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
  Purpose

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.

  Eligibility

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

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00977301

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

No publications provided

Responsible Party: D.M. Burger, PharmD, PhD, Radboud University Nijmegen Medical Centre
ClinicalTrials.gov 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
interaction
pharmacokinetics

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Antipsychotic Agents
Olanzapine
Ritonavir
Fosamprenavir
Tranquilizing Agents
Central Nervous System Depressants
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Psychotropic Drugs
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Gastrointestinal Agents
Serotonin Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on August 20, 2014