scholarly journals An open-label, randomized, single intravenous dosing study to investigate the effect of fixed-dose combinations of tenofovir/lamivudine or atazanavir/ritonavir on the pharmacokinetics of remdesivir in Ugandan healthy volunteers (RemTLAR)

Trials ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Stephen I. Walimbwa ◽  
Julian P. Kaboggoza ◽  
Catriona Waitt ◽  
Pauline Byakika-Kibwika ◽  
Antonio D’Avolio ◽  
...  
Keyword(s):  
Antiretroviral Therapy ◽  
Healthy Volunteers ◽  
Emerging Infectious Diseases ◽  
Crossover Design ◽  
Fixed Dose ◽  
Open Label ◽  
Fixed Sequence ◽  
Treatment Regimens ◽  
Link Type ◽  
Drug Concentrations

Abstract Background Remdesivir is a novel broad-spectrum antiviral therapeutic with activity against several viruses that cause emerging infectious diseases. The purpose of this study is to explore how commonly utilized antiretroviral therapy (tenofovir disoproxil fumarate/lamivudine [TDF/3TC] and atazanavir/ritonavir [ATV/r]) influence plasma and intracellular concentrations of remdesivir. Methods This is an open-label, randomized, fixed sequence single intravenous dosing study to assess pharmacokinetic interactions between remdesivir and TDF/3TC (Study A, crossover design) or TDF/3TC plus ATV/r (Study B). Healthy volunteers satisfying study entry criteria will be enrolled in the study and randomized to either Study A; N=16 (Sequence 1 or Sequence 2) or Study B; N=8. Participants will receive standard adult doses of antiretroviral therapy for 7 days and a single 200mg remdesivir infusion administered over 60 min. Pharmacokinetic blood sampling will be performed relative to the start of remdesivir infusion; predose (before the start of remdesivir infusion) and 30 min after the start of remdesivir infusion. Additional blood samples will be taken at 2, 4, 6, 12, and 24 h after the end of remdesivir infusion. Discussion This study will characterize the pharmacokinetics of remdesivir from a typical African population in whom clinical use is anticipated. Furthermore, this study will deliver pharmacokinetic datasets for remdesivir drug concentrations and demographic characteristics which could support pharmacometric approaches for simulation of remdesivir treatment regimens in patients concurrently using tenofovir/lamivudine and/or atazanavir/ritonavir. Trial registration ClinicalTrials.gov NCT04385719. Registered 13 May 2020.

scholarly journals An open-label, randomized, single intravenous dosing study to investigate the effect of fixed dose combinations of tenofovir/lamivudine or atazanavir/ritonavir on the pharmacokinetics of remdesivir in Ugandan healthy volunteers (RemTLAR)

2021 ◽  
Author(s):  
Stephen Ian Walimbwa ◽  
Julian Paul Kaboggoza ◽  
Catriona Waitt ◽  
Pauline Byakika-Kibwika ◽  
Antonio D'Avolio ◽  
...  
Keyword(s):  
Antiretroviral Therapy ◽  
Healthy Volunteers ◽  
Emerging Infectious Diseases ◽  
Crossover Design ◽  
Fixed Dose ◽  
Open Label ◽  
Fixed Sequence ◽  
Blood Samples ◽  
Treatment Regimens ◽  
Drug Concentrations

Abstract Background: Remdesivir is a novel broad-spectrum antiviral therapeutic with activity against several viruses that cause emerging infectious diseases. The purpose of this study is to explore how commonly utilized antiretroviral therapy (tenofovir disoproxil fumarate /lamivudine [TDF/3TC] and atazanavir/ritonavir [ATV/r]) influence plasma and intracellular concentrations of remdesivir. Methods: This is an open label, randomized, fixed sequence single intravenous dosing study to assess pharmacokinetic interactions between remdesivir and TDF/3TC (Study A, Crossover design) or TDF/3TC plus ATV/r (Study B). Healthy volunteers satisfying study entry criteria will be enrolled in the study and randomized to either Study A; N=16 (Sequence 1 or Sequence 2) or Study B; N=8. Participants will receive standard adult doses of antiretroviral therapy for seven days and a single 200mg remdesivir infusion administered over 60 minutes. Pharmacokinetic blood sampling will be performed relative to start of remdesivir infusion; predose (before start of remdesivir infusion) and 30 minutes after start of remdesivir infusion. Additional blood samples will be taken at 2, 4, 6, 12 and 24 hours after end of remdesivir infusion. Discussion: This study will characterize the pharmacokinetics of remdesivir from a typical African population in whom clinical use is anticipated. Furthermore, this study will deliver pharmacokinetic datasets for remdesivir drug concentrations and demographic characteristics which could support pharmacometric approaches for simulation of remdesivir treatment regimens in patients concurrently using tenofovir/lamivudine and/or atazanavir/ritonavir. Trial registration: ClinicalTrials.gov, ID:NCT04385719

