A Drug Interaction Study Between Simvastatin, Atorvastatin, Rosuvastatin, and GSK2248761 in Healthy Subjects.

NCT01138072 | Completed Phase 1

• 1 other identifier: 113818
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

Brief Summary

This study is a Phase I, open-label, single-sequence drug interaction study to evaluate the effect of repeated doses of GSK2248761 on the pharmacokinetics of simvastatin, atorvastatin, and rosuvastatin in healthy adult subjects. In this study, approximately 14 subjects will receive single doses of simvastatin, atorvastatin, and rosuvastatin on two occasions, once alone and once following administration of repeated doses of GSK2248761. Safety evaluations and serial PK samples will be collected during each treatment period. A follow-up visit will occur 7-14 days after the last dose of study drug.

Conditions

Infection, Human Immunodeficiency Virus

Keywords

GSK2248761, atorvastatin, rosuvastatin, simvastatin, drug interaction, pharmacokinetics

Outcome Measures

Primary Outcomes (3)

• Plasma simvastatin and simvastatin acid Cmax, AUC(0-infinity) and AUC(0-t) following oral administration of a single dose of simvastatin 20mg alone and in combination with GSK2248761 200mg once daily.

  18 days

• Plasma atorvastatin Cmax, AUC(0-infinity) and AUC(0-t) following oral administration of a single dose of atorvastatin 20mg alone and in combination with GSK2248761 200mg once daily.

  21 days

• Plasma rosuvastatin Cmax, AUC(0-∞) and AUC(0-t) following oral administration of a single dose of rosuvastatin 10mg alone and in combination with GSK2248761 200mg once daily.

  25 days

Secondary Outcomes (3)

• Plasma ortho and para-hydroxy atorvastatin Cmax, AUC(0-infinity) and AUC(0-t) following oral administration of a single dose of atorvastatin 20mg alone and in combination with GSK2248761 200mg once daily.

  21 days

• Plasma simvastatin, simvastatin acid, atorvastatin, ortho and para-hydroxy atorvastatin, and rosuvastatin tmax, t1/2, and percent AUCex.

  25 days

• Safety and tolerability parameters including adverse event, concurrent medication, clinical laboratory, ECG, and vital sign assessments.

  25 days

Study Arms (7)

Treatment A

EXPERIMENTAL

Simvastatin 20mg (single dose) Day 1

Drug: Simvastatin

Treatment B

EXPERIMENTAL

Atorvastain 20 mg (single dose) Day 3

Drug: Atorvastatin

Treatment C

EXPERIMENTAL

Rosuvastatin 10mg (single dose) Day 7

Drug: Rosuvastatin

Treatment X

EXPERIMENTAL

GSK2248761 200mg single dose Day 10-14, Day 16-17, Day 19-21, Day 23-24

Drug: GSK2248761

Treatment D

EXPERIMENTAL

GSK2248761 200mg + simvastatin 20 mg Day 15

Drug: GSK2248761; Drug: Simvastatin

Treatment E

EXPERIMENTAL

GSK2248761 200mg + atorvastatin 20 mg Day 18

Drug: GSK2248761; Drug: Atorvastatin

Treatment F

EXPERIMENTAL

GSK2248761 200mg + rosuvastatin 20 mg Day 22

Drug: GSK2248761; Drug: Rosuvastatin

Interventions

GSK2248761 DRUG

200mg once daily

Treatment D; Treatment E; Treatment F; Treatment X

Simvastatin DRUG

20 mg Simvastatin single dose

Treatment A; Treatment D

Atorvastatin DRUG

20 mg atorvastatin single dose

Treatment B; Treatment E

Rosuvastatin DRUG

10 mg rosuvastatin single dose

Treatment C; Treatment F

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.
• 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.
• 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 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).
• 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

• GlaxoSmithKline: lead

Study Sites (1)

GSK Investigational Site

Austin, Texas, 78744, United States

Location

Related Publications (1)

• Piscitelli S, Kim J, Gould E, Lou Y, White S, de Serres M, Johnson M, Zhou XJ, Pietropaolo K, Mayers D. Drug interaction profile for GSK2248761, a next generation non-nucleoside reverse transcriptase inhibitor. Br J Clin Pharmacol. 2012 Aug;74(2):336-45. doi: 10.1111/j.1365-2125.2012.04194.x.

  PMID: 22288567 DERIVED

MeSH Terms

Conditions

Infections; Acquired Immunodeficiency Syndrome

Interventions

IDX 899; Simvastatin; Atorvastatin; Rosuvastatin Calcium

Condition Hierarchy (Ancestors)

HIV Infections; 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

Intervention Hierarchy (Ancestors)

Lovastatin; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Pyrroles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heptanoic Acids; Fatty Acids; Lipids; Sulfonamides; Amides; Fluorobenzenes; Hydrocarbons, Fluorinated; Hydrocarbons, Halogenated; Sulfones; Sulfur Compounds; Pyrimidines

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: June 3, 2010
• First Posted: June 7, 2010
• Study Start: June 1, 2010
• Primary Completion: August 1, 2010
• Study Completion: August 1, 2010
• Last Updated: November 5, 2010

Record last verified: 2010-11

Locations

US (1)