Text Size

An Interaction Study to Assess Drug Levels in Fasting Healthy Adult Subjects

This study has been completed.
Sponsor:
Collaborator:
GlaxoSmithKline
Information provided by (Responsible Party):
Garden State Infectious Disease Associates, PA
ClinicalTrials.gov Identifier:
NCT00802074
First received: December 3, 2008
Last updated: August 29, 2012
Last verified: August 2012
History of Changes
  Purpose

To date, no study has investigated whether there is a drug interaction between the protease inhibitor fosamprenavir and the integrase inhibitor raltegravir. COL112775 is a randomized, open-label, 6-arm, 3-period, drug interaction study to assess steady-state plasma amprenavir (APV) and raltegravir (RTG) pharmacokinetics in 48 healthy, fasting, HIV-negative adults after administration of a 7-day regimen of RTG 400mg BID alone and after 14-day regimens of unboosted fosamprenavir (FPV) 1400mg twice daily (BID), FPV 700mg/RTV 100mg BID, or FPV 1400mg/ritonavir (RTV) 100mg once daily (QD) with and without concurrent RTG 400mg BID. Blood samples for drug concentration measurement will be collected over 12 hours at the end of each dosing period. Subjects will undergo a physical examination, CBC with differential, HIV test, hepatitis B/C test, liver function test, renal function analysis, and lipid panel at screening, and all of these tests, except those for HIV and hepatitis B/C, will be repeated at follow-up post-study. Adverse events and adherence (by pill count and medication diary) will be assessed by the investigator/study personnel at the end of each dosing period


Condition Intervention
Healthy
 Drug: Raltegravir
Drug: Fosamprenavir

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Factorial Assignment
Masking: Open Label
Official Title: A Randomized, Open-Label, Six-Period, Drug Interaction Study to Assess Steady-State Plasma Amprenavir (APV) and Raltegravir (RTG) Pharmacokinetics Following Administration of RTG 400 mg BID for 14 Days Alone and in Combination With 14 Days of Either Fosamprenavir (FPV) 1400 mg BID, FPV 700 mg BID + RTV 100 mg BID or FPV 1400 mg + RTV 100 mg QD in Healthy Adult Subjects When Under Fasting Conditions

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by Garden State Infectious Disease Associates, PA:

Primary Outcome Measures:
  • To compare fasting steady-state plasma APV PK following administration of FPV 1400mg BID, FPV 700mg/RTV 100 mg BID, or FPV 1400mg/RTV 100mg QD with and without concurrent RTG 400mg BID. [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • To compare steady-state plasma RTG PK following administration of RTG 400mg BID alone and following co-administration with FPV 1400mg BID, FPV 700mg/RTV 100 mg BID, or FPV 1400mg/RTV 100mg QD [ Time Frame: 6 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • To evaluate the safety and tolerability of RTG 400mg BID plus FPV (when given as either 1400mg BID, 1400mg/RTV 100mg QD or 700mg/RTV 100mg BID) [ Time Frame: 6 months ] [ Designated as safety issue: No ]

Enrollment: 48
Study Start Date: December 2008
Study Completion Date: April 2009
Primary Completion Date: March 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 1
RTG 400mg BID; FPV 1400mg BID; FPV 1400mg BID + RTG 400mg BID
 Drug: Raltegravir
400mg BID
Other Names:
  • Isentress
  • MK-0518
Drug: Fosamprenavir
1400mg BID, 700 mg BID or 1400 mg QD
Other Name: Lexiva
Active Comparator: 2
RTG 400mg BID; FPV 1400mg BID + RTG 400mg BID; FPV 1400mg BID
 Drug: Raltegravir
400mg BID
Other Names:
  • Isentress
  • MK-0518
Drug: Fosamprenavir
1400mg BID, 700 mg BID or 1400 mg QD
Other Name: Lexiva
Active Comparator: 3
RTG 400mg BID; FPV 700mg BID + RTV 100mg BID; FPV 700mg BID + RTV 100mg BID + RTG 400mg BID
 Drug: Raltegravir
400mg BID
Other Names:
  • Isentress
  • MK-0518
Drug: Fosamprenavir
1400mg BID, 700 mg BID or 1400 mg QD
Other Name: Lexiva
Active Comparator: 4
RTG 400mg BID; FPV 700mg BID + RTV 100mg BID + RTG 400mg BID; FPV 700mg BID + RTV 100mg BID
 Drug: Raltegravir
400mg BID
Other Names:
  • Isentress
  • MK-0518
Drug: Fosamprenavir
1400mg BID, 700 mg BID or 1400 mg QD
Other Name: Lexiva
Active Comparator: 5
RTG 400mg BID; FPV 1400mg QD + RTV 100mg QD; FPV 1400mg QD + RTV 100mg QD + RTG 400mg BID
 Drug: Raltegravir
400mg BID
Other Names:
  • Isentress
  • MK-0518
Drug: Fosamprenavir
1400mg BID, 700 mg BID or 1400 mg QD
Other Name: Lexiva
Active Comparator: 6
RTG 400mg BID; FPV 1400mg QD + RTV 100mg QD + RTG 400mg BID; FPV 1400mg QD + RTV 100mg QD
 Drug: Raltegravir
400mg BID
Other Names:
  • Isentress
  • MK-0518
Drug: Fosamprenavir
1400mg BID, 700 mg BID or 1400 mg QD
Other Name: Lexiva

