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

Local Tolerability and Pharmacokinetic Evaluation of Cyclops Dry Powder Hydroxychloroquine Inhalation in Healthy Volunteers; a Pilot Study

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.

Study Overview

• Status: Completed
• Conditions: Covid19
• Intervention / Treatment: Drug: inhaled hydroxychloroquine

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 1

Contacts and Locations

Study Locations

• Netherlands
  • Groningen, Netherlands
    • University Medical Center Groningen

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Local tolerability	Number of patients with a lung function deterioration (a drop of forced expiratory volume in 1 second (FEV1) of >15%.	35 minutes after inhalation
Local tolerability	Number of patients with a lung function deterioration (a drop of forced expiratory volume in 1 second (FEV1) of >15%.	95 minutes after inhalation
Local tolerability	Number of patients that report cough, or any other adverse event after inhalation.	5 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetic parameter	Calculated actual inhaled dose	0,5 hour
Pharmacokinetic parameter	Cmax	3,5 hours
Pharmacokinetic parameter	Tmax	3,5 hours

Collaborators and Investigators

• Sponsor: University Medical Center Groningen

Study record dates

Study Major Dates

• Study Start (Actual): September 15, 2020
• Primary Completion (Actual): October 15, 2020
• Study Completion (Actual): November 1, 2020

Study Registration Dates

• First Submitted: July 27, 2020
• First Submitted That Met QC Criteria: July 31, 2020
• First Posted (Actual): August 4, 2020

Study Record Updates

• Last Update Posted (Actual): November 10, 2020
• Last Update Submitted That Met QC Criteria: November 9, 2020
• Last Verified: November 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Respiration Disorders; Respiratory Aspiration; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antirheumatic Agents; Antiprotozoal Agents; Antiparasitic Agents; Antimalarials; Hydroxychloroquine
• Other Study ID Numbers: CARRIED-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No