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Trial registered on ANZCTR


Registration number
ACTRN12614001240639
Ethics application status
Approved
Date submitted
30/10/2014
Date registered
26/11/2014
Date last updated
27/06/2016
Type of registration
Retrospectively registered

Titles & IDs
Public title
A study to determine the safety, tolerability and pharmacokinetics of ZYAN1 following oral administration in healthy volunteers.
Scientific title
A randomized, double-blind, placebo-controlled Phase I clinical study to evaluate the safety, tolerability and pharmacokinetics of ZYAN1, a novel PHD-2 Inhibitor, following oral administration in healthy volunteers.
Secondary ID [1] 285564 0
Nil
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Anemia 293391 0
Hypoxia related disorders 293595 0
Condition category
Condition code
Blood 293674 293674 0 0
Anaemia

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The interventional product, ZYAN1, will be administered as an oral tablet.

The first part of the study (Plan I) is an single ascending dose (SAD) cohort (panel) design in which different patient panels will receive ZYAN1 1001 as a single dose. The starting dose in first panel will be 10 mg. Subsequent doses will be 25 mg, 50 mg, 100 mg, 150 mg, 200 mg and 300 mg for panel 2, 3, 4, 5, 6 and 7. The subsequent panels will be conducted in new healthy males provided the previous panel is well tolerated.

The second part of the study (Plan II) is a multiple ascending dose (MAD) cohort (panel) design in which different patient panels will receive the same single dose of ZYAN1 1001 on Day 1, Day 3 and Day 5. The starting dose in first panel will be x1 mg where "x" stands for starting dose which will be decided based on the results of the SAD study. Subsequent doses will be x2 mg, x3 mg and x4 mg for panel 2, 3 and 4. The subsequent panels will be conducted in new healthy males provided the previous panel is well tolerated.

In the third part of the study (Plan III), ZYAN1 1001 will be administered once in fed and fasted conditions to healthy males and healthy females. The dose for this part will be decided based on the results of the first part of the study.

The IP will be administered to the volunteer at site under the supervision of a trained study personnel. IP accountability will be documented in a log and verified by an unblinded monitor.
Intervention code [1] 290515 0
Treatment: Drugs
Comparator / control treatment
The comparator/ control for this trial is oral tablet of matching placebo.
Control group
Placebo

Outcomes
Primary outcome [1] 293487 0
The primary outcome is to determine the safety and tolerability parameters including adverse events, clinical, laboratory, electrocardiogram, and vital signs assessments.
Timepoint [1] 293487 0
Plan I and Plan III - Measurements to be taken daily up to Day 8 following dosing on Day 1.

Plan II - Measurements to be taken daily up to Day 12 following dosing on Day 1, Day 3 and Day 5.
Secondary outcome [1] 311146 0
1. Pharmacokinetics (PK) after single and multiple oral dose administrations in healthy male volunteers.

Blood and urine assessments were carried out for PK analysis.
Timepoint [1] 311146 0
Plan I and Plan III - To be assessed 15 times on Day 1, twice on Day 2 and once on Day 3 and Day 4.

Plan II - To be assessed 15 times on Day 1 and Day 5, twice on Day 2, Day 3, Day 4 and Day 6 and once on Day 7 and Day 8.


up to Day 12 following dosing on Day 1, Day 3 and Day 5 .
Secondary outcome [2] 311463 0
2. Pharmacodynamic (PD) effect after single and multiple oral dose administrations in healthy male volunteers.

Blood assessments were carried out for PD analysis.
PD assessments included EPO, Haemoglobin, Hematocrit and Reticulocyte Count.
Timepoint [2] 311463 0
EPO assessments were carried out as follows:

Plan I and Plan III - To be assessed 15 times on Day 1, twice on Day 2 and once on Day 3 and Day 4.

Plan II - To be assessed 15 times on Day 1 and Day 5, twice on Day 2, Day 3, Day 4 and Day 6 and once on Day 7 and Day 8.


