Pharmacokinetic Drug-drug Interaction Study Between RaltEgravir and CITALopram in Healthy Subjects (RECITAL).
Information source: Radboud University
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: HIV; Depression
Intervention: raltegravir (Drug); citalopram (Drug)
Phase: Phase 1
Status: Completed
Sponsored by: Radboud University
Summary
Depression is the most common mental health disorder among HIV-patients. Recognizing and
treating depression is important in order to improve quality of life and health outcomes in
those living with HIV. In clinical practice selective serotonin reuptake inhibitors (SSRIs)
are used most frequently in HIV patients with depressive symptoms. A complicating factor in
the concomitant use of antiretroviral agents and antidepressant therapy is the occurrence of
drug-drug interactions. Citalopram can be seen as one of the preferred SSRIs in
HIV-infected patients because citalopram has a relatively favourable drug interaction
profile compared to other SSRIs. Raltegravir is an HIV-1 integrase inhibitor and is
frequently being used as antiretroviral agent in combination with tenofovir/emtricitabine in
HIV-patients. Raltegravir has shown sustained antiretroviral activity, is generally well
tolerated and has little propensity to interact with other drugs because it does not inhibit
or induce CYP450 enzymes. Theoretically, no clinically relevant drug interaction is expected
between raltegravir and citalopram as raltegravir is not a CYP2D6 substrate and thus will
not be affected by the possible inhibition of CYP2D6 by citalopram. Raltegravir is
metabolized by UGT but citalopram is not known to influence UGT. A possible interaction may
occur through inhibition of P-gp mediated transport of raltegravir by citalopram. However,
even when no drug interaction is expected theoretically, it may be recommended to collect
sufficient clinical evidence to support this hypothesis because unexpected interactions with
raltegravir have been observed in the past. In order to be able to recommend raltegravir and
citalopram concomitant use, a pharmacokinetic study in healthy volunteers is proposed.
Clinical Details
Official title: Pharmacokinetic Drug-drug Interaction Study Between RaltEgravir and CITALopram in Healthy Subjects (RECITAL).
Study design: Allocation: Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Crossover Assignment, Masking: Open Label
Primary outcome: raltegravir AUC and citalopram AUC
Secondary outcome: Adverse Events
Eligibility
Minimum age: 18 Years.
Maximum age: 55 Years.
Gender(s): Both.
Criteria:
Inclusion Criteria:
1. Subject is at least 18 and not older than 55 years at screening.
2. Subject does not smoke more than 10 cigarettes, 2 cigars, or 2 pipes per day for at
least 3 months prior to Day 1.
3. Subject has a Quetelet Index (Body Mass Index) of 18 to 30 kg/m2, extremes included.
4. Subject is able and willing to sign the Informed Consent Form prior to screening
evaluations.
5. 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.
6. Subject has a normal blood pressure and pulse rate, according to the Investigator's
judgement.
Exclusion Criteria:
1. Documented history of sensitivity/idiosyncrasy to medicinal products or excipients.
2. Positive HIV test.
3. Positive hepatitis B or C test.
4. 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 study.
5. Therapy with any drug (for two weeks preceding Day 1), except for acetaminophen.
6. 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.
7. Relevant history or presence of QT syndrome, prolonged QTc time, bradycardia,
hypokalaemia or hypomagnesaemia, recent acute myocardial infarction, or uncompensated
heart failure.
8. Relevant history or current condition that might interfere with drug ab-sorption,
distribution, metabolism or excretion.
9. History of or current abuse of drugs, alcohol or solvents.
10. Inability to understand the nature and extent of the study and the pro-cedures
required.
11. Participation in a drug study within 60 days prior to Day 1.
12. Donation of blood within 60 days prior to Day 1.
13. Febrile illness within 3 days before Day 1.
Locations and Contacts
CRCN Radboud university medical center, Nijmegen, Netherlands
Additional Information
Abstract 53: Pharmacokinetic drug-drug interaction study between raltegravir and citalopram in healthy volunteers.
Starting date: January 2014
Last updated: July 21, 2015
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