TMC125-TiDP2-C187: A Phase I, Open-label Trial to Investigate the Pharmacokinetic Interaction Between TMC125 and Two Antifungal Agents (Fluconazole and Voriconazole), All at Steady-state in Healthy Subjects.

NCT00740389 | Completed Phase 1

• 1 other identifier: CR014992
• Study Type: interventional
• Target: 18
• Locations: 0 countries
• Sites: N/A

Brief Summary

This is a Phase I, open-label, 3-period crossover trial to investigate the pharmacokinetic interaction (process by which a drug is absorbed, distributed, metabolised and eliminated by the body) between TMC125 and fluconazole, and between TMC125 and voriconazole.

Conditions

HIV; AIDS; Fungal Infection

Keywords

TMC125-C187; TMC125-TiDP2-C187; HIV; AIDS; Fungal Infection; Pharmacokinetics

Outcome Measures

Primary Outcomes (1)

• Pharmacokinetics of TMC125, voriconazole and fluconazole

Secondary Outcomes (1)

• short-term safety and tolerability of the coadministration of voriconazole or fluconazole and TMC125

Interventions

TMC125 DRUG

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Non-smoking or smoking no more than 10 cigarettes, or 2 cigars, or 2 pipes per day for at least 3 months prior to screening
• Body Mass Index (BMI) of 18.0 to 30.0 kg/m2, extremes included. BMI is calculated as the weight (in kg) divided by the square of height (in m)
• Informed Consent Forms signed voluntarily before first trial-related activity
• Able to comply with protocol requirements
• Healthy on the basis of medical evaluation that reveals the absence of any clinically relevant abnormality and includes a physical examination (including skin examination), medical and surgical history, electrocardiogram (ECG), vital signs and the results of blood biochemistry, hematology and a urinalysis carried out at Screening.

You may not qualify if:

• A positive HIV-1 or HIV-2 test at study screening
• Female, except if postmenopausal since more than two years, or post-hysterectomy or surgically sterilized (without reversal operation)
• History or evidence of current use of alcohol, barbiturate, amphetamine, recreational or narcotic drug use which in the investigator's opinion would compromise subject's safety and/or compliance with study procedures
• Hepatitis A infection, hepatitis B infection, or hepatitis C infection at study screening
• A positive urine drug test at study screening or on Day -1 of each session. Urine will be tested for the presence of amphetamines, benzodiazepines, cocaine, cannabinoids and opioids
• Currently active or underlying gastrointestinal, cardiovascular, neurologic, psychiatric, metabolic, renal, hepatic, respiratory, inflammatory or infectious disease
• Currently significant diarrhea, gastric stasis or constipation that in the investigator's opinion could influence drug absorption or bioavailability
• Any history of significant skin disease. Previously demonstrated clinically significant allergy or hypersensitivity to fluconazole, voriconazole and/or any of the excipients of the investigational medication administered in this trial
• Clinical evidence or history of long QT syndrome and history of additional risk factors for Torsade de Pointes, such as cardiomyopathy, heart failure, hypokalemia, family history of known Long QT Syndrome, or sudden unexplained death at a young age (= 40 years) in a firstdegree relative (i.e., biological parent, sibling, or offspring)
• Clinically relevant heart rhythm disturbances known or suggested by history, or on 12-lead ECG at screening or on Day 1 (predose) of the first treatment period
• Electrolyte abnormalities (hypokalemia, hypocalcemia, hypomagnesemia), grade 2 or greater, within 21 days prior to intake of the investigational medication
• History of galactose intolerance, lactase deficiency or glucose-galactose malabsorption
• Use of concomitant medication, including over-the-counter products and dietary supplements
• Systemic over-the-counter medication must have been discontinued at least 7 days prior to the first dose of study medication
• prescribed medication and all products containing Hypericum perforatum (e.g. St. John's wort) must have been discontinued at least 14 days before the first dose of study medication, except for paracetamol

Sponsors & Collaborators

• Tibotec Pharmaceuticals, Ireland: lead

Related Publications (1)

• Kakuda TN, Van Solingen-Ristea R, Aharchi F, Smedt GD, Witek J, Nijs S, Vyncke V, Hoetelmans RM. Pharmacokinetics and short-term safety of etravirine in combination with fluconazole or voriconazole in HIV-negative volunteers. J Clin Pharmacol. 2013 Jan;53(1):41-50. doi: 10.1177/0091270011433329. Epub 2013 Jan 24.

  PMID: 23400742 DERIVED

Related Links

• Clinical Study Report Synopsis of TMC125-TiDP2-C187: A Phase I, open-label trial to investigate the pharmacokinetic interaction between TMC125 and two antifungal agents (fluconazole and voriconazole), all at steady-state in healthy volunteers.

MeSH Terms

Conditions

Acquired Immunodeficiency Syndrome; Mycoses

Interventions

etravirine

Condition Hierarchy (Ancestors)

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

Study Officials

• Tibotec Pharmaceuticals Clinical Trial

  Tibotec Pharmaceutical Limited

  STUDY DIRECTOR

Study Design

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

Study Record Dates

• First Submitted: August 21, 2008
• First Posted: August 25, 2008
• Study Start: September 1, 2008
• Primary Completion: January 1, 2009
• Study Completion: January 1, 2009
• Last Updated: June 9, 2011

Record last verified: 2010-04