Clinical Research Directory

A Study to Learn About the Effect of Study Medicine Called PF-08653944 on How Quickly the Stomach Empties Its Content in Healthy Adults With Overweight or Obesity

This study looks at how a study medicine called PF-08653944 affects how quickly the stomach empties food after eating. It is being done in adults who are overweight or have obesity. Participants will receive the study medicine for a short period, and doctors will measure how the medicine moves through the stomach and monitor safety. The goal is to better understand how this medicine works in the body and to check for any side effects. The information from this study may help researchers plan future studies of this medicine.

Pharmacogenomic Association Study in Indian Children With Acute Lymphoblastic Leukemia

A five-year prospective observational cohort study. The study is focused on observing the relation between static germline variants and therapeutic response in Indian children with acute lymphoblastic leukemia (ALL). The project is an International multicenter setup. This collaborative research project between Switzerland and India includes one main center in Geneva that has conceptualized, designed, received grants for the study and two investigating centers in India (Puducherry and New-Delhi) involved in study design, patient care and recruitment for this specific study. All the participants for the study will be recruited form these two centers in India, and no patient recruitment is planned at main center i.e. Geneva. The study will be conducted in two phases. The first aims to investigate genetic predisposition (static germline variants) to early chemotherapy treatment related toxicities (TRTs). The second aims to investigate somatic genetic markers associated with the efficacy of steroid treatment among patients undergoing the standardized IciCLe-ALL-14 treatment protocol. A total of 500 children with ALL will be recruited to investigate primary objective of the study i.e. TRT, and a subset of 250 patients will be included to investigate another research question i.e. response to steroid therapy.

Pharmacogenomic and Circulating Biomarkers for CDK4/6 Inhibitors

The goal of this research study is to reduce adverse effects of anti-cancer medications known as kinase inhibitors, while preserving their therapeutic benefits. There have been major advances in the way cancers are treated. A class of drugs known as kinase inhibitors have proven to be highly effective for the treatment of cancers, including lung, kidney, gastrointestinal, and breast cancers. However, kinase inhibitor medications are well known for having unpredictable side effects. The body breaks down (metabolizes) medications such as kinase inhibitors using an enzyme known as cytochrome P450 3A4 (CYP3A4). CYP3A4 is the most important drug metabolizing enzyme in humans due to the fact that it is involved in the metabolism of nearly half of all prescribed medications and almost all of the currently prescribed kinase inhibitors. Among patients, there can be nearly 400 times difference in how efficiently CYP3A4 metabolizes drugs. Remarkably, very little is known about the role of genetic differences in CYP3A4 and a gene known as pregnane X receptor (PXR). PXR serves as a sensor for drugs in the body and helps to regulate how much CYP3A4 is made. Currently, there are no predictive biomarkers, whether in genes (genomic) or circulating in blood (endogenous) that could aid treating oncologists with regards predicting adverse effects or suboptimal response to this important class of anticancer drugs. The goal is to carry out DNA sequencing for genetic changes in CYP3A4 and PXR to assess differences in enzyme activity of not only common, but also rare genetic variants. CYP3A4 activity will be determined in participants blood samples based on break down products of the drug tamoxifen as well as cholesterol, the latter called 4β-hydroxycholesterol, both known to be influenced by the CYP3A4 enzyme. Since cholesterol is naturally made in the body, comparing blood cholesterol to 4β-hydroxycholesterol levels will be a biomarker of CYP3A4 metabolic activity that can be measured in anyone. Furthermore, circulating CYP3A4 messenger RNA from human blood will be measured as another independent marker of CYP3A4 gene expression. A model will be generated that includes these biomarkers of CYP3A4 expression and function, as well as genetic variation in CYP3A4 and PXR, that will aid in better identifying which patients may be at risk for loss of benefit or toxicity from kinase inhibitor therapy. This model will be evaluated in 100 breast cancer patients undergoing chemotherapy with kinase inhibitors, namely cyclin-dependent kinases CDK4 and CDK6 inhibitor (abemaciclib, ribociclib or palbociclib), as such kinase inhibitors are widely prescribed for breast cancer and are known to be broken down by CYP3A4.

Variation in Drug Interactions in People With HIV (PLWH) Aged 60 Years and Older.

Several cohort studies have recently shown a significant increase in the mean age of PLWH ( People Living With HIV) and in the prevalence of people in advanced age in the various cohorts, as a result of the marked increase in the mean life expectancy of these people achieved by modern antiretroviral combination therapies. However, the high prevalence of comorbidities exposes PLWH in old age to the need to take multiple drug treatments in addition to antiretroviral therapy, with the gradually increasing risk of unfavorable pharmacokinetic interactions between antiretroviral drugs and drugs taken to treat the comorbidities. This project consists of an observational, cohort, retrospective, single-center study and aims to evaluate the variation in the number and type of clinically significant drug interactions between antiretroviral therapy and concomitant therapies in PLWH aged \>60 years on stable antiretroviral therapy who, for any reason at the Clinician's discretion, have made a switch from ongoing antiretroviral therapy to the bictegravir/emtricitabine/tenofovir alafenamide regimen.

Assessment of Drug-drug Interactions Between Feminizing Hormone Therapy and Emtricitabine/Tenofovir Alafenamide Concomitantly for Pre-exposure Prophylaxis Among Transgender Women

Recent studies have showed that there were significant drug-drug interactions (DDI) from feminizing hormone therapy (FHT) towards emtricitabine/tenofovir disoproxil fumarate (F/TDF)-based pre-exposure prophylaxis (PrEP) among transgender women (TGW). New strategies for PrEP among TGW who use FHT are urgently needed. Because tenofovir alafenamide (TAF) can achieve higher intracellular TFV-DP levels with lower tenofovir plasma concentrations, it is promising that both plasma TFV and intracellular TFV-DP levels might not be significantly affected by FHT. The current study aims to determine the pharmacokinetics DDI between FHT and F/TAF-based PrEP among TGW.

Assessment of Drug-drug Interactions Between Masculinizing Hormone Therapy and Antiretroviral Agents Concomitantly for Pre-exposure Prophylaxis Among Transgender Men

There are currently no published studies addressing drug-drug interactions (DDI) between masculinizing hormone therapy (MHT) and pre-exposure prophylaxis (PrEP) among transgender men (TGM). This could lead to concerns and subsequent prioritizing MHT over PrEP among TGM. Because tenofovir alafenamide (TAF) can achieve higher intracellular tenofovir diphosphate (TFV-DP) levels with lower tenofovir plasma concentrations, it is promising that both plasma tenofovir (TFV) and intracellular TFV-DP levels might not be significantly affected by MHT. The current study aims to determine the pharmacokinetics (PK) DDI between MHT and daily PrEP among TGM.