A clinical study to investigate the safety, tolerability, pharmacokinetics and pharmacodynamics of orally administered ZYG19 in volunteers.

Phase 1

Completed

Conditions: 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.

Registration Number: CTRI/2011/12/002238

Lead Sponsor: Zydus Research Centre

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. xml:namespace prefix = o ns = "urn:schemas-microsoft-com:office:office" /

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.

Detailed Description: Not available

Recruitment & Eligibility

Status: Completed

Sex: All

Target Recruitment: 96

Inclusion Criteria

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: â€¢Their HbA1c should be â‰¥ 7% and â‰¤ 9% at screening â€¢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:- ïƒ¼Metformin ïƒ¼GLP-1 agonist (e.g. Exenatide etc..) ïƒ¼DPP IV inhibitors ( Sitagliptin, Vildagliptin etc..).

Exclusion Criteria

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).

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Safety and tolerability	Safety and tolerability \| Plans I,II and III[upto \| Day 8] \| Plan IV [ upto Day 21 ]

Secondary Outcome Measures

Name	Time	Method
PK, PD & Relationships between drug exposures and PD parameters either with or without OGTT	PK: 1.Blood â€¢Plans I, II, III:[Time frame: pre dose to 168 hrs]

Trial Locations

Locations (1): Zydus Reseach Centre
🇮🇳
Ahmadabad, GUJARAT, India
Zydus Reseach Centre
🇮🇳Ahmadabad, GUJARAT, India
Dr Aplesh Kumar Patel
Principal investigator
02717665555
AlpeshkumarJPatel@zyduscadila.com