Pharmacokinetic Drug-drug Interaction Study Between RaltEgravir and CITALopram in Healthy Subjects (RECITAL).
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.
|Study Design:||Allocation: Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Crossover Assignment
Masking: Open Label
|Official Title:||Pharmacokinetic Drug-drug Interaction Study Between RaltEgravir and CITALopram in Healthy Subjects (RECITAL).|
- raltegravir AUC and citalopram AUC [ Time Frame: at steady state: day 5 of raltegravir treatment and day 16 or later for citalopram ] [ Designated as safety issue: No ]
To assess the effect of multiple dose citalopram on the steady state pharmacokinetics of raltegravir and vice versa by intrasubject comparison in healthy subjects.
- The comparison of steady state raltegravir (400 mg BID for 5 days) pharmacokinetics (AUC0-12h, Cmax, C12h) with steady state citalopram (20 mg QD) vs. raltegravir alone by intrasubject comparison.
- The comparison of steady state citalopram (20 mg QD) pharmacokinetics (AUC0-24h, Cmax, C24h) with steady state raltegravir (400 mg BID) vs. citalopram alone by intrasubject comparison.
- Adverse Events [ Time Frame: up to approximately 13 weeks (from screening until the last study visit) ] [ Designated as safety issue: Yes ]Adverse events will be scored and laboratory measurements for safety will be collected frequently from screening onwards (maximum 4 weeks before the start of the study) until the last study visit (Day 60) or longer if applicable.
|Study Start Date:||January 2014|
|Estimated Study Completion Date:||July 2014|
|Estimated Primary Completion Date:||April 2014 (Final data collection date for primary outcome measure)|
Active Comparator: raltegravir alone
raltegravir 400 mg BID for 5 days
Other Name: isentress
Active Comparator: citalopram alone
citalopram 10 mg QD for 3 days, followed by citalopram 20 mg QD for 13-14 days
Other Name: citalopram
Experimental: raltegravir + citalopram
raltegravir 500 mg BID and citalopram 20 mg QD for 5 days
Other Name: isentressDrug: citalopram
Other Name: citalopram
|Contact: David Burger, PharmD, PhD||+31243616405||David.Burger@radboudumc.nl|
|Contact: Maren Blonk, PharmD||+31243616405||Maren.Blonk@radboudumc.nl|
|CRCN Radboud university medical center||Not yet recruiting|
|Contact: Bas Schouwenberg, MD +31243668333 Bas.Schouwenberg@radboudumc.nl|
|Principal Investigator: Bas Schouwenberg, MD|