Trial document




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  DRKS00021573

Trial Description

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Title

Impact of pantoprazole on absorption and disposition of hydroxychloroquine, a drug used in Covid-19

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Trial Acronym

K724_HCQ-PPI

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URL of the Trial

[---]*

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Brief Summary in Lay Language

In this study, we will evaluate the effect of pantoprazole (a proton-pump inhibitor) on hydroxychloroquine absorption (uptake into the body after oral ingestion) in healthy volunteers. Proton-pump inhibitors reduce stomach acid production and are used in heartburn due to acid reflux and in other indications. Hydroxychloroquine is used for malaria and in other indications and is currently evaluated as a potential treatment of patients with coronavirus disease COVID-19.

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Brief Summary in Scientific Language

Concomitant administration of proton-pump inhibitors (PPI) such as pantoprazole can affect the absorption of other drugs. Whether PPI affect the absorption of hydroxychloroquine, which may have therapeutic potential in patients with COVID-19, is currently unknown. In this single-dose, parallel-group pharmacokinetic trial we will evaluate the effect of pantoprazole on hydroxychloroquine in healthy volunteers.

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Do you plan to share individual participant data with other researchers?

Yes

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Description IPD sharing plan:

Data can be provided by reasonable request at principle investigator

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Organizational Data

  •   DRKS00021573
  •   2020/04/27
  •   [---]*
  •   yes
  •   Approved
  •   AFmo-265/2020, Ethik-Kommission I der Medizinischen Fakultät Heidelberg
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Secondary IDs

  •   2020-001470-30 
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Health Condition or Problem studied

  •   healthy volunteers
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Interventions/Observational Groups

  •   PPI-Arm: Treatment with pantoprazole in addition to the trial medication hydoxychloroquine, midazolam and yohimbine
  •   Control-Arm: no pantoprazole in addition to the trial medication
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Characteristics

  •   Interventional
  •   [---]*
  •   Randomized controlled trial
  •   Open (masking not used)
  •   [---]*
  •   Other
  •   Other
  •   Parallel
  •   I
  •   N/A
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Primary Outcome

Evaluation of the effect of the proton-pump Inhibitor (PPI) pantoprazole on the absorption of HCQ in healthy volunteers

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Secondary Outcome

Comparison of HCQ concentrations in whole blood as compared to plasma and intracellular concentration in PBMCs and evaluation of HCQ as a perpetrator drug in DDI at the Level of cytochrome P450 CYP3A and CYP2D6

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Countries of Recruitment

  •   Germany
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Locations of Recruitment

  • University Medical Center 
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Recruitment

  •   Actual
  •   2020/04/30
  •   24
  •   Monocenter trial
  •   National
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Inclusion Criteria

  •   Both, male and female
  •   18   Years
  •   60   Years
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Additional Inclusion Criteria

1. Age 18-60 y inclusive at the time of consent,

2. Males and females of child-bearing potential who are willing to use a highly effective method of contraception during the treatment and for 3 months after last administration of the IMP or women not of child-bearing potential (WNCBP) or individuals who are convincingly sexually abstinent.

3. Understanding, ability, and willingness to fully comply with trial interventions and restrictions,

4. Willingness to participate in a genotyping study (K093), and

5. Ability to provide written, personally signed and dated informed consent to participate in the trial, in accordance with the International Conference on Harmonisation (ICH) Good Clinical Practice (GCP) Guideline E6, and applicable regulations, prior to any trial-related interventions.

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Exclusion Criteria

1. Clinically significant or relevant abnormalities in the medical history, physical examination, and laboratory evaluation as assessed by the investigator,

2. Any medical disorder that may require treatment or make the participant unlikely to fully complete the trial, or any condition that presents undue risk from the IMPs or trial interventions,

3. Clinically relevant ongoing or clinically relevant history of physical or psychiatric illness as judged by the investigator,

4. Pregnancy or breast feeding,

5. Any acute or chronic illness or clinically relevant finding known or expected to modify absorption, distribution, metabolism, or excretion of HCQ, midazolam, yohimbine, or pantoprazole,

6. Any known history of severe allergic or anaphylactic reactions to drugs or food or any other clinically significant allergies (except mild forms of hay fever),

7. Any known allergies to the compound or further ingredients of HCQ, quinine, pantoprazole, midazolam, or yohimbine preparations,
8. Prolonged QTc time: women: QTcF > 460 ms, men: QTcF > 440 MS

9. Clinically relevant findings at SCR. Minor deviations of laboratory values from the normal range can be acceptable, if judged by the investigator to be of no clinical relevance for this Trial

10. A positive human immunodeficiency virus and hepatitis C antibody screen,

11. A positive result in the drug screening test

12. Any intake of HCQ, chloroquine or travel to malaria risk regions within the last 3 months,

13. Use of any medication (prescription medication, non-prescription medication including multivitamin or herbal preparations) with active ingredients except hormonal contraception and thyroid hormones, or any intake of substances known to induce or inhibit HCQ-metabolizing enzymes or drug transporters within a period of less than 5 times the respective elimination half-life (t1/2) with regard to the expected date of the first dose of IMP,

14. Consumption of citrus fruits or products of these fruits within 7 d prior to the expected date of first dose of IMP and expected nonadherence to refrain from such products until V5,

15. Expected nonadherence to refrain from alcohol 24 h prior to V1 until V5 of this trial, or excessive alcohol consumption.

16. Intake of quinine, or consumption of quinine-containing drinks (bitter lemon, tonic water, bitter orange)

17. Use of an IMP within 30 d prior to the expected date of receiving the first dose of IMP or active enrolment in another drug or vaccine clinical trial.

18. Contraindications to HCQ use

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Addresses

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Sources of Monetary or Material Support

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Status

  •   Recruiting complete, follow-up complete
  •   2020/07/23
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Trial Publications, Results and other Documents

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* This entry means the parameter is not applicable or has not been set.