An Interaction Study to Assess Drug Levels in Healthy Adult Subjects - Full Text View

Purpose

To date, no study has investigated whether there is a drug interaction between the protease inhibitor fosamprenavir and the integrase inhibitor raltegravir. COL111242 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, HIV-negative adults after administration of a 7-day regimen of RTG 400mg twice a day (BID) alone and after 14-day regimens of unboosted fosamprenavir (FPV) 1400mg twice daily (BID), FPV 700mg/Ritonavir (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, complete blood count (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 Drug: Ritonavir


Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Pharmacokinetics Study Intervention Model: Factorial Assignment Masking: Open Label
Official Title:	Steady-State Plasma Amprenavir (APV) and Raltegravir (RTG) Pharmacokinetics After Fosamprenavir (FPV) and Raltegravir (RTG) Are Each Administered Alone Versus in Combination With or Without Ritonavir (RTV) Boosting in Healthy Adult Subjects

Resource links provided by NLM:

Drug Information available for: Ritonavir Fosamprenavir Fosamprenavir sodium Fosamprenavir calcium Raltegravir Raltegravir potassium

U.S. FDA Resources

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

Primary Outcome Measures:

Cmin/Cmax: Steady-state Plasma Amprenavir (APV) Pharmacokinetics (PK) Following Admin of Fosamprenavir (FPV) 1400mg BID, FPV 700mg/Ritonavir (RTV) 100 mg BID, or FPV 1400mg/RTV 100mg QD With and Without Concurrent Raltegravir (RTG) 400mg BID. [ Time Frame: Day 14 of the FPV 1400mg BID, FPV 1400mg/RAL 400mg BID, FPV 700mg/RTV 100mg BID, FPV 700mg/RTV 100mg/RAL 400mg BID, FPV 1400mg/RTV 100mg QD, and FPV 1400mg/RTV 100mg QD plus RAL 400mg BID regimens ] [ Designated as safety issue: No ]
APV minimum concentration (Cmin), maximum concentration (Cmax), area under the plasma concentration-time curve (AUC), and oral clearance (CL/F) as determined from APV concentrations observed in blood samples obtained at baseline, and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours during the BID regimens (FPV 1400mg BID, FPV 700mg/RTV 100 mg BID), and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 24 hours during the QD regimen (FPV 1400mg/RTV 100mg QD). As Groups A and B received the same regimens (albeit in different order), PK data for these two groups were collated, then assessed. For the same reason, PK data from Groups C and D regimens were collated before assessment, as were the PK data from Groups E and F
AUC: Steady-state Plasma Amprenavir (APV) Pharmacokinetics (PK) Following Admin of Fosamprenavir (FPV) 1400mg BID, FPV 700mg/Ritonavir (RTV) 100 mg BID, or FPV 1400mg/RTV 100mg QD With and Without Concurrent Raltegravir (RTG) 400mg BID. [ Time Frame: Day 14 of the FPV 1400mg BID, FPV 1400mg/RAL 400mg BID, FPV 700mg/RTV 100mg BID, FPV 700mg/RTV 100mg/RAL 400mg BID, FPV 1400mg/RTV 100mg QD, and FPV 1400mg/RTV 100mg QD plus RAL 400mg BID regimens ] [ Designated as safety issue: No ]
APV minimum concentration (Cmin), maximum concentration (Cmax), area under the plasma concentration-time curve (AUC), and oral clearance (CL/F) as determined from APV concentrations observed in blood samples obtained at baseline, and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours during the BID regimens (FPV 1400mg BID, FPV 700mg/RTV 100 mg BID), and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 24 hours during the QD regimen (FPV 1400mg/RTV 100mg QD). As Groups A and B received the same regimens (albeit in different order), PK data for these two groups were collated, then assessed. For the same reason, PK data from Groups C and D regimens were collated before assessment, as were the PK data from Groups E and F
CL/F: Steady-state Plasma Amprenavir (APV) Pharmacokinetics (PK) Following Administration of Fosamprenavir (FPV) 1400mg BID, FPV 700mg/Ritonavir (RTV) 100 mg BID, or FPV 1400mg/RTV 100mg QD With and Without Concurrent Raltegravir (RTG) 400mg BID. [ Time Frame: Day 14 of the FPV 1400mg BID, FPV 1400mg/RAL 400mg BID, FPV 700mg/RTV 100mg BID, FPV 700mg/RTV 100mg/RAL 400mg BID, FPV 1400mg/RTV 100mg QD, and FPV 1400mg/RTV 100mg QD plus RAL 400mg BID regimens ] [ Designated as safety issue: No ]
APV minimum concentration (Cmin), maximum concentration (Cmax), area under the plasma concentration-time curve (AUC), and oral clearance (CL/F) as determined from APV concentrations observed in blood samples obtained at baseline, and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours during the BID regimens (FPV 1400mg BID, FPV 700mg/RTV 100 mg BID), and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 24 hours during the QD regimen (FPV 1400mg/RTV 100mg QD). As Groups A and B received the same regimens (albeit in different order), PK data for these two groups were collated, then assessed. For the same reason, PK data from Groups C and D regimens were collated before assessment, as were the PK data from Groups E and F
