HIVPhase 1RECITALNCT01978782
Pharmacokinetic Drug-drug Interaction Study Between RaltEgravir and CITALopram in Healthy Subjects (RECITAL).
A Phase 1 study testing raltegravir and citalopram in people with HIV and Depression, run by Radboud University Medical Center at 1 site in Netherlands.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- HIV, Depression
- What is being tested?
- raltegravir and citalopram
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 1 siteNetherlands
- Study dates
- Jan 2014to Apr 2014
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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 Day 1.
- 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.
Who cannot join
- 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 study.
- Therapy with any drug (for two weeks preceding Day 1), except for acetaminophen.
- 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.
Show all 13Show fewer
- Relevant history or presence of QT syndrome, prolonged QTc time, bradycardia, hypokalaemia or hypomagnesaemia, recent acute myocardial infarction, or uncompensated heart failure.
- Relevant history or current condition that might interfere with drug ab-sorption, distribution, metabolism or excretion.
- History of or current abuse of drugs, alcohol or solvents.
- Inability to understand the nature and extent of the study and the pro-cedures required.
- Participation in a drug study 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.
Trial locations and contacts
1 site in 1 country.
About this study
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.
- Conditions
- HIV, Depression
- Being tested
- raltegravir, citalopram
- Keywords
- raltegravir, citalopram, pharmacokinetics, drug-drug interaction
- Medical subject headings
- Depression
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
raltegravirDrug
Also called isentress
citalopramDrug
| Study group | Role | What they receive |
|---|---|---|
| raltegravir alone | Active comparator | raltegravir 400 mg BID for 5 days Receives: Drug: raltegravir |
| citalopram alone | Active comparator | citalopram 10 mg QD for 3 days, followed by citalopram 20 mg QD for 13-14 days Receives: Drug: citalopram |
| raltegravir + citalopram | Experimental | raltegravir 500 mg BID and citalopram 20 mg QD for 5 days Receives: Drug: raltegravir; Drug: citalopram |
What is being measured
The primary outcome is the main question the study is designed to answer.
raltegravir AUC and citalopram AUC
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.
Measured: at steady state: day 5 of raltegravir treatment and day 16 or later for citalopram
Secondary outcomes (1)
Adverse Events
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.
Measured: up to approximately 13 weeks (from screening until the last study visit)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Nov 2013 (estimated)
- Study startJan 2014
- Primary completionApr 2014
- Study completionApr 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for HIVStudies of the same condition, open and under way.
- More trials run by Radboud University Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- Radboud University Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01978782
- Sponsor's protocol ID
- UMCN-AKF12.04
- Other IDs
- 2012-005148-50
- Acronym
- RECITAL
- Status last verified
- Jul 2015
- First submitted
- 22 Oct 2013
- Last updated
- 19 Oct 2020
- Results posted
- No
- Data monitoring committee
- No
Publications
Blonk MI, Langemeijer CC, Colbers AP, Hoogtanders KE, van Schaik RH, Schouwenberg BJ, Burger DM. Pharmacokinetic drug-drug interaction study between raltegravir and citalopram. Antivir Ther. 2016;21(2):143-52. doi: 10.3851/IMP2993. Epub 2015 Sep 16.
PubMed 26375942
Study at a glance
From the registry record, last updated by the sponsor on 19 Oct 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pharmacokinetic Drug-drug Interaction Study Between RaltEgravir and CITALopram in Healthy Subjects (RECITAL).
- ClinicalTrials.gov ID
- NCT01978782
- Acronym / sponsor ID
- RECITAL / UMCN-AKF12.04
- Conditions
- HIV, Depression
- Keywords
- raltegravir, citalopram, pharmacokinetics, drug-drug interaction
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- Radboud University Medical CenterUniversity, hospital or other
- Study start
- Jan 2014
- Primary completion
- Apr 2014 (actual)
- Study completion
- Apr 2014 (actual)
- First posted
- 8 Nov 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| raltegravir alone | Active comparator | Drug: raltegravirraltegravir 400 mg BID for 5 days |
| citalopram alone | Active comparator | Drug: citalopramcitalopram 10 mg QD for 3 days, followed by citalopram 20 mg QD for 13-14 days |
| raltegravir + citalopram | Experimental | Drug: raltegravir, Drug: citalopramraltegravir 500 mg BID and citalopram 20 mg QD for 5 days |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- 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 Day 1.
- 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.
Key exclusion criteria (13 listed)
- 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 study.
- Therapy with any drug (for two weeks preceding Day 1), except for acetaminophen.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| raltegravirAlso: isentress | Drug | raltegravir + citalopram, raltegravir alone |
| citalopram | Drug | citalopram alone, raltegravir + citalopram |
Primary outcome
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.
1 secondary outcome
Adverse Events
Time frame: up to approximately 13 weeks (from screening until the last study visit)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Oct 2020.
- Results publication: PubMed 26375942Blonk MI, Langemeijer CC, Colbers AP, Hoogtanders KE, van Schaik RH, Schouwenberg BJ, Burger DM. Pharmacokinetic drug-drug interaction study between raltegravir and citalopram. Antivir Ther. 2016;21(2):143-52. doi: 10.3851/IMP2993. Epub 2015 Sep 16.
- Abstract 53: Pharmacokinetic drug-drug interaction study between raltegravir and citalopram in healthy volunteers.Link provided by the sponsor.
- paperLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing raltegravir and citalopram in people with HIV and Depression, run by Radboud University Medical Center at 1 site in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 19 Oct 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
raltegravir AUC and citalopram AUC (time frame: at steady state: day 5 of raltegravir treatment and day 16 or later for citalopram). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01978782, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Oct 2020.