Detailed Description:

This randomized, open-label, six-arm, three-period drug interaction study will recruit 48 healthy volunteers so as to obtain a minimum of 36 evaluable subjects at a single study center in the U.S. The study will have a screening visit, 3 treatment visits for PK sampling and a follow-up visit. The screening visit will be conducted within 30 days prior to receiving the first dose. Subjects will then be randomized into 1 of 6 treatment groups as shown below:

Cohort Size Period 1 Period 2 Period 3 Sample Days 1 to 7 Days 1-14 Days 1-14

A 8 RTG 400mg BID, FPV 1400mg BID, FPV 1400mg BID + RTG 400mg BID

B 8 RTG 400mg BID, FPV 1400mg BID + RTG 400mg BID , FPV 1400mg BID

C 8 RTG 400mg BID, FPV 700mg BID + RTV 100mg BID, FPV 700mg BID + RTV 100mg BID + RTG 400mg BID

D 8 RTG 400mg BID, FPV 700mg BID + RTV 100mg BID + RTG 400mg BID, FPV 700mg BID + RTV 100mg BID

E 8 RTG 400mg BID, FPV 1400mg QD + RTV 100mg QD, FPV 1400mg QD + RTV 100mg QD + RTG 400mg BID

F 8 RTG 400mg BID, FPV 1400mg QD + RTV 100mg QD + RTG 400mg BID, FPV 1400mg QD + RTV 100mg QD

Study subjects will enter the clinic in the morning prior to dosing in a fasting state and remain at the center for 12 hours following each dose. Fourteen to 21 days following completion of the third dosing period, study subjects will return to the clinic for follow-up assessment. The total duration of the study will be approximately 86 days from screening through follow up. Blood samples for drug concentration measurement of amprenavir (APV) and raltegravir (RTG) concentrations will be collected over 12 hours at the end of each dosing period (at 0 [baseline], 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours post-dose). Subjects will undergo a physical examination, CBC with differential, HIV test, hepatitis B/C test, liver function test, renal function analysis, and lipid panel at screening, and all of these tests except those for HIV and hepatitis B/C will be repeated at follow-up post-study. Adverse events and adherence (by pill count and medication diary) will be assessed by the investigator/study personnel at the end of each dosing period. Evaluable patients will be required to have adhered to at least 95% of their study drug doses. Plasma APV concentrations will be analyzed using a validated high-performance liquid chromatography method with tandem mass spectrometric detection (HPLC/MS/MS) and plasma RTG concentrations by triple quadruple mass spectrometry. Plasma APV and RTG pharmacokinetic parameters measured will include maximum concentration (Cmax), time to maximum concentration (Tmax), minimum concentration (Cmin), and area under the concentration-time curve (AUC). All these parameters, except Tmax, will be log-transformed before statistical analysis. Analysis of variance, considering treatment as a fixed effect and subject as a random effect will be performed using SAS, and assuming a treatment ratio for steady-state APV PK parameters as 1.0, the 90% confidence intervals will be within the range 0.81-1.24

  Eligibility

Ages Eligible for Study:   18 Years to 64 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Healthy subjects with no clinically significant abnormality identified by physician by evaluation of medical history, physical examination, clinical laboratory tests or vital signs.
  • Between 18 and 64 years.

