| CTRI Number |
CTRI/2011/12/002238 [Registered on: 15/12/2011] Trial Registered Prospectively |
| Last Modified On: |
23/10/2015 |
| Post Graduate Thesis |
No |
| Type of Trial |
Interventional |
|
Type of Study
|
Drug |
| Study Design |
Other |
|
Public Title of Study
|
A clinical study to investigate the safety, tolerability, pharmacokinetics and pharmacodynamics of orally administered ZYG19 in volunteers. |
|
Scientific Title of Study
|
A prospective, randomized, double blind, placebo controlled, study of orally administered ZYG19 to investigate the safety, tolerability, pharmacokinetics and pharmacodynamics in volunteers. |
| Trial Acronym |
|
|
Secondary IDs if Any
|
| Secondary ID |
Identifier |
| ZYG19/1001 version 01, 1st April 2011 |
Protocol Number |
|
|
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
|
| Name |
Dr AlpeshKumar Patel |
| Designation |
Principal Investigator |
| Affiliation |
Zydus Research Centre |
| Address |
Zydus Research Centre,Cadila Healthcare Limited,Survey No. 396/403, Opp. Sarvotam Hotel, Nr. Nova
Petrochemicals,Sarkhej-Bavla N.H. No. 8A, Moraiya, Ahmedabad-382213 Gujarat,
India
Cadila Healthcare Limited ,Zydus Cadila House,
TPS 5, Service road,Vile Parle(E),Mumbai400057
Ahmadabad
GUJARAT
382213
India |
| Phone |
91-2717-665555 |
| Fax |
91-2717-665355 |
| Email |
AlpeshkumarJPatel@zyduscadila.com |
|
Details of Contact Person
Scientific Query
|
| Name |
Dr R H Jani |
| Designation |
Senior Vice President |
| Affiliation |
Zydus Research Centre |
| Address |
Zydus Research Centre, Cadila Healthcare Limited
Survey No. 396/403, Opp. Sarvotam Hotel, Nr. Nova Petrochemicals,
Sarkhej-Bavla N.H. No. 8A, Moraiya, Ahmedabad-382213 Gujarat,
India
Cadila Healthcare Limited,Zydus Cadila House,
TPS 5, Service road,Vile Parle(E)
Mumbai
MAHARASHTRA
400057
India |
| Phone |
91-22-26186052 |
| Fax |
91-22-26151735 |
| Email |
rhjani@zyduscadila.com |
|
Details of Contact Person
Public Query
|
| Name |
Dr R H Jani |
| Designation |
Senior Vice President |
| Affiliation |
Cadila Health Care limited |
| Address |
Zydus Research Centre, Cadila Healthcare Limited
Survey No. 396/403, Opp. Sarvotam Hotel, Nr. Nova Petrochemicals,
Sarkhej-Bavla N.H. No. 8A, Moraiya, Ahmedabad-Gujarat,
India Phone: +Fax: +
Cadila Healthcare Limited,Zydus Cadila House,
TPS 5, Service road,Vile Parle(E)
Mumbai
MAHARASHTRA
382213
India |
| Phone |
91-22-26186052 |
| Fax |
91-22-26151735 |
| Email |
rhjani@zyduscadila.com |
|
|
Source of Monetary or Material Support
|
|
|
Primary Sponsor
|
| Name |
Zydus Research Centre |
| Address |
Survey No. 396/403, Opp. Sarvottam Hotel, Nr. Nova Petrochemicals,
Sarkhej-Bavla N.H. No. 8A, Moraiya, Ahmedabad-382213 Gujarat, India
|
| Type of Sponsor |
Pharmaceutical industry-Indian |
|
|
Details of Secondary Sponsor
|
|
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Countries of Recruitment
|
India |
|
Sites of Study
|
| No of Sites = 1 |
| Name of Principal
Investigator |
Name of Site |
Site Address |
Phone/Fax/Email |
| Dr Aplesh Kumar Patel |
Zydus Reseach Centre |
Clinical Reseach Department, Zydus Reasech Centre, Survey No.396/403,Sarkhej-Bavla N.H.No.8A,Moraiya
Ahmadabad
GUJARAT |
02717665555
02717665355
AlpeshkumarJPatel@zyduscadila.com |
|
|
Details of Ethics Committee
|
| No of Ethics Committees= 1 |
| Name of Committee |
Approval Status |
| Dr Alpeshkumar patel, Independent Ethics Commiittee-Aditya, Ahmadabad |
Submittted/Under Review |
|
|
Regulatory Clearance Status from DCGI
|
|
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Health Condition / Problems Studied
|
| Health Type |
Condition |
| Healthy Human Volunteers |
If there are more than 2 incidences of hypoglycemia in 2 of 6 healthy volunteers on ZYG19, the study will be continued in diabetic subjects.
