malaria prophylaxis in HIV patients MedDRA version: 8.1 Level: LLT Classification code 10025494 Term: Malaria prophylaxis
Conditions
Interventions
Trade Name: Malarone
Pharmaceutical Form: Coated tablet
INN or Proposed INN: ATOVAQUONE
CAS Number: 95233184
Concentration unit: g gram(s)
Concentration type: equal
Concentration number: 0.250-
INN or
Sponsors
Dept. of Clinical Pharmacy, Radboud UMC Nijmegen, The Netherlands
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Healthy volunteers: 1.Subject is at least 18 and not older than 65 years of age on the day of dosing of atovaquone/proguanil. 2.Subject does not smoke more than 10 cigarettes, 2 cigars, or 2 pipes per day for at least 3 months prior to the first dosing. 3.Subject has a Quetelet Index (Body Mass Index) of 18 to 30 kg/m2, extremes included. 4.Subject is able and willing to sign the Informed Consent Form prior to screening evaluations. 5.Subject is in good age-appropriate health condition as established by medical history, physical examination, results of biochemistry, haematol-ogy and urinalysis testing within 4 weeks prior to the first dose.Results of biochemistry, haematology and urinalysis testing should be within the laboratory's reference ranges (see Appendix A of study protocol). If not, the subject is included on condition that the Investigator judges that the deviations are not clinically relevant. This should be clearly recorded. 6.Subject has a normal blood pressure and pulse rate, according to the In-vestigator's judgement. HIV patients: 1.HIV-infected as documented by positive HIV antibody test and confirmed by Western Blot. 2.CD4+ > 200 * 106 /L. 3.Subject is at least 18 and not older than 65 years of age at the day of dosing of atovaquone/proguanil. 4.Subject has a Quetelet Index (Body Mass Index) of 18 to 30 kg/m2, extremes included. 5.Subject is able and willing to sign the Informed Consent Form prior to screening evaluations. 6.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. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Healthy volunteers: 1.History of sensitivity/idiosyncrasy to atovaquone/proguanil or chemically related compounds or excipients. 2.Positive HIV test. 3.Positive HbsAg test (hepatitis B) or positive hepatitis C test. 4.Therapy with any drug (for two weeks preceding dosing), except for paracetamol. 5.Creatinine clearance 3 times upper limit of normal (see Appendix A for normal ranges of clinical laboratory values). 14.Febrile illness within 3 days before the first dose HIV infected patients: 1.History of sensitivity/idiosyncrasy to atovaquone/proguanil or chemically related compounds or excipients. 2.Suspicion of non-adherence to the HIV medication. 3.Current diarrhoea. 4.Relevant history or current condition that might interfere with drug absorp-tion, distribution, metabolism or excretion. 5.Inability to understand the nature and extent of the trial and the procedures required. 6.Pregnant female (as confirmed by an HCG test performed less than 3 weeks before the first dose) or breast-feeding female. 7.Abnormal serum transminases determined as levels being > 3 times upper limit of normal (see Appendix A for normal ranges of clinical laboratory values). 8.Creatinine clearance < 60 mL/min (calculated from serum creatinine). 9.Any change in antiretroviral medication within 1 month immediately preceding the dose of atovaquone/proguanil. 10.Concomitant use of medications that interfere with atovaquone or proguanil pharmacokinetics: anti-coagulants, aurothioglucose, chloroquine, cimetidine, fluoxetine, fluvoxamine, metoclopramide, omeprazole, magnesiumtrisilicate, rifabutin, rifampin, tetracycline, thyphoid vaccine, topiramate. 11.Use of a HAART regime containing both lopinavir/ritonavir and an other protease inhibitor or an NNRTI. 12.Use of a HAART regime containing both atazanavir/ritonavir and an other protease inhibitor or an NNRTI. 13.Use of a HAART regime containing both efavirenz and one or more prote-ase inhibitors or nevirapine. 14.Active hepatobiliary or hepatic disease 15.Alcohol abuse
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine the effect of antiretroviral agents (low-dose ritonavir + lopinavir, low dose ritonavir + atazanavir, efavirenz) on the pharmacokinetics of single dose atovaquone determined by intersubject comparison. ;Secondary Objective: -To determine the effect of antiretroviral agents (low-dose ritonavir + lopinavir, low dose ritonavir + atazanavir, efavirenz) on the pharmacokinetics of single dose proguanil determined by intersubject comparison. -To evaluate the safety of combined use of single dose atovaquone/proguanil and lopinavir/ritonavir, atazanavir/ritonavir and efavirenz. ;Primary end point(s): The effect of lopinavir/ritonavir, atazanavir/ritonavir and efavirenz on atovaquone pharmacokinetics (AUC, Cmax). | — |
Countries
Netherlands
Outcome results
None listed