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Trial registered on ANZCTR


Registration number
ACTRN12613000374763
Ethics application status
Approved
Date submitted
26/03/2013
Date registered
8/04/2013
Date last updated
18/04/2013
Type of registration
Retrospectively registered

Titles & IDs
Public title
A Phase 1 Single Blind, Randomized, Single-Dose, Safety, Tolerability, Pharmacodynamic, and Pharmacokinetic Study of ZY7318 (pegylated recombinant human erythropoietin) in Healthy Volunteers
Scientific title
A Phase 1 single-blind, single-treatment, pharmacodynamic and pharmacokinetic study of ZY7318 (pegylated recombinant human erythropoietin) in thirty two(32) healthy adult male volunteers
Secondary ID [1] 282192 0
Nil
Universal Trial Number (UTN)
U1111-1141-1074
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Healthy volunteers study and investigational product would be targeted for secondary anemia due to renal cause. 288701 0
Condition category
Condition code
Renal and Urogenital 289049 289049 0 0
Kidney disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
A Phase 1 single-blind,single-treatment, pharmacodynamic and pharmacokinetic study of ZY7318 (pegylated recombinant human erythropoietin) in thirty two(32) healthy adult male volunteers enrolled in four cohorts, each consisting of eight (8) subjects. Each cohort of 8 subjects will consist of 6 subjects assigned to active study drug and 2 subjects assigned to placebo.
For each cohort, six(6) subjects will receive active study drug and two
(2)subjects will receive placebo as per the randomization sequence. Randomization ratio would be 3:1. Being a single blind study,only subjects would be kept blinded. The
Principal Investigator or designee will review adverse events and vital signs of the first 2 dosed subjects (1 active treatment,1 placebo) at 24 hours before approving the dosing of the subsequent subjects in each cohort.

Each cohort must be completed and reviewed by the Principal Investigator and the Medical Monitor,or their designees, after three days once last subject dosed in that cohort before moving to the next higher dose cohort.
Cohort wise Investigational product dosage & administration would be as follows:--

1st cohort - ZY7318 0.15 mcg/kg

2nd cohort - ZY7318 0.3 mcg/kg

3rd cohort - ZY7318 0.6 mcg/kg

4th cohort - ZY7318 0.9 mcg/kg

Placebo (Sterile Normal Saline Solution)

Route of administration would be subcutaneous route.
Intervention code [1] 286796 0
Treatment: Drugs
Comparator / control treatment
Comparator arm would be placebo which would be sterile normal saline solution
Control group
Placebo

Outcomes
Primary outcome [1] 289162 0
To assess the safety and tolerability of increasing doses of ZY7318 in healthy male volunteers e.g. abnormal lab parameter, if any, vomiting, headache, etc.

1. Number of subjects with adverse events;
2. Physical examinations (Vital Signs);
3. Electrocardiograms (ECG);
4. Laboratory tests (including hematology, biochemistry,
and urinalysis).
Timepoint [1] 289162 0
12 lead ECG would be at Day 1 & Day 42.
laboratory tests would be analyzed at screening, admission day, Day 1, 2 3, 12, 21, 28 & Day 42.
Vital signs would be measured through the conduct of the study beginning from screening to Day 42.
Secondary outcome [1] 301948 0
To determine the pharmacodynamic and pharmacokinetic profile of ZY7318 in healthy male volunteers based on the following parameters:
1. Pharmacodynamic Evaluation
a. Change in reticulocyte count, over time for 21
days across various treatment groups;
b. Change in Hemoglobin level;
c. Change in Hematocrit level.
2. Pharmacokinetic Evaluation:
a. Peak serum concentration (Cmax);
b. Time to reach peak serum concentration (Tmax);
c. Area under serum concentration vs. time curve till
the last time point (AUC 0-t);
d. Area under serum concentration vs. time curve
extrapolated to the infinity
e. The residual area in percentage
f. Serum elimination half-life (t 1/2);
g. Elimination rate constant
Timepoint [1] 301948 0
Day 42 after drug administration

Eligibility
Key inclusion criteria
1. Able to provide written Informed Consent;
2. Ability to communicate effectively with study personnel;
3. Willingness to adhere to the protocol requirements;
4. Male healthy volunteers;
5. Age greater than or equal to 18 years and less than or equal to 45 years;
6. Body Mass Index=20-=30 kg/m2.
7. In good general health with no clinically significant illness seen on physical examination or ongoing medical history,as determined by the Investigator;
8. Documented 12 lead ECG with no clinically significant abnormalities, as determined by the Investigator;
9. No clinically significant abnormalities in screening or Day-1 laboratory tests, as determined by the Investigator;
10. Hemoglobin between 12-17g/dL.
Minimum age
18 Years
Maximum age
45 Years
Sex
Males
Can healthy volunteers participate?
Yes
Key exclusion criteria
1. Any prior treatment with Erythropoiesis-Stimulating Agents (ESAs);

