Interaction Between Fosamprenavir/Ritonavir and a Single-dose Olanzapine (FORZA)

Phase 1

Completed

• Conditions: HIV Infections
• Interventions: Drug: fosamprenavir/ritonavir; Drug: olanzapine

• Registration Number: NCT00977301
• Lead Sponsor: Radboud University Medical Center

Brief Summary

The effect of fosamprenavir/ritonavir (steady state) on the pharmacokinetics of a single dose of olanzapine will be studied.

In this study, the investigators expect an inducible effect of fosamprenavir/ritonavir on the CYP1A2 and UGT metabolism of olanzapine.

Detailed Description

Psychosis and other mental illnesses are commonly described in patients infected with the human immunodeficiency virus (HIV). New-onset psychosis is estimated to occur in up to 15% of patients infected with HIV while 5 to 7% of patients with HIV-infection suffer from pre-existing mental illnesses including schizophrenia. Olanzapine could be an attractive antipsychotic in HIV/AIDS patients with schizophrenia.

Because olanzapine is a substrate for both UGT and CYP1A2, the pharmacokinetics of olanzapine might be influenced by low-dose ritonavir in combination with fosamprenavir. The current study is designed to test this hypothesis. Furthermore, in this study we evaluate the safety of such combination.

Study Timeline

• Study First Submitted: 2009-08-17
• Study First Submitted QC: 2009-09-14
• Study First Posted: 2009-09-15
• Study Start: 2009-11
• Primary Completion: 2010-08
• Study Completion: 2010-08
• Status Verified: 2020-11
• Last Update Submitted: 2020-11-26
• Last Update Posted: 2020-11-30

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 24

Inclusion Criteria

• Subject is at least 18 and not older than 55 years at screening.
• Subject has a Quetelet Index (Body Mass Index) of 18 to 30 kg/m2, extremes included.
• Subject is able and willing to sign the Informed Consent Form prior to screening evaluations.
• Subject is in good age-appropriate health condition as established by medical history, physical examination, electro-cardiography, results of biochemistry, haematology 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. If laboratory results are not within the reference ranges, the subject is included on condition that the Investigator judges that the deviations are not clinically relevant. This should be clearly recorded.
• Subject has a normal blood pressure and pulse rate, according to the Investigator's judgement.

Exclusion Criteria

• Documented history of sensitivity/idiosyncrasy to medicinal products or excipients.
• Positive HIV test.
• Positive hepatitis B or C test.
• Pregnant female (as confirmed by an HCG test performed less than 4 weeks before the first dose) or breast-feeding female. Female subjects of childbearing potential without adequate contraception, e.g. hysterectomy, bilateral tubal ligation, (non-hormonal) intrauterine device, total abstinence, double barrier methods, or two years post-menopausal. They must agree to take precautions in order to prevent a pregnancy throughout the entire conduct of the trial.
• Therapy with any drug (for two weeks preceding dosing), except for paracetamol.
• Relevant history or presence of pulmonary disorders (especially COPD), cardiovascular disorders, neurological disorders (especially seizures and migraine), psychiatric disorders, glaucoma, gastro-intestinal disorders, renal and hepatic disorders, hormonal disorders (especially diabetes mellitus), coagulation disorders.
• 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.
• Febrile illness within 3 days before the first dose.
• History of narrow-angle glaucoma.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
fosamprenavir/ritonavir/olanzapine	fosamprenavir/ritonavir	single dose of 15 mg olanzapine after 13 days of fosamprenavir/ritonavir 700mg/100mg BID
single dose olanzapine	olanzapine	Single dose of 10 mg olanzapine
fosamprenavir/ritonavir/olanzapine	olanzapine	single dose of 15 mg olanzapine after 13 days of fosamprenavir/ritonavir 700mg/100mg BID

Primary Outcome Measures

Name	Time	Method
olanzapine concentrations	pharmacokinetic curve after a single dose of olanzapine alone or added to steady state fosamprenavir/ritonavir

Secondary Outcome Measures

Name	Time	Method
adverse events	entire study

Trial Locations

Locations (1)

CRCN, Radboud Universtity Nijmegen Medical Centre; 🇳🇱 Nijmegen, Netherlands