A Clinical Study to Evaluate Safety, Tolerability and Pharmacokinetics of Oral ZYGK1 in Healthy Volunteers

Diabetes Clinical Trial

Official title:

A Randomized, Double Blind Placebo Controlled Phase 1 Clinical Study to Evaluate the Safety, Tolerability and Pharmacokinetics of ZYGK1, a Novel Glucokinase Activator, Following Oral Administration in Healthy Volunteers

Clinical Trial Details — Status: Suspended

Administrative data

• NCT number: NCT01472809
• Other study ID #: ZYGK1/1001
• Secondary ID: CTRI/2011/12/002
• Status: Suspended
• Phase: Phase 1
• First received: November 9, 2011
• Last updated: November 20, 2015
• Start date: December 2011

Study information

• Verified date: November 2015
• Source: Cadila Healthcare Limited
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationIndia: Central Drugs Standard Control Organization
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to determine (1) whether ZYGK1 is safe and well tolerated, (2) the pharmacokinetics (what body does to ZYGK1) and (3) pharmacodynamics (what drugs does to the body) in the healthy and diabetic subject.

Description:

This study will be a randomized, double blind, placebo controlled study and is divided into four plans:

1. Plan I: Single Ascending Dose (SAD) Study

2. Plan II: Multiple Ascending Dose (MAD)Study

3. Plan III: Gender Effect study

4. Plan IV: Food Effect study

First Plan I, Plan III and Plan IV will be conducted in healthy volunteers. After reviewing the results, decision shall be taken whether the multiple ascending doses shall be studied in healthy human volunteers or in subjects with type 2 diabetes.

Recruitment information / eligibility

• Status: Suspended
• Enrollment: 96
• Est. primary completion date: December 2012
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 45 Years

Eligibility

Inclusion Criteria:

1. Age: 18-45 years

2. Mentally, physically, and legally eligible to give informed consent

3. Male and female volunteers weighing between 50-75 kg and 45-75 kg (4) respectively.

4. Ability to communicate effectively with the study personnel

5. Willingness to adhere to the protocol requirements

6. For gender effect study, only females with history of sterility or at least one year menopause or use of long acting nonhormonal contraceptive measures (e.g., intrauterine device) will be recruited.

7. At least one panel, in single ascending dose and multiple ascending dose will include subjects with type 2 diabetes as defined by American Diabetes Association

Exclusion Criteria:

1. Presence or history of hypersensitivity to any of the active or inactive ingredients of ZYGK1 formulation

2. Presence or history of pancreatitis at any time (Serum Amylase/Serum Lipase more than upper normal limit (UNL))

3. Presence or history of severe gastrointestinal disease in the last 6 months

4. Presence or history of renal insufficiency at any time (serum creatinine >UNL)

5. Active liver disease and/or liver transaminases greater than 1.5 X UNL

6. 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)

7. Abnormal bleeding time (BT), clotting time (CT), prothrombin time (PT), and activated partial prothrombin time (APTT)

8. History or presence of any medication in the last 14 days

9. History or presence of significant alcoholism or drug abuse within the past 1 year

10. History or presence of significant smoking (more than 10 cigarettes per day) or consumption of tobacco products (more than 10 times per day)

11. Difficulty with donating blood

12. 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

13. Pulse rate less than 60 minute and more than 100/minute

14. Any clinically significant laboratory findings during screening

15. History or presence of any clinically significant electrocardiogram (ECG) abnormalities during screening

16. Major illness and/or major surgery in last 3 months

17. Volunteers who have participated in any drug research study other than the present trial within past 3 months

18. Volunteers who have donated one unit (350 ml) of blood in the past 3 months

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Diabetes

Intervention

Drug:
• ZYGK1
ZYGK1 Tablets: 0.125, 0.25, 0.5, 1, 2, .... mg. Dose escalation will continue till single AE occurs in any block of 3 volunteers on ZYGK1 or pharmacokinetic (dose linearity) saturation is reached or desired PK/PD effect is achieved
• Placebo
Placebo Tablets: 0.125, 0.25, 0.5, 1, 2, ... mg

Locations

Country	Name	City	State
India	Clinical R&D, Zydus Research Center, Cadila Healthcare Limited, NH No.8, Moraiya	Ahmedabad	Gujarat

Sponsors (1)

Lead Sponsor	Collaborator
Cadila Healthcare Limited

Country where clinical trial is conducted

India, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety and tolerability	Safety and tolerability for-; Plan I, Plan III and Plan IV [Time frame: up to Day 8]; Plan II [Time frame: upto Day 14]; Frequency of adverse events will be assessed at each dose level.	Upto 14 Days	Yes
Secondary	Pharmacokinetics	Pharmacokinetics after oral administration of ZYGK1 in; Plan I, III and IV: [Time frame: 0.25 - 168 hrs post drug administration]; Plan II: [Time frame:Day 1: 0.25 - 12 hours, Day 2-6: 0, 2, 4 Hours, Day: 0.25-168 hours post drug administration]; Effects of food on the pharmacokinetics will be assessed in healthy subjects.	7 Days	No
Secondary	Pharmacodynamics	Plasma glucose, serum insulin, C-peptide and glucagoan estimate -; Plane I and Plan III [Time frame: Day 0 and Day 1: upto 4 hours post oral glucose 75 grams]; Plan II [Time frame: Day 0, Day 1 and Day 7: upto 4 hours post oral glucose 75 grams]; Plan IV: [Time frame: Period 2: Day 0 and Day 1: upto 4 hours post meal]	7 Days	No