ClinicalTrials.gov
ClinicalTrials.gov Menu

Pharmacokinetic Drug-drug Interaction Study Between RaltEgravir and CITALopram in Healthy Subjects (RECITAL). (RECITAL)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT01978782
Recruitment Status : Completed
First Posted : November 8, 2013
Last Update Posted : July 22, 2015
Sponsor:
Information provided by (Responsible Party):
Radboud University

Study Description
Go to 
Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
Brief 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.

Condition or disease Intervention/treatment Phase
HIV Depression Drug: raltegravir Drug: citalopram Phase 1

Study Design
Go to 
Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 24 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Official Title: Pharmacokinetic Drug-drug Interaction Study Between RaltEgravir and CITALopram in Healthy Subjects (RECITAL).
Study Start Date : January 2014
Actual Primary Completion Date : April 2014
Actual Study Completion Date : April 2014

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arms and Interventions
Go to 
Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Arm Intervention/treatment
Active Comparator: raltegravir alone
raltegravir 400 mg BID for 5 days
 Drug: raltegravir
Other Name: isentress
Active Comparator: citalopram alone
citalopram 10 mg QD for 3 days, followed by citalopram 20 mg QD for 13-14 days
 Drug: citalopram
Experimental: raltegravir + citalopram
raltegravir 500 mg BID and citalopram 20 mg QD for 5 days
 Drug: raltegravir
Other Name: isentress
Drug: citalopram


Outcome Measures
Go to 
Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Primary Outcome Measures :
  1. raltegravir AUC and citalopram AUC [ Time Frame: at steady state: day 5 of raltegravir treatment and day 16 or later for citalopram ]

    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.


Secondary Outcome Measures :
  1. Adverse Events [ Time Frame: up to approximately 13 weeks (from screening until the last study visit) ]
    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.


Eligibility Criteria
Go to 
Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

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, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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.
Contacts and Locations
Go to 
Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01978782


Locations
Netherlands
CRCN Radboud university medical center
Nijmegen, Netherlands
Sponsors and Collaborators
Radboud University
More Information
Go to 
Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Additional Information:
Abstract 53: Pharmacokinetic drug-drug interaction study between raltegravir and citalopram in healthy volunteers.  This link exits the ClinicalTrials.gov site

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: Radboud University
ClinicalTrials.gov Identifier: NCT01978782     History of Changes
Other Study ID Numbers: UMCN-AKF12.04
2012-005148-50 ( EudraCT Number )
First Posted: November 8, 2013    Key Record Dates
Last Update Posted: July 22, 2015
Last Verified: July 2015

Keywords provided by Radboud University:
raltegravir
citalopram
pharmacokinetics
drug-drug interaction

Additional relevant MeSH terms:
Raltegravir Potassium
Citalopram
Dexetimide
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
HIV Integrase Inhibitors
Integrase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Serotonin Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Membrane Transport Modulators
 Neurotransmitter Agents
Serotonin Agents
Physiological Effects of Drugs
Antidepressive Agents, Second-Generation
Antidepressive Agents
Psychotropic Drugs
Antiparkinson Agents
Anti-Dyskinesia Agents
Parasympatholytics
Autonomic Agents
Peripheral Nervous System Agents
Muscarinic Antagonists
Cholinergic Antagonists
Cholinergic Agents