A Study to Investigate the Safety and Tolerability of Single and Repeat Doses of PC786

Pulmocide

Status and phase: Completed; Phase 1

Conditions: Respiratory Syncytial Virus (RSV)

Treatments: Drug: PC786 - Single doses; Drug: PC786 - Repeat doses; Drug: Placebo - Single doses; Drug: Placebo - Repeat doses

Study type: Interventional

Funder types: Industry

Identifiers

NCT03236233

PC_RSV_001

2016-000934-22 (EudraCT Number)

Details and patient eligibility

About

This study investigates the safety, tolerability and pharmacokinetics of single and repeat doses of PC786.

Enrollment: 39 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

All subjects (Cohorts 1, 2, 3 & 4)

• Must be 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 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 contraception from the time of the first dose, until 90 days after receipt of the final dose of study medication.
• Females must have a negative serum β human chorionic gonadotropin (β-hCG) test at screening and a negative urinary pregnancy test at Day -1.
• Subject must be willing and able to adhere to the restrictions and prohibitions required by this protocol.
• Each subject must sign an informed consent form (ICF) indicating that he or she understands the purpose and requirements of the study and that they are willing to participate.
• 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 at screening and pre-dose.

Healthy Subjects (Cohorts 1, 2 & 3)

• Healthy as determined by a physician based on a full medical examination including medical history, physical examination and laboratory tests performed at screening and pre-dose.
• Spirometry readings (FEV1 and FVC) to be ≥ 80% of predicted value and FEV1/FVC ratio > 0.7 at screening

Subjects with Asthma (Cohort 4)

• Documented diagnosis of asthma, first diagnosed at least 12 months prior to the screening visit.
• Subject must demonstrate a PC20 methacholine ≤ 8 mg/mL at the screening visit.
• Have an FEV1 >60% of predicted normal value at least 6 h after the last use of a short acting β-agonist (SABA).
• Have stable asthma based on physician assessment at screening and prior to randomisation
• Subject must be otherwise healthy on the basis of a full medical examination including medical history, physical examination and laboratory tests performed at screening.

Exclusion criteria

All subjects (Cohorts 1, 2, 3 & 4)

• 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
• Are taking over the counter medications other than vitamins or multivitamins and herbal medication, within 14 days prior to Screening
• History of regular alcohol consumption within 6 months of the study of an average weekly intake of >21 units for males, or >14 units for females
• Definite or suspected history of drug or alcohol abuse within the previous 5 years.
• A smoker (regular or irregular), or has smoked or used nicotine-containing products (including e-cigarettes) within the 6 months prior to screening
• A positive test for HIV-1 & -2 antibodies at screening.
• A 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 pre-dose
• Received an experimental drug or used an experimental medical device within 3 months before the first dose of the study drug is scheduled.
• Allergy to any of the active or inactive ingredients in the study medication.
• History of drug, or other allergy that would contraindicate participation.
• Donation of blood in excess of 500 mL within a 3 month period prior to dosing
• 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
• Pregnant or lactating female
• Any other reason that the Investigator considers makes the subject unsuitable to participate.

Healthy Subjects (Cohorts 1, 2 & 3)

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

Subjects with Asthma (Cohort 4)

• Has ever had an episode of life-threatening asthma defined as respiratory arrest, intubation for asthma, or ICU admission for asthma.
• Presence of clinically significant diseases other than asthma, hyper-responsive airways, seasonal allergic rhinitis or atopic diseases
• Has 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.
• Has 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Quadruple Blind

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39 participants in 3 patient groups

Single dose - healthy subjects

Experimental group

Treatment:

Drug: PC786 - Single doses

Drug: Placebo - Single doses

Repeat dose - healthy subjects

Experimental group

Treatment:

Drug: PC786 - Repeat doses

Drug: Placebo - Repeat doses

Single dose - subjects with asthma

Experimental group

Treatment:

Drug: PC786 - Single doses

Drug: Placebo - Single doses