HIVPhase 1DDI CoartemNCT01876966

Interaction Between Etravirine or Darunavir/Ritonavir and Artemether / Lumefantrine

A Phase 1 study testing Etravirine, Darunavir/ritonavir and artemether/lumefantrine in people with HIV, run by Janssen Pharmaceutica N.V., Belgium.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

Search all trials

Trial summary

The purpose of this study is to investigate the pharmacokinetic interaction between etravirine and artemether/lumefantrine and darunavir/ritonavir and artemether/lumefantrine in healthy Human Immunodeficiency Virus- (HIV-)negative patients. Read more about this study

Who is it for?: Ages 18 to 55 yearsHealthy volunteers can take part
Conditions the study is for: HIV
What is being tested?: Etravirine, Darunavir/ritonavir and artemether/lumefantrine
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 33 participants
Where: No sites listed yet
Study dates: Mar 2011to Jul 2011
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
Healthy volunteers accepted
Adult

Who may be able to join

if of childbearing potential or if male, use a highly effective method of birth control.
Able to comply with protocol requirements.
A BMI (weight in kg divided by the square of height in meters) of 18.5 to 30.0 kg/m2, extremes included.
healthy on the basis of a medical evaluation
Non-smoking for at least 3 months prior to selection.

Who cannot join

previously demonstrated clinically significant allergy, hypersensitivity or intolerance to any of the investigational medications or its excipients
Use of concomitant medication, including over-the-counter products and dietary supplements.
Having participated in more than 1 study (single or multiple dose) with ETR (TMC125), DRV (TMC114), dapivirine (TMC120) and/or rilpivirine (TMC278, formerly known as R278474), or having developed a rash, erythema or urticaria while participating in a study with the aforementioned compounds.
A positive pregnancy test or breast feeding at screening or on Day 1.
Any condition that, in the opinion of the investigator, would compromise the study or the well-being of the patient or prevent the patient from meeting or performing study requirements

About this study

Official title: A Phase I, Partially Randomized, Open Label, Two-way, Two Period Cross-over Study to Investigate the Pharmacokinetic Interaction Between Etravirine or Darunavir/Rtv and Artemether/Lumefantrine at Steady-state in Healthy HIV-negative Subjects

Read the detailed description

This is a Phase I, partially randomized, open-label, single-center, two-way, two-period cross-over study to investigate the pharmacokinetic interaction between etravirine (ETR) or darunavir/ritonavir (DRV/rtv) and the antimalarial drugs artemether/lumefantrine at steady-state in healthy human immunodeficiency virus (HIV)-negative patients. The study population will consist of 32 healthy patients, equally divided over 2 panels. Patients in Panel 1 will be treated with ETR and artemether/lumefantrine; patients in Panel 2 will be treated with DRV/rtv and artemether/lumefantrine. Treatment A will consist of 3 days of treatment with artemether/lumefantrine. Treatment B will consist of 200 mg ETR twice daily (b.i.d.) (Panel 1) or 600/100 mg DRV/rtv b.i.d. (Panel 2) from Day 1 to Day 21 with a single dose of ETR (Panel 1) or DRV/rtv (Panel 2) in the morning on Day 22. From Day 8, 3 days of treatment with artemether/lumefantrine. In a first stage of treatment in Panel 2, only 4 patients will be allowed to start Treatment B. Based on the ECG results of the first 4 patients with evaluable ECG data after assessments on Day 11 (66 hours after the combined intake of DRV/rtv and artemether/lumefantrine), the Sponsor will decide whether additional patients can be allowed to start Treatment B. There will be a washout period of at least 4 weeks between Treatments A and B. Half of the patients of Panel 1 (8 patients) and Panel 2 (8 patients) will be randomized to sequence AB and half will be randomized to sequence BA. Randomization in Panel 2 will occur in two steps. In Step 1, 4 patients will be allocated to sequence BA and evaluated for QTc prolongation. Based on the outcome of their ECG results, the Sponsor will decide whether the remainder of patients will be randomized in Step 2, i.e. 4 patients to BA and 8 patients to AB (1:2 randomization). Serial pharmacokinetic assessments will be determined for Panels 1 and 2 in Treatments A and B for artemether and its metabolite dihydroartemisinin (DHA) after the first intake of artemether/lumefantrine over 8 hours and after the last intake of artemether/lumefantrine over 72 hours (3 days), and for lumefantrine after the last intake of artemether/lumefantrine over 264 hours (11 days). Serial pharmacokinetic assessments will be determined for ETR (Panel 1) or DRV and rtv (Panel 2) over the 12-hour dosing interval on Day 8 (after the morning intake) and Day 11 (after the last dose of artemether/lumefantrine) of Treatment B. All ETR, DRV/rtv and artemether/lumefantrine treatments will be administered under fed conditions and will be taken within 10 minutes after completion of a meal. Safety and tolerability evaluations will be recorded on an ongoing basis.

