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A Study to Evaluate the Bioequivalence of a Combined Formulated Tablet Compared With Maraviroc and Combivir™

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT01597648
First received: May 3, 2012
Last updated: May 17, 2012
Last verified: May 2012
  Purpose

This is a study in healthy adult subjects to evaluate the bioequivalence of a Combined Formulated Tablet compared with maraviroc and Combivir administered concurrently versus maraviroc + Combivir. 42 subjects will be enrolled in the study such that 40 subjects complete dosing and critical assessments. The total duration of a subject's participation will be approximately 33 to 35 days, including a screening period (Day −21 to Day −1), 2 treatment periods (Days 1-3), at least a 7-day washout between Period 1 and Period 2, and a follow-up visit 7 to 14 days after the last dose of study drug in Period 2. Each dosing period will begin the evening prior to dosing and extend until 48 hours (Day 3) after dosing. Subjects will be randomly assigned to receive 1 of the following 2 treatments in Period 1 then crossover to receive the alternate treatment in Period 2:

In Sequence 1 (N=21) subjects will receive Treatment A followed by a 7 day washout and Treatment B. In Sequence 2 (N=21) subjects will receive Treatment B followed by a 7 day washout and Treatment A. Treatment A consists of 1 tablet of maraviroc 300 mg, lamivudine 150 mg, and zidovudine 300 mg as a combined formulation after an overnight fast. Treatment B consists of 1 tablet of maraviroc 300 mg + 1 tablet of Combivir taken concurrently after an overnight fast. On Day 1 of each treatment period, subjects will receive study drug in the morning after an overnight fast of at least 8 hours. Study drug will be administered with 240 mL of water. Dosing in each treatment period will be separated by a minimum washout period of at least 7 days between doses. All subjects will undergo safety and other assessments. Subjects may be discharged after all study procedures are completed on the morning of Day 3, with instructions to return for the next study period or the follow-up visit, as appropriate. The follow-up visit will occur 7 to 14 days after the last dose of study drug in Period 2. Pharmacokinetic blood samples will be collected during each treatment period for evaluation of maraviroc, lamivudine, and zidovudine before dosing and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36, and 48 hours after dosing (total of 16 PK time points per treatment period). Protocol waivers or exemptions are not allowed, with the exception of immediate safety concerns. Therefore, adherence to the study protocol requirements, including those specified in the Time and Events Table, are essential and required for study conduct.


Condition Intervention Phase
Infection, Human Immunodeficiency Virus I
Drug: Maraviroc
Drug: Combivir
Drug: GSK2838510
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Bio-equivalence Study
Intervention Model: Crossover Assignment
Masking: Open Label
Official Title: A Randomized, Open-Label, Crossover Study to Evaluate the Bioequivalence of a Combined Formulated Tablet Compared With Maraviroc and Combivir™ Administered Concurrently in Healthy Adult Subjects

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Safety parameters: AEs, vital signs, ECG, body temperature and laboratory assessments, including haematology, clinical biochemistry and cardiac troponin [ Time Frame: Approximately 5 weeks from first dose to the follow-up visit ] [ Designated as safety issue: Yes ]
    To assess the safety and tolerability of single and repeat inhaled doses of GSK2339345 administered by an aqueous droplet inhaler

  • Assessment of oropharyngeal sensation perturbation via a 4 point scale [ Time Frame: Approximately 5 weeks from first dose to the follow-up visit ] [ Designated as safety issue: Yes ]
    To assess the changes in oropharyngeal sensation caused by single and repeat inhaled doses of GSK2339345 administered by an aqueous droplet inhaler


Secondary Outcome Measures:
  • Plasma concentrations of GSK2339345 and single and repeat dose derived pharmacokinetic parameters including Cmax, tmax, AUC(0-t), AUC(0-inf), and AUC(0- τ), as appropriate where data allow [ Time Frame: Approximately 5 weeks from first dose to the follow-up visit ] [ Designated as safety issue: No ]
    To evaluate the systemic pharmacokinetics of single and repeat doses of inhaled GSK2339345 in healthy volunteers administered by an aqueous droplet inhaler

  • Identification of taste of the solution and rating on 11 point scale to rate pleasantness or unpleasantness [ Time Frame: Approximately 5 weeks from first dose to the follow-up visit ] [ Designated as safety issue: No ]
    To assess the palatability of GSK2339345 administered by an aqueous droplet inhaler


Enrollment: 42
Study Start Date: November 2011
Study Completion Date: January 2012
Primary Completion Date: January 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Sequence 1
Treatment A: 1 tablet of GSK2838510 (maraviroc 300 mg, lamivudine 150 mg, and zidovudine 300 mg as a combined formulation) after an overnight fast Washout Treatment B: 1 tablet of maraviroc 300 mg + 1 tablet of Combivir taken concurrently after an overnight fast.
Drug: Maraviroc
300 mg
Drug: Combivir
1 tablet: lamivudine 150mg, zidovudine 300mg
Drug: GSK2838510
Maraviroc 300mg, lamivudine 150mg, zidovudine 300mg
Experimental: Sequence 2

Treatment B: 1 tablet of maraviroc 300 mg + 1 tablet of Combivir taken concurrently after an overnight fast.

