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

This study is currently recruiting participants.
Verified May 2013 by St Stephens Aids Trust
Sponsor:
Information provided by (Responsible Party):
St Stephens Aids Trust
ClinicalTrials.gov Identifier:
NCT01841593
First received: April 16, 2013
Last updated: May 10, 2013
Last verified: May 2013
  Purpose

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, subjects will take 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.

The duration of involvement in the study will be up to 22 days plus a screening visit which will take place up to 4 weeks prior to the start of the study, and a follow up visit which takes place 7-14 days after the last dose of study medication.

This study is randomised (like flipping a coin) into two groups who will receive the same study medications, but in a different order (this is known as a crossover study). The subject and the study doctor will know which study medications you are taking at all times during the study.

The subject will need to stay at the study centre all day (12-14 hours) on three occasions during the study.


Condition Intervention Phase
HIV
Drug: Raltegravir
Drug: Amlodipine
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Treatment

Resource links provided by NLM:


Further study details as provided by St Stephens Aids Trust:

Primary Outcome Measures:
  • Pharmacokinetics of raltegravir and amlodipine co-administration [ Time Frame: 21/22 days ] [ Designated as safety issue: Yes ]

    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.



Secondary Outcome Measures:
  • Safety and tolerability of raltegravir and amlodipine co-administration [ Time Frame: 21/22 days ] [ Designated as safety issue: Yes ]

    To investigate the safety and tolerability of raltegravir and amlodipine co-administration. Adverse events observed by the Investigator, or reported by the subject, and any remedial action taken, will be recorded in the subject's CRF and should be verifiable in the subject's notes throughout the study. The nature of each event, time of onset after drug administration, duration and severity will be documented together with the Investigator's opinion of the causal relationship to the treatment (unrelated, unlikely, possible, probable, and definite).

    All patients, whether withdrawn prematurely or not, will be included in the safety analysis. All safety data and adverse events will be summarised.



Estimated Enrollment: 16
Study Start Date: April 2013
Estimated Primary Completion Date: August 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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:

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01841593

Contacts
Contact: Dr Marta Boffito 020 3315 6507 Marta.Boffito@chelwest.nhs.uk

Locations
United Kingdom
St Stephen's AIDS Trust Recruiting
London, United Kingdom, SW10 9TH
Contact: Dr Marta Boffito    020 8746 5601    Marta.Boffito@chelwest.nhs.uk   
Principal Investigator: Dr Marta Boffito         
Sponsors and Collaborators
St Stephens Aids Trust
  More Information

No publications provided

Responsible Party: St Stephens Aids Trust
ClinicalTrials.gov Identifier: NCT01841593     History of Changes
Other Study ID Numbers: SSAT 051
Study First Received: April 16, 2013
Last Updated: May 10, 2013
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency

Additional relevant MeSH terms:
Amlodipine
Calcium Channel Blockers
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Cardiovascular Agents
Therapeutic Uses
Vasodilator Agents
Antihypertensive Agents

ClinicalTrials.gov processed this record on April 20, 2014