CTRI

CTRI Number

CTRI/2016/02/006665 [Registered on: 19/02/2016] Trial Registered Prospectively

Last Modified On:

16/11/2016

Post Graduate Thesis

Type of Trial

Interventional

Type of Study

Drug

Study Design

Randomized, Parallel Group, Placebo Controlled Trial

Public Title of Study

Clinical study to evaluate the safety, tolerability and pharmacokinetics of ZYAN1, a novel PHD-2 Inhibitor, following oral administration in healthy volunteers.

Scientific Title of Study

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 IDs if Any
Modification(s)

Secondary ID	Registry
ZYAN1 1001 Ver. 03 Dated 18 April 2015	Protocol Number

Details of Principal Investigator or overall Trial Coordinator (multi-center study)

Name	Dr Kevinkumar Kansagra
Address	Survey No. 396/403, Opp. Sarvotam Hotel, Nr. Nova Petrochemicals, Sarkhej-Bavla N.H. No. 8A, Village : Moraiya, Ahmedabad, India Ahmadabad GUJARAT 382213 India
Phone	912717665555
Fax	912717665355
Email	kevinkumarkansagra@zyduscadila.com

Details Contact Person
Scientific Query

Name	Dr R H Jani
Address	Survey No. 396/403, Opp. Sarvotam Hotel, Nr. Nova Petrochemicals, Sarkhej-Bavla N.H. No. 8A, Village : Moraiya, Ahmedabad, India Ahmadabad GUJARAT 382213 India
Phone	912717665555
Fax	912717665355
Email	clinical@zyduscadila.com

Details Contact Person
Public Query

Name	Dr R H Jani
Address	Survey No. 396/403, Opp. Sarvotam Hotel, Nr. Nova Petrochemicals, Sarkhej-Bavla N.H. No. 8A, Village : Moraiya, Ahmedabad, India Ahmadabad GUJARAT 382213 India
Phone	912717665555
Fax	912717665355
Email	clinical@zyduscadila.com

Source of Monetary or Material Support

Cadila Healthcare Limited. Zydus Research Centre, Survey No. 396/403, Opp. Sarvotam Hotel, Nr. Nova Petrochemicals, Sarkhej-Bavla N.H. No. 8A, Village: Moraiya, Ahmedabad 382213, Gujarat, India

Primary Sponsor

Name	Cadila Healthcare Limited
Address	Zydus Research Centre, Survey No. 396/403, Opp. Sarvotam Hotel, Nr. Nova Petrochemicals, Sarkhej-Bavla N.H. No. 8A, Village: Moraiya Ahmadabad, Pincode- 382213 Gujarat, India
Type of Sponsor	Pharmaceutical industry-Indian

Details of Secondary Sponsor

Name	Address
NIL	NIL

Countries of Recruitment

India

Sites of Study
Modification(s)

No of Sites = 2
Contact Person	Name of Site	Site Address	Phone/Fax/Email
Dr Jason Lickliter	Centre for Clinical Studies (CCS)-Phase I study conduction completed as per TGA	Centre for Clinical Studies (CCS) A division of Nucleus Network Alfred Medical Research Precinct 5/89 Commercial Road Melbourne, VIC, 3004, AUSTRALIA Not Applicable	61390768900 J.Lickliter@nucleusnetwork.com.au
Dr Kevinkumar Kansagra	Zydus Research Centre (Centre 2)	Survey No. 396/403, Opp. Sarvotam Hotel, Nr. Nova Petrochemicals, Sarkhej-Bavla N.H. No. 8A, Village : Moraiya, Ahmedabad-382213 Gujarat, India Ahmadabad	912717665555 912717665355 kevinkumarkansagra@zyduscadila.com

Details of Ethics Committee

No of Ethics Committees= 1
Name of Committee	Approval Status
Ethics Committee of Care Institute of Medical Sciences	Approved

Regulatory Clearance Status from DCGI

Status

Approved/Obtained

Health Condition / Problems Studied

Health Type	Condition
Healthy Human Volunteers	NA, as healthy volunteers.

Intervention / Comparator Agent

Type	Name	Details
Comparator Agent	Placebo	Orally given.
Intervention	ZYAN1 Tablets	PHD2 inhibitor, ZYAN1 shall be given in dose of 10, 25, 50, 100 and 150 mg orally.

Inclusion Criteria

Age From	18.00 Year(s)
Age To	65.00 Year(s)
Gender	Both
Details	1. Healthy male or female between 18 and 65 years of age. 2. Hemoglobin: Males -12.8 – 14.9 g/dL and Females 11.3- 14.9 g/dl. 3. Male subjects must agree to use one of the contraception methods during the study. 4. Body weight > 55 kg and BMI within the range 18 - 30 kg/m2. 5. Capable of giving written informed consent, which includes compliance with protocol. 6. QTc < 450msec. 7. For gender effect study, only females with history of sterility or at least 1 year menopause or use of long acting non hormonal contraceptive measures (e.g., intrauterine device) will be recruited.

