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

NCT04497519 | Completed Phase 1 DMC

• 1 other identifier: CARRIED-01
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

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.

Conditions

Covid19

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (3)

• Pharmacokinetic parameter

  0,5 hour

• Pharmacokinetic parameter

  3,5 hours

• Pharmacokinetic parameter

  3,5 hours

Interventions

inhaled hydroxychloroquine DRUG

ascending dose of iHCQ

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

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

Sponsors & Collaborators

• University Medical Center Groningen: lead

Study Sites (1)

University Medical Center Groningen

Groningen, Netherlands

Location

MeSH Terms

Conditions

COVID-19

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: Healthy volunteers

Study Record Dates

• First Submitted: July 27, 2020
• First Posted: August 4, 2020
• Study Start: September 15, 2020
• Primary Completion: October 15, 2020
• Study Completion: November 1, 2020
• Last Updated: November 10, 2020

Record last verified: 2020-11

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1)