Willing to use oral contraceptives to avoid menstruation, if necessary, while taking part in this trial;
Documentation of no abnormality on Pap test, including grossly bloody smear, within 3 months prior to screening;
Willing to refrain from participation in any other research trial for the duration of this trial;
Willing to provide adequate locator information for trial retention purposes and be reachable per local standard procedures [e.g., by home visit or telephone; or via family or close neighbour contacts (confidentiality to be maintained)];
Willing to agree to abstain from oral contact with her genitalia for gel use period, as well as for a total of 3 days (72 hours) after the biopsy procedure:
Willing to remain sexually abstinent for the gel use period in this trial;
Hepatitis B and C negative at the time of enrollment.
Exclusion Criteria:
Currently pregnant or having had their last pregnancy outcome within 3 months prior to screening;
Currently breast-feeding;
Currently or within two months of participation in any other clinical research trial involving investigational or marketed products prior to screening;
Untreated symptomatic urogenital infections, e.g., urinary tract or other sexually transmitted infections, or other gynaecological conditions such as vaginal itching, pain, or discharge, within 2 weeks prior to enrolment;
Presence of any abnormal clinically significant physical finding on the vulva, vaginal walls or cervix during pelvic examination and/or colposcopy at pre-enrolment;
History of urogenital or uterine prolapse, undiagnosed vaginal bleeding, urethral obstruction, incontinence or urge incontinence;
Current vulvar or vaginal symptoms/abnormalities that could influence the trial results;
Pap test result that requires cryotherapy, biopsy, treatment (other than for infection); or further evaluation [this includes any findings of atypical squamous cells of undetermined significance (ASCUS)];
Symptomatic genital HSV infection or a history of genital herpetic infection;
Any Grade 2, 3 or 4 haematology, chemistry or urinalysis laboratory abnormality at baseline (screening) according to the DAIDS Table for Grading Adverse Events (NOTE: This table can be found at: http://rcc.tech-res.com/safetyandpharmacovigilance;and a standardized version will be provided to the research centre in the Study Operations Manual);
Unexplained, abnormal bleeding per vagina during or following vaginal intercourse, or gynaecologic surgery within 90 days prior to enrollment;
Any history of anaphylaxis or severe allergy resulting in angioedema; or a history of sensitivity/allergy to latex or silicone;
Any serious acute, chronic or progressive disease (e.g., any known history of neoplasm, cancer, diabetes, cardiac disease, autoimmune disease, HIV, AIDS, or blood dyscrasias), or signs of cardiac disease, renal failure, or severe malnutrition;
Have undergone a hysterectomy;
History of drug abuse within 1 year of enrollment;
Any condition(s) that, in the opinion of the Investigator, might interfere with adherence to trial requirements or evaluation of the trial objectives.
12. IPD Sharing Statement
Learn more about this trial
A Safety and Pharmacokinetic Study for Dapivirine and Maraviroc Gel in Belgium
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