Cmin/Cmax: Steady-state Plasma RTG PK Following Admin 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: Day 7 of the RAL 400mg BID regimen and Day 14 of the RAL 400mg/FPV 1400mg BID, RAL 400mg/FPV 700mg/RTV 100mg BID, and RAL 400mg BID Plus FPV 1400mg/RTV 100mg QD regimens ] [ Designated as safety issue: No ]
RAL minimum concentration (Cmin), maximum concentration (Cmax), area under the plasma concentration-time curve (AUC), and oral clearance (CL/F) as determined from RAL concentrations observed in blood samples obtained at baseline, and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours during the period when RAL 400mg BID was administered with the FPV-Containing BID regimens (FPV 1400mg BID, FPV 700mg/RTV 100 mg BID), and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 24 hours during the period when RAL 400mg BID was administered with the FPV QD regimen (FPV 1400mg/RTV 100mg QD). As Groups A and B received the same regimens (albeit in different order), PK data for these two groups were collated, then assessed. For the same reason, PK data from Groups C and D regimens were collated before assessment, as were the PK data from Groups E and F.
AUC: Steady-state Plasma Amprenavir (APV) Pharmacokinetics (PK) Following Administration of Fosamprenavir (FPV) 1400mg BID, FPV 700mg/Ritonavir (RTV) 100 mg BID, or FPV 1400mg/RTV 100mg QD With and Without Concurrent Raltegravir (RTG) 400mg BID. [ Time Frame: Day 7 of the RAL 400mg BID regimen and Day 14 of the RAL 400mg/FPV 1400mg BID, RAL 400mg/FPV 700mg/RTV 100mg BID, and RAL 400mg BID Plus FPV 1400mg/RTV 100mg QD regimens ] [ Designated as safety issue: No ]
APV minimum concentration (Cmin), maximum concentration (Cmax), area under the plasma concentration-time curve (AUC), and oral clearance (CL/F) as determined from APV concentrations observed in blood samples obtained at baseline, and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours during the BID regimens (FPV 1400mg BID, FPV 700mg/RTV 100 mg BID), and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 24 hours during the QD regimen (FPV 1400mg/RTV 100mg QD). As Groups A and B received the same regimens (albeit in different order), PK data for these two groups were collated, then assessed. For the same reason, PK data from Groups C and D regimens were collated before assessment, as were the PK data from Groups E and F
CL/F: Steady-state Plasma Amprenavir (APV) Pharmacokinetics (PK) Following Administration of Fosamprenavir (FPV) 1400mg BID, FPV 700mg/Ritonavir (RTV) 100 mg BID, or FPV 1400mg/RTV 100mg QD With and Without Concurrent Raltegravir (RTG) 400mg BID. [ Time Frame: Day 7 of the RAL 400mg BID regimen and Day 14 of the RAL 400mg/FPV 1400mg BID, RAL 400mg/FPV 700mg/RTV 100mg BID, and RAL 400mg BID Plus FPV 1400mg/RTV 100mg QD regimens ] [ Designated as safety issue: No ]
APV minimum concentration (Cmin), maximum concentration (Cmax), area under the plasma concentration-time curve (AUC), and oral clearance (CL/F) as determined from APV concentrations observed in blood samples obtained at baseline, and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours during the BID regimens (FPV 1400mg BID, FPV 700mg/RTV 100 mg BID), and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 24 hours during the QD regimen (FPV 1400mg/RTV 100mg QD). As Groups A and B received the same regimens (albeit in different order), PK data for these two groups were collated, then assessed. For the same reason, PK data from Groups C and D regimens were collated before assessment, as were the PK data from Groups E and F

Secondary Outcome Measures:

Number of Participants Who Experienced Adverse Events [ Time Frame: Day 0 through Day 49 ] [ Designated as safety issue: No ]
Safety/tolerability data included all adverse events (AEs) reported within the time frame of each regimen evaluated. The intent was to compare adverse events for each sequence and not for each regimen. The regimens for which AE information was culled were:
- RAL 400mg BID alone
- FPV 1400mg BID alone
- FPV 700mg/RTV 100 mg BID alone
- FPV 1400mg/RTV 100mg QD alone
- FPV 1400mg BID combined with RAL 400mg BID
- FPV 700mg/RTV 100 mg BID combined with RAL 400mg BID
- FPV 1400mg/RTV 100mg QD combined with RAL 400mg BID The severity of reported AEs was graded according to DAIDS criteria, Version 1.0 (National Institute of Allergy and Infectious Diseases (NIAID). Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 1.0. Division of Acquired Immunodeficiency Syndrome (DAIDS), Washington D.C.; 2004.


