Relative Bioavailability Study of Two New Dolutegravir/Abacavir/Lamivudine Fixed Dose Combination Tablets

This study has been completed.
Sponsor:
Collaborators:
Shionogi
GlaxoSmithKline
Information provided by:
ViiV Healthcare
ClinicalTrials.gov Identifier:
NCT01366547
First received: May 26, 2011
Last updated: August 4, 2011
Last verified: August 2011
  Purpose

Dolutegravir (DTG, GSK1349572) is a next-generation integrase inhibitor (INI) currently in phase 3 clinical trials for human immunodeficiency virus (HIV). Fixed-dose combinations (FDCs) have greatly simplified the treatment of patients with HIV. While Atripla (an FDC of tenofovir (TDF), emtricitabine (FTC) and efavirenz (EFV)) has become the preferred first line regimen due in large part to its convenient presentation as a full treatment regimen in a single product, other options are needed. A fixed-dose combination of DTG/abacavir (ABC)/lamivudine (3TC) is one such opportunity.

This is a single-center, randomized, open-label, 3-period crossover study in healthy adult subjects to evaluate the single-dose relative bioavailability of two experimental oral DTG 50 mg/ABC 600 mg/3TC 300 mg FDC tablet formulations compared to co-administration of the separate tablet formulations (DTG 50 mg tablet and EPZICOM), with each dose administered in the fasted state. Approximately 18 subjects will be enrolled and randomized to one of 6 different treatment sequences. There will be a screening visit within 30 days prior to the first dose of study drug and a follow up visit within 7-14 days after the last dose. There will be a 7 day washout between doses in each treatment period.

The following PK parameters for DTG, ABC and 3TC will be measured: area under the concentration curve from time zero (pre-dose) extrapolated to infinite time (AUC(0-infinity)), Area under the concentration-time curve from time zero (pre-dose) to the time of the last quantifiable concentration (AUC (0-t)), maximum observed concentration (Cmax), lag time before observation of drug concentrations (tlag), time of occurrence of Cmax (tmax), terminal phase half-life (t½), apparent clearance following oral dosing (CL/F) and apparent terminal phase volume of distribution (Vz/F).


Condition Intervention Phase
Healthy Subjects
Infection, Human Immunodeficiency Virus
Drug: Dolutegravir 50 mg/abacavir 600 mg/lamivudine 300 mg
Drug: Dolutegravir 50 mg
Drug: abacavir 600 mg/lamivudine 300 mg
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Crossover Assignment
Masking: Open Label
Official Title: A Randomized, Open-Label, Single‑Dose, 3‑Period, Crossover Evaluation of the Relative Bioavailability of Two Experimental Fixed-Dose Combination Tablet Formulations of Dolutegravir 50 mg/Abacavir 600 mg/Lamivudine 300 mg Compared to Co‑Administered Dolutegravir 50 mg and EPZICOM™ (Abacavir 600 mg/Lamivudine 300 mg) Tablets in Healthy Adult Subjects

Resource links provided by NLM:


Further study details as provided by ViiV Healthcare:

Primary Outcome Measures:
  • Plasma DTG AUC(0-infinity) [ Time Frame: 48 hours post dose ] [ Designated as safety issue: No ]
  • Plasma ABC AUC(0-infinity) [ Time Frame: 48 hours post dose ] [ Designated as safety issue: No ]
  • Plasma 3TC AUC(0-infinity) [ Time Frame: 48 hours post dose ] [ Designated as safety issue: No ]
  • Plasma DTG AUC(0-t) [ Time Frame: 48 hours post dose ] [ Designated as safety issue: No ]
  • Plasma ABC AUC(0-t) [ Time Frame: 48 hours post dose ] [ Designated as safety issue: No ]
  • Plasma 3TC AUC(0-t) [ Time Frame: 48 hours post dose ] [ Designated as safety issue: No ]
  • Plasma DTG Cmax [ Time Frame: 48 hours post dose ] [ Designated as safety issue: No ]
  • Plasma ABC Cmax [ Time Frame: 48 hours post dose ] [ Designated as safety issue: No ]
  • Plasma 3TC Cmax [ Time Frame: 48 hours post dose ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Change from baseline in 12-lead ECG [ Time Frame: 48 hours post dose ] [ Designated as safety issue: No ]
  • Plasma DTG tlag [ Time Frame: 48 hours post dose ] [ Designated as safety issue: No ]
  • Number of subjects with adverse events [ Time Frame: 48 hours post dose ] [ Designated as safety issue: No ]
  • Toxicity grading of clinical laboratory tests [ Time Frame: 48 hours post dose ] [ Designated as safety issue: No ]
  • Change from baseline in vital signs (BP and HR) [ Time Frame: 48 hours post dose ] [ Designated as safety issue: No ]
  • Plasma ABC tlag [ Time Frame: 48 hours post dose ] [ Designated as safety issue: No ]
  • Plasma 3TC tlag [ Time Frame: 48 hours post dose ] [ Designated as safety issue: No ]
  • Plasma DTG tmax [ Time Frame: 48 hours post dose ] [ Designated as safety issue: No ]
  • Plasma ABC tmax [ Time Frame: 48 hours post dose ] [ Designated as safety issue: No ]
  • Plasma 3TC tmax [ Time Frame: 48 hours post dose ] [ Designated as safety issue: No ]
  • Plasma DTG t½ [ Time Frame: 48 hours post dose ] [ Designated as safety issue: No ]
  • Plasma ABC t½ [ Time Frame: 48 hours post dose ] [ Designated as safety issue: No ]
  • Plasma 3TC t½ [ Time Frame: 48 hours post dose ] [ Designated as safety issue: No ]
  • Plasma DTG CL/F [ Time Frame: 48 hours post dose ] [ Designated as safety issue: No ]
  • Plasma ABC CL/F [ Time Frame: 48 hours post dose ] [ Designated as safety issue: No ]
  • Plasma 3TC CL/F [ Time Frame: 48 hours post dose ] [ Designated as safety issue: No ]
  • Plasma DTG Vz/F [ Time Frame: 48 hours post dose ] [ Designated as safety issue: No ]
  • Plasma ABC Vz/F [ Time Frame: 48 hours post dose ] [ Designated as safety issue: No ]
  • Plasma 3TC Vz/F [ Time Frame: 48 hours post dose ] [ Designated as safety issue: No ]

