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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00977301
Recruitment Status : Completed
First Posted : September 15, 2009
Last Update Posted : January 10, 2011
Information provided by:
Radboud University

August 17, 2009
September 15, 2009
January 10, 2011
November 2009
August 2010   (Final data collection date for primary outcome measure)
olanzapine concentrations [ Time Frame: pharmacokinetic curve after a single dose of olanzapine alone or added to steady state fosamprenavir/ritonavir ]
Same as current
Complete list of historical versions of study NCT00977301 on Archive Site
adverse events [ Time Frame: entire study ]
Same as current
Not Provided
Not Provided
Interaction Between Fosamprenavir/Ritonavir and a Single-dose Olanzapine (FORZA)
The Effect of FOsamprenavir/Ritonavir on the Pharmacokinetics of a Single-dose of the Antipsychotic Agent olanZApine (FORZA)

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.

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.

Phase 1
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
HIV Infections
  • Drug: fosamprenavir/ritonavir
    16 days 700mg/100mg RTV BID
  • Drug: olanzapine
    15 mg olanzapine single dose
  • Drug: olanzapine
    10 mg olanzapine single dose
  • Experimental: fosamprenavir/ritonavir/olanzapine
    single dose of 15 mg olanzapine after 13 days of fosamprenavir/ritonavir 700mg/100mg BID
    • Drug: fosamprenavir/ritonavir
    • Drug: olanzapine
  • Active Comparator: single dose olanzapine
    Single dose of 10 mg olanzapine
    Intervention: Drug: olanzapine
Jacobs BS, Colbers AP, Velthoven-Graafland K, Schouwenberg BJ, Burger DM. Effect of fosamprenavir/ritonavir on the pharmacokinetics of single-dose olanzapine in healthy volunteers. Int J Antimicrob Agents. 2014 Aug;44(2):173-7. doi: 10.1016/j.ijantimicag.2014.03.014. Epub 2014 May 23.

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Same as current
August 2010
August 2010   (Final data collection date for primary outcome measure)

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.
Sexes Eligible for Study: All
18 Years to 55 Years   (Adult)
Contact information is only displayed when the study is recruiting subjects
UMCN-AKF 08.04
Not Provided
Not Provided
D.M. Burger, PharmD, PhD, Radboud University Nijmegen Medical Centre
Radboud University
Principal Investigator: David Burger, PharmD, PhD Radboud University
Radboud University
January 2011

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP