An Interaction Study to Assess Drug Levels in Healthy Adult Subjects

NCT00764465 | Completed Phase 2 Results

• 1 other identifier: COL112237
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 1

Brief Summary

To date, no study has investigated whether there is a drug interaction between the protease inhibitor fosamprenavir and the entry inhibitor maraviroc. COL112237 is a randomized, open-label, 6-arm, 3-period, drug interaction study to assess steady-state plasma amprenavir (APV) and maraviroc (MVC) pharmacokinetics in 48 healthy, HIV-negative adults after administration of a 7-day regimen of MVC 300mg 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 MVC 300mg 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.

Conditions

Healthy

Keywords

Healthy Subjects; Pharmacokinetics study; Pharmacokinetics of medications

Outcome Measures

Primary Outcomes (4)

• 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 (Maraviroc) MVC 300mg BID.

  Amprenavir (APV) is the active ingredient/metabolite of Fosamprenavir (FPV).

  Day 14 of the FPV 1400mg BID, FPV 1400mg/MVC 300mg BID, FPV 700mg/RTV 100mg BID, FPV 700mg/RTV 100mg/MVC 300mg BID, FPV 1400mg/RTV 100mg QD, and FPV 1400mg/RTV 100mg QD plus MVC 300mg BID regimens

• 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 (Maraviroc) MVC 300mg BID.

  Amprenavir (APV) is the active ingredient/metabolite of Fosamprenavir (FPV).

  Day 14 of the FPV 1400mg BID, FPV 1400mg/MVC 300mg BID, FPV 700mg/RTV 100mg BID, FPV 700mg/RTV 100mg/MVC 300mg BID, FPV 1400mg/RTV 100mg QD, and FPV 1400mg/RTV 100mg QD plus MVC 300mg BID regimens

• Cmin/Cmax: Steady-state Plasma MVC PK Following Administration of RTV

  Amprenavir (APV) is the active ingredient/ metabolite of Fosamprenavir (FPV). MVC minimum concentration (Cmin), maximum concentration (Cmax), and area under the plasma concentration-time curve (AUC), as determined from MVC 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 MVC 300mg 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 MVC 300mg 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.

  Day 7 of the MVC 300mg BID regimen and Day 14 of the MVC 300mg/FPV 1400mg BID, MVC 300mg/FPV 700mg/RTV 100mg BID, and MVC 300mg BID Plus FPV 1400mg/RTV 100mg QD regimens

• AUC: Steady-state Plasma MVC PK Following Administration of RTV

  Amprenavir (APV) is the active ingredient/ metabolite of Fosamprenavir (FPV). MVC minimum concentration (Cmin), maximum concentration (Cmax), and area under the plasma concentration-time curve (AUC), as determined from MVC 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 MVC 300mg 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 MVC 300mg 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.

  Day 7 of the MVC 300mg BID regimen and Day 14 of the MVC 300mg/FPV 1400mg BID, MVC 300mg/FPV 700mg/RTV 100mg BID, and MVC 300mg BID Plus FPV 1400mg/RTV 100mg QD regimens

Secondary Outcomes (1)

• Number of Participants Who Experienced an Adverse Event

  Day 0 through Day 49

Study Arms (6)

Group A

ACTIVE COMPARATOR

Period 1-Maraviroc 300mg BID Period 2- Fosamprenavir 1400mg BID Period 3- Fosamprenavir 1400mg BID + Maraviroc 300mg BID

Drug: Maraviroc; Drug: Fosamprenavir

Group B

ACTIVE COMPARATOR

Period 1-Maraviroc 300mg BID Period 2-Fosamprenavir 1400mg BID + Maraviroc 300mg BID Period 3-Fosamprenavir 1400mg BID

Drug: Maraviroc; Drug: Fosamprenavir

Group C

ACTIVE COMPARATOR

Period 1-Maraviroc 300mg BID Period 2-Fosamprenavir 700mg BID + Ritonavir 100mg BID Period 3-Fosamprenavir 700mg BID + Ritonavir 100mg BID + Maraviroc 300mg BID

Drug: Maraviroc; Drug: Fosamprenavir; Drug: Ritonavir

Group D

ACTIVE COMPARATOR

Period 1-Maraviroc 300mg BID Period 2-Fosamprenavir 700mg BID + Ritonavir 100mg BID + Maraviroc 300mg BID Period 3-Fosamprenavir 700mg BID + Ritonavir 100mg BID

Drug: Maraviroc; Drug: Fosamprenavir; Drug: Ritonavir

Group E

ACTIVE COMPARATOR

Period 1-Maraviroc 300mg BID Period 2-Fosamprenavir 1400mg QD + Ritonavir 100mg QD Period 3- Fosamprenavir 1400mg QD + Ritonavir 100mg QD + Maraviroc 300mg BID

Drug: Maraviroc; Drug: Fosamprenavir; Drug: Ritonavir

Group F

ACTIVE COMPARATOR

Period 1-Maraviroc 300mg BID Period 2-Fosamprenavir 1400mg QD + Ritonavir 100mg QD + Maraviroc 300mg BID Period 3-Fosamprenavir 1400mg QD + Ritonavir 100mg QD

Drug: Maraviroc; Drug: Fosamprenavir; Drug: Ritonavir

Interventions

Maraviroc DRUG

300 mg BID

Group A; Group B; Group C; Group D; Group E; Group F

Fosamprenavir DRUG

1400 mg BID, 700 mg BID or 1400 mg QD

Also known as: Lexiva

Group A; Group B; Group C; Group D; Group E; Group F

Ritonavir DRUG

100 mg BID, 100 mg QD

Also known as: Norvir

Group C; Group D; Group E; Group F

Eligibility Criteria

• Age: 18 Years - 64 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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 follicle stimulating hormone (FSH) levels consistent with menopause.
• child-bearing 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/mm\^3; platelets \> 50,000/mm\^3; 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.

You may not qualify if:

• 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 nonsteroidal antiinflammatory drug (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.

Sponsors & Collaborators

• Garden State Infectious Disease Associates, PA: lead
• GlaxoSmithKline: collaborator

Study Sites (1)

Garden State Infectious Disease Associates,PA

Voorhees Township, New Jersey, 08043, United States

Location

MeSH Terms

Interventions

Maraviroc; fosamprenavir; Ritonavir

Intervention Hierarchy (Ancestors)

Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Thiazoles; Sulfur Compounds

Limitations and Caveats

Data for primary outcomes are not available per intervention . Values reported as means are uncertain measure type (data no longer available).

Results Point of Contact

• Title: David Condoluci
• Organization: GSIDA

dcondoluci@gsida.org

856-566-3190

Study Officials

• David V Condoluci, DO

  GSIDA

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 1, 2008
• First Posted: October 2, 2008
• Study Start: October 1, 2008
• Primary Completion: December 1, 2008
• Study Completion: December 1, 2008
• Last Updated: January 29, 2016
• Results First Posted: January 29, 2016

Record last verified: 2016-01

Locations

US (1)