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Trial registered on ANZCTR


Registration number
ACTRN12615000984594
Ethics application status
Approved
Date submitted
15/09/2015
Date registered
21/09/2015
Date last updated
11/05/2016
Type of registration
Prospectively registered

Titles & IDs
Public title
A Phase I study of orally inhaled PB01 in healthy male participants following single and repeat administration.
Scientific title
Randomised, double-blind, placebo-controlled Phase I study to evaluate the safety, tolerability and pharmacokinetics of single and multiple doses of orally inhaled PB01 administered to healthy subjects.
Secondary ID [1] 287437 0
Nil
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Airway inflammation and fibrosis 296102 0
Condition category
Condition code
Respiratory 296356 296356 0 0
Other respiratory disorders / diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
PB01 solution for oral inhalation is administered using a nebuliser and consists of PB01 in 20mM sodium phosphate buffer and 500 mM sodium chloride, pH 7.

Stage 1 (Single Ascending Dose)
PB01 will be administered via oral inhalation as a single dose. The starting dose level is 3 mg (Cohort 1) with provision to escalate to 9 mg (Cohort 2), 20 mg (Cohort 3) and 30 mg (Cohort 4) subject to Safety Review Committee assessment of each preceding dose level Cohort.

Study medication will be administered by an Aerogen Aeroneb Go vibrating mesh nebuliser which delivers 3 mL of study medication in approximately 7 minutes and 6 mL of study medication in approximately 13 minutes. Participants will be admitted to the study unit on Day -1 (the day prior to administration of study medication) and trained on the use of the Aeroneb Go nebuliser. Participants will be required to fast (from food) for at least 10 hours prior to administration of study medication on Day 1. On Day 1, study medication will be administered by inhalation under the supervision of the clinical site personnel and participants will be confined to the study unit for a further 24 hours. On Day 2, participants will be discharged from the study unit after completion of all study procedures. Participants will attend the study unit on Day 5 (+2) for an End of Study Evaluation. Pharmacokinetic (PK) sampling for PB01 PK determination will be included in this Stage.

Stage 2 (Multiple Ascending Dose)
Dose levels to be determined from results of Stage 1. Up to three dose levels are planned. PB01 will be administered via oral inhalation once a day for 14 consecutive days.

Eligible participants will be admitted to the study unit on Day -1 (the day prior to administration of study medication) and trained on the use of the Aeroneb Go nebuliser. Prior to administration of study medication on Day 1 and Day 14, participants will be required to fast (from food) for at least 10 hours. On Day 1, study medication will be administered by inhalation under the supervision of the clinical site personnel. Dosing will continue once daily on Days 2-14 inclusive, under supervision. Participants will be confined to the study unit throughout the 14 day dosing period and will be discharged from the study unit on Day 15. On Day 21(+2) participants will attend the study unit on an End of Study Evaluation. PK sampling for PB01 PK determination will be included in this Stage.

Participants from Stage 1 will not be used for Stage 2. For both Stages, the investigator is responsible for maintaining accurate study medication accountability records throughout the study. Drug accountability will be performed by the monitor during monitoring visits to reconcile the number of study medication syringes dispensed with that used/returned.
Intervention code [1] 292747 0
Treatment: Drugs
Comparator / control treatment
Placebo solution for oral inhalation contains vehicle only, which consists of 20mM sodium phosphate buffer and 500 mM sodium chloride, pH 7.

Participants will be randomised in a ratio of 3:1 to receive either PB01 or Placebo, with the exception of the first two participants (i.e. the sentinel participants) within each dose level cohort who will be randomised in a ratio of 1:1 to ensure that one participant receives PB01 and one participant receives Placebo.
Control group
Placebo

