GSK1349572 Drug Interaction Study With Atazanavir/Ritonavir and Atazanavir

NCT00883935 | Completed Phase 1

• 1 other identifier: 111854
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to compare the amount of GSK1349572 (study drug) in the blood when given with and without atazanavir/ritonavir or atazanavir and to compare the blood levels of atazanavir when given with GSK1349572 to historical data for atazanavir.

Conditions

Healthy Volunteer

Keywords

GSK1349572; Atazanavir; Ritonavir; Reyataz; Norvir; healthy; pharmacokinetic

Outcome Measures

Primary Outcomes (1)

• Plasma GSK1349572 steady-state AUC(0-tau), Cmax, C0, Ctau, and Cmin following administration of GSK1349572 30mg q24h for 5 days and following co-administration with ATV/RTV 300/100mg q24h or ATV 400mg q24h for 14 days.

  19 days

Secondary Outcomes (3)

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

  19 days

• Plasma GSK1349572 PK parameters: tmax, tmin, CL/F and t½, following administration of GSK1349572 30mg q24h for 5 days and following co-administration with ATZ/RTV 300/100mg q24h or ATZ 400mg q24h for 14 days.

  19 days

• Plasma ATV PK parameters, including AUC(0-tau), Cmax, Ctau, and Cmin following co-administration of GSK1349572 30mg q24h and ATV/RTV 300/100mg q24h or ATV 400mg q24h for 14 days.

  19 days

Study Arms (2)

Sequence 2

EXPERIMENTAL

In the first treatment period, all subjects will receive GSK1349572 30mg q24h for 5 days (treatment A). In period two, subjects will receive GSK1349572 30mg q24h in combination with ATV 400mg q24h (treatment C) for 14 days. There will be no washout between treatment periods. Day 1 of Period 2 will be the day after Day 5 of Period 1. Subjects will have a screening visit within 30 days prior to the first dose of study drug, two treatment periods, and a follow-up visit 7-14 days after the last dose of study drug.

Drug: GSK1349572; Drug: Atazanavir 400 mg

Sequence 1

EXPERIMENTAL

In the first treatment period, all subjects will receive GSK1349572 30mg q24h for 5 days (treatment A). In period two, subjects will receive GSK1349572 30mg q24h in combination with ATV/RTV 300/100mg q24h (treatment B) for 14 days. There will be no washout between treatment periods. Day 1 of Period 2 will be the day after Day 5 of Period 1. Subjects will have a screening visit within 30 days prior to the first dose of study drug, two treatment periods, and a follow-up visit 7-14 days after the last dose of study drug.

Drug: GSK1349572; Drug: Atazanavir 300 mg; Drug: Ritonavir

Interventions

GSK1349572 DRUG

GSK1349572 30 mg once a day for 5 days in Period 1 and 14 days in Period 2

Sequence 1; Sequence 2

Atazanavir 300 mg DRUG

Atazanavir 300 mg once per day for 14 days in Period 2

Also known as: ATV, REYATAZ. REYATAZ is a registered trademark of Bristol-Myers Squibb Company

Sequence 1

Atazanavir 400 mg DRUG

Atazanavir 400 mg once a day for 14 days in Period 2

Also known as: REYATAZ. REYATAZ is a registered trademark of Bristol-Myers Squibb Company, ATV

Sequence 2

Ritonavir DRUG

Ritonavir 100 mg once a day for 14 days in Period 2

Also known as: NORVIR. NORVIR is a registered trademark of Abbott Labs, RTV

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:

• AST, ALT, and alkaline phosphatase less than or equal to 1.5xULN. Total bilirubin must be less than ULN.
• 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 65 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 defined as pre-menopausal females with a documented tubal ligation, hysterectomy or bilateral oophorectomy; or postmenopausal defined as 12 months of spontaneous amenorrhea \[in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) \> 40 MlU/ml and estradiol \< 40 pg/ml (\<140 pmol/L) is confirmatory\].
• Male subjects must agree to use one of the contraception methods listed in the protocol. This criterion must be followed from the time of the first dose of study medication until 14 days post-last dose.
• 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 18.0-32.0 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, 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, peptic ulceration, inflammatory bowel disease or pancreatitis 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.
• History of significant renal or hepatobiliary diseases. Subjects with a history of nephrolithiasis will be excluded.

Sponsors & Collaborators

• GlaxoSmithKline: lead
• Shionogi: collaborator

Study Sites (1)

GSK Investigational Site

Austin, Texas, 78744, United States

Location

MeSH Terms

Interventions

dolutegravir; Atazanavir Sulfate; Ritonavir

Intervention Hierarchy (Ancestors)

Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Oligopeptides; Peptides; Amino Acids, Peptides, and Proteins; Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Study Design

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

Study Record Dates

• First Submitted: April 16, 2009
• First Posted: April 20, 2009
• Study Start: April 1, 2009
• Primary Completion: June 1, 2009
• Study Completion: June 1, 2009
• Last Updated: June 22, 2009

Record last verified: 2009-06

Locations

US (1)