Drug Interaction Study Between GSK1349572 and Tipranavir/Ritonavir in Healthy Volunteers

NCT01068925 | Completed Phase 1

• 1 other identifier: 113096
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to determine whether there is a drug interaction between GSK1349572 and the HIV protease inhibitors Tipranavir/Ritonavir (TPV/RTV).

Conditions

Infection, Human Immunodeficiency Virus; HIV Infections

Keywords

healthy volunteer; pharmacokinetics; HIV, GSK1349572, tipranavir, ritonavir, drug interaction

Outcome Measures

Primary Outcomes (1)

• Plasma GSK1349572 steady-state AUC(0-tau), Cmax, C0, Ctau, and Cmin following administration of GSK1349572 50mg QD for 5 days and following co-administration with TPV/RTV 500/200mg BID for 5 days.

  17 days

Secondary Outcomes (2)

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

  31 days

• Plasma GSK1349572 PK parameters: tmax, tmin, CL/F and t½, following administration of GSK1349572 50mg QD for 5 days and following co-administration with TPV/RTV 500/200mg BID for 5 days

  17 days

Study Arms (3)

ARM 1

EXPERIMENTAL

Arm 1: GSK1349572 QD for 5 days (Treatment A).

Drug: GSK1349572

ARM 2

EXPERIMENTAL

ARM 2: TPV/RTV 500/200mg BID (Treatment B).

Drug: GSK1349572

ARM 3

EXPERIMENTAL

ARM 3: GSK1349572 50mg QD and TPV/RTV 500/200mg BID (Treatment C).

Drug: GSK1349572

Interventions

GSK1349572 DRUG

1. GSK1349572 QD x 5 days 2. TPV/RTV 500/200mg BID x 7 days 3. GSK1349572 50mg QD and TPV/RTV 500/200mg BID x 5 days

Also known as: TPV/RTV 500/200mg BID x 7 days, GSK1349572 QD x 5 days, GSK1349572 50mg QD and TPV/RTV 500/200mg BID x 5 days

ARM 1; ARM 2; ARM 3

Eligibility Criteria

• Age: 18 Years - 55 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, laboratory tests and ECG.
• Male or female between 18 and 55 years of age inclusive, at the time of signing the informed consent.
• AST, ALT, alkaline phosphatase and bilirubin within normal ranges. A single repeat is allowed to determine eligibility.
• A female subject is eligible to participate if she is of:
• Non-childbearing potential defined as pre-menopausal females with a documented tubal ligation, hysterectomy or bilateral oophorectomy; or postmenopausal defined as 12 months of spontaneous amenorrhea \[in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) \> 40 MlU/ml and estradiol \< 40 pg/ml (\<140 pmol/L) is confirmatory\].
• Child-bearing potential and agrees to use one of the contraception methods listed in Section 8.1 for an appropriate period of time (as determined by the product label or investigator) prior to the start of dosing to sufficiently minimize the risk of pregnancy at that point. Female subjects must agree to continue to use contraception until at least 3 days after the last dose of study drug.
• 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:

• 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, including sulfa-containing drugs, 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, antacids, iron supplements, 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.
• Use of NSAIDs or aspirin compounds within 21 days of the first dose of study medication.
• 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.
• History of 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.
• 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, peptic ulceration, inflammatory bowel disease or pancreatitis should be excluded.
• Any patient with a history of bleeding diathesis, gastrointestinal bleeding or at increased risk of bleeding such as frequent nose bleeds, high blood pressure, heavy menses, von Willebrand disease, and personal or family history of bleeding disorders
• 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.

Sponsors & Collaborators

• ViiV Healthcare: lead
• Shionogi: collaborator
• GlaxoSmithKline: collaborator

Study Sites (1)

GSK Investigational Site

Austin, Texas, 78744, United States

Location

Related Publications (1)

• Song I, Borland J, Chen S, Guta P, Lou Y, Wilfret D, Wajima T, Savina P, Peppercorn A, Castellino S, Wagner D, Hosking L, Mosteller M, Rubio JP, Piscitelli SC. Effects of enzyme inducers efavirenz and tipranavir/ritonavir on the pharmacokinetics of the HIV integrase inhibitor dolutegravir. Eur J Clin Pharmacol. 2014 Oct;70(10):1173-9. doi: 10.1007/s00228-014-1732-8. Epub 2014 Aug 23.

  PMID: 25146692 BACKGROUND

MeSH Terms

Conditions

Infections; Acquired Immunodeficiency Syndrome; HIV Infections

Interventions

dolutegravir

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: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 12, 2010
• First Posted: February 15, 2010
• Study Start: February 15, 2010
• Primary Completion: April 5, 2010
• Study Completion: April 5, 2010
• Last Updated: June 24, 2019

Record last verified: 2019-06

Locations

US (1)