Effect of Steady-State Faldaprevir on Pharmacokinetics of Atorvastatin or Rosuvastatin in Healthy Volunteers: A Prospective Open-Label, Fixed-Sequence Crossover Study

2017 ◽  
Vol 57 (10) ◽  
pp. 1305-1314 ◽  
Author(s):  
Fenglei Huang ◽  
Kristell Marzin ◽  
Rüdiger Koenen ◽  
Klaus Peter Kammerer ◽  
Natalja Strelkowa ◽  
...  
Keyword(s):  
Steady State ◽  
Crossover Study ◽  
Healthy Volunteers ◽  
Open Label ◽  
Fixed Sequence

scholarly journals Pharmacokinetics of Single-Dose and Multi-Dose of Lovastatin/Niacin ER Tablet in Healthy Volunteers

2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
Yan-yan Jia ◽  
Song Ying ◽  
Chen-tao Lu ◽  
Jing Yang ◽  
Li-kun Ding ◽  
...  
Keyword(s):  
Drug Interaction ◽  
Healthy Volunteers ◽  
Least Square ◽  
Fixed Dose ◽  
Pharmacokinetic Parameters ◽  
Open Label ◽  
Mixed Dyslipidemia ◽  
Dose Oral ◽  
Dose Combination ◽  
Healthy Chinese

An extended-release (ER) niacin and lovastatin fixed-dose combination has been developed for the treatment of primary hypercholesterolemia and mixed dyslipidemia. The purpose of the present study was to examine the drug interaction between niacin and lovastatin after multi-dose oral administration of lovastatin/niacin ER combination in healthy Chinese volunteers. A single-center, randomized, open-label, 5-period crossover study was conducted in thirty healthy volunteers aged 18 to 45 years with a washout period of 8 days. Subjects were randomized to receive multiple doses of treatment A (1 500 mg niacin ER tablet), B (1 20 mg lovastatin tablet), C (1 20 mg lovastatin and 500 mg niacin-ER tablet), D (2 10 mg lovastatin and 350 mg niacin-ER tablets) or E (2 10 mg lovastatin and 500 mg niacin-ER tablets) in 1 of 5 sequences (ABCDE, BCDEA, CDEAB, DEABC, EABCD) per period. Lovastatin, niacin and its metabolites (nicotinuric acid and nicotinamide) were determined in plasma by LC/MS method. Pharmacokinetic parameters were calculated, and least square mean ratios and 90% confidence intervals for Cmax⁡ and AUC (0–24) were determined for lovastatin/niacin ER versus niacin ER or lovastatin. It revealed that the formulation had no potential drug interaction in healthy Chinese volunteers when the dosage was increased from 500 mg to 1000 mg.

scholarly journals Novel combined single dose anti-hepatitis C therapy: a pilot study

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Gamal Shiha ◽  
Reham Soliman ◽  
Mohamed Elbasiony ◽  
Noureldien H. E. Darwish ◽  
Shaker A. Mousa
Keyword(s):  
Viral Load ◽  
Hepatitis C ◽  
Virologic Response ◽  
Fixed Dose ◽  
The Novel ◽  
Open Label ◽  
Genotype 4 ◽  
Treatment Regimens ◽  
Treatment Naïve ◽  
To Receive

AbstractThe new anti-hepatitis C virus (HCV) molecules improve treatment regimens and outcomes, but there are drawbacks. New combinations should target the HCV infectious cycle and be effective against all HCV genotypes. We developed the novel formulation Catvira, composed of epigallocatechingallate (EGCG) + sofosbuvir + ribavirin. Here, we compared Catvira to sofosbuvir + ribavirin tablets in patients with CHC genotype 4 in a randomized open-label efficacy and safety study. Treatment-naïve and treatment-experienced patients (n = 80) were randomly assigned to receive a single daily fixed dose of Catvira or sofosbuvir + ribavirin for 12 or 24 weeks. Both Catvira and sofosbuvir + ribavirin yielded similar outcomes of viral load (p < 0.001). Patients receiving Catvira had a significantly more rapid rate of viral load decline with sustained virologic response (SVR12) achieved by 90% of patients receiving 12 weeks of treatment. Catvira did not impact hemoglobin levels while sofosbuvir + ribavirin showed significant decline in hemoglobin levels after 24 weeks (p < 0.05). In this clinical trial (ClinicalTrials.gov Identifier NCT02483156), we found that Catvira administered daily for 12 or 24 weeks is safe, effective, and well-tolerated in both naïve and treatment-experienced patients with HCV genotype 4.

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