Haemoglobin, Hematocrit and Reticulocyte Count were assessed as follows:

Plan I and Plan III - To be assessed thrice on Day 1 and once on Day 2, 3, 4, 5, 6, 7 and 8.

Plan II - To be assessed thrice on Day 1, Day 3 and Day 5, and once daily on Day 2, Day 4, Day 6, 7, 8, 9, 10, 11 and 12.

Secondary outcome [3] 311464 0
3. Gender effects: Pharmacokinetics and safety parameters in female volunteers at preselected single dose will be compared with the results of similar single-dose study in male volunteers.

Blood and urine assessments were carried out for PK and safety analysis.
Timepoint [3] 311464 0
Plan I and Plan III - To be assessed 15 times on Day 1, twice on Day 2 and once on Day 3 and Day 4.

Secondary outcome [4] 311465 0
4. Effect of food on pharmacokinetics in male and female volunteers

Blood and urine assessments were carried out for PK analysis.
Timepoint [4] 311465 0
Plan I and Plan III - To be assessed 15 times on Day 1, twice on Day 2 and once on Day 3 and Day 4.

Plan II - To be assessed 15 times on Day 1 and Day 5, twice on Day 2, Day 3, Day 4 and Day 6 and once on Day 7 and Day 8.

Eligibility
Key inclusion criteria
- healthy volunteers
- hemoglobin: males - 12.8 - 17.5 g/dl, females - 11.3 - 15.9 g/dl.
- B.W. > 55 kg, BMI - 18-30 kg/m2
- QTc < 450 msec
- females must not be pregnant and males and females must agree to use contraception during the study.
- able to give informed consent and comply with protocol.
Minimum age
18 Years
Maximum age
65 Years
Gender
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
- history or presence of severe gastrointestinal or systemic disorders (e.g. respiratory, endocrine, immunological, dermatological, neurological, psychiatric disease etc.)
- history or presence of renal insufficiency
- active liver disease/ liver transaminase greater than 1.5 X UNL
- history or presence of significant alcoholism or drug abuse within past 1 year
- history or presence of significant smoking/ consumption of tobacco/nicotine products and positive urine cotinine test at screening and check-in.
- difficulty in donating blood
- clinically significant laboratory findings during screening
- history or presence of clinically significant ECG abnormalities
- major illness/ surgery in last 3 months
- participated in drug research study within past 3 months
- donated 350 mL of blood in last 3 months
- used over-the-counter/ prescription/ herbal medications/ supplements within 30 days prior to receiving study drug.

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)
After informed consent has been obtained, all screening tests establishing subject eligibility will be performed within a period of 14 days before dosing. Subjects will be admitted to the clinical facility on Day -1.

For Plan I and Plan II - In order to avoid risks, subjects will be randomised in 2 blocks.

For Plan III - Males and females will be enrolled. All subjects will be administered a single oral dose of ZYAN1 to assess the effects of food and gender difference on safety and pharmacokinetics effect.

Randomization was carried out by an independent statistician. Allocation was concealed by use of pre labelled drug boxes containing subject randomization numbers and use of sealed opaque envelopes.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
The investigational product (test or placebo) received by each volunteer will be determined according to the randomization schedule.

In Plan I and II, randomization will be done in such a way that in each panel volunteers will receive ZYAN1 or placebo. In Plan III, all volunteers will receive ZYAN1.

The randomization will be generated using SAS software.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s

Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint(s)
Safety
Statistical methods / analysis
1. Descriptive statistics for each of the PK parameters will be performed.
2. Dose-relationship with Cmax and AUC0-t will be evaluated for different doses.
3. Pharmacodynamic parameters will be evaluated using pre- and post- treatment clinical and laboratory findings.
4. Descriptive statistics for the PD and safety parameters will be performed.
5. To determine whether there is significant difference in the PD and safety variables post dose compared to Baseline or not, a paired t-test at a two-sided tail for a = 0.05 significance level will be performed.
6. To determine the effect of food in males, a t-test at a two-sided tail for a = 0.05 significance level will be performed.
7. WinNonlin Professional Software - Version 5.3, SAS Software, and MS Excel will be used for PK analysis, randomization and statistical analysis.

