CompletedNCT01841593Updated Sep 29, 2014Results posted

A Two Way Cross Over Pharmacokinetic Interaction Study Between Raltegravir and Amlodipine in Healthy Volunteers

A Phase 1 interventional study of Raltegravir and Amlodipine in HIV, sponsored by St Stephens Aids Trust. Completed at 1 site in United Kingdom. Open to participants aged 18 Years to 65 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2014-09-29.

Sponsored by St Stephens Aids Trust · Phase 1, Interventional, and Treatment

Phase: Phase 1
Study type: Interventional
Enrollment: 19
Allocation: Randomized
Ages: 18 Years to 65 Years
Sex: All

Study 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). 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 studied

In context

Lead sponsor

St Stephens Aids Trust is the lead sponsor of 45 studies on the registry; none are open to participants now.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 18 Years to 65 Years
Sexes eligible: All
Accepts healthy volunteers: Yes

Inclusion criteria

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
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

Exclusion criteria

Exclusion Criteria:

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
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

Study design

Phase: Phase 1
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover assignment
Masking: None (open label)
Enrollment: 19 participants (actual)

Study arms

Experimental
Group A
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
Drug: Raltegravir · Drug: Amlodipine
Experimental
Group B
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
Drug: Raltegravir · Drug: Amlodipine

Interventions

DrugRaltegravir
Isentress 400mg tablet taken twice daily
Also known as: Isentress
DrugAmlodipine
generic amlodipine 5mg tablets (Accord healthcare Limited, UK)
Also known as: Amlodipine 5mg tablets

What researchers measure

Primary outcomes

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.
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))
Raltegravir C12h
measured concentration 12 hours after dose in the absence, and presence, of amlodipine.
Time frame: 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
Time frame: 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.
Time frame: 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
Time frame: Post-dose on day 7 of daily dosing

Results

Posted Sep 29, 2014

Participant flow

First Intervention (Days 1 to 7)

Participant flow — First Intervention (Days 1 to 7)
Milestone	Group A (Raltegravir Then Amlodipine)	Group B (Amlodipine Then Raltegravir)
Started	12	7
Completed	12	6
Not completed	0	1
Withdrew: Protocol violation	0	1

Second Intervention (Days 8 to 14)

Participant flow — Second Intervention (Days 8 to 14)
Milestone	Group A (Raltegravir Then Amlodipine)	Group B (Amlodipine Then Raltegravir)
Started	12	6
Completed	11	6
Not completed	1	0
Withdrew: Adverse event	1	0

Third Intervention (Days 15 to 21)

Participant flow — Third Intervention (Days 15 to 21)
Milestone	Group A (Raltegravir Then Amlodipine)	Group B (Amlodipine Then Raltegravir)
Started	11	6
Completed	11	6
Not completed	0	0

Outcome measures

PrimaryMaximum 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.

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))
Reported as:: Geometric mean · ng/mL

Maximum Observed Concentration (Cmax) of Raltegravir and Amlodipine Without and With Co-administration of the Other Studied Drug.
ng/mL	Raltegravir PK (Alone)	Raltegravir PK (Administered With Amlodipine)	Amlodipine PK (Alone)	Amlodipine PK (Administered With Raltegravir)
Maximum Observed Concentration (Cmax) of Raltegravir and Amlodipine Without and With Co-administration of the Other Studied Drug.	1178 (966 to 2318)	1866 (1779 to 4511)	8.47 (7.58 to 10.0)	8.49 (7.65 to 9.94)

PrimaryRaltegravir C12h

measured concentration 12 hours after dose in the absence, and presence, of amlodipine.

Time frame:: 12 hours post-dose on day 7 of daily dosing.
Reported as:: Geometric mean · ng/mL

Raltegravir C12h
ng/mL	Raltegravir PK (Alone)	Raltegravir PK (Administered With Amlodipine)
Raltegravir C12h	48 (35 to 95)	37 (30 to 67)

PrimaryAmlodipine C24h

measured concentration 24 hours after dose in the absence, and presence, of raltegravir

Time frame:: 12 hours post-dose on day 7 of daily dosing.
Reported as:: Geometric mean · ng/mL

Amlodipine C24h
ng/mL	Amlodipine PK (Alone)	Amlodipine PK (Administered With Raltegravir)
Amlodipine C24h	4.91 (4.23 to 6.36)	4.55 (4.11 to 5.34)

PrimaryRaltegravir AUC(0-12h )

AUC0-12h: Area under the concentration time curve over 12 hours in the absence, and presence, of amlodipine.

Time frame:: Post dose after day 7 of daily dosing
Reported as:: Geometric mean · ng*h/mL

Raltegravir AUC(0-12h )
ng*h/mL	Raltegravir PK (Alone)	Raltegravir PK (Administered With Amlodipine)
Raltegravir AUC(0-12h )	4600 (3888 to 7652)	6410 (5649 to 12138)

PrimaryAmlodipine AUC(0-24h)

AUC0-24h: Area under the concentration time curve 24 hours in the absence, and presence, of raltegravir

Time frame:: Post-dose on day 7 of daily dosing
Reported as:: Geometric mean · ng*h/mL

Amlodipine AUC(0-24h)
ng*h/mL	Amlodipine PK (Alone)	Amlodipine PK (Administered With Raltegravir)
Amlodipine AUC(0-24h)	166.0 (146.3 to 202.9)	165.9 (148.7 to 195.8)

Adverse events

Collected over Event data collected from time of signing informed consent at screen, until discharge from study (14 days after completion).. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
Group A	—	1/12 (8.3%)	6/12 (50%)
Group B	—	0/7 (0%)	3/7 (42.9%)

Most frequent serious events

Most frequent serious events
Event	Group A	Group B
GastroenteritisGastrointestinal disorders	1/12	0/7

Most frequent other events

Most frequent other events
Event	Group A	Group B
vomitingGastrointestinal disorders	0/12	1/7
insect biteSkin and subcutaneous tissue disorders	0/12	1/7
light-headedNervous system disorders	0/12	1/7
CellulitisSkin and subcutaneous tissue disorders	1/12	0/7
thrombophlebitisVascular disorders	1/12	0/7
gingivitisSkin and subcutaneous tissue disorders	1/12	0/7
pruritic rashSkin and subcutaneous tissue disorders	1/12	0/7
HeadacheNervous system disorders	1/12	0/7
pedal oedemaSkin and subcutaneous tissue disorders	1/12	0/7

Baseline characteristics

All enrolled participants who completed at least two of three pharmacokinetic sessions for comparison were included in the analysis.

Age, Categorical
Age, Categorical(Participants)	Group A	Group B	Total
<=18 years	0	0	0
Between 18 and 65 years	11	6	17
>=65 years	0	0	0

Sex: Female, Male
Sex: Female, Male(Participants)	Group A	Group B	Total
Female	10	3	13
Male	1	3	4

Study locations

1 site

St Stephen's AIDS Trust
London, SW10 9TH, United Kingdom

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Sep 29, 2014, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT01841593
Lead sponsor: St Stephens Aids Trust
Responsible party: Sponsor
First posted: Apr 26, 2013
Start date: Apr 2013
Primary completion: Sep 2013
Completion: Sep 2013
Results posted: Sep 29, 2014
Last update: Sep 29, 2014

Study contacts

Marta Boffito, Dr

principal investigator · St Stephen's AIDS Trust

Oversight

Data monitoring committee: No

View the source record on ClinicalTrials.gov ↗

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This study is completed, as verified in Sep 2014. You cannot join it, but the record below documents what was studied.

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