Safety and Pharmacokinetics of Dapivirine/Maraviroc Vaginal Ring

NCT01363037 | Completed Phase 1 DMC

• 1 other identifier: MTN-013/IPM 026
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 3

Brief Summary

The purpose of this study is to assess the pharmacokinetics of the combination dapivirine and maraviroc vaginal ring and determine whether it is safe when used continuously for 28 days by healthy women in the United States.

Conditions

HIV Infections

Keywords

HIV infections; Anti-HIV agents; HIV-1

Outcome Measures

Primary Outcomes (2)

• Safety: To assess and compare safety of VRs containing 25 mg dpv, or 100 mg mrv, or 25 mg dpv + 100 mg mrv, the endpoint was the proportion of women in the four arms experiencing specific, protocol defined safety events during the study (see description)

  * Genitourinary events Grade 1 or higher as defined by the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 1.0, Dec 2004 (Clarification dated August 2009), Addendum 1, (Female Genital Grading Table for Use in Microbicide Studies) judged to be related to study product * Adverse events Grade 2 or higher as defined by the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 1.0, Dec 2004 (Clarification dated August 2009)

  7.5 weeks

• Pharmacokinetics: Assessments of systemic and local concentrations of dapivirine and maraviroc in plasma, vaginal fluids and cervical tissue, respectively

  Assessed during and after 28 days' of continuous use of a vaginal ring containing 25 mg dapivirine, or 100 mg maraviroc, or 25 mg dapivirine + 100 mg maraviroc.

  7.5 weeks

Secondary Outcomes (2)

• Evaluate the acceptability of the study VR in HIV-uninfected sexually abstinent women over 28 days of use

  28 days

• Evaluate the adherence to the study VR in HIV-uninfected sexually abstinent women over 28 days of use

  28 days

Study Arms (4)

Dapivirine-Maraviroc Vaginal Ring

EXPERIMENTAL

Drug: Dapivirine-Maraviroc Vaginal Ring

Placebo Vaginal Ring

PLACEBO COMPARATOR

Other: Placebo Vaginal Ring

Maraviroc Vaginal Ring

ACTIVE COMPARATOR

Drug: Maraviroc Vaginal Ring

Dapivirine Vaginal Ring

ACTIVE COMPARATOR

Drug: Dapivirine Vaginal Ring

Interventions

Dapivirine Vaginal Ring DRUG

dosage form: dapivirine vaginal ring dosage:25 mg frequency:continuous use duration:28 days

Dapivirine Vaginal Ring

Maraviroc Vaginal Ring DRUG

dosage form: maraviroc vaginal ring dosage:100 mg frequency:continuous use duration:28 days

Maraviroc Vaginal Ring

Placebo Vaginal Ring OTHER

dosage form: placebo vaginal ring dosage:N/A frequency:continuous use duration:28 days

Placebo Vaginal Ring

Dapivirine-Maraviroc Vaginal Ring DRUG

dosage form: combination vaginal ring dosage:25 mg dapivirine + 100 mg maraviroc frequency:continuous use duration:28 days

