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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Cadila Healthcare Limited
ClinicalTrials.gov Identifier:
NCT01472809
First received: November 9, 2011
Last updated: January 29, 2014
Last verified: January 2014
  Purpose

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.


Condition Intervention Phase
Diabetes
Drug: ZYGK1
Drug: Placebo
Phase 1

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

Resource links provided by NLM:


Further study details as provided by Cadila Healthcare Limited:

Primary Outcome Measures:
  • Safety and tolerability [ Time Frame: Upto 14 Days ] [ Designated as safety issue: Yes ]

    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.



Secondary Outcome Measures:
  • Pharmacokinetics [ Time Frame: 7 Days ] [ Designated as safety issue: No ]

    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.


  • Pharmacodynamics [ Time Frame: 7 Days ] [ Designated as safety issue: No ]

    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]


Estimated Enrollment: 96
Study Start Date: December 2011
Estimated Study Completion Date: April 2014
Estimated Primary Completion Date: January 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo
Placebo tablets
Drug: Placebo
Placebo Tablets: 0.125, 0.25, 0.5, 1, 2, ... mg
Other Name: Placebo
Experimental: 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

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

Other Name: ZYGK1

Detailed 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.

  Eligibility

Ages Eligible for Study:   18 Years to 45 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01472809

Locations
India
Clinical R&D, Zydus Research Center, Cadila Healthcare Limited, NH No.8, Moraiya
Ahmedabad, Gujarat, India, 382213
Sponsors and Collaborators
Cadila Healthcare Limited
Investigators
Study Director: Rajendrakumar H Jani, PhD(Medical) Clinical R&D, Zydus Research Center, Cadila Healthcare Limited, Moraiya, Ahmedabad-382213, Gujarat, India
Principal Investigator: Kevinkumar Kansagra, MD Clinical R&D, Zydus Research Center, Cadila Healthcare Limited, Moraiya, Ahmedabad-382213, Gujarat, India
  More Information

No publications provided

Responsible Party: Cadila Healthcare Limited
ClinicalTrials.gov Identifier: NCT01472809     History of Changes
Other Study ID Numbers: ZYGK1/1001, CTRI/2011/12/002249
Study First Received: November 9, 2011
Last Updated: January 29, 2014
Health Authority: United States: Food and Drug Administration
India: Central Drugs Standard Control Organization

Keywords provided by Cadila Healthcare Limited:
ZYGK1
Cadila
Zydus
ZRC
Zydus Research Center
Phase 1
Diabetes

Additional relevant MeSH terms:
Diabetes Mellitus
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases

ClinicalTrials.gov processed this record on April 16, 2014