Conditions: HIV
Being tested: Etravirine, Darunavir/ritonavir, artemether/lumefantrine
Keywords: HIV, pharmacokinetic interaction, healthy HIV-negative person

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

EtravirineDrug
200 mg ETR b.i.d. from Day 1 to Day 21 with a single 200 mg dose of ETR in the morning on Day 22
Darunavir/ritonavirDrug
DRV/rtv 600/100 mg b.i.d. from Day 1 to Day 21 with a single dose of DRV/rtv in the morning on Day 22
artemether/lumefantrineDrug
3 days of treatment with artemether/lumefantrine 80/480 mg (6 doses of 4 tablets [20/120 mg] at 0, 8, 24, 36, 48, and 60 hours)

Study groups in NCT01876966
Study group	Role	What they receive
ETR, artemether/lumefantrine	Experimental	treatment with artemether/lumefantrine 80/480 mg during 3 days (treatment A) and treatment during 22 days with etravirine for 22 days and artemether/lumefantrine 80/480 mg from day 8 to day 11 (treatment B) with a washout of at least 4 weeks between the 2 treatment periods Receives: Drug: Etravirine; Drug: artemether/lumefantrine
DRV/rtv, artemether/lumefantrine	Experimental	treatment with artemether/lumefantrine 80/480 mg during 3 days (treatment A) and treatment during 22 days with darunavir/ritonavir and artemether/lumefantrine 80/480 mg from day 8 to day 11 (treatment B) with a washout of at least 4 weeks between the 2 treatment periods Receives: Drug: Darunavir/ritonavir; Drug: artemether/lumefantrine

What is being measured

The primary outcome is the main question the study is designed to answer.

effect of ETR or DRV/rtv on the plasma concentrations of artemether, lumefantrine and dihydroartemisinin
the effect of ETR or DRV/rtv on the pharmacokinetics of artemether, lumefantrine and the artemether metabolite dihydroartemisinin (DHA) after single and multiple dose(s) in healthy subjects. plasma concentrations: minimum (Cmin) and maximum (Cmax): artemether and DHA (Day 11 of Treatment B versus Day 4 of Treatment A, Days 11-14 of Treatment B versus Days 4-7 of Treatment A ), lumefantrine (Days 11-22 of Treatment B versus Days 4-15 of Treatment A ); Cmax artemether and DHA (Day 8-9 of Treatment B versus Day 1-2 of Treatment A )
Measured: Treatment A: Day 1-2 & Day 4-15; Treatment B: Day 8-9 & Day 11-22
effect of ETR or DRV/rtv on the Area under the concentration-time curve (AUC) in plasma for artemether, lumefantrine and dihydroartemisinin
effect of ETR or DRV/rtv on the AUC from time of administration (0 hours) to 8 hours after dosing (AUC8h): artemether and DHA (Day 8-9 of Treatment B versus Day 1-2 of Treatment A); AUC from 0 to 12 hours (AUC 12h) artemether and DHA (Day 11 of Treatment B versus Day 4 of Treatment A ); AUC from 0 to 264 hours (AUC264h) lumefantrine (Days 11-22 of Treatment B versus Days 4-15 of Treatment A ; AUC from 0 to the last time point with a measurable concentration post dosing (AUClast) artemether and DHA (Days 11-14 of Treatment B versus Days 4-7 of Treatment A )
Measured: Treatment A: Day 1-2 & Day 4-15; Treatment B: Day 8-9 & 11-22
Plasma concentrations of ETR, DRV and rtv
Cmin and Cmax for ETR, DRV and ritonavir (Day 11 of Treatment B versus Day 8 of Treatment B )
Measured: Treatment B: Day 8 & Day 11
Area under the concentration-time curve (AUC) in plasma for ETR, DRV and rtv
AUC from time of administration to 12 hours after dosing (AUC12h) for ETR, DRV and ritonavir (Day 11 of Treatment B versus Day 8 of Treatment B)
Measured: Treatment B: Day 8 & Day 11

