A Study to Assess Relative Bioavailability and Food Effect of New Formulations of GSK2248761

This study has been completed.
Sponsor:
Information provided by:
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT01031472
First received: December 10, 2009
Last updated: November 2, 2010
Last verified: November 2010
  Purpose

This is a single-center, randomized, two part, open-label, crossover study in healthy adult subjects to assess the effect of up to three formulations on the relative bioavailability of GSK2248761 100mg administered with and without food. Part A will evaluate two new formulations compared to the current formulation. Part B will evaluate one additional formulation if the bioavailability of the two formulations in Part A do not meet pre-specified criteria. Safety evaluations and serial PK samples will be collected during each treatment period. A follow-up visit will occur 7-10 days after the last dose of study drug.


Condition Intervention Phase
Infection, Human Immunodeficiency Virus
Drug: GSK2248761 formulation 1
Drug: GSK2248761 reference formulation
Drug: GSK2248761 formulation 3
Drug: GSK2248761 formulation 2 or 4
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Bio-availability Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Single-center, Randomized, Two Part, Open-label, Crossover Study to Assess the Relative Bioavailability and Food Effect of New Formulations of GSK2248761 in Healthy Adult Subjects

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Plasma GSK2248761 AUC(0-infinity), AUC(0-tau), and Cmax. [ Time Frame: Up to 5 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Plasma GSK2248761 t½, tlag, tmax, %AUCex, and CL/F [ Time Frame: Up to 5 weeks ] [ Designated as safety issue: No ]
  • Safety and tolerability parameters, including adverse events, concurrent medication, clinical laboratory screens, ECG, and vital signs assessments [ Time Frame: Up to 5 weeks ] [ Designated as safety issue: No ]

Enrollment: 24
Study Start Date: December 2009
Study Completion Date: March 2010
Primary Completion Date: March 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Part A
Subjects will be randomized in a three way crossover design to either a single dose of GSK2248761 100mg Gelucire capsule administered with food and a single dose of 100mg of formulation 1 or a single dose of 100mg of formulation 3 administered in the fed and fasted state
Drug: GSK2248761 formulation 1
100mg GSK2248761 formulation 1- fasted 100mg GSK2248761 formulation 1 - with food (moderate fat meal)
Drug: GSK2248761 reference formulation
GSK2248761 100mg Gelucire reference capsule with food
Drug: GSK2248761 formulation 3
100mg GSK2248761 formulation 3 fasted 100mg GSK2248761 formulation 3 with food (moderate fat meal)
Experimental: Part B
A total of twelve subjects who complete Part A will participate in Part B. Subjects from Part A will be asked to participate on a first come first serve basis until there are 12 subjects, at which time enrolment to Part B will be closed. Part B will be a 2 way cross over study design. Subjects will be randomized to one of a single dose of GSK2248761 100mg Formulation 2 or 4 (based on the evaluation of Part A data) administered with food or in the fasted state. Subjects in Part B will not receive the reference formulation since they previously received this in Part A
Drug: GSK2248761 formulation 2 or 4
100mg GSK2248761 formulation 2 or 4 - fasted 100mg GSK2248761 formulation 2 or 4 - with food (moderate fat meal)

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 50 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Healthy as determined by a responsible and experienced physician, based on a medical evaluation including medical history, physical examination, vital signs, laboratory tests, and ECGs.
  • Male or female between 18 and 50 years of age inclusive, at the time of signing the informed consent.
  • A female subject is eligible to participate if she is of non-childbearing potential (i.e., physiologically incapable of becoming pregnant) including any female who:
  • Is pre-menopausal with a documented bilateral tubal ligation, bilateral oophorectomy (removal of the ovaries) or hysterectomy, or is post-menopausal defined as 12 months of spontaneous amenorrhea. A follicle stimulating hormone (FSH) level will be performed to confirm a post-menopausal status. For this study, FSH levels > 40 MlU/ml is confirmatory.
  • Male subjects must agree to use one of the contraception methods listed in Section 8.1. This criterion must be followed from the time of the first dose of study medication until the follow-up visit.
  • Body weight greater than or equal to 50 kg for men and greater than or equal to 45 kg for women and body mass index (BMI) within the range 18.5-31.0 kg/m2 (inclusive).
  • Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form

Exclusion Criteria:

  • As a result of the medical interview, physical examination, or screening investigations, the Investigator considers the subject unfit for the study.
  • The subject has a positive pre-study drug/alcohol screen. A minimum list of drugs that will be screened for include amphetamines, barbiturates, cocaine, opiates, cannabinoids and benzodiazepines.
  • Unwilling to refrain from the use of illicit drugs and adhere to other protocol-stated restrictions while participating in the study.
  • History of regular alcohol consumption within 6 months of the study.
  • Unwilling to abstain from alcohol for 48 hours prior to the start of dosing until collection of the final pharmacokinetic sample during each treatment period.
  • History or regular use of tobacco- or nicotine-containing products within 3 months prior to screening.
  • History/evidence of symptomatic arrhythmia, angina/ischemia, coronary artery bypass grafting (CABG) surgery or percutaneous transluminal coronary angioplasty (PCTA) or any clinically significant cardiac disease.
  • History/evidence of clinically significant pulmonary disease.
  • Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
  • Subjects with a pre-existing condition interfering with normal gastrointestinal anatomy or motility, hepatic and/or renal function, that could interfere with the absorption, metabolism, and/or excretion of the study drugs. Subjects with a history of cholecystectomy should be excluded.
  • 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).
  • The subject has received GSK2248761 in a previous clinical trial.
  • 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. In addition, if heparin is used during PK sampling, subjects with a history of sensitivity to heparin or heparin-induced thrombocytopenia should not be enrolled.
  • Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56 day period. Note: this does not include plasma donation.
  • A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening.
  • A positive test for HIV antibody.
  • AST, ALT, alkaline phosphatase and bilirubin greater than or equal to 1.5xULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).
  • Pregnant females as determined by positive serum hCG test at screening or prior to dosing.
  • Lactating females.
  • The subject's systolic blood pressure is outside the range of 90-140mmHg, or diastolic blood pressure is outside the range of 45-90mmHg or heart rate is outside the range of 50-100bpm for female subjects or 45-100 bpm for male subjects at Screening and predose Day 1.
  • Cardiac conduction abnormalities on a single 12-lead ECG at screening or predose Day 1.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01031472

Locations
United States, New York
GSK Investigational Site
Buffalo, New York, United States, 14202
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided

Responsible Party: E.D. Derilus; Clinical Disclosure Advisor, GSK Clinical Disclosure
ClinicalTrials.gov Identifier: NCT01031472     History of Changes
Other Study ID Numbers: 113391
Study First Received: December 10, 2009
Last Updated: November 2, 2010
Health Authority: United States: Food and Drug Administration

Keywords provided by GlaxoSmithKline:
HIV, relative bioavailability, food effect, GSK2248761, healthy subjects
HIV Seronegativity

Additional relevant MeSH terms:
Immunologic Deficiency Syndromes
Acquired Immunodeficiency Syndrome
HIV Infections
Immune System Diseases
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Slow Virus Diseases

ClinicalTrials.gov processed this record on September 16, 2014