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

NCT02715570 | Completed Phase 1

• 2 other identifiers: PC_ASP_0012015-003327-64
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Aspergillosis

Keywords

Aspergillus species; Filamentous fungi; 14-alpha Demethylase Inhibitors; Anti-Infective Agents; Antifungal Agents; Enzyme Inhibitors; Aspergillosis; Allergic Bronchopulmonary; Asthma

Outcome Measures

Primary Outcomes (5)

• 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 Outcomes (2)

• Plasma concentration data of PC945

  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)

  Cohort 3 only - Day 1, 8 hours

Other Outcomes (1)

• Determination of exogenous fungal flora

  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

Study Arms (3)

Single dose - healthy volunteers

EXPERIMENTAL

Drug: PC945 - single doses; Drug: Placebo - single doses

Repeat dose - healthy volunteers

EXPERIMENTAL

Drug: PC945 - repeat doses; Drug: Placebo - repeat doses

Single dose - asthmatic patients

EXPERIMENTAL

Drug: PC945 - single doses; Drug: Placebo - single doses

Interventions

PC945 - single doses DRUG

Safety and tolerability of single doses

Single dose - asthmatic patients; Single dose - healthy volunteers

Placebo - single doses DRUG

Safety and tolerability of single doses

Single dose - asthmatic patients; Single dose - healthy volunteers

PC945 - repeat doses DRUG

Safety and tolerability of repeat doses

Repeat dose - healthy volunteers

Placebo - repeat doses DRUG

Safety and tolerability of repeat doses

Repeat dose - healthy volunteers

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Pulmocide Ltd: lead

Study Sites (1)

Parexel EPCU

Harrow, Middlesex, HA1 3UJ, United Kingdom

Location

MeSH Terms

Conditions

Aspergillosis; Asthma

Condition Hierarchy (Ancestors)

Mycoses; Bacterial Infections and Mycoses; Infections; Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Study Officials

• Muna Albayaty, MBChB, FFPM, MSc

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  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 16, 2016
• First Posted: March 22, 2016
• Study Start: October 23, 2017
• Primary Completion: April 27, 2018
• Study Completion: April 27, 2018
• Last Updated: May 1, 2018

Record last verified: 2018-04

Locations

GB (1)