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Trial registered on ANZCTR


Registration number
ACTRN12613000400763
Ethics application status
Approved
Date submitted
9/04/2013
Date registered
12/04/2013
Date last updated
31/07/2013
Type of registration
Retrospectively registered

Titles & IDs
Public title
A study to compare the capsule formulation of BIT225 to the original powder formulation in healthy participants.
Scientific title
A Phase I, Open-Label, Randomised, Single Dose, Crossover Pharmacokinetic Study Comparing a Capsule Formulation of BIT225 to the Current Oral Suspension Administered in Healthy Participants.
Secondary ID [1] 282249 0
BIT225-007
Universal Trial Number (UTN)
U1111-1141-4972
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Hepatits C Virus 288776 0
Condition category
Condition code
Infection 289128 289128 0 0
Other infectious diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
BIT225 powder 400mg, single dose, oral administration
or
BIT225 4 x 100mg capsules, single dose, oral administration

followed by the alternate dose form 10-14 days later.
Dosing will supervised within a Phase I unit.
The concentration of drug in the blood will be measured using a validated assay as described in the primary outcome.
Intervention code [1] 286866 0
Treatment: Drugs
Comparator / control treatment
The original powder formulation is the control.
Control group
Active

Outcomes
Primary outcome [1] 289241 0
To compare the pharmacokinetic characteristics of a single dosage of BIT225 suspension (400 mg) and capsule formulation (4 x 100 mg) in healthy participants.
The concentration of BIT225 in the blood will be measured using a validated liquid chromatography/ mass spectrometry method.
Pharmacokinetic parameters such as the area under the concentration (AUC) versus time curve, maximum concentration (Cmax), time to maximum concentration (Tmax), half life, clearance will be used to assess the primary outcome.
Timepoint [1] 289241 0
96 hours
Secondary outcome [1] 302092 0
To compare the tolerability of BIT225 400 mg in suspension compared to 4 x 100 mg BIT225 capsule formulation following a single dosage in healthy participants.
Tolerability will be assessed by comparison of treatment emergent adverse events, changes in vital signs, ECG parameters, and routine laboratory tests.
Timepoint [1] 302092 0
up to 14 days post dose

Eligibility
Key inclusion criteria
1. Be male or female (of non-child bearing potential), aged between 18 and 49 years (inclusive).
2. Healthy participants – defined as participants who are free from clinically significant illness or disease as determined by their medical history, physical examination, 12- lead ECG (QTc less than 450 ms) and clinical laboratory determinations.
3. Normotensive (systolic BP less than 140 mm Hg and diastolic BP less than 90 mm Hg).
4. Body Mass Index (BMI) btween 19 and 29 kg/m2.
5. Weight between 55 kg and 110kg.
6. Participants who smoke less than one cigarette or tobacco form (including cigars) per month in the last 12 months.
7. Adequate venous access in the left or right arm to allow collection of a number of blood samples.
8. Fluent in the English language.
9. Provide written informed consent to participate in the study and be willing to comply with the study procedures.
10. No abnormal finding of clinical relevance at the screening evaluation.
11. Agree to use a combination of two approved methods of contraception, from screening and until 30 days after administration of the study drug.
12. Females must have a negative pregnancy test at Screening (baseline) and Day -1.
Minimum age
18 Years
Maximum age
49 Years
Gender
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
1. Currently taking or have taken antiretroviral therapy in the last 30 days.
2. Any condition that would interfere with drug absorption (e.g. chronic diarrhoea).
3. A history of pancreatitis or hepatitis within the previous 3 years.
4. Abnormal laboratory test results, deemed clinically significant by the Medical Officer (Principal Investigator or medically qualified nominee), within 21 days before enrolment, including anaemia (haemoglobin less than 11.0 g/dl for men and 10.0 g/dl for women), neutropenia, thrombocytopenia and elevated liver function test results more than two times the upper limit of normal. Renal function impairment (Creatinine clearance less than 50mL/min).
5. Unable to withhold concomitant medication for 48 hours prior to dosing and for the duration of confinement.
6. As a result of medical review, physical examination or screening investigations, the Medical Officer considers the participant unfit for the study.
7. Positive urine drug test or alcohol breath test at screening.
8. Use of macrolide antibiotics (eg. Erythromycin), azole antifungal agents (eg. Ketoconazole) within 30 days of study dosing.
9. Evidence of clinically relevant oral, cardiovascular, haematological, gastrointestinal, hepatic, renal, endocrine, pulmonary, neurologic, psychiatric or skin disorder.
10. History of epilepsy.
11. History of coronary diseases, peripheral vascular diseases, cerebrovascular accident, transient ischaemic attack, uncontrolled hypertension or signs/symptoms of ischaemic heart disease.
12. Acute therapy for a serious infection within 30 days of study entry.
13. Positive screening test for Hepatitis B surface antigen (HBsAg) or Hepatitis C antibody and HIV.
14. Have participated in a clinical trial or receipt of an experimental therapy within 60 days prior to dosing.
15. Blood donation of greater than 550 mL within 90 days before the first dose administration.
16. Consumption of grapefruit or grapefruit juice within 14 days prior to the first day of study confinement and through to completion of the confinement period.
17. Those who regularly drink more than four (4) units of alcohol daily (1 unit = 300 mL beer, 1 glass wine, 1 measure spirit) or those who may have difficulty abstaining from alcohol during the 36 hours prior to dose administration and until completion of blood sampling.
18. Unwilling or unable to fast for the 10 hours prior to dosing.
19. Women of child bearing potential, pregnant or breast feeding women.
20. Male partners of pregnant females.