Secondary outcomes (3)

Number of Participants with Adverse Events as a Measure of Safety and Tolerability
short-term safety and tolerability of coadministration of ETR or DRV/rtv and artemether/lumefantrine in healthy subjects.
Measured: at screening, during treatment and at day 7 and 30, 31 or 32 after last study medication intake
Profile of pharmacokinetics of ETR by cytochrome P450 (CYP)2C9 and CYP2C19 genotype
the effect of CYP2C9 and CYP2C19 genotypes will be evaluated by comparison of these genotypes with the Cmax and AUC12 for ETR
Measured: Treatment B: Day 8
Profile of pharmacokinetics of artemether and DHA after single and multiple dose(s)
Cmax (both periods), AUC8h (Day 1-2) and AUClast (Day 4-7) for artemether and DHA
Measured: Treatment A: Day 1-2 & Day 4-7

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Mar 2011Jul 2011

First posted13 Jun 2013 (estimated)
Study startMar 2011
Primary completionJul 2011
Study completionJul 2011

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: Health services research
Allocation: Randomised
Intervention model: Crossover
Masking: None (open label)
Enrolment: 33 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01876966
Sponsor's protocol ID: CR018409
Other IDs: 2010-023289-31, TMC125VIR1001
Acronym: DDI Coartem
Status last verified: Jun 2013
First submitted: 19 Nov 2012
Last updated: 13 Jun 2013
Results posted: No
Data monitoring committee: No

Publications

Kakuda TN, DeMasi R, van Delft Y, Mohammed P. Pharmacokinetic interaction between etravirine or darunavir/ritonavir and artemether/lumefantrine in healthy volunteers: a two-panel, two-way, two-period, randomized trial. HIV Med. 2013 Aug;14(7):421-9. doi: 10.1111/hiv.12019. Epub 2013 Feb 26.
PubMed 23441978

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

Official record

Not yet recruiting
HealthMpowerment Korea: Pilot Testing the Cultural Adaptation of a Digital HIV Intervention for Men Who Have Sex With Men in South Korea
HIV Infections, HIV Prevention and Care
Not yet recruiting
Prescribe to Prevent HIV: A Hybrid Trial Helping Addiction Clinics Prevent HIV & Infections Through Safer Drug Use Support
People Who Use Opioids/People With Opioid Use Disorder (OUD)
Recruiting
Evaluating the Impact of Using the B-OK Bottles for HIV and ART Literacy in South Africa
HIV, HIV Treatment
Recruiting
Trial Phase: Syndemic Adapted Medly Uganda
Mental Health
RecruitingObservational study
Olfactory Function and Model-Based Behavior in People Living With HIV and SUD
HIV, Substance Use Disorder

All HIV trials

Study at a glance

From the registry record, last updated by the sponsor on 13 Jun 2013. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase I, Partially Randomized, Open Label, Two-way, Two Period Cross-over Study to Investigate the Pharmacokinetic Interaction Between Etravirine or Darunavir/Rtv and Artemether/Lumefantrine at Steady-state in Healthy HIV-negative Subjects
ClinicalTrials.gov ID: NCT01876966
Acronym / sponsor ID: DDI Coartem / CR018409
Conditions: HIV
Keywords: HIV, pharmacokinetic interaction, healthy HIV-negative person
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 33 participants (actual)
Lead sponsor: Janssen Pharmaceutica N.V., BelgiumIndustry (pharma, biotech, devices)
Study start: Mar 2011
Primary completion: Jul 2011 (actual)
Study completion: Jul 2011 (actual)
First posted: 13 Jun 2013 (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.

