HIVPhase 1NCT01841593
A Two Way Cross Over Pharmacokinetic Interaction Study Between Raltegravir and Amlodipine in Healthy Volunteers
A Phase 1 study testing Raltegravir and Amlodipine in people with HIV, run by St Stephens Aids Trust at 1 site in United Kingdom.
Trial summary
The purpose of the study is to look at the levels of an HIV medication (raltegravir) in the blood, and how it is affected if raltegravir is taken at the same time as another medicine for high blood pressure (amlodipine). Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- HIV
- What is being tested?
- Raltegravir and Amlodipine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 19 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Apr 2013to Sep 2013
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Subjects must meet all of the following inclusion criteria within 28 days prior to the baseline visit:
- The ability to understand and sign a written informed consent form, prior to participation in any screening procedures and must be willing to comply with all study requirements
- Male or non-pregnant, non-lactating females
- Between 18 to 65 years, inclusive
- Body Mass Index (BMI) of 18 to 35 kg/m2, inclusive.
- Women of childbearing potential (WOCBP) must be using an adequate method of contraception to avoid pregnancy throughout the study and for a period of at least 12 weeks after the study
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- Willing to consent to their personal details being entered onto The Over-volunteering Prevention Scheme (TOPS) database
- Willing to provide photographic identification at each visit.
- Registered with a GP in the UK
Who cannot join
- Subjects who meet any of the following exclusion criteria are not to be enrolled in this study.
- Any significant acute or chronic medical illness including hypertension (BP persistently >140/90 mmHg) or hypotension (BP persistently <90/60 mmHg)
- Evidence of organ dysfunction or any clinically significant deviation from normal in physical examination, vital signs, ECG or clinical laboratory determinations
- Positive blood screen for hepatitis B surface antigen and/or C antibodies
- Positive blood screen for HIV-1 and/or 2 antibodies
- Current or recent (within 3 months) gastrointestinal disease
Show all 12Show fewer
- Clinically relevant alcohol or drug use (positive urine drug screen) or history of alcohol or drug use considered by the Investigator to be sufficient to hinder compliance with treatment, follow-up procedures or evaluation of adverse events. Smoking is permitted, but tobacco intake should remain consistent throughout the study
- Exposure to any investigational drug or placebo within 3 months of first dose of study drug
- Use of any other drugs (unless approved by the Investigator), including over-the-counter medications and herbal preparations, within two weeks prior to first dose of study drug, unless approved/prescribed by the Principal Investigator as known not to interact with study drugs.
- Females of childbearing potential without the use of effective non-hormonal birth control methods, or not willing to continue practising these birth control methods for at least 12 weeks after the end of the treatment period
- Previous allergy to any of the constituents of the pharmaceuticals administered in this trial
- Lactose intolerance
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Two Way Cross Over Pharmacokinetic (PK) Interaction Study Between Raltegravir and Amlodipine in Healthy Volunteers
The purpose of the study is to look at the levels of an HIV medication (raltegravir) in the blood, and how it is affected if raltegravir is taken at the same time as another medicine for high blood pressure (amlodipine). Many patients with HIV will also have high blood pressure, so it is important to know which drugs for each of these conditions can be taken together without affecting how well they work individually.
Over a 3 week period, participants took amlodipine for 2 weeks, and raltegravir for 2 weeks, with the middle week being on both drugs. The investigators will look at and compare the levels of these two drugs in the blood after subjects have taken them separately and both together.
This study is randomised into two groups with both study medications received by all participants in a three-period crossover pattern; randomisation determined which medication was taken first. Once randomised allocation was performed, medications were administered in an open-label fashion.
Read the detailed description
HIV-negative male and female volunteers will be enrolled, after written confirmation of informed consent, in a phase I, open-label, cross-over, PK study (approved by Westminster Research Ethics Committee and UK Regulatory Authorities; Eudra number 2012-005400-18).
Subjects are randomized to receive either raltegravir 400mg twice-daily (seven days), followed by raltegravir 400mg twice-daily plus amlodipine 5mg once-daily (seven days), followed by amlodipine 5mg once-daily alone (seven days), or the same treatments in the opposite order, in the fasted state (at least eight hours) with 240mL of water.
Intensive PK sampling and safety laboratory analysis are performed at the end of each phase (Days 7, 14 and 21). Raltegravir and amlodipine plasma concentrations will be analysed by a validated liquid chromatography-mass spectrometry (LC-MS/MS) method.
PK parameters are determined by non-compartmental methods [WinNonlin Phoenix (version 6.1; Pharsight Corp, Mountain View, CA, USA]. These are the concentrations measured 12 and 24 hours post-dose (C12h, C24h) for raltegravir and amlodipine, respectively; the maximum concentration (Cmax); and the area under the curve over 12 and 24 hours (AUC12h, AUC24h) for raltegravir and amlodipine, respectively.
