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Local Tolerability and Pharmacokinetic Evaluation of Cyclops Dry Powder Hydroxychloroquine Inhalation in Healthy Volunteers

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ClinicalTrials.gov Identifier: NCT04497519
Recruitment Status : Completed
First Posted : August 4, 2020
Last Update Posted : November 10, 2020
Sponsor:
Information provided by (Responsible Party):
Onno Akkerman, University Medical Center Groningen

Brief Summary:

Rationale:

This protocol describes a study on the local tolerability of dry powder hydroxychloroquine using the Cyclops in healthy volunteers.

Objective:

  • Primary objective is to assess the local tolerability of dry powder hydroxychloroquine sulphate via the Cyclops at different dosages.
  • Secondary objective is to investigate systemic pharmacokinetic parameters of dry powder hydroxychloroquine sulphate via the Cyclops at different dosages.

Study design: single center, ascending dose study Study population: twelve healthy volunteers

Main study parameters/endpoints:

The local tolerability of the inhalation of dry powder hydroxychloroquine sulphate (5, 10 and 20 mg) defined by a lung function deterioration (a drop of forced expiratory volume in 1 second (FEV1) of >15%), cough, or any other reported adverse event. Pharmacokinetic parameters will be derived from calculated actual inhaled dose (dose minus remainder in inhaler after inhalation) and in blood samples drawn pre-dose, at 0.5 and 2 and 3.5 hrs after inhalation. The inspiratory parameters during the inhalation maneuver are critical to explore predictors for drug exposure. The following parameters will be measured/calculated: dPmax (maximum pressure drop), Vi (inhaled volume), Ti (total inhalation time), PIF (peak inspiratory flow rate), MIF (mean inspiratory flow rate) and the FIR (average flow increase rate between 20% and 80% of PIF).

Nature and extent of the burden and risks associated with participation, benefit and group relatedness: The participants included are healthy volunteers. They will receive three different doses of hydroxychloroquine sulphate using the dry powder inhaler (DPI) with (at least) seven days in between doses. Before using the dry powder inhaler (DPI), they will receive instructions and their inspiratory flow will be tested. To investigate local tolerability, lung function tests will be performed, and the occurrence of adverse events will be scored. Furthermore, before each test dose an indwelling cannula will be inserted and blood samples will be taken before and after each test dose. Four blood samples will be collected with each inhaled dose. Finally, five ECGs will be obtained to monitor for QT prolongation, one at the screenings visit, one at base-line and one after each inhalation.


Condition or disease Intervention/treatment Phase
Covid19 Drug: inhaled hydroxychloroquine Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 12 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description: Healthy volunteers
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Local Tolerability and Pharmacokinetic Evaluation of Cyclops Dry Powder Hydroxychloroquine Inhalation in Healthy Volunteers; a Pilot Study
Actual Study Start Date : September 15, 2020
Actual Primary Completion Date : October 15, 2020
Actual Study Completion Date : November 1, 2020

Resource links provided by the National Library of Medicine



Intervention Details:
  • Drug: inhaled hydroxychloroquine
    ascending dose of iHCQ


Primary Outcome Measures :
  1. Local tolerability [ Time Frame: 35 minutes after inhalation ]
    Number of patients with a lung function deterioration (a drop of forced expiratory volume in 1 second (FEV1) of >15%.

  2. Local tolerability [ Time Frame: 95 minutes after inhalation ]
    Number of patients with a lung function deterioration (a drop of forced expiratory volume in 1 second (FEV1) of >15%.

  3. Local tolerability [ Time Frame: 5 hours ]
    Number of patients that report cough, or any other adverse event after inhalation.


Secondary Outcome Measures :
  1. Pharmacokinetic parameter [ Time Frame: 0,5 hour ]
    Calculated actual inhaled dose

  2. Pharmacokinetic parameter [ Time Frame: 3,5 hours ]
    Cmax

  3. Pharmacokinetic parameter [ Time Frame: 3,5 hours ]
    Tmax



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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Healthy volunteer
  • Age 18-65 years
  • Obtained written informed consent

Exclusion Criteria:

  1. Pregnancy or breastfeeding. Women in the fertility period and without using proper contraceptives will undergo a urine pregnancy test.
  2. Contra-indication to (hydroxy)chloroquine or quinine (allergic reaction, prolonged QTc-interval (> 450 msec), long-QT syndrome (LQTS), retinopathy, epilepsia, myasthenia gravis, G6PD-deficiency).
  3. Concurrent use of ciclosporin, digoxin, ritonavir, tamoxifen or tranylcypromine.
  4. Concurrent use of high risk QTc prolongating drugs (amiodarone, erythromycin (daily dose > 1000 mg) or sotalol)16.
  5. COVID-19 like symptoms, such as fever, couch, or sore throat; only by history taking.

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): NCT04497519


Locations
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Netherlands
University Medical Center Groningen
Groningen, Netherlands
Sponsors and Collaborators
University Medical Center Groningen
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Responsible Party: Onno Akkerman, Principal Investigator, University Medical Center Groningen
ClinicalTrials.gov Identifier: NCT04497519    
Other Study ID Numbers: CARRIED-01
First Posted: August 4, 2020    Key Record Dates
Last Update Posted: November 10, 2020
Last Verified: November 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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COVID-19
Respiratory Aspiration
Respiratory Tract Infections
Infections
Pneumonia, Viral
Pneumonia
Virus Diseases
Coronavirus Infections
Coronaviridae Infections
Nidovirales Infections
RNA Virus Infections
Lung Diseases
Respiratory Tract Diseases
Respiration Disorders
Pathologic Processes
Hydroxychloroquine
Antimalarials
Antiprotozoal Agents
Antiparasitic Agents
Anti-Infective Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antirheumatic Agents