Overview

Drug Interaction Study Between Dolutegravir and an Oral Contraceptive Containing Norgestimate and Ethinylestradiol

Status:
Completed
Trial end date:
2012-03-01
Target enrollment:
0
Participant gender:
Female
Summary
Dolutegravir (DTG, GSK1349572 is an integrase inhibitor that is currently in Phase 3 clinical development for the treatment of HIV infection. DTG will likely be used in women on oral contraceptives (OC) for birth control. Based on accumulated non-clinical and clinical drug metabolism and pharmacokinetic data, there is a low likelihood of drug interaction between DTG and most widely used OC drugs. The primary objective of this study is to evaluate the effect of DTG administration on the pharmacokinetics and pharmacodynamics of a commonly used oral contraceptive product, Ortho-Cyclen (combination of norgestimate and ethinyl estradiol), in healthy female subjects. Each subject will participate in a Run-in period (if needed), followed by two treatment periods. Approximately 16 subjects will be randomized in a cross-over fashion to either Ortho-Cyclen with DTG or Ortho-Cyclen with Placebo for 10 days and switch to the alternate treatment for another 10 days. Subjects will return to the study center for final follow up evaluations 7 - 14 days after the final dose of study medication.
Phase:
Phase 1
Accepts Healthy Volunteers?
Accepts Healthy Volunteers
Details
Lead Sponsor:
ViiV Healthcare
Collaborators:
GlaxoSmithKline
Shionogi
Treatments:
Contraceptive Agents
Contraceptives, Oral
Dolutegravir
Fluoroquinolones
Moxifloxacin
Norgestimate
Norgestimate, ethinyl estradiol drug combination
Criteria
Inclusion Criteria:

- Alanine aminotransferase (ALT), alkaline phosphatase and bilirubin greater than or
equal to 1.5 times the upper limit of normal (ULN)

- Healthy female subjects, as determined by a responsible and experienced physician,
based on a medical evaluation including medical history, physical examination,
laboratory tests and cardiac monitoring. A subject with a clinical abnormality or
laboratory parameters outside the reference range for the population being studied
except for ALT, alkaline phosphatase and bilirubin as above may be included only if
the Investigator feels that the finding is unlikely to introduce additional risk
factors and will not interfere with the study procedures.

- Female, between 18 and 40 years of age inclusive, at the time of signing the informed
consent.

- Women of childbearing potential must use OC Ortho-Cyclen in combination with one of
the following appropriate contraceptive methods:a)Complete abstinence from intercourse
for at least 14 days prior to the first dose of investigational product (Day 1 of
Period 1), throughout the study, and for the subsequent poststudy monitoring or; b) A
barrier method plus a spermicide (e.g., condom or diaphragm with spermicidal
foam/gel/cream/ suppository for at least 14 days prior to the first dose of
investigational product [Day 1 of Period 1]) throughout the study, and for the
subsequent poststudy monitoring or; c)Sterilization (vasectomy) of male partner prior
to commencement of female subject's last normal menstrual period prior to
administration of study drug, and the male partner is the sole partner for that female
subject.

- The subject's BMI is 19 to 30 kg/m2 and body weight ≥50 kg (110 lbs) and <114 kg (<250
lbs);

- Capable of giving written informed consent, which includes compliance with the
requirements and restrictions listed in the consent form;

- Single QTcB < 450 msec; or QTc < 480 msec in subjects with Bundle Branch Block.

Exclusion Criteria:

- A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody
result within 3 months of screening

- Current or chronic history of liver disease, or known hepatic or biliary abnormalities
(with the exception of Gilbert's syndrome or asymptomatic gallstones).

- A positive pre-study drug/alcohol screen.

- A positive test for HIV antibody.

- History of regular alcohol consumption within 6 months of the study defined as an
average weekly intake of >7 drinks for females. One drink is equivalent to 12 g of
alcohol: 12 ounces (360 ml) of beer, 5 ounces (150 ml) of wine or 1.5 ounces (45 ml)
of 80 proof distilled spirits.

- The subject has participated in a clinical trial and has received an investigational
product within the following time period prior to the first dosing day in the current
study: 30 days, 5 half-lives or twice the duration of the biological effect of the
investigational product (whichever is longer).

- Use of prescription or non-prescription drugs, including vitamins, herbal and dietary
supplements (including St John's Wort) within 7 days (or 14 days if the drug is a
potential enzyme inducer) or 5 half-lives (whichever is longer) 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.

- History of sensitivity to any of the study medications, or components thereof or a
history of drug or other allergy that, in the opinion of the investigator or GSK
Medical Monitor, contraindicates their participation.

- Where participation in the study would result in donation of blood or blood products
in excess of 500 mL within a 56 day period.

- Women of childbearing potential who are unwilling or unable to use an appropriate
method of contraception (see inclusion criteria) from at least 14 days prior to the
first dose of investigational product until completion of the follow-up visit;

- Pregnant females as determined by positive hCG test at screening or prior to dosing.

- Lactating females.

- Unwillingness or inability to follow the procedures outlined in the protocol.

- Subject is mentally or legally incapacitated.

- History of any condition that would contraindicate OC administration (including
hypertension, stroke, ischemic heart disease, venous thromboembolism or family history
of thromboembolism, known factor V Leiden mutation or other gene mutations associated
with increased risk of thromboembolism, migraine headaches, carcinoma of the breast,
liver or endometrium, gallbladder disease, history of undiagnosed abnormal uterine
bleeding, etc.).

- If heparin is used during pharmacokinetic sampling, subjects with a history of
sensitivity to heparin or heparin-induced thrombocytopenia.

- Consumption of red wine, seville oranges, grapefruit or grapefruit juice and/or
pummelos, exotic citrus fruits, grapefruit hybrids or fruit juices from 7 days prior
to the first dose of study medication.

- Unwilling to abstain from tobacco use from the screening visit until the follow-up
visit.

- Females with conditions or concurrent medications that could adversely affect hormone
levels e.g. oopherectomies and females receiving drug eluting IUDs (e.g. Mirena).