Enrollment:	44
Study Start Date:	January 2008
Study Completion Date:	March 2008
Primary Completion Date:	March 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: Group A Period 1-Raltegravir 400mg BID Period 2-Fosamprenavir 1400mg BID Period 3-Fosamprenavir 1400mg BID + Raltegravir 400mg BID	Drug: Raltegravir 400mg BID Other Name: Isentress MK-0518 Drug: Fosamprenavir 1400mg BID, 700 mg BID or 1400 mg QD Other Name: Lexiva
Active Comparator: Group B Period 1-Raltegravir 400mg BID Period2-Fosamprenavir 1400mg BID + Raltegravir 400mg BID Period 3-Fosamprenavir 1400mg BID	Drug: Raltegravir 400mg BID Other Name: Isentress MK-0518 Drug: Fosamprenavir 1400mg BID, 700 mg BID or 1400 mg QD Other Name: Lexiva
Active Comparator: Group C Period 1-Raltegravir 400mg BID Period 2-Fosamprenavir 700mg BID + Ritonavir 100mg BID Period 3-Fosamprenavir 700mg BID + Ritonavir 100mg BID + Raltegravir 400mg BID	Drug: Raltegravir 400mg BID Other Name: Isentress MK-0518 Drug: Fosamprenavir 1400mg BID, 700 mg BID or 1400 mg QD Other Name: Lexiva Drug: Ritonavir 100 mg BID or QD Other Name: Norvir
Active Comparator: Group D Period 1-Raltegravir 400mg BID Period 2-Fosamprenavir 700mg BID + Ritonavir 100mg BID + Raltegravir 400mg BID Period 3-Fosamprenavir 700mg BID + Raltegravir 100mg BID	Drug: Raltegravir 400mg BID Other Name: Isentress MK-0518 Drug: Fosamprenavir 1400mg BID, 700 mg BID or 1400 mg QD Other Name: Lexiva Drug: Ritonavir 100 mg BID or QD Other Name: Norvir
Active Comparator: Group E Period 1-Raltegravir 400mg BID Period 2-Fosamprenavir 1400mg QD + Ritonavir 100mg QD Period 3-Fosamprenavir 1400mg QD + Ritonavir 100mg QD + Raltegravir 400mg BID	Drug: Raltegravir 400mg BID Other Name: Isentress MK-0518 Drug: Fosamprenavir 1400mg BID, 700 mg BID or 1400 mg QD Other Name: Lexiva Drug: Ritonavir 100 mg BID or QD Other Name: Norvir
Active Comparator: Group F Period 1-Raltegravir 400mg BID Period 2-Fosamprenavir 1400mg QD + Ritonavir 100mg QD + Raltegravir 400mg BID Period 3-Fosamprenavir 1400mg QD + Ritonavir 100mg QD	Drug: Raltegravir 400mg BID Other Name: Isentress MK-0518 Drug: Fosamprenavir 1400mg BID, 700 mg BID or 1400 mg QD Other Name: Lexiva Drug: Ritonavir 100 mg BID or QD Other Name: Norvir

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Eligibility


Ages Eligible for Study:	18 Years and older (Adult, Senior)
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	Yes

Criteria

Inclusion Criteria:

Age > 18 years
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/mm^3; platelets > 50,000/mm^3; hematocrit > 25%);
Non-smoker
Willingness and ability to adhere to treatment and follow-up procedures;
The ability to understand and sign a written informed consent form.

Exclusion Criteria:

They fail to meet the above inclusion 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
Are receiving medications that are contraindicated or result in significant drug-drug interactions with RTV (including, but not limited to, triazolam, astemizole, ergot medications, cisapride, midazolam, bepridil, or rifampin)
Have a significant documented sulfa allergy (e.g., Stevens-Johnson Syndrome)
HIV, Hepatitis B or C positive
Cigarette/cigar/pipe smokers
They are pregnant or lactating. All other women of childbearing potential must use effective method(s) of contraception throughout the study participation and for 30 days following the end of the study.

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: NCT00614991

Sponsors and Collaborators

Garden State Infectious Disease Associates, PA

GlaxoSmithKline

Investigators


Principal Investigator:	David V Condoluci, DO	GSIDA

More Information


Responsible Party:	Garden State Infectious Disease Associates, PA
ClinicalTrials.gov Identifier:	NCT00614991 History of Changes
Other Study ID Numbers:	COL111242
Study First Received:	February 1, 2008
Results First Received:	March 24, 2015
Last Updated:	January 27, 2016
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:


Ritonavir Fosamprenavir Raltegravir Potassium HIV Protease Inhibitors Protease Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Anti-HIV Agents	Anti-Retroviral Agents Antiviral Agents Anti-Infective Agents Cytochrome P-450 CYP3A Inhibitors Cytochrome P-450 Enzyme Inhibitors HIV Integrase Inhibitors Integrase Inhibitors

ClinicalTrials.gov processed this record on September 23, 2016