Drug-drug Interactions Between Antiretroviral Drugs and Cardiovascular Drugs in Elderly Patients

NCT03515772 | Completed FDA Drug

• 1 other identifier: HIV-Interactions
• Study Type: observational
• Target: 21
• Locations: 1 country
• Sites: 2

Brief 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.

Conditions

HIV Infections; Drug Interactions; Cardiovascular Diseases

Keywords

dolutegravir; darunavir; amlodipine; rosuvastatin; atorvastatin

Outcome Measures

Primary Outcomes (3)

• Circulating exposure (AUC) to cardiovascular agent amlodipine

  Area under the curve (AUC) of the cardiovascular drug, namely amlodipine, in the presence of darunavir/ritonavir (inhibitory effect hypothesized) or dolutegravir (no inhibitory effect predicted).

  2 weeks

• Circulating exposure (AUC) to cardiovascular agent atorvastatin

  Area under the curve (AUC) of the cardiovascular drug, namely atorvastatin in the presence of darunavir/ritonavir (inhibitory effect hypothesized) or dolutegravir (no inhibitory effect predicted).

  2 weeks

• Circulating exposure (AUC) to cardiovascular agent rosuvastatin

  Area under the curve (AUC) of the cardiovascular drug, namely rosuvastatin in the presence of darunavir/ritonavir (inhibitory effect hypothesized) or dolutegravir (no inhibitory effect predicted).

  2 weeks

Secondary Outcomes (1)

• Circulating exposure (AUC) to another cardiovascular agent, if one appears frequently associated with HIV agents

  2 weeks

Study Arms (6)

Amlodipine with Dolutegravir

This is the "control" group regarding HIV drug interaction potential on amlodipine

Amlodipine with Darunavir

This is the "case" group regarding HIV drug interaction potential on amlodipine

Drug: Co-administration of darunavir with a cardiovascular drug

Atorvastatin with Dolutegravir

This is the "control" group regarding HIV drug interaction potential on atorvastatin

Atorvastatin with Darunavir

This is the "case" group regarding HIV drug interaction potential on atorvastatin

Drug: Co-administration of darunavir with a cardiovascular drug

Rosuvastatin with Dolutegravir

This is the "control" group regarding HIV drug interaction potential on rosuvastatin

Rosuvastatin with Darunavir

This is the "case" group regarding HIV drug interaction potential on rosuvastatin

Drug: Co-administration of darunavir with a cardiovascular drug

Interventions

Co-administration of darunavir with a cardiovascular drug DRUG

Co-administration of darunavir, an HIV agent considered prone to induce drug interactions, with a cardiovascular drug (amlodipine, atorvastatin or rosuvastatin). Note that a patient will be able to participate in the intervention group and the control group if a change in his/her anti-HIV treatment occurs (study partly parallel and partly in cross-over).

Amlodipine with Darunavir; Atorvastatin with Darunavir; Rosuvastatin with Darunavir

Eligibility Criteria

• Sex: all
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

HIV patients treated with the anti-HIV agents dolutegravir or darunavir, while simultaneously receiving cardiovascular agents, namely amlodipine, atorvastatin or rosuvastatin

You may qualify if:

• documented HIV-infection
• informed consent as documented by signature (Appendix Informed Consent Form)
• included in the SHCS and followed-up in the HIV Clinic in Lausanne or in Basel
• treatment with a HIV therapy including either once-daily ritonavir-boosted darunavir or dolutegravir (or others ARV drugs for the exploratory investigations)
• treatment with one or eventually 2 of the comedications of interest, i.e. amlodipine, atorvastatin or rosuvastatin (or any drug potentially involved in clinically relevant DDI for the exploratory investigations).
• Ability to comply with the study requirements

You may not qualify if:

• Presence of severe comorbidities (i.e. cirrhosis (Child-Pugh score C), heart failure (NYHA 3-4), advanced kidney impairment (KDOQI 4-5)) which can substantially impact the pharmacokinetic of drugs and significantly confound the study results.
• Presence of interacting non HIV comedications (i.e comedications with known, strong inhibitory or inducing effects on drug metabolizing cytochromes and drug transporters, which might significantly confound the study results)
• Participants incapable of jugement or participants under tutelage
• Known or suspected non-compliance, drug or alcohol abuse considered at risk to significantly confound the study results
• Inability to follow the procedures of the study, e.g. due to language problems, psychological disorders, dementia of the participant,
• Enrolment of the investigator, his/her family members, employees and other dependent persons.
• Women who are pregnant or breastfeeding

Sponsors & Collaborators

• Centre Hospitalier Universitaire Vaudois: lead

Study Sites (2)

Universitätsspital Basel

Basel, 4031, Switzerland

Location

Centre Hospitalier Universitaire Vaudois (CHUV)

Lausanne, 1011, Switzerland

Location

Related Publications (1)

• Courlet P, Guidi M, Alves Saldanha S, Stader F, Traytel A, Cavassini M, Stoeckle M, Buclin T, Marzolini C, Decosterd LA, Csajka C; and the Swiss HIV Cohort Study. Pharmacokinetic/Pharmacodynamic Modelling to Describe the Cholesterol Lowering Effect of Rosuvastatin in People Living with HIV. Clin Pharmacokinet. 2021 Mar;60(3):379-390. doi: 10.1007/s40262-020-00946-3. Epub 2020 Oct 29.

  PMID: 33124006 DERIVED

Related Links

• Website of the Service of Clinical Pharmacology at CHUV, Lausanne

Biospecimen

Retention: SAMPLES WITHOUT DNA

Plasma samples

MeSH Terms

Conditions

HIV Infections; Cardiovascular Diseases

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Study Officials

• Thierry Buclin, Prof.

  Service of Clinical Pharmacology

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor Dr

Study Record Dates

• First Submitted: April 23, 2018
• First Posted: May 4, 2018
• Study Start: April 23, 2018
• Primary Completion: August 29, 2019
• Study Completion: August 29, 2019
• Last Updated: July 28, 2020

Record last verified: 2020-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF
• Time Frame: after end of study and publication
• Access Criteria: Motivated request

Locations

CH (2)