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

This study has been completed.
Information provided by:
Radboud University Identifier:
First received: August 17, 2009
Last updated: January 7, 2011
Last verified: January 2011

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.

Condition Intervention Phase
HIV Infections
Drug: fosamprenavir/ritonavir
Drug: olanzapine
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: The Effect of FOsamprenavir/Ritonavir on the Pharmacokinetics of a Single-dose of the Antipsychotic Agent olanZApine (FORZA)

Resource links provided by NLM:

Further study details as provided by Radboud University:

Primary Outcome Measures:
  • olanzapine concentrations [ Time Frame: pharmacokinetic curve after a single dose of olanzapine alone or added to steady state fosamprenavir/ritonavir ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • adverse events [ Time Frame: entire study ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 24
Study Start Date: November 2009
Study Completion Date: August 2010
Primary Completion Date: August 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: fosamprenavir/ritonavir/olanzapine
single dose of 15 mg olanzapine after 13 days of fosamprenavir/ritonavir 700mg/100mg BID
Drug: fosamprenavir/ritonavir
16 days 700mg/100mg RTV BID
Drug: olanzapine
15 mg olanzapine single dose
Active Comparator: single dose olanzapine
Single dose of 10 mg olanzapine
Drug: olanzapine
10 mg olanzapine single dose

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.


Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes

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.
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Please refer to this study by its identifier: NCT00977301

CRCN, Radboud Universtity Nijmegen Medical Centre
Nijmegen, Netherlands
Sponsors and Collaborators
Radboud University
Principal Investigator: David Burger, PharmD, PhD Radboud University
  More Information

Publications automatically indexed to this study by Identifier (NCT Number):
Responsible Party: D.M. Burger, PharmD, PhD, Radboud University Nijmegen Medical Centre Identifier: NCT00977301     History of Changes
Other Study ID Numbers: UMCN-AKF 08.04 
Study First Received: August 17, 2009
Last Updated: January 7, 2011
Health Authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Keywords provided by Radboud University:
HIV infection

Additional relevant MeSH terms:
HIV Infections
Immune System Diseases
Immunologic Deficiency Syndromes
Lentivirus Infections
RNA Virus Infections
Retroviridae Infections
Sexually Transmitted Diseases
Sexually Transmitted Diseases, Viral
Virus Diseases
Anti-HIV Agents
Anti-Infective Agents
Anti-Retroviral Agents
Antipsychotic Agents
Antiviral Agents
Autonomic Agents
Central Nervous System Depressants
Cytochrome P-450 CYP3A Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Enzyme Inhibitors
Gastrointestinal Agents
HIV Protease Inhibitors
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Neurotransmitter Uptake Inhibitors
Peripheral Nervous System Agents processed this record on May 25, 2016