The Influence of GINkGo Biloba on the Pharmacokinetics of the UGT Substrate raltEgraviR (GINGER)

This study has been completed.
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Radboud University
ClinicalTrials.gov Identifier:
NCT01246804
First received: November 22, 2010
Last updated: November 26, 2012
Last verified: November 2012
  Purpose

The objective of this study is to evaluate the effect of ginkgo biloba (steady state) on the pharmacokinetics of a single dose of the UGT-substrate raltegravir. Furthermore the safety profile of the combination is studied.


Condition Intervention Phase
HIV Infections
Depression
Mild Cognitive Impairment
Drug: raltegravir single dose
Drug: ginkgo biloba multiple dose
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Crossover Assignment
Masking: Open Label
Official Title: The Influence of GINkGo Biloba on the Pharmacokinetics of the UGT Substrate raltEgraviR (GINGER)

Resource links provided by NLM:


Further study details as provided by Radboud University:

Primary Outcome Measures:
  • raltegravir concentrations [ Time Frame: pharmacokinetic curve after a single dose of raltegravir alone or added to steady state ginkgo biloba ] [ Designated as safety issue: No ]
    To determine the effect of chronic use of ginkgo biloba on the single-dose pharma-cokinetics (AUC0-inf, AUC0-12, Cmax, C12) of raltegravir 400mg in healthy volunteers.


Secondary Outcome Measures:
  • adverse events [ Time Frame: during entire study ] [ Designated as safety issue: Yes ]
    To determine the safety of a single dose of raltegravir 400mg when combined with chronic use of ginkgo biloba.


Enrollment: 18
Study Start Date: November 2010
Study Completion Date: May 2011
Primary Completion Date: March 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: ginkgo biloba + raltegravir
15 days ginkgo biloba 120mg BID + raltegravir 400mg SD
Drug: raltegravir single dose
single dose 400mg raltegravir
Other Name: Isentress
Drug: ginkgo biloba multiple dose
15 days ginkgo biloba 120mg BID
Other Name: Tavonin
Active Comparator: raltegravir
single dose raltegravir 400mg
Drug: raltegravir single dose
single dose 400mg raltegravir
Other Name: Isentress

Detailed Description:

Ginkgo biloba is an alternative medicine that is popular among HIV-infected patients because if its claimed positive effects on memory, concentration and depression. Alternative medicine can cause drug-drug interactions with regular HIV-medication. Raltegravir is a newly developed HIV integrase inhibitor. It is metabolized in the liver by UGT1A1 and therefore its pharmacokinetic profile can be influenced by inhibitors or inducers of UGT1A1. So far there are no data of the potential effect of ginkgo biloba on glucuronidation in vivo. The current study is designed to evaluate the potential inductive effect of ginkgo biloba on the pharmacokinetics of raltegravir and the safety profile when used in 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 does not smoke more than 10 cigarettes, 2 cigars, or 2 pipes per day for at least 3 months prior to the first dosing
  • 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, electrocardiography, results of biochemistry, haematology and urinalysis testing within 4 weeks prior to Day 1. 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 Day 1) 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, 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 Day 1.
  • Donation of blood within 60 days prior to Day 1.
  • Febrile illness within 3 days before Day 1.
  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: NCT01246804

Locations
Netherlands
CRCN, Radboud University Medical Centre
Nijmegen, Netherlands
Sponsors and Collaborators
Radboud University
Merck Sharp & Dohme Corp.
Investigators
Principal Investigator: David M Burger, PharmD, PhD Radboud University
  More Information

Additional Information:
No publications provided

Responsible Party: Radboud University
ClinicalTrials.gov Identifier: NCT01246804     History of Changes
Other Study ID Numbers: UMCN-AKF 10.02
Study First Received: November 22, 2010
Last Updated: November 26, 2012
Health Authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Keywords provided by Radboud University:
HIV infections
interaction
pharmacokinetics

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
Mild Cognitive Impairment
Depression
Infection
Cognition Disorders
Delirium, Dementia, Amnestic, Cognitive Disorders
Mental Disorders
Behavioral Symptoms
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

ClinicalTrials.gov processed this record on September 16, 2014