- Conditions
- HIV
- Being tested
- Raltegravir, Amlodipine
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RaltegravirDrug
Also called Isentress
Isentress 400mg tablet taken twice daily
AmlodipineDrug
Also called Amlodipine 5mg tablets
generic amlodipine 5mg tablets (Accord healthcare Limited, UK)
| Study group | Role | What they receive |
|---|---|---|
| Group A | Experimental | DAYS 1 to 7: raltegravir 400 mg BID DAYS 8 to 14: raltegravir 400 mg BID PLUS amlodipine 5 mg OD DAYS 15 to 21: amlodipine 5 mg OD Receives: Drug: Raltegravir; Drug: Amlodipine |
| Group B | Experimental | DAYS 1 to 7: amlodipine 5 mg OD DAYS 8 to 14: raltegravir 400 mg BID PLUS amlodipine 5 mg OD DAYS 15 to 21: raltegravir 400 mg BID Receives: Drug: Raltegravir; Drug: Amlodipine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum Observed Concentration (Cmax) of Raltegravir and Amlodipine Without and With Co-administration of the Other Studied Drug.
To investigate the pharmacokinetics of raltegravir and amlodipine co-administration. The pharmacokinetic parameters calculated for raltegravir and amlodipine will be trough concentration (Ctrough), defined as the concentration at 24 hours after the observed drug dose, the maximum observed plasma concentration (Cmax), elimination half-life (t1/2), time point at Cmax (Tmax), and total drug exposure, expressed as the area under the plasma concentration-time curve from 0-24 hours after dosing (AUC0-24h).
All pharmacokinetic parameters will be calculated using non-compartmental modeling techniques (WinNonlin®) and all statistical calculations performed and analyzed using SAS version 9.1 or SPSS V17.0.
Measured: Day 7 of each intervention (0 (pre-dose), 2, 4, 8 and 12 hours post dose (both drugs) and 24 hours post dose (amlodipine only))
Raltegravir C12h
measured concentration 12 hours after dose in the absence, and presence, of amlodipine.
Measured: 12 hours post-dose on day 7 of daily dosing.
Amlodipine C24h
measured concentration 24 hours after dose in the absence, and presence, of raltegravir
Measured: 12 hours post-dose on day 7 of daily dosing.
Raltegravir AUC(0-12h )
AUC0-12h: Area under the concentration time curve over 12 hours in the absence, and presence, of amlodipine.
Measured: Post dose after day 7 of daily dosing
Amlodipine AUC(0-24h)
AUC0-24h: Area under the concentration time curve 24 hours in the absence, and presence, of raltegravir
Measured: Post-dose on day 7 of daily dosing
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Apr 2013 (estimated)
- Study startApr 2013
- Primary completionSep 2013
- Study completionSep 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for HIVStudies of the same condition, open and under way.
- 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
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 19 participants (actual)
Sponsor and investigators
- Lead sponsor
- St Stephens Aids Trust
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Marta Boffito, Dr, Principal investigator, St Stephen's AIDS Trust
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01841593
- Sponsor's protocol ID
- SSAT 051
- Status last verified
- Sep 2014
- First submitted
- 16 Apr 2013
- Last updated
- 29 Sep 2014
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 29 Sep 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Two Way Cross Over Pharmacokinetic (PK) Interaction Study Between Raltegravir and Amlodipine in Healthy Volunteers
- ClinicalTrials.gov ID
- NCT01841593
- Acronym / sponsor ID
- SSAT 051
- Conditions
- HIV
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 19 participants (actual)
- Lead sponsor
- St Stephens Aids TrustUniversity, hospital or other
- Study start
- Apr 2013
- Primary completion
- Sep 2013 (actual)
- Study completion
- Sep 2013 (actual)
- First posted
- 26 Apr 2013 (estimated)
- Results
- Posted 29 Sep 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of the study is to look at the levels of an HIV medication (raltegravir) in the blood, and how it is affected if raltegravir is taken at the same time as another medicine for high blood pressure (amlodipine). Many patients with HIV will also have high blood pressure, so it is important to know which drugs for each of these conditions can be taken together without affecting how well they work individually.
Over a 3 week period, participants took amlodipine for 2 weeks, and raltegravir for 2 weeks, with the middle week being on both drugs. The investigators will look at and compare the levels of these two drugs in the blood after subjects have taken them separately and both together.
This study is randomised into two groups with both study medications received by all participants in a three-period crossover pattern; randomisation determined which medication was taken first. Once randomised allocation was performed, medications were administered in an open-label fashion.
Detailed description
HIV-negative male and female volunteers will be enrolled, after written confirmation of informed consent, in a phase I, open-label, cross-over, PK study (approved by Westminster Research Ethics Committee and UK Regulatory Authorities; Eudra number 2012-005400-18).
Subjects are randomized to receive either raltegravir 400mg twice-daily (seven days), followed by raltegravir 400mg twice-daily plus amlodipine 5mg once-daily (seven days), followed by amlodipine 5mg once-daily alone (seven days), or the same treatments in the opposite order, in the fasted state (at least eight hours) with 240mL of water.
