A Study to Evaluate the Effect of Boceprevir and Telaprevir on Dolutegravir Pharmacokinetics in Healthy Adult Subjects (ING115697).
| Status: | Completed |
|---|---|
| Conditions: | HIV / AIDS, HIV / AIDS, HIV / AIDS |
| Therapuetic Areas: | Immunology / Infectious Diseases |
| Healthy: | No |
| Age Range: | 18 - 65 |
| Updated: | 3/29/2017 |
| Start Date: | March 1, 2012 |
| End Date: | May 1, 2012 |
A Phase I, Open Label, Randomized, Two Cohort, Two Period, Oneway Study to Evaluate the Effect of Boceprevir and Telaprevir onDolutegravir Pharmacokinetics in Healthy Adult Subjects (ING115697)
Dolutegravir (DTG, GSK1349572) is an integrase inhibitor that is currently in Phase 3
clinical development for the treatment of human immunodeficiency virus (HIV) infection.
Co-infection with Hepatitis C (HCV) is common in HIV-infected subjects therefore it is
expected that DTG will be coadministered with treatments for HCV. Boceprevir (BCV) and
Telaprevir (TVR) are protease inhibitors for the treatment of HCV that were recently
approved by the Food and Drug Administration/European Medicines Agency (FDA/EMA) and have
rapidly been adopted to "standard of care" in combination with pegylated interferon and
ribavarin. This is a single-center, open-label, two-cohort, two-period, one-way, study in
healthy adult subjects. A total of approximately 32 subjects will be enrolled, in order to
obtain 24 evaluable subjects (12 per cohort). In the first treatment period, all subjects
will receive DTG 50 mg once daily for 5 days (treatment A). In period 2, subjects will
receive DTG 50 mg once daily plus either BCV 800 mg q8h (treatment B) for 10 days or TVR 750
mg q8h (treatment C) for 10 days. There will be no washout between treatments. Safety
evaluations and serial PK samples will be collected during each treatment period.
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.
This study will be conducted at one center in the US, with healthy adult male and female
subjects.
clinical development for the treatment of human immunodeficiency virus (HIV) infection.
Co-infection with Hepatitis C (HCV) is common in HIV-infected subjects therefore it is
expected that DTG will be coadministered with treatments for HCV. Boceprevir (BCV) and
Telaprevir (TVR) are protease inhibitors for the treatment of HCV that were recently
approved by the Food and Drug Administration/European Medicines Agency (FDA/EMA) and have
rapidly been adopted to "standard of care" in combination with pegylated interferon and
ribavarin. This is a single-center, open-label, two-cohort, two-period, one-way, study in
healthy adult subjects. A total of approximately 32 subjects will be enrolled, in order to
obtain 24 evaluable subjects (12 per cohort). In the first treatment period, all subjects
will receive DTG 50 mg once daily for 5 days (treatment A). In period 2, subjects will
receive DTG 50 mg once daily plus either BCV 800 mg q8h (treatment B) for 10 days or TVR 750
mg q8h (treatment C) for 10 days. There will be no washout between treatments. Safety
evaluations and serial PK samples will be collected during each treatment period.
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.
This study will be conducted at one center in the US, with healthy adult male and female
subjects.
Inclusion Criteria:
- ALT, alkaline phosphatase and bilirubin ≤ 1.5xULN (isolated bilirubin >1.5xULN is
acceptable if bilirubin is fractionated and direct bilirubin <35%). A single repeat
is allowed for eligibility determination.
- Single QTcB
- Healthy as determined by a responsible and experienced physician, based on a medical
evaluation including medical history, physical examination, laboratory tests and ECG.
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
agrees that the finding is unlikely to introduce additional risk factors and will not
interfere with the study procedures. Subjects with haemoglobin, WBC or neutrophil
count values outside the normal range should always be excluded from enrollment. A
single repeat is allowed for eligibility determination.
- 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 or hysterectomy;
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 (<147 pmol/L) is confirmatory]. Child-bearing potential and
is abstinent1 or 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 use contraception until the
follow-up visit.
- Body weight ≥ 50 kg for males and 45 kg for females 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:
- A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody
result within 3 months of screening
- Current or chronic history of liver disease, or known hepatic or biliary
abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
- 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.
- A positive test for HIV antibody.
- History of regular alcohol consumption within 6 months of the study defined as:
an average weekly intake of >14 drinks for males or >7 drinks for females. One drink is
equivalent to 12 g of alcohol: 12 ounces (360 ml) of beer, 5 ounces (150 ml) of wine or
1.5 ounces (45 ml) of 80 proof distilled spirits.
- 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).
- Unable to refrain from the 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
islonger) 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.
- Where participation in the study would result in donation of blood or blood products
in excess of 500 mL within a 56 day period
- Pregnant females as determined by positive serum or urine hCG test at screening or
prior to dosing.
- Lactating females.
- Unwillingness or inability to follow the procedures outlined in the protocol.
- Subject is mentally or legally incapacitated.
- If heparin is used during PK sampling, subjects with a history of sensitivity to
heparin or heparin-induced thrombocytopenia should not be enrolled.
- Unable to refrain from consumption of seville oranges, grapefruit or grapefruit juice
and/or pummelos, exotic citrus fruits, grapefruit hybrids or fruit juices containing
these products from 7 days prior to the first dose of study medication.
- The subject's systolic blood pressure at screening visit 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. A single repeat is allowed for eligibility determination.
- Exclusion criteria for screening ECG (a single repeat is allowed for eligibility
determination): Males Females Heart rate <45 and >100 bpm <50 and >100 bpm PR
Interval <120 and >220 msec QRS duration <70 and >120 msec QTc interval (Bazett) >450
msec
- Evidence of previous myocardial infarction (Does not include ST segment changes
associated with repolarization).
- Any clinically significant arrhythmia, any clinically significant conduction
abnormality (including but not specific to left or right complete bundle branch
block, AV block [2nd degree or higher], Wolf Parkinson White [WPW] syndrome),
sinus pauses>3 seconds, and non-sustained or sustained ventricular tachycardia
(≥3 consecutive ventricular ectopic beats).
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