Washout Treatment A: 1 tablet of GSK2838510 (maraviroc 300 mg, lamivudine 150 mg, and zidovudine 300 mg as a combined formulation) after an overnight fast

Drug: Combivir
1 tablet: lamivudine 150mg, zidovudine 300mg

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Healthy male and female subjects 18 to 55 years of age (inclusive); healthy as determined by a responsible physician, based on a medical evaluation, including medical history, vital sign measurements, physical examination, clinical laboratory tests, and 12-lead 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 and the Medical Monitor agree that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures.
  • A female subject is eligible to participate if she is of: Non childbearing potential, defined as premenopausal 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] greater than 40 MlU/mL and estradiol less than 40 pg/mL (less than 146.8 pmol/L) is confirmatory). Childbearing potential and is abstinent (abstinence from penile-vaginal intercourse must be consistent with the preferred and usual lifestyle of the subject) or agrees to use 1 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 30 days after the study.
  • The subject has alanine aminotransferase, alkaline phosphatase, and bilirubin less than and equal to 1.5 × ULN (isolated bilirubin >1.5 × ULN is acceptable if bilirubin is fractionated and direct bilirubin is less than 35%).
  • Subject has a QTcB <450 msec.
  • The subject has a body mass index (BMI) between 18.5 and 31.0 kg/m2 (inclusive) and a total body weight greater than and equal to 45 kg for females and ≥50 kg for males.
  • The subject provides written informed consent.
  • The subject is a current nonsmoker greater than 3 months.

Exclusion Criteria:

  • The subject has a positive prestudy drug/alcohol screen. At minimum, the drug screen will include alcohol, cotinine, 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).
  • The subject has a history of sensitivity to any of the study drugs, or components thereof, or a history of drug or other allergy that, in the opinion of the investigator or Medical Monitor, contraindicates the subject's participation.
  • The subject is unable to refrain from the use of prescription or nonprescription drugs, including vitamins and 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 drug, unless in the opinion of the investigator and Medical Monitor the medication will not interfere with the study procedures or compromise subject safety.
  • The subject has a history of regular alcohol consumption within 6 months of the study defined as an average weekly intake of greater than 14 drinks/week for men or greater than 7 drinks/week for women.
  • The subject has consumed red wine, Seville oranges, grapefruit, or grapefruit juice within 7 days prior of the first dose of study drug.
  • The female subject is pregnant as determined by positive serum or urine human chorionic gonadotrophin (hCG) test at screening or before dosing.
  • The female subject is lactating.
  • The subject is unwilling or unable to follow the procedures outlined in the protocol.
  • The subject has 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. A subject with a history of cholecystectomy, peptic ulceration, inflammatory bowel disease, or pancreatitis should be excluded.
  • The subject has a positive prestudy hepatitis B surface antigen, hepatitis C antibody, or HIV antibody result.
  • The subject has a history of Gilbert's disease.
  • The subject's 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 has systolic blood pressure outside the range of 90-140 mmHg, diastolic blood pressure outside the range of 45-90 mmHg, or heart rate outside the range of 50-100 bpm for female subjects or 45-100 bpm for male subjects. A single repeat measurement is allowed for eligibility determination.
  • The subject meets any of the following exclusion criteria for the screening ECG (a single repeat ECG is allowed for eligibility determination): Males heart rate: less than 45 or greater than 100 bpm; females heart rate: less than 50 or greater than 100 bpm; Males and females PR interval: less than 120 or greater than 220 msec; Males and females QRS duration: less than 70 or greater than 120 msec; Males and females QTcB: greater than 450 msec. Evidence of previous myocardial infarction (does not include ST segment changes associated with repolarization). Any conduction abnormality (including but not specific to left or right complete bundle branch block, atrioventricular block [2nd degree or higher], and Wolf Parkinson White syndrome). Sinus pauses greater than 3 seconds. Any significant arrhythmia which, in the opinion of the principal investigator and Medical Monitor, will interfere with the safety for the individual subject. Nonsustained or sustained ventricular tachycardia (greater than and equal to 3 consecutive ventricular ectopic beats).
  • The subject is unwilling or unable to follow the procedures outlined in the protocol.
  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: NCT01597648

Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT01597648     History of Changes
Other Study ID Numbers: 115325
Study First Received: May 3, 2012
Last Updated: May 17, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by GlaxoSmithKline:
Combivir™, HIV, bioequivalence, Combined Formulated Tablet, Combined Formulated Tablet, HIV, bioequivalence, Combivir, Selzentry™, Celsentri™, lamivudine, zidov

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

ClinicalTrials.gov processed this record on November 23, 2014