A Study to Investigate the Safety, Tolerability and Pharmacokinetics of Single and Repeat Doses of PC945

A Randomised, Single-blind, Placebo-controlled, Study to Assess the Safety and Tolerability of Single Escalating and Repeat, Inhaled Doses of PC945 in Healthy Subjects Combined With a Randomised, Single-blind, Placebo-controlled, Parallel Group to Assess the Safety and Tolerability of a Single Dose of Inhaled PC945 in Subjects With Mild Asthma

PC945 is a new medicine being developed for treatment of fungal lung diseases. The main purpose of this study is to investigate the safety, tolerability and pharmacokinetics of single and repeat doses of PC945

Study Overview

• Status: Completed
• Conditions: Aspergillosis
• Intervention / Treatment: Drug: PC945 - single doses; Drug: Placebo - single doses; Drug: PC945 - repeat doses; Drug: Placebo - repeat doses

• Study Type: Interventional
• Enrollment (Actual): 29
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • Middlesex
    • Harrow, Middlesex, United Kingdom, HA1 3UJ
      • Parexel Epcu

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:

All subjects (Cohorts 1, 2 & 3)

• Male or female, aged between 18 and 65 years inclusive (at the time of consent) who fit one of the following criteria: Women of childbearing potential who are willing and able to use required contraception from screening until 30 days after receipt of the final dose; Women of non-childbearing potential defined as being amenorrhoeic or have been permanently sterilised; Men who are willing and able to use required contraception from the time of the first dose, until 90 days after receipt of the final dose of study medication.
• Females with a negative pregnancy test at screening and at Day -1.
• Willing and able to adhere to the restrictions and prohibitions required by this protocol.
• Signed informed consent form.
• Body weight ≥ 50 kg and body mass index (BMI) within the range 18 - 30 kg/m2 (inclusive).
• Average QTcF <450 msec at screening and pre-dose.
• Vital signs assessments within normal ranges

Healthy Subjects (Cohorts 1 and 2)

• Healthy as determined by a physician based on a full medical examination.
• Spirometry readings (FEV1 and FVC) to be ≥ 80% of predicted value and FEV1/FVC ratio > 0.7 at screening.

Subjects with Asthma (Cohort 3)

• Diagnosis of asthma.
• Positive result to methacholine challenge at the screening visit.
• FEV1 >60% of predicted normal value at screening.
• Stable asthma based on physician assessment at screening, with no changes of therapy in the 12 weeks prior to screening and no hospitalization or visit to accident and emergency for asthma in the 12 months prior to screening
• Otherwise healthy on the basis of a full medical examination at screening

Exclusion Criteria:

All subjects (Cohorts 1, 2 & 3)

• Any acute illness.
• Upper or lower respiratory tract infection within 4 weeks of the screening visit or randomisation.
• Use of prescription medications within 14 days of the Screening visit.
• Taking over the counter (OTC) medications other than vitamins or multivitamins, within 14 days prior to Screening.
• History of regular alcohol consumption within 6 months of the study with average weekly intake of >21 units for males, or >14 units for females.
• History of drug or alcohol abuse within the previous 5 years.
• Smoker (regular or irregular), or has smoked or used nicotine-containing products (including e-cigarettes) within the 6 months prior to screening or has a smoking history of ≥ 10 pack years.
• Positive test for HIV-1 & -2 antibodies at screening.
• Positive pre-study hepatitis B surface antigen or positive hepatitis C antibody result at screening.
• Positive test for alcohol, smoking or drugs of abuse at screening or Day -1.
• Received an experimental drug or used an experimental medical device within last 3 months.
• Allergy to any of the active or inactive ingredients in the study medication.
• Donation of blood in excess of 500 mL within a 3 month period prior to dosing, or if study participation would result in blood loss in excess of 500 mL in a 3 month period.
• Mentally or legally incapacitated.
• An employee of the Sponsor or contract research organisation (CRO), or a relative of an employee of the Sponsor or CRO.
• Unable or unwilling to undergo multiple venepuncture procedures or poor access to veins suitable for cannulation.
• Pregnant or lactating female

Healthy subjects (Cohorts 1 and 2)

• Any chronic illness or clinically relevant abnormality identified on the screening medical assessment, laboratory tests or ECG.