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)
Allocation is not concealed.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation by placing all 14 randomisation numbers in a box. The first 7 numbers withdrawn were allocated to receive the powder formulation in the first cycle.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Crossover
Other design features
Phase
Phase 1
Type of endpoint(s)
Pharmacokinetics
Statistical methods / analysis
Descriptive statistics such as mean, standard deviation and coefficient of variation for all pharmacokinetic parameters will be calculated.
The number of participants was based on the FDA Guidance for Industry, Bioavailability and Bioequivalence Studies for Orally Administered Drug Products (2003).

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)
WA
Recruitment postcode(s) [1] 6656 0
6009 - Nedlands

Funding & Sponsors
Funding source category [1] 287015 0
Commercial sector/Industry
Name [1] 287015 0
Biotron Limited
Address [1] 287015 0
Suite 1.9, 56 Delhi Rd
North Ryde NSW 2113
Country [1] 287015 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Biotron Limited
Address
Suite 1.9, 56 Delhi Rd
North Ryde NSW 2113
Country
Australia
Secondary sponsor category [1] 285798 0
None
Name [1] 285798 0
Address [1] 285798 0
Country [1] 285798 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 289055 0
Bellberry Limited
Ethics committee address [1] 289055 0
229 Greenhill Road
Dulwich
South Australia 5065
Ethics committee country [1] 289055 0
Australia
Date submitted for ethics approval [1] 289055 0
Approval date [1] 289055 0
26/03/2013
Ethics approval number [1] 289055 0

Summary
Brief summary
BIT225 powder has been used in several trials to date to investigate safety and effectiveness. A capsule formulation, being a more acceptable dose form than the powder, has been developed for use in future trials and as a possible future marketed formulation. This trial is to compare a single dose of the capsule to a single dose of the powder to see how much of the drug gets into the bloodstream and how long does the body take to remove it, what is the maximum concentration of the drug in the bloodstream after a single dose, and how well the capsule is tolerated compared to the powder form.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 39006 0
Dr Janakan Krishnarajah
Address 39006 0
Linear Clinical Research Limited
1st Floor, B Block,
Hospital Avenue,
Nedlands WA 6009
Country 39006 0
Australia
Phone 39006 0
+61 8 6382 5100
Fax 39006 0
+61 8 9381 4453
Email 39006 0
jkrishnarajah@linear.org.au
Contact person for public queries
Name 39007 0
Dr Michelle Miller
Address 39007 0
Biotron Limited
Suite 1.9, 56 Delhi Rd
North Ryde NSW 2113
Country 39007 0
Australia
Phone 39007 0
+61 2 9805 0488
Fax 39007 0
+61 2 9805 0688
Email 39007 0
mmiller@biotron.com.au
Contact person for scientific queries
Name 39008 0
Dr Michelle Miller
Address 39008 0
Biotron Limited
Suite 1.9, 56 Delhi Rd
North Ryde NSW 2113
Country 39008 0
Australia
Phone 39008 0
+61 2 9805 0488
Fax 39008 0
+61 2 9805 0688
Email 39008 0
mmiller@biotron.com.au

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