Recruitment
Recruitment status
Recruiting
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)
VIC
Recruitment postcode(s) [1] 8857 0
3004 - Melbourne

Funding & Sponsors
Funding source category [1] 290168 0
Commercial sector/Industry
Name [1] 290168 0
Cadila Healthcare Limited
Address [1] 290168 0
Survey No. 396/403, Opp. Sarvotam Hotel, Nr. Nova Petrochemicals, Sarkhej-Bavla N.H. No. 8A, Moraiya, Ahmedabad - 382213
Country [1] 290168 0
India
Primary sponsor type
Commercial sector/Industry
Name
Cadila Healthcare Limited
Address
Survey No. 396/403, Opp. Sarvotam Hotel, Nr. Nova Petrochemicals, Sarkhej-Bavla N.H. No. 8A, Moraiya, Ahmedabad - 382213
Country
India
Secondary sponsor category [1] 288879 0
Commercial sector/Industry
Name [1] 288879 0
CPR Pharma Services Pty Ltd (acting as a local sponsor in Australia)
Address [1] 288879 0
28 Dalgleish Street, Thebarton, SA 5031
Country [1] 288879 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 291877 0
Bellberry Human Research Ethics Committee
Ethics committee address [1] 291877 0
129 Glen Osmond Road, Eastwood SA 5063
Ethics committee country [1] 291877 0
Australia
Date submitted for ethics approval [1] 291877 0
17/09/2014
Approval date [1] 291877 0
21/10/2014
Ethics approval number [1] 291877 0
2014-09-488

Summary
Brief summary
This is a first in man trial with ZYAN1. The primary aim of this study is to establish the safety and tolerability while the secondary aim is to understand the pharmacokinetics, pharmacodynamics, gender and food effect of ZYAN1 in healthy volunteers.
Trial website
Trial related presentations / publications
Public notes
This study is divided into 3 parts referred to as Plans which are as follows:

Plan I - Single dose study - Total 7 panels - 8 subjects in each Panel. Total 56
Plan II - Multiple dose study - Total 4 panels - 8 subjects in each Panel. Total 32
Plan III - Food and gender effect study - Total 1 panel - 12 subject in this Panel. Total 12

Total Number of subjects - 56+32+12 = 100

Contacts
Principal investigator
Name 52334 0
Dr Jason Lickliter
Address 52334 0
Centre for Clinical Studies (CCS), A division of Nucleus Network, Alfred Medical Research Precinct, 5/89 Commercial Road, Melbourne, VIC 3004
Country 52334 0
Australia
Phone 52334 0
+61 03 9076 8900
Fax 52334 0
+61 03 9076 8911
Email 52334 0
j.lickliter@nucleusnetwork.com.au
Contact person for public queries
Name 52335 0
Dr Jason Lickliter
Address 52335 0
Centre for Clinical Studies (CCS), A division of Nucleus Network, Alfred Medical Research Precinct, 5/89 Commercial Road, Melbourne, VIC 3004
Country 52335 0
Australia
Phone 52335 0
+61 03 9076 8900
Fax 52335 0
+61 03 9076 8911
Email 52335 0
j.lickliter@nucleusnetwork.com.au
Contact person for scientific queries
Name 52336 0
Dr Kevinkumar Kansagra
Address 52336 0
Zydus Research Centre, Cadila Healthcare Limited, Survey No. 396/403, Opp. Sarvottam Hotel, Nr. Nova Petrochemicals, Sarkhej- Bavla N.H. No. 8A, Moraiya, Ahmedabad 382213
Country 52336 0
India
Phone 52336 0
+91 2717 665555
Fax 52336 0
+91 2717 665355
Email 52336 0
kevinkumarkansagra@zyduscadila.com

No information has been provided regarding IPD availability
Summary results
No Results