|
|
|
Intervention / Comparator Agent
|
| Type |
Name |
Details |
| Comparator Agent |
Placebo |
1. Route of administration: Oral 2. Frequency: Plan I: Placebo shall be administered a single oral dose in the overnight fasting condition. Plan II: Placebo will be given either once or twice daily for 07 days orally depending upon the PK results of Plan I. Plan III: single oral dose of Placebo will be administered in the overnight fasting condition. Plan IV: In the food effect study, single dose of Placebo will be given in both the periods.
|
| Intervention |
ZYG19 |
1. Route of administration: Oral 2. Frequency: Plan I: ZYG19 shall be administered a single oral dose in the overnight fasting condition. Plan II: ZYG19 will be given either once or twice daily for 07 days orally depending upon the PK results of Plan I. Plan III: single oral dose of ZYG19 will be administered in the overnight fasting condition. Plan IV: In the food effect study, single dose of ZYG19 will be given in both the periods. |
|
Inclusion Criteria
Modification(s)
|
| 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. A female subject is eligible to participate, if she has no-childbearing potential (e.g., postmenopausal or post-hysterectomy).
2.Male subjects must agree to use one of the contraception methods during the study.
3.BMI within the range 20 - 29.9 kg/m2
4.Capable of giving written informed consent, which includes compliance with protocol.
5.QTcB or QTcF < 450msec.
6.In case if Type 2 diabetic subjects are invited for the study:
•Their HbA1c should be ≥ 7% and ≤ 9% at screening
•They should meet ADA criteria (Annexure VII) and a history of either not having any therapy for last 03 months or history of stabilization on one of the following for 03 months:-
Metformin
GLP-1 agonist (e.g. Exenatide etc..)
DPP IV inhibitors ( Sitagliptin, Vildagliptin etc..)
|
|
| ExclusionCriteria |
| Details |
1.History of drug and/or alcohol abuse
2.Body Mass Index (BMI): less than 20 or more than 29.9 kg/m2
3.Presence or history of any of the following disorders/disease within the past 3 months, that might have impact on the clinical trial as judged by the investigator-
a)cardiovascular,
b)cerebrovascular,
c)dermatological,
d)gastrointestinal,
e)gynecological
f)hematological,
g)hepatic,
h)malignancy,
i)metabolic,
j)musculoskeletal,
k)neurological,
l)psychiatric,
m)renal,
n)respiratory,
o)venereal,
p)any other major disorders.
4.Uncontrolled hypertension (systolic blood pressure more than 150 mm Hg and/or diastolic blood pressure more than 90 mm Hg).
5.History of stomach/gastric surgery, inflammatory bowel disease.
6.Presence or history of pancreatitis, pancreatectomy.
7.Surgery within last 4 weeks or planned major surgery within next 3 months from the date of screening.
8.Participation in a life style modification program within the prior 8 weeks.
9.Weight loss more than 4.5 kg in the 3 months prior to screening visit or use of weight loss medications (prescription or OTC) within 30 days of screening.
10.Allergic reaction to any GLP-1 agonist in the past (e.g. exenatide) or to metacresol
Additional exclusion criteria for diabetic subjects:
1.Any history of type 1 diabetes or diabetic ketoacidosis.