Enrollment: 18
Study Start Date: June 2011
Study Completion Date: July 2011
Primary Completion Date: July 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Single Arm
Subjects will be randomized in a three-way crossover design to receive a single dose of each of two different tablet formulations of dolutegravir 50 mg/abacavir 600 mg/lamivudine 300 mg or dolutegravir 50 mg plus EPZICOM (abacavir 600mg/lamivudine 300 mg). There will be a screening visit within 30 days prior to first dose and a follow-up visit 7-14 days after the last dose.
Drug: Dolutegravir 50 mg/abacavir 600 mg/lamivudine 300 mg
Dolutegravir 50 mg/abacavir 600 mg/lamivudine 300 mg is an experimental fixed dose combination tablet of an experimental integrase inhibitor (dolutegravir) and two FDA approved nucleoside reverse transcriptase inhibitors (abacavir and lamivudine)
Drug: Dolutegravir 50 mg
Dolutegravir is an experimental drug in the integrase inhibitor class that is being studied for the treatment of HIV infection.
Drug: abacavir 600 mg/lamivudine 300 mg
This is an FDA approved fixed dose combination tablet of two nucleoside reverse transcriptase inhibitors
Other Names:
  • KIVEXA. This is a trademark of ViiV Healthcare
  • EPZICOM. This is a trademark of ViiV Healthcare.

Detailed Description:

Official Title - Randomized, Open-Label, Single Dose, 3 Period, Crossover Evaluation of the Relative Bioavailability of Two Experimental Fixed-Dose Combination Tablet Formulations of Dolutegravir 50 mg/Abacavir 600 mg/Lamivudine 300 mg Compared to Co administered Dolutegravir 50 mg and EPZICOM™ (Abacavir 600 mg/Lamivudine 300 mg) Tablets in Healthy Adult Subjects.

ViiV Healthcare is the new sponsor of this study, and GlaxoSmithKline is in the process of updating systems to reflect the change in sponsorship

  Eligibility

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

Inclusion Criteria:

  • Healthy as determined by a responsible and experienced physician, based on a medical evaluation including medical history, physical examination, laboratory tests and cardiac monitoring.
  • 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 or child-bearing potential and agrees to use one of the contraception methods listed in the protocol until the follow-up visit.
  • Male subjects with female partners of child-bearing potential must agree to use one of the contraception methods listed in the protocol until 84 days after the last dose of study drug.
  • Body weight greater than 50 kg for males and greater than 45 kg for females and BMI within the range 18.5- 31.0 kg/m2 (inclusive).
  • ALT, alkaline phosphatase and bilirubin less than 1.5xULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).
  • A negative HLA-B*5701 allele screening assessment
  • Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.

Exclusion Criteria:

  • 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, 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. 7. 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.
  • 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.
  • History of Gilbert's disease.
  • Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56 day period.
  • 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 outside of protocol limits.
  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: NCT01366547

Locations
United States, New York
GSK Investigational Site
Buffalo, New York, United States, 14202
Sponsors and Collaborators
ViiV Healthcare
Shionogi
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials ViiV Healthcare
  More Information

No publications provided

Responsible Party: Cheri Hudson; Clinical Disclosure Advisor, GSK Clinical Disclosure
ClinicalTrials.gov Identifier: NCT01366547     History of Changes
Other Study ID Numbers: 114581
Study First Received: May 26, 2011
Last Updated: August 4, 2011
Health Authority: United States: Food and Drug Administration

Keywords provided by ViiV Healthcare:
Bioavailability
Lamivudine
Dolutegravir
integrase
Abacavir

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

ClinicalTrials.gov processed this record on August 21, 2014