A Study to Evaluate the Effect of Boceprevir and Telaprevir on Dolutegravir Pharmacokinetics in Healthy Adult Subjects (ING115697).

This study has been completed.
Sponsor:
Collaborators:
Shionogi
GlaxoSmithKline
Information provided by (Responsible Party):
ViiV Healthcare
ClinicalTrials.gov Identifier:
NCT01563328
First received: March 22, 2012
Last updated: May 31, 2012
Last verified: May 2012
  Purpose

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.


Condition Intervention Phase
Infection, Human Immunodeficiency Virus
Drug: DTG
Drug: BCV
Drug: TVR
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Parallel Assignment
Masking: Open Label
Official Title: A Phase I, Open Label, Randomized, Two Cohort, Two Period, Oneway Study to Evaluate the Effect of Boceprevir and Telaprevir on Dolutegravir Pharmacokinetics in Healthy Adult Subjects (ING115697)

Resource links provided by NLM:


Further study details as provided by ViiV Healthcare:

Primary Outcome Measures:
  • Plasma steady-state DTG PK parameters AUC(0-τ), Cmax, Cmin, and Cτ [ Time Frame: For 24 hours after dosing on Period 1 Day 5 and Period 2 Day 10 ] [ Designated as safety issue: No ]
    Samples will be collected at predose and at 1, 2, 3, 4, 6, 8, 12 and 24 hours post dose


Secondary Outcome Measures:
  • Safety and tolerability parameters as assessed by change from baseline in vital signs n(BP and HR), number of subjects with adverse events and toxicity grading of clinical laboratory tests. [ Time Frame: Up to 29 days ] [ Designated as safety issue: No ]
  • Plasma steady-state DTG tmax and t1/2 [ Time Frame: For 24 hours after dosing on Period 1 Day 5 and Period 2 Day 10 ] [ Designated as safety issue: No ]
    Samples will be collected at predose and at 1, 2, 3, 4, 6, 8, 12 and 24 hours post dose

  • Plasma steady-state TVR and BCV AUC(0-t), Cmax, Cmin, and Ct [ Time Frame: For 8 hours after dosing on Period 2, Day 10 ] [ Designated as safety issue: No ]
    Samples will be collected at predose and at 1, 2, 3, 4, and 8 hours post dose

  • Plasma steady-state TVR and BCV tmax and t1/2 [ Time Frame: For 8 hours after dosing on Period 2, Day 10 ] [ Designated as safety issue: No ]
    Samples will be collected at predose and at 1, 2, 3, 4, and 8 hours post dose


Enrollment: 32
Study Start Date: March 2012
Study Completion Date: May 2012
Primary Completion Date: May 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cohort 1
DTG x 5 days followed by BCV + DTG x 10 days
Drug: DTG
50 mg q24h
Other Name: Dolutegravir
Drug: BCV
800 mg q8h
Other Name: Boceprevir
Experimental: Cohort 2
DTG x 5 days followed by TVR + DTG x 10 days
Drug: DTG
50 mg q24h
Other Name: Dolutegravir
Drug: TVR
750 mg q8h
Other Name: Telaprevir

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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 <or= 450 msec. A single repeat is allowed for eligibility determination.
  • 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).
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01563328

Locations
United States, Texas
GSK Investigational Site
Austin, Texas, United States, 78744
Sponsors and Collaborators
ViiV Healthcare
Shionogi
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials ViiV Healthcare
  More Information

No publications provided

Responsible Party: ViiV Healthcare
ClinicalTrials.gov Identifier: NCT01563328     History of Changes
Other Study ID Numbers: 115697
Study First Received: March 22, 2012
Last Updated: May 31, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by ViiV Healthcare:
Dolutegravir, GSK1349572, DTG, BCV, TVR, drug interaction

Additional relevant MeSH terms:
Acquired Immunodeficiency Syndrome
HIV Infections
Immunologic Deficiency Syndromes
Immune System Diseases
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Sexually Transmitted Diseases
Sexually Transmitted Diseases, Viral
Slow Virus Diseases
Virus Diseases
Dolutegravir
Anti-HIV Agents
Anti-Infective Agents
Anti-Retroviral Agents
Antiviral Agents
Enzyme Inhibitors
HIV Integrase Inhibitors
Integrase Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on October 23, 2014