2. History of hypersensitivity to erythropoietin or any related drug;

3. Active liver disease and/or liver transaminases greater than 1.5X upper limit of normal;
4. History of anemia;
5. History or presence of blood dyscrasias (e.g. thrombocytopenia, neutropenia);
6. History or presence of thyroid disorders;
7. History of presence of pulmonary disorders (e.g. dyspnea, pneumonia);
8. History or presence of autoimmune disorders (e.g. thyroiditis, rheumatoid arthritis);
9. History or presence of arrhythmia or any other cardiovascular disease
10. Subjects taking drugs that have a narrow therapeutic index(e.g.anti-epileptics,etc.)and drugs that can depress the immune system(e.g. anti-cancer drugs, etc.);
11. Blood pressure less than 90/60 (Systolic/diastolic)mm Hg or more than 140/90 mm Hg;
12. Febrile;
13. Physical examination or 12-lead ECG result(s) considered to be clinically significant by the Investigator;
14. Donated blood within 60 days of screening or otherwise experienced blood loss of>250mL within the same period;
15. Intending to begin new concomitant drug therapy or over-the-counter medication anytime from screening to the time of administration of study drug;
16. Received or intending to receive a vaccination in the two weeks prior to dosing, or any time during study participation;

17. Received treatment with a drug that has not received regulatory approval for an indication during the 60 days preceding study enrollment;
18. History of drug and/or alcohol dependence within past 12 months,and/or positive results on drug of abuse or alcohol tests;
19. Screening laboratory result indicating HIV-positivity, or previously diagnosed with AIDS, AIDS related complex, or other immunodeficiency;
20. Screening laboratory result indicating serologic positivity for hepatitis C antibodies or hepatitis B surface antigens, unless explained by a documented vaccination;
21. Has taken any regular,prescribed,or over-the-counter medication with the exception of acetaminophen (maximum2g/day) or multi-vitamins in the two weeks prior to dosing(other medication may only be taken with the specific approval of the Investigator in consultation with the Medical Monitor);
22. Malignancy within the last 5 years, with the exception of successfully treated basal cell carcinoma and carcinoma in situ uteri;
23. Unable to comply with study attendance, protocol procedures or other study requirements;
24. Any condition that, in the opinion of the investigator, might interfere with study objectives.

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, as only subjects would be kept blinded
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Randomization sheet would be generated by using a software
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Pharmacokinetics / pharmacodynamics
Statistical methods / analysis
Pharmacodynamic Analysis

Pharmacodynamic analysis will calculated using the following assessments:
Change in reticulocyte count, over time for 21 days across the cohorts and treatment groups;
Change in hemoglobin level over 42 days;
Change in hematocrit level over 42 days.

Comparisons between each treatment groups will be made using the difference in least-square means and p-values from the ANOVA model. Statistical significance will be defined as a two- sided p-value <0.05

Pharmacokinetic Analysis

Mean values by treatment received will be calculated for the following PK parameters for ZY7318:

Cmax--the maximum measured serum concentration;
tmax--the time to reach maximum serum concentration;
AUC0-last --the area under the serum concentration versus time curve from time zero to the time of the last measurable serum concentration, calculated by the linear or log/linear
trapezoidal method.
AUC0-inf--the area under the serum concentration versus time curve from time zero to infinity, calculated as:AUCinf = AUCt+(Ct/Kel), where Ct=the last measurable concentration.
z--the apparent elimination rate constant
t1/2--the terminal half-life
CV --coefficient of variation

Based on other safety studies & keeping in mind four different dosages in each cohort, we feel that 32 subjects sample size is adequate to permit assessment of the safety and pharmacokinetics of pegylated erythropoietin-based product.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
1/03/2013
Actual
5/03/2013
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
32
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment postcode(s) [1] 6618 0
4006 - Herston

Funding & Sponsors
Funding source category [1] 286954 0
Commercial sector/Industry
Name [1] 286954 0
Prolong Pharmaceuticals, LLC
Country [1] 286954 0
United States of America
Primary sponsor type
Commercial sector/Industry
Name
Prolong Pharmaceuticals, LLC
Address
300-B Corporate Court South Plainfield, NJ 07080-2415
USA
Country
United States of America
Secondary sponsor category [1] 285741 0
Commercial sector/Industry
Name [1] 285741 0
Southern Star Research
Address [1] 285741 0
Suite 501, 7-9 Merriwa Street, Gordon NSW 2072
Country [1] 285741 0
Australia

Ethics approval
Ethics application status
Approved

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 38766 0
Dr Paul Griffin
Address 38766 0
Q-Pharm Pty Limited
P O Box 78
Royal Brisbane Hospital Qld 4029
Australia
Country 38766 0
Australia
Phone 38766 0
+61 0402 077 302
Fax 38766 0
+61 7 3845 3636
Email 38766 0
[email protected]
Contact person for public queries
Name 38767 0
Glenn Kazo
Address 38767 0
Prolong Pharmaceuticals, 300B Corporate Court, South Plainfield, NJ 07080, USA
Country 38767 0
United States of America
Phone 38767 0
+1-908-444-4651
Fax 38767 0
Email 38767 0
[email protected]
Contact person for scientific queries
Name 38768 0
Abe Abuchowski
Address 38768 0
Prolong Pharmaceuticals
300 Corporate Court
South Plainfield, NJ 07080, USA
Country 38768 0
United States of America
Phone 38768 0
+1-908-444-4650
Fax 38768 0
Email 38768 0
[email protected]

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

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