Clinical Trials Logo

Clinical Trial Summary

Ageing is characterized by physiological changes, which can impact drug pharmacokinetics and thereby cause drug-drug interactions. This study aims to assess the pharmacokinetics of amlodipine, atorvastatin and rosuvastatin in the presence of darunavir/ritonavir (inhibitor of drug metabolizing enzymes and drug transporters), by comparison with dolutegravir (no inhibitory effects on cytochromes or transporters involved in the disposition of the evaluated co-medications), in order to characterize the importance of drug-drug interactions in elderly individuals.


Clinical Trial Description

HIV-infected individuals live longer, making the proportion of older individuals within the HIV infected population constantly growing. Thus, the management of HIV infection is becoming more complex as patients encounter more age related chronic ailments such as hypertension, diabètes and tumors, or acute diseases, sometimes severe, leading to polypharmacy and consequently to potential drug-drug interactions (DDI). In addition, aging is characterized by a decline in the function of elimination organs, which may impact the pharmacokinetics of drugs and thereby the magnitude of DDI.

The principal aim of the study is to determine the importance of DDIs between antiretroviral drugs and commonly prescribed co-medications (namely amlodipine, rosuvastatin and atorvastatin) in HIV-infected patients of the Swiss HIV Cohort Study (SHCS). The investigation will include a majority of patients over 60 years old, yet without excluding younger patients. Pharmacokinetic investigations will be primarily conducted in patients treated with darunavir/ritonavir- or dolutegravir-containing regimens, and who receive one of the cardiovascular drug of interest. The objective is to contrast the effects of darunavir/ritonavir (strong inhibitor of drug metabolizing cytochromes) and dolutegravir (devoid of inhibitory effects on these enzymes), in order to determine the magnitude of the interaction with the co-medication. Besides their common use in elderly HIV-infected patients, amlodipine, atorvastatin and rosuvastatin were primarily selected due to their predisposition to become victims of drug-drug interactions. In addition, the same study framework will possibly serve to examine further drug combinations susceptible to interact, whose exploration could be of interest from a clinical point a view to stimulate future confirmatory research. It will thus be open to investigate associations of other cardiovascular agents with the antiretroviral drugs defined above, or with other antiretroviral drugs.

On a morning selected for investigation, the patient will take the antiretroviral medications together with the comedication of interest with a standard breakfast. Serial blood samples will be collected into EDTA-K monovettes (2.7 ml) from a catheter positioned in the forearm at the following time-points: t = 0 (just before the drug intake) and 30 minutes, 1, 2, 3, 4, 6, 8, 10, and 12 hours after drug intake (a certain flexibility in sampling times is allowed, provided that dosing and sampling times are carefully recorded). The patient will then spend the night at home and return the following morning to provide the last sample of blood 24 hours after drugs intake. In total, 30 ml of blood will be required for a full pharmacokinetic investigation).

A second full pharmacokinetic investigation will be performed for patients undergoing antiretroviral treatment change for clinical reasons. The investigation will be scheduled two weeks after switching treatment, so that a steady-state is reached, and will be performed as described above.

The blood samples will be centrifuged and the separated plasma will be frozen at -80°C until analysis by liquid chromatography tandem mass spectrometry (LC-MS/MS). Pharmacokinetic parameters will be first estimated by classical non-compartmental approaches: Maximal concentration (Cmax), minimal concentration (Cmin), Area Under the Curve (AUC), slope of the terminal phase (Lambda_z), clearance (Cl), half-life (t1/2). These parameters will be compared according to the co-prescription of darunavir/ritonavir versus dolutegravir, using a variance analysis on log-transformed values. The analysis will accommodate partial pairing of parameter values obtained in patients investigated in cross-over, through the inclusion of a random patient factor (assumed to take independent values only between patients). PK parameters of antiretroviral drugs will be simply described. ;


Study Design


Related Conditions & MeSH terms


NCT number NCT03515772
Study type Observational
Source Centre Hospitalier Universitaire Vaudois
Contact
Status Completed
Phase
Start date April 23, 2018
Completion date August 29, 2019

See also
  Status Clinical Trial Phase
Completed NCT05454514 - Automated Medication Platform With Video Observation and Facial Recognition to Improve Adherence to Antiretroviral Therapy in Patients With HIV/AIDS N/A
Completed NCT03760458 - The Pharmacokinetics, Safety, and Tolerability of Abacavir/Dolutegravir/Lamivudine Dispersible and Immediate Release Tablets in HIV-1-Infected Children Less Than 12 Years of Age Phase 1/Phase 2
Recruiting NCT06033547 - A Study to Investigate the Pharmacokinetics, Safety, and Tolerability of Two Different Formulations of Long-acting Cabotegravir in Healthy Adult Participants Phase 1
Completed NCT03067285 - A Phase IV, Open-label, Randomised, Pilot Clinical Trial Designed to Evaluate the Potential Neurotoxicity of Dolutegravir/Lamivudine/Abacavir in Neurosymptomatic HIV Patients and Its Reversibility After Switching to Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide. DREAM Study Phase 4
Completed NCT03141918 - Effect of Supplementation of Bioactive Compounds on the Energy Metabolism of People Living With HIV / AIDS N/A
Recruiting NCT04579146 - Coronary Artery Disease (CAD) in Patients HIV-infected
Completed NCT06212531 - Papuan Indigenous Model of Male Circumcision N/A
Active, not recruiting NCT03256422 - Antiretroviral Treatment Taken 4 Days Per Week Versus Continuous Therapy 7/7 Days Per Week in HIV-1 Infected Patients Phase 3
Completed NCT03256435 - Retention in PrEP Care for African American MSM in Mississippi N/A
Completed NCT00517803 - Micronutrient Supplemented Probiotic Yogurt for HIV/AIDS and Other Immunodeficiencies N/A
Active, not recruiting NCT03572335 - Systems Biology of Diffusion Impairment in Human Immunodeficiency Virus (HIV)
Completed NCT04165200 - Fecal Microbiota Transplantation as a Therapeutic Strategy for Patients Infected With HIV N/A
Recruiting NCT03854630 - Hepatitis B Virus Vaccination in HIV-positive Patients and Individuals at High Risk for HIV Infection Phase 4
Terminated NCT03275571 - HIV, Computerized Depression Therapy & Cognition N/A
Completed NCT02234882 - Study on Pharmacokinetics Phase 1
Completed NCT01618305 - Evaluating the Response to Two Antiretroviral Medication Regimens in HIV-Infected Pregnant Women, Who Begin Antiretroviral Therapy Between 20 and 36 Weeks of Pregnancy, for the Prevention of Mother-to-Child Transmission Phase 4
Recruiting NCT05043129 - Safety and Immune Response of COVID-19 Vaccination in Patients With HIV Infection
Not yet recruiting NCT06072443 - AURORA Study-A Transformative Approach to Support PrEP Medication Persistence
Not yet recruiting NCT05536466 - The Influence of Having Bariatric Surgery on the Pharmacokinetics, Safety and Efficacy of the Novel Non-nucleoside Reverse Transcriptase Inhibitor Doravirine N/A
Recruiting NCT04985760 - Evaluation of Trimer 4571 Therapeutic Vaccination in Adults Living With HIV on Suppressive Antiretroviral Therapy Phase 1