2.History of outpatient insulin use within last 1 year (insulin use while hospitalized is acceptable).
3.Use of medications which are likely to affect blood glucose levels such as hypoglycemic agents, insulin sensitizers over past 7 days.
4.History of impaired hepatic function (AST and/or ALT levels more than or equal to 1.5X UNL) and impaired renal function (estimated Creatinine clearance less than 60 ml/min or S. Creatinine more than 1.5mg/dl).
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Method of Generating Random Sequence
|
Random Number Table |
|
Method of Concealment
|
Pre-numbered or coded identical Containers |
|
Blinding/Masking
|
Participant and Investigator Blinded |
|
Primary Outcome
|
| Outcome |
TimePoints |
| Safety and tolerability |
Safety and tolerability
Plans I,II and III[upto
Day 8]
Plan IV [ upto Day 21 ] |
|
|
Secondary Outcome
|
| Outcome |
TimePoints |
| PK, PD & Relationships between drug exposures and PD parameters either with or without OGTT |
PK: 1.Blood •Plans I, II, III:[Time frame: pre dose to 168 hrs]
•Plan IV: [Pre-dose to 168 hrs post dose on Day 14]
2. Urine: •Plans I, II, III: [Time frame: pre dose to 36-48 hrs post dose on Day 3]
•Plan IV: [Pre-dose to 36-48 hrs of first dose on Day 14]
PD: Plasma glucose, GLP-1, Serum insulin- peptide
•PlansI, II,III:[Time frame: 24.5 hrs pre dose-Day 0 up to 4 hours after dosing on Day 01]
•Plan IV [Time frame: 24.5hrs pre dose-Day 0 upto 4hours after dosing on Day 14]
|
|
|
Target Sample Size
|
Total Sample Size="96"
Sample Size from India="96"
Final Enrollment numbers achieved (Total)= ""
Final Enrollment numbers achieved (India)="" |
|
Phase of Trial
|
Phase 1 |
|
Date of First Enrollment (India)
|
30/12/2011 |
| Date of Study Completion (India) |
Date Missing |
| Date of First Enrollment (Global) |
Date Missing |
| Date of Study Completion (Global) |
Date Missing |
|
Estimated Duration of Trial
|
Years="0"
Months="6"
Days="0" |
Recruitment Status of Trial (Global)
Modification(s)
|
Not Applicable |
| Recruitment Status of Trial (India) |
Completed |
|
Publication Details
|
|
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Individual Participant Data (IPD) Sharing Statement
|
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
|
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Brief Summary
|
Diabetes and its frequent association with obesity is one of the major growing concerns related to public health. A world-wide effort is directed towards the discovery of new treatments that alleviate this medical problem. As part of this effort, the G-protein-coupled receptor GPR119 has recently attracted attention because of evidence from in vitro systems and animal models that its modulation may produce favorable effects on glucose homoeostasis, food intake/body weight gain and possibly also b-cell preservation. GPR119 is a member of the G-protein coupled receptors that acts via cAMP pathway and is expressed predominantly in the pancreas (beta-cells) and gastrointestinal tract (endocrine cells) in humans. It augments glucose stimulated insulin secretion (GSIS) pathway. Thus targeting GPR119 as a therapy for diabetes is expected to be free from the risk of hypoglycemia, which otherwise is a common problem for almost all anti-diabetic therapies. The exact mechanism by which it acts on obesity still remains un-elucidated.
Our aim was to identify a novel chemical entity that will activate this receptor and decrease the blood glucose level. Decreasing feed intake and/or body weight will be an added benefit.
ZYG19 is a novel and potent small molecular entity designed & developed at Zydus Research Centre. It has shown in-vitro activation of GPR119 receptor in cell-based assays and anti-hyperglycemic effects in animal models. ZYG19 has been extensively tested in a variety of nonclinical safety studies that evaluated acute and repeat dose toxicity, genotoxicity and male reproductive toxicity.It appears to have an acceptable safety profile for initiating the clinical trials below the declared NOAEL levels.
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