Detailed description

Study design

Primary purpose: Health services research
Allocation: Randomised
Intervention model: Crossover
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
ETR, artemether/lumefantrine	Experimental	Drug: Etravirine, Drug: artemether/lumefantrinetreatment with artemether/lumefantrine 80/480 mg during 3 days (treatment A) and treatment during 22 days with etravirine for 22 days and artemether/lumefantrine 80/480 mg from day 8 to day 11 (treatment B) with a washout of at least 4 weeks between the 2 treatment periods
DRV/rtv, artemether/lumefantrine	Experimental	Drug: Darunavir/ritonavir, Drug: artemether/lumefantrinetreatment with artemether/lumefantrine 80/480 mg during 3 days (treatment A) and treatment during 22 days with darunavir/ritonavir and artemether/lumefantrine 80/480 mg from day 8 to day 11 (treatment B) with a washout of at least 4 weeks between the 2 treatment periods

Who may qualify

Ages: 18 to 55 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult

Key inclusion criteria (5 listed)

if of childbearing potential or if male, use a highly effective method of birth control.
Able to comply with protocol requirements.
A BMI (weight in kg divided by the square of height in meters) of 18.5 to 30.0 kg/m2, extremes included.
healthy on the basis of a medical evaluation
Non-smoking for at least 3 months prior to selection.

Key exclusion criteria (5 listed)

previously demonstrated clinically significant allergy, hypersensitivity or intolerance to any of the investigational medications or its excipients
Use of concomitant medication, including over-the-counter products and dietary supplements.
Having participated in more than 1 study (single or multiple dose) with ETR (TMC125), DRV (TMC114), dapivirine (TMC120) and/or rilpivirine (TMC278, formerly known as R278474), or having developed a rash, erythema or urticaria while participating in a study with the aforementioned compounds.
A positive pregnancy test or breast feeding at screening or on Day 1.
Any condition that, in the opinion of the investigator, would compromise the study or the well-being of the patient or prevent the patient from meeting or performing study requirements

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
Etravirine200 mg ETR b.i.d. from Day 1 to Day 21 with a single 200 mg dose of ETR in the morning on Day 22	Drug	ETR, artemether/lumefantrine
Darunavir/ritonavirDRV/rtv 600/100 mg b.i.d. from Day 1 to Day 21 with a single dose of DRV/rtv in the morning on Day 22	Drug	DRV/rtv, artemether/lumefantrine
artemether/lumefantrine3 days of treatment with artemether/lumefantrine 80/480 mg (6 doses of 4 tablets [20/120 mg] at 0, 8, 24, 36, 48, and 60 hours)	Drug	DRV/rtv, artemether/lumefantrine, ETR, artemether/lumefantrine

