Clinical trial NCT01404806: GSK1349572 Exposure in Blood, Cervicovaginal Fluid, and Cervical and Vaginal Tissue in Healthy Female Subjects
Official title: A Phase 1, Open Label, Study in Healthy Female Subjects to Describe GSK1349572 Exposure in Blood, Cervicovaginal Fluid, and Cervical and Vaginal Tissue Following Single and Multiple Dosing of GSK1349572
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Adult Females
Lead sponsor: University of North Carolina, Chapel Hill
Sponsor class: OTHER
Collaborators: name: GlaxoSmithKline
First posted: 2011-07-28
Enrollment: 10
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 35
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

Brief summary: The purpose of this study is to describe drug concentrations of an investigational HIV medication, GSK1349572, in blood plasma, cervicovaginal fluid, vaginal and cervical tissue in HIV negative women.

Detailed description: Purpose: The purpose of this study is to describe first dose and steady state pharmacokinetics of GSK1349572 in cervicovaginal fluid (CVF) and vaginal (VT) and cervical (CT) tissue compared to blood plasma (BP) in HIV-1 negative women. Based on current literature, GSK1349572 has demonstrated a desirable pharmacokinetic profile in BP, including low to moderate pharmacokinetic variability (CV% 9-41), extended t1/2 (13-15h) and trough concentrations which remain 25-fold higher than the protein-adjusted IC90 \~0.064µg/mL for wild type virus. Understanding pharmacokinetic behavior of GSK1349572 in multiple female biological compartments will inform its role in sterilizing the genital tract in HIV-infected women, as well as protect mucosal tissue against HIV infection (pre/post-exposure prophylaxis).

Eligibility criteria: Inclusion Criteria:

* Healthy pre-menopausal female subjects between the ages of 18 and 35 years, inclusive, with an intact uterus and cervix.
* Body Mass Index (BMI) of approximately 18-30 kg/m2 and a total body weight of \>50kg (110 lbs)
* Negative serum pregnancy test at screening and should be using at least one of the following methods of contraception:

  1. Abstinence
  2. Bilateral tubal ligation
  3. Condom with spermicidal gel or foam
  4. Stable male partner who has had a vasectomy, or stable female only partners
  5. Hormonal contraceptives (oral) provided the subject remains on the treatment until the follow-up visit and has been using oral contraceptives for at least 3 months prior to the first dose of trial medication
* Must agree to abstain from use of intravaginal products for 72 hours prior to the screening visit
* Must agree to abstain from any sexual activity for 72 hours prior to the Day 1 study visit and through study completion
* Previous gynecological examination with documentation of a normal Pap smear within the last year as part of clinical care
* Regular menstrual cycles with at least 21 days between menses (unless on contraception that causes amenorrhea or irregular menses)

Exclusion Criteria:

* Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at time of dosing)
* History of hysterectomy, loop electrosurgical excision procedure (LEEP), conization or cryosurgery
* Pregnant or lactating
* Unwilling to refrain from sexual intercourse or from using intra-vaginal medications/products from 72 hours prior to Day 1 until discharge from the study
* Any condition possibly affecting drug absorption (eg, gastrectomy)
* Positive urine drug screen
* Active hepatitis B infection
* Active hepatitis C infection
* A positive test for bacterial vaginosis, syphilis, gonorrhea, chlamydia, HIV, HSV-2 (active lesions) or trichomonas at screening
* History of regular use of tobacco- or nicotine-containing products exceeding 5 cigarettes per day within 3 months prior to screening
* History of regular alcohol consumption exceeding 14 drinks \[1 drink = 5 ounces (150mL)\] of wine or 12 ounces (360mL) of beer or 1.5 ounces (45mL) of spirits per week
* History of bleeding or clotting disorders
* Documented allergic reaction to lidocaine, silver nitrate, ferric subsulfate solution (Monsel's solution) or any iron containing products.
* Treatment with an investigational drug within 4 months preceding the first dose of trial medication.
* Use of clinically significant prescription or non-prescription drugs within 7 days prior to the first dose of study medication, unless in the opinion of the Investigator and GSK Medical Monitor the medication will not interfere with the study procedures or compromise subject safety.
* Blood donation of approximately 1 pint (500mL) within 56 days prior to dosing.
* History of sensitivity to heparin or heparin-induced thrombocytopenia.
* Unwilling to abstain from alcohol use from 48 hours prior to the first dose of study medication until after the follow-up visit.
* Using an intrauterine device for contraception.
* Using depo-medroxyprogesterone (DepoProvera®) for contraception.
* Systolic blood pressure is outside the range of 90-140mmHg, diastolic blood pressure is outside the range of 45-90mmHg or heart rate is outside the range of 50-100 bpm for female subjects even after a single repeat reading.
* Any clinically significant abnormalities to pulse or conduction observed on screening ECG

Primary outcomes:
measure: Area under the concentration time curve in blood plasma after a single dose
timeFrame: 24 hours
measure: Peak Concentration (Cmax) after a single dose in blood plasma
timeFrame: 24 hours
measure: Area under the concentration time curve in cervicovaginal fluid after a single dose
timeFrame: 24 hours
measure: Area under the concentration time curve in cervical and vaginal tissue after a single dose
timeFrame: 24 hours
measure: Peak Concentration (Cmax) after a single dose in cervicovaginal fluid
timeFrame: 24 hours
measure: Peak Concentration (Cmax) after a single dose in cervical and vaginal tissue
timeFrame: 24 hours
measure: Area under the concentration time curve for cervicovaginal fluid at steady state
timeFrame: 72 hours
measure: Area under the concentration time curve in cervical and vaginal tissue at steady state
timeFrame: 24 hours
measure: Peak concentration (Cmax) in cervicovaginal fluid at steady state
timeFrame: 72 hours
measure: Peak concentration (Cmax) in blood plasma at steady state
timeFrame: 24 hours
measure: Area under the concentration time curve in blood plasma at steady state
timeFrame: 72 hours
measure: Peak concentration (Cmax) in blood plasma at steady state
timeFrame: 72 hours
measure: Area under the concentration time curve ratios after a single dose
timeFrame: 24 hours
measure: Area under the concentration time curve ratios at steady state
timeFrame: 72 hours
Secondary outcomes:
Other outcomes:
Locations:
city: Chapel Hill
country: United States
facility: University of North Carolina, Chapel Hill
state: North Carolina
Study officials:
affiliation: University of North Carolina, Chapel Hill
name: Kristine B. Patterson, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Adams JL, Patterson KB, Prince HM, Sykes C, Greener BN, Dumond JB, Kashuba AD. Single and multiple dose pharmacokinetics of dolutegravir in the genital tract of HIV-negative women. Antivir Ther. 2013;18(8):1005-13. doi: 10.3851/IMP2665. Epub 2013 Jul 31.