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

NCT01841593 | Completed Phase 1 Results

• 1 other identifier: SSAT 051
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

HIV

Outcome Measures

Primary Outcomes (5)

• 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.

  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.

  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

  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.

  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

  Post-dose on day 7 of daily dosing

Study Arms (2)

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

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

Drug: Raltegravir; Drug: Amlodipine

Interventions

Raltegravir DRUG

Isentress 400mg tablet taken twice daily

Also known as: Isentress

Group A; Group B

Amlodipine DRUG

generic amlodipine 5mg tablets (Accord healthcare Limited, UK)

Also known as: Amlodipine 5mg tablets

Group A; Group B

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• St Stephens Aids Trust: lead

Study Sites (1)

St Stephen's AIDS Trust

London, London, SW10 9TH, United Kingdom

Location

MeSH Terms

Interventions

Raltegravir Potassium; Amlodipine

Intervention Hierarchy (Ancestors)

Pyrrolidinones; Pyrrolidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Dihydropyridines; Pyridines

Results Point of Contact

• Title: Dr. Marta Boffito
• Organization: SSAT Research, Chelsea & Westminster Hospital

marta.boffito@chelwest.nhs.uk

+442033155601

Study Officials

• Marta Boffito, Dr

  St Stephen's AIDS Trust

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 16, 2013
• First Posted: April 26, 2013
• Study Start: April 1, 2013
• Primary Completion: September 1, 2013
• Study Completion: September 1, 2013
• Last Updated: September 29, 2014
• Results First Posted: September 29, 2014

Record last verified: 2014-09

Locations

GB (1)