ExclusionCriteria

Details

1. Presence or history of severe gastrointestinal disease in the last 6 months.
2. Presence or history of renal insufficiency at any time {Serum creatinine more than upper normal limit (UNL)}.
3. Active liver disease and/or liver transaminase greater than 1.5 X UNL.
4. History or presence of other systemic disorders or diseases (e.g., respiratory, gastrointestinal, endocrine, immunological,dermatological, neurological, psychiatric disease or any other body system involvement).
5. History or presence of significant alcoholism or drug abuse within the past 1 year.
6. History or presence of significant smoking (more than 10 cigarettes per day) or consumption of tobacco/nicotine products (more than 10 times per day) and having a positive urine cotinine test at screening and check-in.
7. Difficulty with donating blood.
8. Systolic blood pressure more than 140 mmHg and less than 100 mmHg and diastolic blood pressure more than 90 mmHg and less than 60 mmHg.
9. Pulse rate less than 50/minute and more than 100/minute.
10. Any clinically significant laboratory findings during screening.
11. History or presence of any clinically significant electrocardiogram (ECG) abnormalities during screening.
12. Major illness and/or major surgery in last 3 months.
13. Volunteers who have participated in any drug research study other than the present trial within past 3 months.
14. Volunteers who have donated one unit (350 ml) of blood in the past 3 months.
15. Use of any over-the-counter (OTC) or prescription medications within the 30 days or 5 half-lives (whichever is longer), prior to receiving study drug.
16. Use of any herbal medicines (eg, St. John’s wort) and supplements within the 30 days prior to receiving study drug.
17. Strenuous activity (as assessed by the investigator) is prohibited from 2 days prior to admission until discharge from the unit.
18. For gender effect study, female volunteers with following criteria will not be recruited:
-History of pregnancy or lactation in the past 3 months.
-Fertile female volunteers not protected against pregnancy by adequate long-term anti-fertility measures.
-History of less than 1 year of menopause and not using adequate long-term anti-fertility measures.
-Using hormonal contraceptives.
-Using hormone replacement therapy.
-Unable to give assurance for protection against pregnancy for 3 months after the participation in this trial.
-Positive urine pregnancy test on the day of check-in.
-Positive serum β-hCG level at the screening visit.

Method of Generating Random Sequence

Computer generated randomization

Method of Concealment

Pharmacy-controlled Randomization

Blinding/Masking

Participant, Investigator and Outcome Assessor Blinded

Primary Outcome

Outcome	TimePoints
Safety and tolerability parameters including adverse events, clinical, laboratory, electrocardiogram, and vital signs assessments.	Clinical examination, vital signs like oral temperature, sitting blood pressure and pulse and laboratory tests will be done at screening and at time points described as per protocol. Continuous ECG monitoring and 12-lead ECG will be done as per time points desctibed in the protocol.

Secondary Outcome

Outcome

TimePoints

1. Pharmacokinetics (PK) after single and multiple oral dose
administrations in healthy male volunteers.
2. Pharmacodynamic (PD) effect after single and multiple oral dose administrations in healthy male volunteers.
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.
4. Effect of food on pharmacokinetics in male and female volunteers.

The venous blood samples and urine samples will be collected for
Pharmacokinetic, pharmacodynamic & EPO concentration measurement at defined time points as per protocol.

Target Sample Size

Total Sample Size="84"
Sample Size from India="84"

Phase of Trial

Phase 1

Date of First Enrollment (India)
Modification(s)

03/03/2016

Date of First Enrollment (Global)

No Date Specified

Estimated Duration of Trial

Years="0"
Months="3"
Days="0"

Recruitment Status of Trial (Global)
Modification(s)

Completed

Recruitment Status of Trial (India)

Completed

Publication Details

Brief Summary

This study will be a randomized, double-blind, placebo-controlled, multi-Centre trial. The objective of this study is to evaluate the safety, tolerability and pharmacokinetics of ZYAN1, a novel PHD2 Inhibitor, following oral administration in healthy volunteers.

According to the dosage schedules, the study has been divided in the following three plans- Plan I (single dose study), Plan II (Multiple dose Study), Plan III - Gender and Food effect study. An approximately 84 subjects shall be enrolled. At least one panel will be conducted in centre 2 (India) on selected dose from selected plan as per the study protocol.

The volunteers, who are found normal and healthy at the time of screening, satisfy inclusion and exclusion criteria and are willing to give the informed consent, will be invited to participate in the study.

Any adverse event (AE), either clinical/laboratory, will be recorded and assessed for severity, seriousness and causality. Frequency of AEs with ZYAN1 will be compared with the placebo group. Further dose escalation will be stopped as per stopping criteria.