Subjects with asthma (Cohort 3)

• Had an episode of life-threatening asthma.
• Presence of clinically significant diseases other than asthma, hyper-responsive airways, seasonal allergic rhinitis or atopic diseases.
• Experienced an acute asthma exacerbation in the 12 months prior to screening requiring hospitalisation or accident and emergency treatment or management with systemic or injectable steroids.
• Uncontrolled, or moderate to severe asthma based on PI assessment and/or use of prohibited medications, or has required treatment with these therapies in the previous 12 weeks.
• History or presence of any known conditions contraindicated for methacholine challenge.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Single dose - healthy volunteers	Drug: PC945 - single doses; Safety and tolerability of single doses; Drug: Placebo - single doses; Safety and tolerability of single doses
Experimental: Repeat dose - healthy volunteers	Drug: PC945 - repeat doses; Safety and tolerability of repeat doses; Drug: Placebo - repeat doses; Safety and tolerability of repeat doses
Experimental: Single dose - asthmatic patients	Drug: PC945 - single doses; Safety and tolerability of single doses; Drug: Placebo - single doses; Safety and tolerability of single doses

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of treatment emergent adverse events	Assessment of number of adverse events reported by subjects following dosing	Cohort 1 - 12 weeks; Cohort 2 - 7 weeks; Cohort 3 - 6 weeks
12-lead ECG assessment	Change from pre-dose values	Cohort 1 - 12 weeks; Cohort 2 - 7 weeks; Cohort 3 - 6 weeks
Vital signs assessment (blood pressure and heart rate - measured together)	Change for pre-dose values	Cohort 1 - 12 weeks; Cohort 2 - 7 weeks; Cohort 3 - 6 weeks
Clinical laboratory assessments (blood and urine samples - measured together)	Change from pre-dose values	Cohort 1 - 12 weeks; Cohort 2 - 7 weeks; Cohort 3 - 6 weeks
Spirometry assessment (FEV1 & FVC - measured together)	Change from pre-dose values	Cohort 1 - 12 weeks; Cohort 2 - 7 weeks; Cohort 3 - 6 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma concentration data of PC945	Blood levels of PC945 measured after dosing	Cohort 1 (4 treatment periods) & Cohort 3 (1 treatment period) Day1 = 8 samples; Day2 = 2 samples; Day3 = 1 sample; F/U = 1 sample. Cohort 2 - Days1&7 = 10 samples; Days2,5,6 = 1 sample; Day8 = 2 samples; Day9 = 1 sample; F/U = 1 sample
Spirometry assessment (FEV1)	Observed drops in FEV1 assessment after dosing patients with mild asthma	Cohort 3 only - Day 1, 8 hours

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Determination of exogenous fungal flora	Assessment of fungal flora found in mouth and throat after dosing	Cohort 1 (4 treatment periods) & Cohort 3 (1 treatment period) Day1 = 1 sample; Day3 = 1 sample. Cohort 2, Day 1 = 1 sample; Day 9 = 1 sample

Collaborators and Investigators

• Sponsor: Pulmocide Ltd
• Investigators: Principal Investigator: Muna Albayaty, MBChB, FFPM, MSc, cro

Study record dates

Study Major Dates

• Study Start (Actual): October 23, 2017
• Primary Completion (Actual): April 27, 2018
• Study Completion (Actual): April 27, 2018

Study Registration Dates

• First Submitted: March 16, 2016
• First Submitted That Met QC Criteria: March 16, 2016
• First Posted (Estimate): March 22, 2016

Study Record Updates

• Last Update Posted (Actual): May 1, 2018
• Last Update Submitted That Met QC Criteria: April 30, 2018
• Last Verified: April 1, 2018

More Information

Terms related to this study

• Keywords: Asthma; Anti-Infective Agents; Enzyme Inhibitors; Antifungal Agents; Aspergillosis; Filamentous fungi; Aspergillus species; 14-alpha Demethylase Inhibitors; Allergic Bronchopulmonary
• Additional Relevant MeSH Terms: Infections; Bacterial Infections and Mycoses; Mycoses; Aspergillosis
• Other Study ID Numbers: PC_ASP_001; 2015-003327-64 (EudraCT Number)

Drug and device information, study documents

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