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Trial record 2 of 35 for:    remdesivir

Drug-drug Interactions Between Remdesivir and Commonly Used Antiretroviral Therapy (RemTLAR)

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ClinicalTrials.gov Identifier: NCT04385719
Recruitment Status : Not yet recruiting
First Posted : May 13, 2020
Last Update Posted : May 13, 2020
Sponsor:
Collaborators:
University of Liverpool
EDCTP
Information provided by (Responsible Party):
Makerere University

Brief Summary:
Ebola and HIV are found predominately in the same regions of the world and countries in sub-Saharan Africa are most affected by both diseases. For Ebola, no approved therapies exist. However, new investigational drugs are being evaluated to understand if they are effective against the Ebola virus. Remdesivir is an anti-Ebola investigational drug for the treatment of Ebola. Little is known about how the blood levels of remdesivir relate to how effective it is in patients with HIV taking antiretroviral therapy. This study will explore how commonly utilized ART (tenofovir/lamivudine and atazanavir/ritonavir) affect the drug levels of remdesivir.

Condition or disease Intervention/treatment Phase
Ebola HIV/AIDS Drug: Remdesivir Phase 2

Detailed Description:

The study is designed as an open-label, randomized, fixed sequence, single intravenous dosing study to assess the effects of antiretrovirals on remdesivir pharmacokinetics.

The selection of healthy volunteers, as opposed to patients with HIV, avoids the greatest possible extent confounding factors, such as enzyme or transporter activity alteration in inflammatory states, concomitant medications potentially impacting drug disposition and other factors which are commonly present in a population of patients and cannot be easily eliminated.

Objectives:

Primary objective

  1. To assess the safety and tolerability of single intravenous doses of remdesivir in adult healthy volunteers
  2. To evaluate the intracellular pharmacokinetics of single dose intravenous remdesivir with or without co-administration of oral fixed-dose combination tenofovir/lamivudine with patients serving as their own controls

Secondary objectives

  1. To evaluate the difference in plasma and intracellular pharmacokinetics of intravenous remdesivir among healthy volunteers receiving tenofovir/lamivudine versus healthy volunteers receiving tenofovir/lamivudine plus atazanavir/ritonavir tablets.
  2. To generate a population pharmacokinetic model to describe inter-individual variability in intracellular pharmacokinetics of remdesivir

Exploratory objectives

1. To describe polymorphic variants of relevant kinases that activate TFV and explore possible consequences on remdesivir PK.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 24 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: 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
Estimated Study Start Date : July 2020
Estimated Primary Completion Date : April 2021
Estimated Study Completion Date : June 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Ebola HIV/AIDS

Arm Intervention/treatment
Experimental: Study A Sequence 1

Single dose remdesivir 150mg IV on Day 1

Wash out period Day 2-7

TDF/3TC 300/300mg tablets OD from Day 8-14 single dose remdesivir 150mg IV on Day 14

Drug: Remdesivir
Remdesivir (GS-5734) is a nucleoside analogue with in vitro activity against filoviruses EBOV, SUDV, BDBV and MARV, in addition to arenaviruses and coronaviruses
Other Name: GS-5734

Experimental: Study A Sequence 2

TDF/3TC 300/300mg tablets OD from Day 1-7 single dose remdesivir 150mg IV on Day 7

Wash out period Day 8-14

Single dose remdesivir 150mg IV on Day 15

Drug: Remdesivir
Remdesivir (GS-5734) is a nucleoside analogue with in vitro activity against filoviruses EBOV, SUDV, BDBV and MARV, in addition to arenaviruses and coronaviruses
Other Name: GS-5734

Experimental: Study B
TDF/3TC/ATV/r 300/300/300/100mg tablets OD from Day 1-7 single dose remdesivir 150mg IV infusion on Day 7
Drug: Remdesivir
Remdesivir (GS-5734) is a nucleoside analogue with in vitro activity against filoviruses EBOV, SUDV, BDBV and MARV, in addition to arenaviruses and coronaviruses
Other Name: GS-5734




Primary Outcome Measures :
  1. Number of adverse events categorised by body system [ Time Frame: 30 days ]
    The number of adverse events will be tabulated by body system. All safety parameters will be listed by cohort, subject and visit/time and summarized by treatment and visit/time. No formal statistical hypotheses of the safety or tolerability are to be tested.

  2. Percentage of participants with adverse events categorised by body system [ Time Frame: 30 days ]
    The incidence of adverse events will be tabulated by body system. All safety parameters will be listed by cohort, subject and visit/time and summarized by treatment and visit/time. No formal statistical hypotheses of the safety or tolerability are to be tested.

  3. Peak Concentration (CMax) of remdesivir in peripheral blood mononuclear cells (PBMCs) and Plasma [ Time Frame: last measurable time-point (24 hours) ]
    maximum plasma and intracellular concentration [Cmax] of remdesivir with or without co-administration of antiretroviral drugs.

  4. Time to maximum concentration (TMax) of remdesivir in peripheral blood mononuclear cells (PBMCs) and Plasma [ Time Frame: last measurable time-point (24 hours) ]
    Time to maximum concentration of remdesivir in plasma and PBMCs with or without co-administration of antiretroviral therapy

  5. Terminal elimination half-life of remdesivir in plasma and PBMCs [ Time Frame: 24 hours ]
    terminal elimination half life of remdesivir in peripheral blood mononuclear cells (PBMCs) and Plasma with or without co-administration of antiretroviral therapy.