Intensive PK sampling and safety laboratory analysis are performed at the end of each phase (Days 7, 14 and 21). Raltegravir and amlodipine plasma concentrations will be analysed by a validated liquid chromatography-mass spectrometry (LC-MS/MS) method.
PK parameters are determined by non-compartmental methods [WinNonlin Phoenix (version 6.1; Pharsight Corp, Mountain View, CA, USA]. These are the concentrations measured 12 and 24 hours post-dose (C12h, C24h) for raltegravir and amlodipine, respectively; the maximum concentration (Cmax); and the area under the curve over 12 and 24 hours (AUC12h, AUC24h) for raltegravir and amlodipine, respectively.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Group A | Experimental | Drug: Raltegravir, Drug: AmlodipineDAYS 1 to 7: raltegravir 400 mg BID DAYS 8 to 14: raltegravir 400 mg BID PLUS amlodipine 5 mg OD DAYS 15 to 21: amlodipine 5 mg OD |
| Group B | Experimental | Drug: Raltegravir, Drug: AmlodipineDAYS 1 to 7: amlodipine 5 mg OD DAYS 8 to 14: raltegravir 400 mg BID PLUS amlodipine 5 mg OD DAYS 15 to 21: raltegravir 400 mg BID |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Subjects must meet all of the following inclusion criteria within 28 days prior to the baseline visit:
- The ability to understand and sign a written informed consent form, prior to participation in any screening procedures and must be willing to comply with all study requirements
- Male or non-pregnant, non-lactating females
- Between 18 to 65 years, inclusive
- Body Mass Index (BMI) of 18 to 35 kg/m2, inclusive.
Key exclusion criteria (12 listed)
- Subjects who meet any of the following exclusion criteria are not to be enrolled in this study.
- Any significant acute or chronic medical illness including hypertension (BP persistently >140/90 mmHg) or hypotension (BP persistently <90/60 mmHg)
- Evidence of organ dysfunction or any clinically significant deviation from normal in physical examination, vital signs, ECG or clinical laboratory determinations
- Positive blood screen for hepatitis B surface antigen and/or C antibodies
- Positive blood screen for HIV-1 and/or 2 antibodies
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: IsentressIsentress 400mg tablet taken twice daily | Drug | Group A, Group B |
| AmlodipineAlso: Amlodipine 5mg tabletsgeneric amlodipine 5mg tablets (Accord healthcare Limited, UK) | Drug | Group A, Group B |
Primary outcome
Maximum Observed Concentration (Cmax) of Raltegravir and Amlodipine Without and With Co-administration of the Other Studied Drug.
Time frame: Day 7 of each intervention (0 (pre-dose), 2, 4, 8 and 12 hours post dose (both drugs) and 24 hours post dose (amlodipine only))
To investigate the pharmacokinetics of raltegravir and amlodipine co-administration. The pharmacokinetic parameters calculated for raltegravir and amlodipine will be trough concentration (Ctrough), defined as the concentration at 24 hours after the observed drug dose, the maximum observed plasma concentration (Cmax), elimination half-life (t1/2), time point at Cmax (Tmax), and total drug exposure, expressed as the area under the plasma concentration-time curve from 0-24 hours after dosing (AUC0-24h). All pharmacokinetic parameters will be calculated using non-compartmental modeling techniques (WinNonlin®) and all statistical calculations performed and analyzed using SAS version 9.1 or SPSS V17.0.
Raltegravir C12h
Time frame: 12 hours post-dose on day 7 of daily dosing.
measured concentration 12 hours after dose in the absence, and presence, of amlodipine.
Amlodipine C24h
Time frame: 12 hours post-dose on day 7 of daily dosing.
measured concentration 24 hours after dose in the absence, and presence, of raltegravir
Raltegravir AUC(0-12h )
Time frame: Post dose after day 7 of daily dosing
AUC0-12h: Area under the concentration time curve over 12 hours in the absence, and presence, of amlodipine.
Amlodipine AUC(0-24h)
Time frame: Post-dose on day 7 of daily dosing
AUC0-24h: Area under the concentration time curve 24 hours in the absence, and presence, of raltegravir
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Sep 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Marta Boffito, Dr principal investigator
St Stephen's AIDS Trust
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 Amlodipine in people with HIV, run by St Stephens Aids Trust at 1 site in United Kingdom.
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 9 inclusion and 12 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 29 Sep 2014. 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 United Kingdom. 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?
Yes. Results are posted in the registry (first posted 29 Sep 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Maximum Observed Concentration (Cmax) of Raltegravir and Amlodipine Without and With Co-administration of the Other Studied Drug. (time frame: Day 7 of each intervention (0 (pre-dose), 2, 4, 8 and 12 hours post dose (both drugs) and 24 hours post dose (amlodipine only))). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 29 Sep 2014; AzTrials last refreshed its copy on 2 Nov 2026.