Pharmacokinetics (PK) Study of Once Daily Darunavir/Ritonavir and Twice and Once Daily Raltegravir in HIV-infected Subjects

NCT01047995 | Completed Phase 1

• 2 other identifiers: SSAT 0312008-008321-30
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 2

Brief Summary

The study aims to help us understand if the HIV drugs darunavir (taken with ritonavir) and raltegravir will affect each other when they are given at the same time. The purpose of the study is to assess the pharmacokinetics (how a drug is absorbed, distributed and eliminated from your body) of darunavir and ritonavir when these are taken with and without raltegravir. The duration of the study will be up to 50 days plus a screening visit which will take place up to 4 weeks prior to the start of the study, and a follow up visit which takes place 1-2 weeks after the last dose of study medication. Subjects will continue to take 2 of their usual drugs (those called nucleoside reverse transcriptase inhibitors -NRTI) throughout the study. For the first 21 days subjects will take their usual NRTI plus raltegravir 400mg twice daily. After this, subjects will also receive either: Group 1) Darunavir/ritonavir 800mg/100mg once daily AND raltegravir 400mg twice daily or Group 2) Darunavir/ritonavir 800mg/100mg once daily AND raltegravir 800mg once daily Subjects will take this regimen for 14 days. Subjects will be randomly allocated to either Group 1 or 2. You will have an equal (50/50) chance of being allocated to Group 1 or 2.

Conditions

HIV Infections

Outcome Measures

Primary Outcomes (1)

• Steady state plasma and intracellular concentrations of darunavir/ritonavir once daily with and without raltegravir and raltegravir twice and once daily

  50 days

Secondary Outcomes (2)

• Safety and tolerability of darunavir/ritonavir and raltegravir when co-administered to HIV-infected subjects

  50 days

• Association between genetic polymorphisms in drug disposition genes and drug exposure

  50 days

Study Arms (2)

Group 1

ACTIVE COMPARATOR

Phase 1, all subjects (n = 24): Raltegravir 400 mg twice daily for 21 days Phase 2 Group 1 (n = 12): Darunavir/ritonavir 800/100 mg once daily plus raltegravir 400 mg twice daily for 14 days Phase 3, all subjects (n = 24): Darunavir/ritonavir 800/100 mg once daily for 14 days.

Drug: Raltegravir plus Darunavir/ritonavir

Group 2

ACTIVE COMPARATOR

Phase 1, all subjects (n = 24): Raltegravir 400 mg twice daily for 21 days Phase 2, Group 2 (n = 12): Darunavir/ritonavir 800/100 mg once daily plus raltegravir 800 mg once daily for 14 days Phase 3, all subjects (n = 24): Darunavir/ritonavir 800/100 mg once daily for 14 days.

Drug: Raltegravir plus Darunavir/ritonavir

Interventions

Raltegravir plus Darunavir/ritonavir DRUG

Phase 1, all subjects (n = 24): Raltegravir 400 mg twice daily for 21 days Phase 2 Group 1 (n = 12): Darunavir/ritonavir 800/100 mg once daily plus raltegravir 400 mg twice daily for 14 days Phase 3, all subjects (n = 24): Darunavir/ritonavir 800/100 mg once daily for 14 days.

Also known as: darunavir = TMC114, ritonavir = Norvir trade name, raltegravir = MK-0518, brand name Isentress

Group 1

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• The ability to understand and sign a written informed consent form, prior to participation in any screening procedure and must be willing to comply with all study requirements.
• Male or non-pregnant, non-lactating females.
• Between 18 to 65 years, inclusive.
• Documented HIV-1 infection and plasma HIV RNA at screening visit below 400 copies/mL.
• (Note retesting of screening viral load is allowed).
• Women of childbearing potential (WOCBP) must be using an adequate method of contraception to avoid pregnancy throughout the study.
• CD4 count \> 100 at screening (Note retesting of screening CD4 count is allowed).
• Receiving an antiretroviral regimen including two NRTIs and an NNRTI or a boosted protease inhibitor or an integrase inhibitor, without any history of virological failure (history of drug switches is allowed only if the reason was tolerability/toxicity/convenience of dosing).
• Agrees not to change regimen, outside the study recommendations, from baseline until end of the treatment period unless this is medically indicated as decided by the treating physician.

You may not qualify if:

• Any serious or active medical or psychiatric illness which, in the opinion of the investigator, would interfere with subject treatment, assessment, or compliance with the protocol. This would include any active clinically significant renal, cardiac, hepatic, pulmonary, vascular, metabolic disorders or malignancy.
• Have a body mass index (BMI) \>35
• Presence of any current active AIDS defining illness (Category C conditions according to the CDC Classification System for HIV Infection 1993) with the following exceptions:
• Stable cutaneous Kaposi's Sarcoma
• Clinically relevant alcohol or drug use (positive urine drug screen, with the exception of cannabinoids) or history of alcohol or drug use considered by the Investigator to be sufficient to hinder compliance with treatment, follow-up procedures or evaluation of adverse events. Smoking is permitted, but tobacco intake should remain consistent throughout the study.
• The use of disallowed concomitant therapy (See Concomitant Medication and treatment, section 5.2).
• Females of childbearing potential without the use of effective non-hormonal birth control methods or not willing to continue practicing these birth control methods for at least 14 days after the end of the treatment period.
• Previous allergy to any of the constituents of the pharmaceuticals administered in this trial.
• Subjects with clinical or laboratory evidence of significantly decreased hepatic or renal function (as determined by the principal investigator).
• Exposure to any investigational drug or placebo within 4 weeks of first dose of study drug

Sponsors & Collaborators

• St Stephens Aids Trust: lead

Study Sites (2)

St Stephen's Centre, Chelsea and Westminster Hospital NHS Foundation Trust

London, London, SW10 9NH, United Kingdom

Location

St Stephens Centre, Chelsea & Westminster Hospital

London, SW10 9NH, United Kingdom

Location

MeSH Terms

Conditions

HIV Infections

Interventions

Raltegravir Potassium; Darunavir; Ritonavir

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Pyrrolidinones; Pyrrolidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Sulfonamides; Amides; Organic Chemicals; Carbamates; Acids, Acyclic; Carboxylic Acids; Sulfones; Sulfur Compounds; Furans; Thiazoles; Azoles

Study Officials

• Marta Boffito, Dr

  St Stephen's AIDS Trust

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: January 12, 2010
• First Posted: January 13, 2010
• Study Start: June 1, 2009
• Primary Completion: December 1, 2009
• Study Completion: December 1, 2009
• Last Updated: January 13, 2010

Record last verified: 2010-01

Locations

GB (2)