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

This study has been completed.
Sponsor:
Collaborator:
GlaxoSmithKline
Information provided by:
Radboud University
ClinicalTrials.gov Identifier:
NCT00977301
First received: August 17, 2009
Last updated: January 7, 2011
Last verified: January 2011

August 17, 2009
January 7, 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 ] [ Designated as safety issue: No ]
Same as current
Complete list of historical versions of study NCT00977301 on ClinicalTrials.gov Archive Site
adverse events [ Time Frame: entire study ] [ Designated as safety issue: Yes ]
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.

Interventional
Phase 1
Allocation: Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Crossover Assignment
Masking: 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
    Interventions:
    • Drug: fosamprenavir/ritonavir
    • Drug: olanzapine
  • Active Comparator: single dose olanzapine
    Single dose of 10 mg olanzapine
    Intervention: Drug: olanzapine
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
24
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.
Both
18 Years to 55 Years
Yes
Contact information is only displayed when the study is recruiting subjects
Netherlands
 
NCT00977301
UMCN-AKF 08.04
No
D.M. Burger, PharmD, PhD, Radboud University Nijmegen Medical Centre
Radboud University
GlaxoSmithKline
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