HIVPhase 1NCT00740389
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.
A Phase 1 study testing TMC125 in people with HIV and AIDS, run by Tibotec Pharmaceuticals, Ireland.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 55 years
- Conditions the study is for
- HIV, AIDS, Fungal Infection
- What is being tested?
- TMC125
- How many people
- 18 participants
- Where
- No sites listed yet
- Study dates
- Sep 2008to Jan 2009
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 55 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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.
Who cannot join
- 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
Show all 19Show fewer
- 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
- Participation in an investigational drug trial within 60 days prior to the first intake of trial medication
- Donation of blood or plasma within the 60 days preceding the first drug intake
- Having participated in more than 1 trial with TMC125 (etravirine), TMC120 (dapirivine) and/or TMC278 (rilpivirine, formerly known as R278474) or having developed rash, erythema or urticaria while participating in a trial with the aforementioned compounds
- Subjects with the laboratory abnormalities at screening as defined by the Division of AIDS and in accordance with the normal ranges of clinical laboratory.
About this study
Official title: 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.
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.
Read the detailed description
In this Phase I, open-label, 3-period crossover trial the potential pharmacokinetic interaction between TMC125 and fluconazole and between TMC125 and voriconazole will be investigated. Fluconazole and voriconazole are triazole antifungal agents.
Fluconazole and voriconazole are inhibitors of CYP isoenzymes 2C19, 2C9 and CYP3A4. Fluconazole is metabolized by the liver to a small extent. Approximately 80% of the administered fluconazole dose appears in the urine in unchanged form. Voriconazole is metabolized by CYP2C19, 2C9 and 3A4. TMC125 is also metabolized by CYP3A, 2C9 and 2C19. Because of the effect of fluconazole and voriconazole on the metabolic pathways relevant for TMC125 metabolism, concomitant administration of TMC125 and fluconazole or voriconazole might increase TMC125 pharmacokinetics. Because of the effect of TMC125 on the metabolic pathways relevant for voriconazole metabolism, concomitant administration of TMC125 and voriconazole might also modify voriconazole pharmacokinetics. Since the elimination of fluconazole is mainly via the kidneys, an effect of TMC125 on fluconazole pharmacokinetics is not expected. The current trial aims to assess the 2-way pharmacokinetic interaction between TMC125 and fluconazole, and between TMC125 and voriconazole, to provide dosing recommendations for combined use in the treatment of HIV infected patients.In this trial the pharmacokinetic interaction between TMC125 and fluconazole, and between TMC125 and voriconazole, all at steady-state will be investigated in 18 healthy subjects. During the first two sessions, each subject will receive 2 treatments (Treatments A and B) in a randomized way. In Treatment A, 200 mg TMC125 twice a day. will be administered from Day 1 to Day 7 with an additional morning dose on Day 8. In Treatment B, 200 mg fluconazole once a day in the morning will be administered from Day 1 to Day 16, co-administered with 200 mg TMC125 twice a day from Day 9 to Day 16.
These sessions are followed by a third session, Treatment C, in which 400 mg voriconazole twice a day will be administered on Day 1 and 200 mg voriconazole twice a day will be administered from Day 2 to Day 15, with an additional morning dose on Day 16. From Day 9 to Day 15, 200 mg TMC125 twice a day will be co-administered, with an additional morning dose on Day 16. All TMC125 and fluconazole intakes will be under fed conditions, within 10 minutes after a meal. Voriconazole will be administered 1.5 hour before a meal. Between subsequent treatment sessions, there will be a washout period of at least 2 weeks. Full pharmacokinetic profiles will be determined for one dosing interval (12 hours) for TMC125 on Day 8 of Treatment A and on Day 16 of Treatments B and C. For fluconazole, full pharmacokinetic profiles will be determined for one dosing interval (24 hours) on Days 8 and 16 of Treatment B. For voriconazole, full pharmacokinetic profiles will be determined for one dosing interval (12 hours) on Days 8 and 16 of Treatment C. Safety and tolerability will be monitored continuously throughout the trial. Treatment A: 200 mg TMC125 twice daily, orally from Day 1 to 7 and a morning dose on Day 8. Treatment B: 200 mg fluconazole once daily, orally from Day 1 to 16, co-administered with 200 mg TMC125 twice daily from Day 9 to 16. Treatment C: 400 mg voriconazole twice daily, orally on Day 1 and 200 mg voriconazole twice daily will be administered from Day 2 to 15, with a morning dose on Day 16. From Day 9 to 15, 200 mg TMC125 twice daily will be co-administered, with a morning dose on Day 16.
- Conditions
- HIV, AIDS, Fungal Infection
- Being tested
- TMC125
- Keywords
- TMC125-C187, TMC125-TiDP2-C187, HIV, AIDS, Fungal Infection, Pharmacokinetics
- Medical subject headings
- Acquired Immunodeficiency Syndrome, Mycoses
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TMC125Drug
What is being measured
The primary outcome is the main question the study is designed to answer.
Pharmacokinetics of TMC125, voriconazole and fluconazole
Secondary outcomes (1)
short-term safety and tolerability of the coadministration of voriconazole or fluconazole and TMC125
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Aug 2008 (estimated)
- Study startSep 2008
- Primary completionJan 2009
- Study completionJan 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for HIVStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- Tibotec Pharmaceuticals, Ireland
- Sponsor type
- Industry (pharma, biotech, devices)
- Investigators
- Tibotec Pharmaceuticals Clinical Trial, Study director, Tibotec Pharmaceutical Limited
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00740389
- Sponsor's protocol ID
- CR014992
- Status last verified
- Apr 2010
- First submitted
- 21 Aug 2008
- Last updated
- 9 Jun 2011
- Results posted
- No
Publications
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.
PubMed 23400742
Study at a glance
From the registry record, last updated by the sponsor on 9 Jun 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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.
- ClinicalTrials.gov ID
- NCT00740389
- Acronym / sponsor ID
- CR014992
- Conditions
- HIV, AIDS, Fungal Infection
- Keywords
- TMC125-C187, TMC125-TiDP2-C187, HIV, AIDS, Fungal Infection, Pharmacokinetics
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 18 participants (actual)
- Lead sponsor
- Tibotec Pharmaceuticals, IrelandIndustry (pharma, biotech, devices)
- Study start
- Sep 2008
- Primary completion
- Jan 2009 (actual)
- Study completion
- Jan 2009 (actual)
- First posted
- 25 Aug 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
In this Phase I, open-label, 3-period crossover trial the potential pharmacokinetic interaction between TMC125 and fluconazole and between TMC125 and voriconazole will be investigated. Fluconazole and voriconazole are triazole antifungal agents.
Fluconazole and voriconazole are inhibitors of CYP isoenzymes 2C19, 2C9 and CYP3A4. Fluconazole is metabolized by the liver to a small extent. Approximately 80% of the administered fluconazole dose appears in the urine in unchanged form. Voriconazole is metabolized by CYP2C19, 2C9 and 3A4. TMC125 is also metabolized by CYP3A, 2C9 and 2C19. Because of the effect of fluconazole and voriconazole on the metabolic pathways relevant for TMC125 metabolism, concomitant administration of TMC125 and fluconazole or voriconazole might increase TMC125 pharmacokinetics. Because of the effect of TMC125 on the metabolic pathways relevant for voriconazole metabolism, concomitant administration of TMC125 and voriconazole might also modify voriconazole pharmacokinetics. Since the elimination of fluconazole is mainly via the kidneys, an effect of TMC125 on fluconazole pharmacokinetics is not expected. The current trial aims to assess the 2-way pharmacokinetic interaction between TMC125 and fluconazole, and between TMC125 and voriconazole, to provide dosing recommendations for combined use in the treatment of HIV infected patients.In this trial the pharmacokinetic interaction between TMC125 and fluconazole, and between TMC125 and voriconazole, all at steady-state will be investigated in 18 healthy subjects. During the first two sessions, each subject will receive 2 treatments (Treatments A and B) in a randomized way. In Treatment A, 200 mg TMC125 twice a day. will be administered from Day 1 to Day 7 with an additional morning dose on Day 8. In Treatment B, 200 mg fluconazole once a day in the morning will be administered from Day 1 to Day 16, co-administered with 200 mg TMC125 twice a day from Day 9 to Day 16.
These sessions are followed by a third session, Treatment C, in which 400 mg voriconazole twice a day will be administered on Day 1 and 200 mg voriconazole twice a day will be administered from Day 2 to Day 15, with an additional morning dose on Day 16. From Day 9 to Day 15, 200 mg TMC125 twice a day will be co-administered, with an additional morning dose on Day 16. All TMC125 and fluconazole intakes will be under fed conditions, within 10 minutes after a meal. Voriconazole will be administered 1.5 hour before a meal. Between subsequent treatment sessions, there will be a washout period of at least 2 weeks. Full pharmacokinetic profiles will be determined for one dosing interval (12 hours) for TMC125 on Day 8 of Treatment A and on Day 16 of Treatments B and C. For fluconazole, full pharmacokinetic profiles will be determined for one dosing interval (24 hours) on Days 8 and 16 of Treatment B. For voriconazole, full pharmacokinetic profiles will be determined for one dosing interval (12 hours) on Days 8 and 16 of Treatment C. Safety and tolerability will be monitored continuously throughout the trial. Treatment A: 200 mg TMC125 twice daily, orally from Day 1 to 7 and a morning dose on Day 8. Treatment B: 200 mg fluconazole once daily, orally from Day 1 to 16, co-administered with 200 mg TMC125 twice daily from Day 9 to 16. Treatment C: 400 mg voriconazole twice daily, orally on Day 1 and 200 mg voriconazole twice daily will be administered from Day 2 to 15, with a morning dose on Day 16. From Day 9 to 15, 200 mg TMC125 twice daily will be co-administered, with a morning dose on Day 16.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (19 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TMC125 | Drug | – |
Primary outcome
Pharmacokinetics of TMC125, voriconazole and fluconazole
1 secondary outcome
short-term safety and tolerability of the coadministration of voriconazole or fluconazole and TMC125
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Jun 2011.
- Derived from this study: PubMed 23400742Kakuda 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.
- 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.Link provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Tibotec Pharmaceuticals Clinical Trial study director
Tibotec Pharmaceutical Limited
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing TMC125 in people with HIV and AIDS, run by Tibotec Pharmaceuticals, Ireland.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 Jun 2011. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Pharmacokinetics of TMC125, voriconazole and fluconazole. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00740389, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Jun 2011.