GSK706769/KALETRA Drug-drug Interaction Study

GlaxoSmithKline (GSK)

Status and phase

Completed

Phase 1

Conditions

Infection, Human Immunodeficiency Virus

Treatments

Drug: GSK706769 & KALETRA

Study type

Interventional

Funder types

Industry

Identifiers

NCT00723775

CRR110744

Details and patient eligibility

About

To compare plasma GSK706769 PK following repeat administration of GSK706769 QD with and without KALETRA (LPV 400 mg/RTV 100mg) q12h

Enrollment

17 patients

Sex

All

Ages

18 to 50 years old

Volunteers

Accepts Healthy Volunteers

Inclusion criteria

Healthy as determined by a responsible physician, based on a medical evaluation including medical history, physical examination, laboratory tests and cardiac monitoring. 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.
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 females with a documented bilateral tubal ligation, bilateral oophorectomy (removal of the ovaries), or hysterectomy;
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. Following confirmation of their post-menopausal status, they can resume use of HRT.
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 medication.
Body weight >= 50 kg (110 lbs.) for men and >=45 kg (99 lbs) for women and 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.

Exclusion criteria

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 defined as:

An average weekly intake of >14 drinks/week for men or >7 drinks/week for women.

Note: 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.

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.
History of significant renal or hepatic diseases.
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 GSK706769 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.

Note: "Study" or "investigational" drugs include GSK706769 or Kaletra

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.

A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening.
A positive test for HIV antibody.
The subject's systolic blood pressure is outside the range of 90-140mmHg, or diastolic blood pressure is outside the range of 45-90mmHg or heart rate is outside the range of 50-100bpm for female subjects or 45-100 bpm for male subjects.
Exclusion criteria for screening ECG per protocol.
Exclusion Criteria for 24-Hour Screening Holter per protocol (conducted only if telemetry is warranted from findings on telemetry from an ongoing repeat dose study):