Primary outcome

effect of ETR or DRV/rtv on the plasma concentrations of artemether, lumefantrine and dihydroartemisinin
Time frame: Treatment A: Day 1-2 & Day 4-15; Treatment B: Day 8-9 & Day 11-22
the effect of ETR or DRV/rtv on the pharmacokinetics of artemether, lumefantrine and the artemether metabolite dihydroartemisinin (DHA) after single and multiple dose(s) in healthy subjects. plasma concentrations: minimum (Cmin) and maximum (Cmax): artemether and DHA (Day 11 of Treatment B versus Day 4 of Treatment A, Days 11-14 of Treatment B versus Days 4-7 of Treatment A ), lumefantrine (Days 11-22 of Treatment B versus Days 4-15 of Treatment A ); Cmax artemether and DHA (Day 8-9 of Treatment B versus Day 1-2 of Treatment A )
effect of ETR or DRV/rtv on the Area under the concentration-time curve (AUC) in plasma for artemether, lumefantrine and dihydroartemisinin
Time frame: Treatment A: Day 1-2 & Day 4-15; Treatment B: Day 8-9 & 11-22
effect of ETR or DRV/rtv on the AUC from time of administration (0 hours) to 8 hours after dosing (AUC8h): artemether and DHA (Day 8-9 of Treatment B versus Day 1-2 of Treatment A); AUC from 0 to 12 hours (AUC 12h) artemether and DHA (Day 11 of Treatment B versus Day 4 of Treatment A ); AUC from 0 to 264 hours (AUC264h) lumefantrine (Days 11-22 of Treatment B versus Days 4-15 of Treatment A ; AUC from 0 to the last time point with a measurable concentration post dosing (AUClast) artemether and DHA (Days 11-14 of Treatment B versus Days 4-7 of Treatment A )
Plasma concentrations of ETR, DRV and rtv
Time frame: Treatment B: Day 8 & Day 11
Cmin and Cmax for ETR, DRV and ritonavir (Day 11 of Treatment B versus Day 8 of Treatment B )
Area under the concentration-time curve (AUC) in plasma for ETR, DRV and rtv
Time frame: Treatment B: Day 8 & Day 11
AUC from time of administration to 12 hours after dosing (AUC12h) for ETR, DRV and ritonavir (Day 11 of Treatment B versus Day 8 of Treatment B)

3 secondary outcomes

Number of Participants with Adverse Events as a Measure of Safety and Tolerability
Time frame: at screening, during treatment and at day 7 and 30, 31 or 32 after last study medication intake
Profile of pharmacokinetics of ETR by cytochrome P450 (CYP)2C9 and CYP2C19 genotype
Time frame: Treatment B: Day 8
Profile of pharmacokinetics of artemether and DHA after single and multiple dose(s)
Time frame: Treatment A: Day 1-2 & Day 4-7

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 13 Jun 2013.
Results publication: PubMed 23441978Kakuda TN, DeMasi R, van Delft Y, Mohammed P. Pharmacokinetic interaction between etravirine or darunavir/ritonavir and artemether/lumefantrine in healthy volunteers: a two-panel, two-way, two-period, randomized trial. HIV Med. 2013 Aug;14(7):421-9. doi: 10.1111/hiv.12019. Epub 2013 Feb 26.

Related trials for HIV

Not yet recruiting
HealthMpowerment Korea: Pilot Testing the Cultural Adaptation of a Digital HIV Intervention for Men Who Have Sex With Men in South Korea
HIV Infections, HIV Prevention and Care
Not yet recruiting
Prescribe to Prevent HIV: A Hybrid Trial Helping Addiction Clinics Prevent HIV & Infections Through Safer Drug Use Support
People Who Use Opioids/People With Opioid Use Disorder (OUD)
Recruiting
Evaluating the Impact of Using the B-OK Bottles for HIV and ART Literacy in South Africa
HIV, HIV Treatment
Recruiting
Trial Phase: Syndemic Adapted Medly Uganda
Mental Health
RecruitingObservational study
Olfactory Function and Model-Based Behavior in People Living With HIV and SUD
HIV, Substance Use Disorder

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.

The record lists no contact. Use the official record to reach the sponsor.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Etravirine, Darunavir/ritonavir and artemether/lumefantrine in people with HIV, run by Janssen Pharmaceutica N.V., Belgium.

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 5 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 13 Jun 2013. 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?

effect of ETR or DRV/rtv on the plasma concentrations of artemether, lumefantrine and dihydroartemisinin (time frame: Treatment A: Day 1-2 & Day 4-15; Treatment B: Day 8-9 & Day 11-22). The study lists 4 primary outcomes in all. 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 NCT01876966, 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 13 Jun 2013.