A Study to Evaluate the Pharmacokinetics of an Oral Contraceptive When Co-administered With GSK2248761 in Healthy Adult Female Subjects.

This study has been terminated.
(In a Phase II study in HIV-infected patients there were a number of seizures, although exact causality could not be assessed phase 1 activity was terminated.)
Sponsor:
Collaborator:
ViiV Healthcare
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT01195974
First received: September 3, 2010
Last updated: February 14, 2014
Last verified: February 2014
  Purpose

This study is a two-period, double-blind study in healthy adult female subjects. Each subject will participate in an oral contraceptive Run-in period prior to the treatment periods. The length of the Run-in Period will be 28 days or longer, depending on the timing of the subject's menstrual cycle and on whether the subject is taking an OC. Each subject will participate in this run-in period (if needed), followed by two treatment periods. Treatment Periods 1 and 2 must be conducted successively. Subjects will be randomized in a cross-over fashion to either YASMIN with GSK2248761 or Placebo for 10 days and switch GSK2248761 or placebo 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.


Condition Intervention Phase
Infection, Human Immunodeficiency Virus
Drug: YASMIN
Drug: GSK2248761
Other: Placebo
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver)
Official Title: A Double-Blind Study to Evaluate the Pharmacokinetics of an Oral Contraceptive Containing Drospirenone and Ethinyl Estradiol When Co-administered With GSK2248761 in Healthy Adult Female Subjects

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • AUC of Drospirenone and Ethinyl Estradiol after YASMIN alone and after YASMIN with GSK2248761. [ Time Frame: 21 days ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Safety and tolerability of all treatments as assessed by 12 lead electrocardiograms, vital signs, adverse events, and clinical laboratory tests. [ Time Frame: two months ] [ Designated as safety issue: No ]
  • The maximum observed plasma concentration, the minimum observed plasma concentration, time of occurrence for maximum drug concentration, time of occurrence for minimum drug concentration and the half life of DRSP and EE [ Time Frame: 21 days ] [ Designated as safety issue: No ]
  • Predose serum levels of Luteinizing Hormone and Follicle-Stimulating Hormone from Periods 1 and 2 [ Time Frame: 21 days ] [ Designated as safety issue: No ]
  • Predose serum levels of progesterone from Periods 1 and 2 [ Time Frame: 21 days ] [ Designated as safety issue: No ]

Enrollment: 13
Study Start Date: September 2010
Study Completion Date: February 2011
Primary Completion Date: February 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Period 1
YASMIN + 200 mg GSK2248761 or Placebo
Drug: YASMIN
YASMIN for 21 days
Drug: GSK2248761
200 mg GSK2248761 taken on Days 1 - 10 or Days 12 - 21
Other: Placebo
Placebo taken on Days 1 - 10 or Days 12 - 21
Experimental: Period 2
YASMIN + 200 mg GSK2248761 or Placebo
Drug: YASMIN
YASMIN for 21 days
Drug: GSK2248761
200 mg GSK2248761 taken on Days 1 - 10 or Days 12 - 21
Other: Placebo
Placebo taken on Days 1 - 10 or Days 12 - 21
Run In Period
YASMIN
Drug: YASMIN
YASMIN for 21 days

Detailed Description:

ViiV Healthcare is the new sponsor of this study, and GlaxoSmithKline is in the process of updating systems to reflect the change in sponsorship

  Eligibility

Ages Eligible for Study:   18 Years to 40 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • AST, ALT, alkaline phosphatase and bilirubin less than or equal to 1.5xULN (isolated bilirubin greater than 1.5xUpper limit of normal is acceptable if bilirubin is fractionated and direct bilirubin less than 35%).
  • 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 may be included only if the Investigator and the GSK Medical Monitor agree 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 the following appropriate contraceptive methods: oral contraceptive YASMIN in combination with 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 post study monitoring or; YASMIN in combination with 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 post study monitoring or; 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 Body Mass Index is 19 to 30 killograms/millimeters squared and body weight greater than or equal to 50 kilograms (110 pounds) and less than 114 kilograms (less than 250 pounds);
  • Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form;
  • Single QTc, QTcB or QTcF less than 450 msec; or QTc less than 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.
  • 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).
  • Exposure to more than four new chemical entities within 12 months prior to the first dosing day.
  • 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 mililiters within a 56 day period.
  • Women of childbearing potential who are unwilling or unable to use an appropriate method of contraception 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, carcinoma of the breast, etc.);
  • History of sensitivity to heparin or heparin-induced thrombocytopenia.
  • Subjects who have asthma or a history of asthma, (e.g., for any FTIH where risk of bronchoconstriction is unknown, or compound specific where risk of bronchoconstriction).
  • 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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01195974

Locations
United States, North Dakota
GSK Investigational Site
Fargo, North Dakota, United States, 58104
Sponsors and Collaborators
GlaxoSmithKline
ViiV Healthcare
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

Publications:
Piscitelli S, Kim J, Gould E, et al. Drug interaction profile for GSK2248761, a next-generation non-nucleoside reverse transcriptase inhibitor. Br J Clin Pharmacol; 2012 Jan 30.[Epub ahead of print.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT01195974     History of Changes
Other Study ID Numbers: 113394
Study First Received: September 3, 2010
Last Updated: February 14, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by GlaxoSmithKline:
oral contraceptive, drug interaction, pharmacokinetics

Additional relevant MeSH terms:
Acquired Immunodeficiency Syndrome
HIV Infections
Immunologic Deficiency Syndromes
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Slow Virus Diseases
Immune System Diseases
Contraceptive Agents
Contraceptives, Oral
Drospirenone and ethinyl estradiol combination
Reproductive Control Agents
Physiological Effects of Drugs
Pharmacologic Actions
Therapeutic Uses
Contraceptive Agents, Female

ClinicalTrials.gov processed this record on April 15, 2014