Outcomes
Primary outcome [1] 296102 0
To evaluate the safety and tolerability of orally inhaled PB01 in healthy male participants following single (Stage 1) dose administration.
Timepoint [1] 296102 0
For Stage 1 (Single Ascending Dose) a single orally inhaled dose of PB01 will be administered on Day 1 of the study for each dose level cohort. Participants will be confined to the study centre from Day -1 and will be discharged on Day 2. Participants will then return on Day 5 (+2) for an End of Study Evaluation. During this time vital signs, physical examination, clinical laboratory determinations (haematology, clinical chemistry, liver function tests, coagulation, urinalysis, Follicle stimulating hormone (FSH) levels), 12 lead electrocardiogram (ECG) reading and spirometry will be performed. Blood samples for determination of the production of antibodies to PB01 will be collected but not assayed unless clinically indicated. All participants will be monitored for adverse events and concomitant medications for the duration of the study and all information received between consent and final visit (Day 5 (+2)) will be recorded in the case report form.
Primary outcome [2] 296164 0
To evaluate the safety and tolerability of orally inhaled PB01 in healthy male participants following repeat (Stage 2) dose administration.
Timepoint [2] 296164 0
For Stage 2 (Multiple Ascending Dose), PB01 will be administered once daily for 14 consecutive days. Participants will be confined to the study centre from Day -1 and will be discharged on Day 15. Participants will then return on Day 21(+2) for an End of Study Evaluation. During this time vital signs, physical examination, clinical laboratory determinations (haematology, clinical chemistry, liver function tests, coagulation, urinalysis, Follicle stimulating hormone (FSH) levels), 12 lead electrocardiogram (ECG) reading and spirometry will be performed. Blood samples for determination of the production of antibodies to PB01 will be collected but not assayed unless clinically indicated. All participants will be monitored for adverse events and concomitant medications for the duration of the study and all information received between consent and final visit (Day 21(+2)) will be recorded in the case report form.
Secondary outcome [1] 317516 0
To evaluate the pharmacokinetics of orally inhaled PB01 in healthy male participants following single (Stage 1) dose administration.
Timepoint [1] 317516 0
Pharmacokinetic parameters for PB01 in serum include Cmax, Tmax, T1/2, AUC(0-t), and AUC (0 - infinity). Blood samples will be collected at pre-dose, immediately after completion of dosage administration, and at 20 minutes (only if dosing has been completed prior to the 20 minute time point), 30 minutes, 45 minutes and at 1, 1.5, 2, 3, 4, 6, 8, 12 hours on Day 1 and 24 hours (Day 2) after commencement of PB01 administration.
Secondary outcome [2] 317665 0
To evaluate the pharmacokinetics of orally inhaled PB01 in healthy male participants following repeat (Stage 2) dose administration.
Timepoint [2] 317665 0
Pharmacokinetic parameters for PB01 in serum include Cmax, Tmax, T1/2, AUC(0-t), and AUC (0 - infinity). Blood samples will be collected at pre-dose, immediately after completion of dosage administration, and at 20 minutes (only if dosing has been completed prior to the 20 minute time point), 30 minutes, 45 minutes and at 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours after commencement of PB01 administration.

Blood sampling will be done for the first dose of study medication administered on Day 1 and for the last dose of study medication administered on Day 14 for this stage (Stage 2) of the study.

