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

NCT01031472 | Completed Phase 1

• 1 other identifier: 113391
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Infection, Human Immunodeficiency Virus; HIV Infections

Keywords

HIV, relative bioavailability, food effect, GSK2248761, healthy subjects; HIV Seronegativity

Outcome Measures

Primary Outcomes (3)

• Area under the concentration-time curve zero to infinity of plasma GSK2248761

  Plasma samples will be collected for the analysis of AUC (0-inf) of GSK2248761.

  Up to 5 weeks

• AUC from time zero to end of dosing interval AUC (0-tau)

  Plasma samples will be collected for the analysis AUC (0-tau) of GSK2248761.

  Up to 5 weeks

• Maximum concentration (Cmax) of GSK2248761

  Plasma samples will be collected for the analysis of Cmax of GSK2248761.

  Up to 5 weeks

Secondary Outcomes (10)

• Terminal half life (t1/2) of GSK2248761

  Up to 5 weeks

• Lag time before observation of drug concentration (tlag) of GSK2248761

  Up to 5 weeks

• Time to Cmax of GSK2248761

  Up to 5 weeks

• Percentage of AUC obtained by extrapolation (%AUCex) for GSK2248761

  Up to 5 weeks

• Apparent clearance following oral dosing (CL/F) for GSK2248761

  Up to 5 weeks

Study Arms (2)

Part A

EXPERIMENTAL

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; Drug: GSK2248761 reference formulation; Drug: GSK2248761 formulation 3

Part B

EXPERIMENTAL

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

Interventions

GSK2248761 formulation 1 DRUG

100mg GSK2248761 formulation 1- fasted 100mg GSK2248761 formulation 1 - with food (moderate fat meal)

Part A

GSK2248761 reference formulation DRUG

GSK2248761 100mg Gelucire reference capsule with food

Part A

GSK2248761 formulation 3 DRUG

100mg GSK2248761 formulation 3 fasted 100mg GSK2248761 formulation 3 with food (moderate fat meal)

Part A

GSK2248761 formulation 2 or 4 DRUG

100mg GSK2248761 formulation 2 or 4 - fasted 100mg GSK2248761 formulation 2 or 4 - with food (moderate fat meal)

Part B

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• ViiV Healthcare: lead
• GlaxoSmithKline: collaborator

Study Sites (1)

GSK Investigational Site

Buffalo, New York, 14202, United States

Location

Related Links

• Results for study 113391 can be found on the ViiV Clinical Study Register.

MeSH Terms

Conditions

Infections; Acquired Immunodeficiency Syndrome; HIV Infections

Condition Hierarchy (Ancestors)

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

Study Officials

• GSK Clinical Trials

  ViiV Healthcare

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 10, 2009
• First Posted: December 14, 2009
• Study Start: December 21, 2009
• Primary Completion: March 11, 2010
• Study Completion: March 11, 2010
• Last Updated: March 27, 2020

Record last verified: 2020-03

Locations

US (1)