Dapivirine-Maraviroc Vaginal Ring

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Age 18 through 40 years (inclusive) at screening, verified per site SOPs
• Able and willing to provide written informed consent to be screened for and take part in the study
• Able and willing to provide adequate locator information, as defined by the site SOPs
• HIV-uninfected, based on testing performed by study staff at Screening and Enrollment (per applicable algorithm in Appendix II)
• In general good health at Screening and Enrollment, as determined by the site IoR or designee
• At Screening, participant states willingness to abstain from receptive sexual activity (including oral, vaginal and anal intercourse) for the 14 days prior to enrollment and for the duration of study participation
• Per participant report, using an effective method of contraception at Enrollment, and intending to continue use of an effective method for the duration of study participation. Effective methods include hormonal methods (except contraceptive vaginal rings), intrauterine device (IUD) inserted at least 28 days prior to enrollment, being a woman who identifies as a woman who has sex with women exclusively, sterilization, and/or sexually abstinent for the past 90 days
• Satisfactory Pap result in the 12 calendar months prior to Enrollment consistent with Grade 0 according to the Female Genital Grading Table for Use in Microbicide Studies Addendum 1 to the DAIDS Table for Grading Adult and Pediatric Adverse Events, Version 1.0, December 2004 (Clarification dated August 2009), or satisfactory evaluation with no treatment required of Grade 1 or higher Pap result per American Society for Colposcopy and Cervical Pathology (ASCCP) guidelines in the 12 calendar months prior to Enrollment.
• Per participant report at Screening and Enrollment, agrees not to participate in other research studies involving drugs, medical devices, or vaginal products for the duration of study participation
• Per participant report at Screening, regular menstrual cycles with at least 21 days between menses (does not apply to participants who report using a progestin-only method of contraception at screening, e.g., Depo-Provera or levonorgestrel-releasing IUD)
• At Screening and Enrollment, participant states a willingness to refrain from inserting any non-study vaginal products or objects into the vagina, including but not limited to, spermicides, female condoms, diaphragms, contraceptive vaginal rings, vaginal medications, menstrual cups, cervical caps (or any other vaginal barrier method), douches, lubricants, sex toys (vibrators, dildos, etc.), and tampons for the 5 days prior to enrollment throughout the duration of study participation. -- Note: At the Screening visit participant also agrees to refrain from the practices listed above for at least 5 days prior to enrollment.

You may not qualify if:

• Participant report of any of the following at Screening:
• Known adverse reaction to silicone, titanium dioxide, or to any of the components of the study products
• Use and/or anticipated use during the period of study participation of CYP3A inducer(s) and/or inhibitor(s)
• Chronic and/or recurrent candidiasis
• Non-therapeutic injection drug use in the 12 months prior to screening
• Post-exposure prophylaxis for HIV exposure within 6 months prior to screening
• Last pregnancy outcome 90 days or less prior to screening
• Currently breastfeeding
• Hysterectomy
• Intends to become pregnant within the next 4 months
• Has plans to relocate away from the study site area in the next 4 months
• Reports participating in any other research study involving drugs, medical devices, or vaginal products 60 days or less prior to enrollment
• At Screening or Enrollment, as determined by the IoR/designee, any significant uncontrolled active or chronic cardiovascular, renal, liver, hematologic, neurologic, gastrointestinal, psychiatric, endocrine, respiratory, immunologic disorder or infectious disease, or at increased risk of cardiovascular events
• Has any of the following laboratory abnormalities at Screening:
• Aspartate aminotransferase (AST) or alanine transaminase (ALT) Grade 1 or higher as per the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events Version 1.0, December, 2004 (Clarification dated August 2009)

Sponsors & Collaborators

• International Partnership for Microbicides, Inc.: lead

Study Sites (3)

University of Alabama at Birmingham

Birmingham, Alabama, 35294, United States

Location

The Fenway Institute/Fenway Community Health

Boston, Massachusetts, 02115, United States

Location

Magee-Womens Hospital of UPMC

Pittsburgh, Pennsylvania, 15213, United States

Location

Related Publications (1)

• Chen BA, Panther L, Marzinke MA, Hendrix CW, Hoesley CJ, van der Straten A, Husnik MJ, Soto-Torres L, Nel A, Johnson S, Richardson-Harman N, Rabe LK, Dezzutti CS. Phase 1 Safety, Pharmacokinetics, and Pharmacodynamics of Dapivirine and Maraviroc Vaginal Rings: A Double-Blind Randomized Trial. J Acquir Immune Defic Syndr. 2015 Nov 1;70(3):242-9. doi: 10.1097/QAI.0000000000000702.

  PMID: 26034880 BACKGROUND

MeSH Terms

Conditions

HIV Infections

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Study Officials

• Beatrice A Chen, MD, MPH

  University of Pittsburgh

  STUDY CHAIR

• Lori Panther, MD, MPH

  The Fenway Institute

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 27, 2011
• First Posted: June 1, 2011
• Study Start: November 1, 2011
• Primary Completion: August 1, 2012
• Study Completion: August 1, 2012
• Last Updated: September 10, 2015

Record last verified: 2015-09

Locations

US (3)