NCT00421473

Brief Summary

Malarone® (atovaquone/proguanil) is frequently used in malaria prophylaxis. Unfortunately, there are indications that certain anti-HIV agents may decrease atovaquone plasma levels by induction of atovaquone metabolism. For travelling HIV patients, the clinical consequences of these possible drug drug interactions are serious, since a diminished exposure to the anti-malarial drug will result in suboptimal prophylaxis of malaria and potential development of drug resistant strains of Plasmodium falciparum. The purpose of this study is to find out if HIV patients using HAART regimes with either lopinavir/ritonavir, atazanavir/ritonavir or efavirenz have lower atovaquone plasma levels than healthy volunteers after a single dose of atovaquone/proguanil.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
79

participants targeted

Target at P50-P75 for phase_4 hiv-infections

Timeline
Completed

Started Mar 2007

Shorter than P25 for phase_4 hiv-infections

Geographic Reach
1 country

5 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

January 11, 2007

Completed
1 day until next milestone

First Posted

Study publicly available on registry

January 12, 2007

Completed
2 months until next milestone

Study Start

First participant enrolled

March 1, 2007

Completed
1.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 1, 2008

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

December 1, 2008

Completed
Last Updated

November 12, 2020

Status Verified

November 1, 2020

Enrollment Period

1.8 years

First QC Date

January 11, 2007

Last Update Submit

November 9, 2020

Conditions

Keywords

HIVMalaria prophylaxisTreatment Experienced

Outcome Measures

Primary Outcomes (1)

  • Pharmacokinetic blood samples will be taken just before dosing Malarone, and 12 samples in the time between 0,5 hour and 168 hours after dosing.

Secondary Outcomes (2)

  • Blood will be taken for genotyping of CYP2C19 at study day 1.

  • HIV-1 RNA and CD4 determination will be done (HIV patients only) at inclusion screening

Interventions

Eligibility Criteria

Age18 Years - 65 Years
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • For healthy volunteers
  • years
  • smoking habits \< 10 cigarettes, 2 cigars or 2 pipes
  • BMI between 18 and 30 kg/m2
  • able and willing to sign informed consent form
  • subject is in a good age-appropriate health condition
  • subject has a normal blood pressure and pulse rate
  • For HIV patients
  • HIV-infected as documented by positive HIV antibody test and confirmed by Western Blot.
  • CD4+ \> 200 \* 10E6 per Liter.
  • years
  • BMI between 18 and 30 kg/m2
  • able and willing to sign informed consent form
  • use of lopinavir/ritonavir, atazanavir/ritonavir or efavirenz for at least 1 month in a dose of 400/100mg bid, 300/100 mg QD, or 600 mg QD respectively

You may not qualify if:

  • History of sensitivity/idiosyncrasy to atovaquone/proguanil or chemically related compounds or excipients.
  • Positive HIV test.
  • Positive HbsAg test (hepatitis B) or positive hepatitis C test.
  • Therapy with any drug (for two weeks preceding dosing), except for paracetamol.
  • Creatinine clearance \< 60 mL/min (calculated from serum creatinine)
  • Current diarrhoea.
  • Relevant history or current condition that might interfere with drug absorption, distribution, metabolism or excretion.
  • History of or current abuse of drugs, alcohol or solvents.
  • Inability to understand the nature and extent of the trial and the procedures required.
  • Participation in a drug trial within 60 days prior to the first dose.
  • Donation of blood within 60 days prior to the first dose.
  • Pregnant female (as confirmed by an HCG test performed less than 3 weeks before the first dose) or breast-feeding female.
  • Abnormal serum transaminases, determined as levels being \> 3 times up-per limit of normal
  • Febrile illness within 3 days before the first dose
  • History of sensitivity/idiosyncrasy to atovaquone/proguanil or chemically related compounds or excipients.
  • +14 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (5)

Alysis Zorggroep loc. Rijnstate

Arnhem, Gelderland, 6800 TA, Netherlands

Location

Radboud University Medical Centre Nijmegen

Nijmegen, Gelderland, 6525 GA, Netherlands

Location

Elisabeth hospital

Tilburg, North Brabant, 5022 GC, Netherlands

Location

Leids Universitair Medisch Centrum

Leiden, South Holland, 2300 RC, Netherlands

Location

Erasmus MC

Rotterdam, South Holland, 3000 CA, Netherlands

Location

Related Publications (1)

  • van Luin M, Van der Ende ME, Richter C, Visser M, Faraj D, Van der Ven A, Gelinck L, Kroon F, Wit FW, Van Schaik RH, Kuks PF, Burger DM. Lower atovaquone/proguanil concentrations in patients taking efavirenz, lopinavir/ritonavir or atazanavir/ritonavir. AIDS. 2010 May 15;24(8):1223-6. doi: 10.1097/QAD.0b013e3283389129.

MeSH Terms

Conditions

HIV InfectionsMalaria

Interventions

atovaquone, proguanil drug combination

Condition Hierarchy (Ancestors)

Blood-Borne InfectionsCommunicable DiseasesInfectionsSexually Transmitted Diseases, ViralSexually Transmitted DiseasesLentivirus InfectionsRetroviridae InfectionsRNA Virus InfectionsVirus DiseasesGenital DiseasesUrogenital DiseasesImmunologic Deficiency SyndromesImmune System DiseasesProtozoan InfectionsParasitic DiseasesMosquito-Borne DiseasesVector Borne Diseases

Study Officials

  • D.M. Burger, Dr.

    Radboud University Medical Centre Nijmegen

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 4
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
PREVENTION
Intervention Model
PARALLEL
Sponsor Type
OTHER

Study Record Dates

First Submitted

January 11, 2007

First Posted

January 12, 2007

Study Start

March 1, 2007

Primary Completion

December 1, 2008

Study Completion

December 1, 2008

Last Updated

November 12, 2020

Record last verified: 2020-11

Locations