An Interaction Study to Assess Drug Levels in Healthy Adult Subjects

This study has been completed.
Sponsor:
Collaborator:
GlaxoSmithKline
Information provided by:
Garden State Infectious Disease Associates, PA
ClinicalTrials.gov Identifier:
NCT00614991
First received: February 1, 2008
Last updated: April 14, 2008
Last verified: April 2008
  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 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

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

Resource links provided by NLM:


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

Primary Outcome Measures:
  • • To compare 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. • To compare steady-state plasma RTG PK following administration of RT [ 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: 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: 1
RTG 400mg BID; FPV 1400mg BID; FPV 1400mg BID + RTG 400mg BID
Drug: Raltegravir
400mg BID
Active Comparator: 2
RTG 400mg BID; FPV 1400mg BID + RTG 400mg BID; FPV 1400mg BID
Drug: Raltegravir
400mg BID
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
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
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
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

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 FPV 1400mg BID

  • RTG 400mg BID

C 8 RTG 400mg BID FPV 700mg BID FPV 700mg BID

  • RTV 100mg BID + RTV 100mg BID
  • RTG 400mg BID

D 8 RTG 400mg BID FPV 700mg BID FPV 700mg BID

  • RTV 100mg BID + RTV 100mg BID
  • RTG 400mg BID

E 8 RTG 400mg BID FPV 1400mg QD FPV 1400mg QD

  • RTV 100mg QD + RTV 100mg QD
  • RTG 400mg BID

F 8 RTG 400mg BID FPV 1400mg QD FPV 1400mg QD

  • RTV 100mg QD + RTV 100mg QD
  • RTG 400mg BID

Study subjects will enter the clinic in the morning prior to dosing 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 and older
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/mm3; platelets > 50,000/mm3; 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

No publications provided

Responsible Party: David V Condoluci, DO Medical Director, GSIDA
ClinicalTrials.gov Identifier: NCT00614991     History of Changes
Other Study ID Numbers: COL111242
Study First Received: February 1, 2008
Last Updated: April 14, 2008
Health Authority: United States: Institutional Review Board

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

ClinicalTrials.gov processed this record on August 21, 2014