In vitro data indicate that raltegravir is not a substrate of UGT1A4 or UGT2B7, but there is no evidence that raltegravir itself does not influence metabolism of other agents mediated by either UGT1A4 or UGT2B7.
ID
Source
Brief title
Condition
- Immunodeficiency syndromes
- Viral infectious disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
To determine the effect of raltegravir on the pharmacokinetics of single-dose
lamotrigine determined by intrasubject comparison.
Secondary outcome
To determine the effect of single-dose lamotrigine on the pharmacokinetics of
raltegravir when compared to historical controls
To evaluate the safety of combined use of single-dose lamotrigine and
ralte-gravir
Background summary
Raltegravir is a newly developed HIV integrase inhibitor. Raltegravir has been
tested in both treatment-naïve and -experienced patients and appears to have an
excellent risk/benefit ratio. Raltegravir is not a substrate of CYP450, but it
is metabolized by glucuronidation via UGT1A1.
Lamotrigine (Lamictal®) is an anticonvulsant drug. It can be used for the
treatment of epilepsy of HIV-infected patients. Furthermore, lamotrigine is
used for the treatment of neuropathic pain. Lamotrigine appears to be one of
the few effective agents for HIV-associated neuropathic pain.
Recent in vitro work suggests that UGT1A4 and UGT2B7 are the main isozymes of
UGT responsible for glucuronidation of lamotrigine; hence lamotrigine can be
considered as a mixed UGT1A4/2B7 probe to evaluate potential drug interactions.
Study objective
In vitro data indicate that raltegravir is not a substrate of UGT1A4 or UGT2B7,
but there is no evidence that raltegravir itself does not influence metabolism
of other agents mediated by either UGT1A4 or UGT2B7.
Study design
open-label gerandomiseerd, cross-over single-centre, fase IV multiple-dose
trial
Intervention
During this study, which lasts 34 days in total, subjects have to take
Raltegravir twice daily during five consecutive days. During two days of the 34
study days Lamotrigine is taken once daily.
During the study 254ml blood is taken from each subject.
- screening ( 4 weeks before start of the trial): 19 ml
- group A # day 1: 14ml, day 2: 14ml, day 4: 79ml, day 5: 7ml, day 6: 14ml, day
29: 7ml, day 32: 79ml, day 33: 7ml day 34: 14ml
- group B # day 1; 7ml, day 4: 79ml, day 5: 7 ml, day 6: 14ml, day 29: 14ml,
day 30: 14ml, day 32: 79ml, day 33: 7ml, day 34: 14ml
Study burden and risks
The side effects of raltegravir can be: dizziness, headache, tiredness.
The side effects of lamotrigine can be: rash, headache, double vision, misty
eyes, tiredness, nausea, dizziness, irritation,sleepyness, sleeplesness, The
needles that are used for bloodtake may cause discomfort or pain at the place
of injection.
The risks of participation are relatively small. Raltegravir tablets are taken
during 5 consecutive days. The side effects are mild. The Lamotrigine
medication is taken on two days in the early morning of an admission day; those
days the subject is under medical attention of the research centre. In the ELLA
study (CMOnr 2005/314) a single dose Lamotrigine was very well tolerated.
Geert Grooteplein 10
6500 HB Nijmegen
Nederland
Geert Grooteplein 10
6500 HB Nijmegen
Nederland
Listed location countries
Age
Inclusion criteria
- men in the age of 18- 55 years
- does not smoke more than 10 cigarettes, 2 cigars or 2 pipes
- has a Quetelet Index between 18 - 30 kg/m2
- willing and able to sign informed consent
- in a good health age-appropriate
- heeft een normale bloeddruk en pols
Exclusion criteria
- sensitivity to medicinal products
- HIV positive
- hepatitis B or C positive
- therapy with any drug, except for paracetamol
- relevant history or presence of pulmonary disorders, cardiovascular disorders, neurological disorders, gastro-intestinal disorders, renal- or hepatic disorders, hormonal disorders especially diabetes mellitus, coagulation disorders
- history 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
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
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In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2007-005405-21-NL |
| CCMO | NL20016.091.07 |