Interaction Between Etravirine or Darunavir/Ritonavir and Artemether / Lumefantrine

NCT01876966 | Completed Phase 1

• 3 other identifiers: CR0184092010-023289-31TMC125VIR1001
• Study Type: interventional
• Target: 33
• Locations: 0 countries
• Sites: N/A

Brief 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. 'Pharmacokinetic interaction' means that one medication can influence the absorption and elimination from the body of the other medication.

Conditions

HIV

Keywords

HIV; pharmacokinetic interaction; healthy HIV-negative person

Outcome Measures

Primary Outcomes (4)

• 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 )

  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 )

  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 )

  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)

  Treatment B: Day 8 & Day 11

Secondary Outcomes (3)

• Number of Participants with Adverse Events as a Measure of Safety and Tolerability

  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

  Treatment B: Day 8

• Profile of pharmacokinetics of artemether and DHA after single and multiple dose(s)

  Treatment A: Day 1-2 & Day 4-7

Study Arms (2)

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

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

Drug: Darunavir/ritonavir; Drug: artemether/lumefantrine

Interventions

Etravirine DRUG

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

ETR, artemether/lumefantrine

Darunavir/ritonavir DRUG

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

DRV/rtv, artemether/lumefantrine

artemether/lumefantrine DRUG

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)

DRV/rtv, artemether/lumefantrine; ETR, artemether/lumefantrine

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Janssen Pharmaceutica N.V., Belgium: lead

Related Publications (1)

• 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.

  PMID: 23441978 RESULT

MeSH Terms

Interventions

etravirine; Darunavir; Ritonavir; Artemether, Lumefantrine Drug Combination

Intervention Hierarchy (Ancestors)

Sulfonamides; Amides; Organic Chemicals; Carbamates; Acids, Acyclic; Carboxylic Acids; Sulfones; Sulfur Compounds; Furans; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Thiazoles; Azoles; Artemether; Artemisinins; Reactive Oxygen Species; Free Radicals; Inorganic Chemicals; Lumefantrine; Fluorenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Sesquiterpenes; Terpenes; Polycyclic Compounds; Drug Combinations; Pharmaceutical Preparations

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: HEALTH SERVICES RESEARCH
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 19, 2012
• First Posted: June 13, 2013
• Study Start: March 1, 2011
• Primary Completion: July 1, 2011
• Study Completion: July 1, 2011
• Last Updated: June 13, 2013

Record last verified: 2013-06