  6. Area under concentration-time curve (AUC) of remdesivir [ Time Frame: last measurable time-point (24 hours) ]
    Area under concentration-time curve of remdesivir in peripheral blood mononuclear cells (PBMCs) and Plasma with or without co-administration of antiretroviral therapy.


Secondary Outcome Measures :
  1. Geometric mean ratio and 90% confidence intervals of remdesivir CMax with and without antiretroviral therapy. [ Time Frame: 24 hours ]
    CMax of remdesivir in plasma and PBMCS will be compared with and without antiretroviral therapy.

  2. Geometric mean ratio and 90% confidence intervals of remdesivir TMax with and without antiretroviral therapy. [ Time Frame: 24 hours ]
    TMax of remdesivir in plasma and PBMCS will be compared with and without antiretroviral therapy.

  3. Geometric mean ratio and 90% confidence intervals of remdesivir terminal elimination half-life with and without antiretroviral therapy. [ Time Frame: 24 hours ]
    t 1/2 of remdesivir in plasma and PBMCS will be compared with and without antiretroviral therapy.

  4. Geometric mean ratio and 90% confidence intervals of remdesivir area under concentration-time curve, with and without antiretroviral therapy. [ Time Frame: 24 hours ]
    AUC (0-t) of remdesivir in plasma and PBMCS will be compared with and without antiretroviral therapy. t is the last measurable time-point



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. Evidence of a personally signed and dated informed consent document indicating that the participant has been informed of all pertinent aspects of the study.
  2. Participants who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
  3. Healthy men and women aged 18 to 55 years of age, and in good health as determined by past medical history, physical examination, vital signs, electrocardiogram, and laboratory tests at screening.
  4. At screening, and all other visits, vital signs (systolic and diastolic blood pressure and pulse rate) will be assessed in the sitting position and again (when required) in the standing position. Sitting vital signs should be within the following ranges:

    I. axillary body temperature between 35.5-37.0 °C II. systolic blood pressure, 90-139 mmHg III. diastolic blood pressure, 50-89 mmHg IV. Pulse rate, 50-90 bpm. If pulse rate is between 40 and 50 bpm, the Investigator may decide to enroll the subject if he/she has history of athletic practice or other regular high cardio-vascular activity and ECG assessment is within normal range.

    Subjects should be excluded if their standing vital signs (relative to sitting) show findings which, in the opinion of the Investigator, are associated with clinical manifestation of postural hypotension (i.e. absence of any other cause). The Investigator should carefully consider enrolling subjects with either a > 20 mmHg decrease in systolic or a >10 mm Hg decrease in diastolic blood pressure, accompanied by a > 20 bpm increase in heart-rate (from sitting to standing).

  5. Subjects must weigh at least 40 kg to participate in the study and must have a body mass index (BMI) within the range 18-30 Kg/m2. BMI= Body weight (kg) / [Height (m)]2
  6. HIV antibody negative at screening.
  7. Women of childbearing potential must be willing to use a highly effective contraception method (eg. IUD or hormonal contraceptive implant, complete abstinence (if genuinely followed)) or consistent use of a barrier method such as male or female condoms plus oral progestin contraceptives for the duration of the study. Non-surgically sterilized men must agree to abstain from sexual intercourse for the duration of the study or use condoms for contraception for the duration of the study.
  8. Hemoglobin concentration equal or greater than 10 g/dL

Exclusion Criteria:

  1. Significant disease affecting cardiac, respiratory, gastrointestinal or neurological symptoms which in the clinician's medical judgment could be worsened by participating in this study or the presence of medical or surgical conditions which could prevent the subject from complying with study procedures.
  2. Serum alanine transaminase (ALT) levels above 2x upper limit of normal (ULN) or total bilirubin > 1.3x ULN
  3. Serum creatinine levels above 1.5x upper limit of normal
  4. Evidence of QT prolongation on electrocardiogram (ECG) QTc (Rate adjusted QT interval) > 450ms (men) or 460ms (women)
  5. Pregnant women or female subjects who are unwilling to use a suitable contraceptive method for the duration of the study (IUD or contraceptive implant)
  6. Likely to be poorly adherent based on clinician's medical judgement
  7. Known to be current injection drug user

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04385719


Contacts
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Contact: Stephen Ian Walimbwa, MD, MSc +256784413950 swalimbwa@idi.co.ug
Contact: Julian Paul Kibudde Kaboggoza, BPharm, MRes +256792178132 jkaboggoza@idi.co.ug

Locations
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Uganda
Infectious Diseases Institute
Kampala, Uganda
Contact: Stephen Okoboi    +256704817590    sokoboi@idi.co.ug   
Sponsors and Collaborators
Makerere University
University of Liverpool
EDCTP
Investigators
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Principal Investigator: Mohammed J Lamorde, PhD Infectious Diseases Institute, Uganda
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Responsible Party: Makerere University
ClinicalTrials.gov Identifier: NCT04385719    
Other Study ID Numbers: PK-24
First Posted: May 13, 2020    Key Record Dates
Last Update Posted: May 13, 2020
Last Verified: May 2020

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
Keywords provided by Makerere University:
Ebola
HIV
Pharmacokinetics
Remdesivir
Drug Interactions