TMC 125 Blood Levels Study

Evaluation of the Pharmacokinetics and Safety of TMC125 Administered Once and Twice-Daily and Following a 2-Week-Treatment Period With Efavirenz in Male and Female Healthy Volunteers.

The purpose of the study is to look at whether changing directly from one medication for HIV (efavirenz) to a new medication for HIV (TMC125) has any effect on the levels of TMC125 in the blood, compared to when TMC125 is taken without efavirenz having been taken immediately beforehand.

The study aims to help the investigators understand whether it is safe to change directly from efavirenz to TMC125 (with no gap between the treatments) in patients who need these treatments.

The study will investigate the blood levels of TMC125 when it is taken both once and twice a day.

Study Overview

• Status: Completed
• Conditions: HIV Infections
• Intervention / Treatment: Drug: TMC125 once daily; Drug: TMC125 twice daily

Detailed Description

Pharmacokinetic parameters of TMC125 will be evaluated when TMC125 is given without and with a 14-day efavirenz intake preceding period in order to evaluate the risk of achieving sub therapeutic concentrations of TMC125 when switching straight from efavirenz containing regimens

Safety and tolerability of medications will also be assessed by questions, physical examination and laboratory parameters. These will be performed at regular intervals during the drug study.

• Study Type: Interventional
• Enrollment (Anticipated): 24
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom, SW10 9th
    • St Stephens Centre, Chelsea & Westminster Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. The ability to understand and sign a written informed consent form, prior to participation in any screening procedures and must be willing to comply with all study requirements
2. Male or non-pregnant, non-lactating females
3. Between 18 to 65 years, inclusive
4. Body Mass Index (BMI) of 18 to 35 kg/m2, inclusive
5. Women of childbearing potential (WOCBP) must be using an adequate method of contraception to avoid pregnancy throughout the study and for a period of at least 1 month after the study

Exclusion Criteria:

1. Any significant acute or chronic medical illness
2. Evidence of organ dysfunction or any clinically significant deviation from normal in physical examination, vital signs, ECG or clinical laboratory determinations
3. Positive blood screen for hepatitis B and/or C antibodies
4. Positive blood screen for HIV-1 and 2 antibodies
5. Current or recent (within 3 months) gastrointestinal disease
6. Clinically relevant alcohol or drug use (positive urine drug screen) 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.
7. Exposure to any investigational drug or placebo within 4 weeks of first dose of study drug
8. Consumption of grapefruit, or Seville oranges or any grapefruit or Seville orange containing product within 1 week of first dose of study drug and for the duration of the study
9. Use of any other drugs, including over-the-counter medications and herbal preparations, within 2 weeks prior to first dose of study drug
10. Females of childbearing potential without the use of effective non-hormonal birth control methods, or not willing to continue practising these birth control methods for at least 30 days after the end of the treatment period
11. Previous allergy to any of the constituents of the pharmaceuticals administered in this trial

Study Plan

How is the study designed?

Design Details

• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
OTHER: 1; Group 1 (n =12): subjects will receive TMC125 400 mg once daily for 14 days followed by 14 days of washout followed by efavirenz 600 mg once daily for 14 days followed by 14 days of TMC125 400 mg once daily	Drug: TMC125 once daily; Group 1 (n =12): subjects will receive TMC125 400 mg once daily for 14 days followed by 14 days of washout followed by efavirenz 600 mg once daily for 14 days followed by 14 days of TMC125 400 mg once daily
OTHER: 2; Group 2 (n = 12): TMC125 200 mg twice daily for 14 days followed by 14 days of washout followed by efavirenz 600 mg once daily for 14 days followed by 14 days of TMC125 200 mg twice daily	Drug: TMC125 twice daily; Group 2 (n = 12): TMC125 200 mg twice daily for 14 days followed by 14 days of washout followed by efavirenz 600 mg once daily for 14 days followed by 14 days of TMC125 200 mg twice daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Steady state plasma concentrations of TMC125 administered once and twice-daily and following a 2-week-treatment period with efavirenz 600 mg once daily	56 days

Secondary Outcome Measures

Outcome Measure	Time Frame
Efavirenz inducing effect on TMC125 metabolism after efavirenz intake cessation evaluation. Safety and tolerability of TMC125 administered once and twice-daily	56 days

Collaborators and Investigators

• Sponsor: St Stephens Aids Trust
• Investigators: Principal Investigator: Marta Boffito, Chelsea & Westminser Healthcare NHS Trust

Study record dates

Study Major Dates

• Study Start: September 1, 2007
• Study Completion (ACTUAL): December 1, 2007

Study Registration Dates

• First Submitted: September 17, 2007
• First Submitted That Met QC Criteria: September 17, 2007
• First Posted (ESTIMATE): September 18, 2007

Study Record Updates

• Last Update Posted (ESTIMATE): September 5, 2008
• Last Update Submitted That Met QC Criteria: September 4, 2008
• Last Verified: September 1, 2008

More Information

Terms related to this study

• Keywords: Healthy volunteers; Pharmacokinetic; TMC125; Efavarinz
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; HIV Infections; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Etravirine
• Other Study ID Numbers: SSAT 024