  • A female subject is eligible to participate if she is neither pregnant nor lactating, and falls into one of the following categories:

    • non-childbearing potential including females with documented (medical report verification) hysterectomy or bilateral oophorectomy, or post-menopausal females defined as being amenorrheic for greater than 1 year and having estradiol and FSH levels consistent with menopause.
    • childbearing potential with a negative serum pregnancy test at screen and who agrees to use one of the following methods of contraception from screening or at least two weeks prior to the first dose (whichever is earlier) until the follow-up visit (any contraception method must be used consistently and correctly, i.e., in accordance with both the product label and the instructions of a physician).
  • Agreement for complete abstinence from intercourse.
  • Double barrier contraception (male condom/spermicide, male condom/diaphragm, diaphragm/spermicide).
  • Any intrauterine device (IUD) with published data showing that the expected failure rate is less than 1% per year (not all IUDs meet this criterion)
  • Any other method with published data showing that the lowest expected failure rate for that method is less than 1% per year.
  • Adequate renal function (calculated creatinine clearance via Cockcroft and Gault method (CrCl) > 50 mL/min).
  • Adequate hepatic function (total bilirubin < 2.5mg/dL; hepatic transaminases < 5x normal).
  • Adequate hematologic function (absolute neutrophil count [ANC] > 750 neutrophils/mm3; platelets > 50,000/mm3; hematocrit > 25%).
  • Non-smoker, defined as not having used nicotine-containing products within the past 6 months.
  • Willingness and ability to adhere to treatment and follow-up procedures.
  • The ability to understand and sign a written informed consent form.
  • Body weight > or =50 kg for males and > or=45 kg for females and body mass index (BMI) in the range of 19 to 30 kg/m2 (BMI = weight [kg]/(height [m])2).

Exclusion Criteria:

  • Have an active infection that required parenteral antibiotics or hospitalization within 2 weeks prior to enrollment.
  • A history of or documented gastrointestinal diseases that impact drug absorption.
  • Have a significant documented sulfa allergy (e.g., Stevens-Johnson Syndrome) or a history of sensitivity to any of the study medications, or components thereof.
  • HIV, Hepatitis B or C positive .
  • Cigarette/cigar/pipe smokers.
  • History of alcohol/drug abuse or dependence within 12 months of the study, or a history of alcohol consumption in the past six months exceeding 7 units/week for women and 14 units/week for men (where 1 unit = 5 ounces of wine or 12 ounces of beer or 1.5 ounces of hard liquor).
  • Treatment with an investigational drug within 30 days or 5 half-lives (whichever is longer) preceding the first dose of study medication.
  • Use of prescription or non-prescription drugs (including aspirin and NSAIDs), vitamins, herbal and dietary supplements within 7 days (or 14 days if the drug is a potential enzyme inducer, such as St. John's Wort) or 5 half-lives (whichever is longer) prior to the first dose of study medication, unless in the opinion of the investigator the medication will not interfere with the study procedures or compromise subject safety.
  • Subjects who have donated plasma within 7 days prior to the screening visit or where participation in this study would result in donation of blood in excess of 500 mL of blood within 56 day period.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00802074

Locations
United States, New Jersey
Garden State Infectious Disease Associates, PA
Voorhees, New Jersey, United States, 08043
Sponsors and Collaborators
Garden State Infectious Disease Associates, PA
GlaxoSmithKline
Investigators
Principal Investigator: David V Condoluci, DO GSIDA
  More Information

No publications provided

Responsible Party: Garden State Infectious Disease Associates, PA
ClinicalTrials.gov Identifier: NCT00802074     History of Changes
Other Study ID Numbers: COL112775
Study First Received: December 3, 2008
Last Updated: August 29, 2012
Health Authority: United States: Institutional Review Board

Keywords provided by Garden State Infectious Disease Associates, PA:
Healthy Subjects
Pharmacokinetics study
Pharmacokinetics of medications

Additional relevant MeSH terms:
Fosamprenavir
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
 Pharmacologic Actions
HIV Protease Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on June 17, 2013