GSK1349572 Drug Interaction Study With Protease Inhibitors

NCT00774735 | Completed Phase 1

• 1 other identifier: 111405
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

A study in healthy volunteers to determine whether there is a drug interaction between GSK1349572 and the HIV protease inhibitors lopinavir/ritonavir and darunavir/ritonavir

Conditions

Healthy Subjects; Infection, Human Immunodeficiency Virus

Keywords

healthy volunteer; darunavir; lopinavir; ritonavir; GSK1349572; integrase; pharmacokinetics

Outcome Measures

Primary Outcomes (1)

• Plasma GSK1349572 steady-state AUC(0-tau), Cmax, Ctau, and Cmin following administration of GSK1349572 30 mg q24h for 5 days and following co-administration with LPV/RTV 400/100 mg q12h or DRV/RTV 600/100 mg q12h for 14 days.

  19 Days

Secondary Outcomes (2)

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

  14 Days after last dose

• Plasma LPV, DRV, and RTV PK parameters, including AUC(0-t), Cmax, and Cmin following co-administration of GSK1349572 30 mg q24h and LPV/RTV 400/100 mg q12h or DRV/RTV 600/100 mg q12h for 14 days.

  19 Days

Study Arms (2)

Sequence 1

EXPERIMENTAL

Drug: GSK1349572

Sequence 2

EXPERIMENTAL

Drug: GSK1349572

Interventions

GSK1349572 DRUG

30 mg given in combination with lopinavir/ritonavir

Sequence 1

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Healthy as determined by a responsible physician, based on a medical evaluation including medical history, physical examination, laboratory tests and cardiac monitoring.
• Male or female between 18 and 65 years of age.
• 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. Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt, HRT should be discontinued for 2 weeks and then the subject rescreened, as HRT can suppress FSH.
• 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 14 days after the last dose of study medication.
• Body weight ≥ 50 kg for men and ≥ 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:

• 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.
• 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)
• 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.
• 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.
• If heparin is used during PK sampling, subjects with a history of sensitivity to heparin or heparin-induced thrombocytopenia should not be enrolled.
• History of regular alcohol consumption within 6 months of the study defined as:
• An average weekly intake of \>14 drinks/week for men or \>7 drinks/week for women. One drink is equivalent to (12 g alcohol) = 5 ounces (150 ml) of wine or 12 ounces (360 ml) of beer or 1.5 ounces (45 ml) of 80 proof distilled spirits.
• Has a history or regular use of tobacco- or nicotine-containing products within 3 months prior to screening.
• Consumption of red wine, seville oranges, grapefruit or grapefruit juice from 7 days prior to the first dose of study medication.
• Pregnant females as determined by positive serum or urine human chorionic gonadotrophin (hCG) test at screening or prior to dosing.
• Lactating females.
• Unwillingness or inability to follow the procedures outlined in the protocol.
• 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.
• 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.

Sponsors & Collaborators

• GlaxoSmithKline: lead
• Shionogi: collaborator

Study Sites (1)

GSK Investigational Site

Buffalo, New York, 14202, United States

Location

Related Publications (2)

• Goffinet C, Allespach I, Oberbremer L, Golden PL, Foster SA, Johns BA, Weatherhead JG, Novick SJ, Chiswell KE, Garvey EP, Keppler OT. Pharmacovirological impact of an integrase inhibitor on human immunodeficiency virus type 1 cDNA species in vivo. J Virol. 2009 Aug;83(15):7706-17. doi: 10.1128/JVI.00683-09. Epub 2009 May 20.

  PMID: 19458008 BACKGROUND

• Song I, Min S, Borland J, et al. The effect of ritonavir-boosted protease inhibitors (PIs) on the HIV integrase inhibitor, S/GSK1349572, in healthy Chemotherapy; September 12-15, 2009; San Francisco, CA. Abstract A1-1304.

  BACKGROUND

MeSH Terms

Conditions

Infections; Acquired Immunodeficiency Syndrome

Interventions

dolutegravir

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

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Study Design

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

Study Record Dates

• First Submitted: October 16, 2008
• First Posted: October 17, 2008
• Study Start: October 1, 2008
• Primary Completion: December 1, 2008
• Study Completion: December 1, 2008
• Last Updated: September 13, 2010

Record last verified: 2010-09

Locations

US (1)