Eligibility
Key inclusion criteria
Able to speak, read and understand English sufficiently to understand the purposes and risks of the study and to provide written informed consent.
Healthy males aged 18 to 55 years inclusive at the time of consent.
Body Mass Index (BMI) of greater than or equal to 18 to less than or equal to 30.0 kg/m2
Normal pulmonary function and performance on pulmonary function tests, defined as Forced expiratory volume measured in one second, expressed in litres (FEV1), and Forced vital capacity, expressed in litres (FVC) both greater than or equal to 80% of their predicted value for age, ethnicity, sex and height.
Participants must be willing and able to comply with scheduled visits, treatment plan, laboratory tests and other study procedures.
Participants must be willing to comply with the medically acceptable contraceptive requirements of the study from Screening to at least 30 days after the last IMP administration.
Minimum age
18 Years
Maximum age
55 Years
Gender
Males
Can healthy volunteers participate?
Yes
Key exclusion criteria
Participants will not be eligible to participate in the study if they meet any of the following criteria:
Clinically significant disease including airway inflammation, haemoptysis or other respiratory disease (except for completely-resolved childhood asthma and symptom free for greater than 5 years).
Participants who have a positive urine cotinine test at Screening or Day -1.
Smokers (i.e. cigarette or tobacco use at any time within the last 18 months).
Use of caffeine-containing foods/beverages/dietary supplements, decaffeinated beverages or alcohol within 48 hours prior to all visits and/or unable to refrain from their use during the study.
Use of prescription or non-prescription (over-the-counter) or complementary medicines, within 14 days prior to Day -1, except occasional use of paracetamol (up to 2g per day).
Respiratory tract infection within the previous four weeks or any infection within 7 days prior to Day -1.
Any clinically significant abnormalities on clinical chemistry, haematology, urinalysis, physical examination, medical history, 12-lead electrocardiogram (ECG), or vital signs as judged by the investigator or sponsor (at Screening and/or Day -1).
Clinically significant abnormality of renal function, defined as Cockcroft Gault creatinine clearance less than 70 ml/min.
Clinically significant abnormality of hepatic function defined as AST or ALT greater than 1.5 times the upper limit of normal.
History or evidence of, or positive test for HIV, hepatitis B or hepatitis C.
Positive urine drug screen or alcohol test during Screening or on-study, or history of drug or alcohol abuse and/or dependence within the past year prior to Day -1.
Participation in another clinical trial or administration of any investigational agent within 8 weeks or 5 half-lives (whichever is longer) prior to Day -1.
History of clinically significant allergic disease requiring medical treatment with medications as judged by the investigator or sponsor.
History of hypersensitivity to follistatin or drugs of the same pharmacological class.
Surgical or medical conditions which could significantly alter drug absorption, distribution, metabolism or excretion.
Major surgery within 3 months prior to Day -1 or anticipated surgery in the study period.
Blood or plasma donation of more than 500 mL during the 3 months prior to Day -1.
History of or current clinically-significant gastrointestinal, hepatic, renal, cardiovascular, respiratory, endocrine, oncological, immunological, neurological, ophthalmological, haematological or psychiatric disorder or any other condition, which in the opinion of the investigator or sponsor would jeopardize the safety of the participant or the validity of the study results.
Unable to refrain from strenuous activity for 48 hours prior to all visits and for the duration of the study.
Unable to use nebuliser.
An employee of the sponsor or research site personnel directly affiliated with this study or their immediate family members defined as a spouse, parent, sibling, or child, whether biological or legally adopted.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint(s)
Safety
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
SA

Funding & Sponsors
Funding source category [1] 292042 0
Commercial sector/Industry
Name [1] 292042 0
Paranta Biosciences Ltd
Address [1] 292042 0
189-191 Balaclava Road, Caulfield North, Victoria 3161
Country [1] 292042 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Paranta Biosciences Ltd
Address
189-191 Balaclava Road, Caulfield North, Victoria 3161
Country
Australia
Secondary sponsor category [1] 290714 0
None
Name [1] 290714 0
Address [1] 290714 0
Country [1] 290714 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 293526 0
Bellberry Limited
Ethics committee address [1] 293526 0
129 Glen Osmond Road, Eastwood SA 5063
Ethics committee country [1] 293526 0
Australia
Date submitted for ethics approval [1] 293526 0
Approval date [1] 293526 0
22/07/2015
Ethics approval number [1] 293526 0

Summary
Brief summary
This study is designed to assess the safety, tolerability and pharmacokinetic profile of orally inhaled PB01 when administered to healthy male volunteers (aged between 18 and 55 years) as a single dose (Stage 1 component of the study) and 14 consecutive once daily doses (Stage 2 component of the study) at dose levels up to 30 mg.
Stages 1 and 2 will be conducted in Australia.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 60014 0
Dr Nicholas Farinola
Address 60014 0
CMAX, A Division of IDT Australia Ltd, Royal Adelaide Hospital, Level 5, East Wing, North Terrace, Adelaide
South Australia 5000
Country 60014 0
Australia
Phone 60014 0
+61 8 8222 3928
Fax 60014 0
Email 60014 0
Nicholas.Farinola@sa.gov.au
Contact person for public queries
Name 60015 0
Mr Ross Barrow
Address 60015 0
Paranta Biosciences Ltd, 189-191 Balaclava Road, Caulfield North, Victoria 3161
Country 60015 0
Australia
Phone 60015 0
+61 3 9526 0021
Fax 60015 0
Email 60015 0
ross.barrow@parantabio.com
Contact person for scientific queries
Name 60016 0
Ms Nuket Desem
Address 60016 0
Paranta Biosciences Ltd, 189-191 Balaclava Road, Caulfield North, Victoria 3161
Country 60016 0
Australia
Phone 60016 0
+61 3 9526 0021
Fax 60016 0
Email 60016 0
nuket.desem@parantabio.com

No information has been provided regarding IPD availability
Summary results
Have study results been published in a peer-reviewed journal?
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary