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A Clinical Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of ZYD1, Following Subcutaneous Administration in Healthy Volunteers (ZYD1)

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ClinicalTrials.gov Identifier: NCT01972893
Recruitment Status : Completed
First Posted : October 31, 2013
Last Update Posted : October 31, 2013
Sponsor:
Information provided by (Responsible Party):
Cadila Healthcare Limited

Brief Summary:

ZYD1 is a novel GLP-1 receptor agonist. The ZYD1 exhibits increased stability to proteolytic cleavage, especially against dipeptidyl peptidase-4 (DPP-IV).

ZYD1 is a potent antidiabetic agent without gastrointestinal side-effects. A first in human (FIH) Phase I study intends to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of ZYD1 in normal healthy adult volunteers.


Condition or disease Intervention/treatment Phase
Type 2 Diabetes Mellitus Drug: ZYD1 Drug: Placebo Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 56 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized, Double-blind, Placebo-controlled Phase I Clinical Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of ZYD1, a Selective Glucagon-like Peptide (GLP) 1 Agonist, Following Subcutaneous Administration in Healthy Volunteers.
Study Start Date : February 2011
Actual Primary Completion Date : March 2012
Actual Study Completion Date : June 2012

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: ZYD1
Tablet ZYD1 5 to 50 mg subcutaneously Once a day (OD) or BID depending upon the pharmacokinetic profile obtained in Plan I (Single dose study)
Drug: ZYD1

Plan I - Tablet ZYD1 - 0.5, 1 , 2, 5, 10, 25 and 50 mg subcutaneously OD after overnight fasting.

Plan II - Tablet ZYD1 - 0.5, 1 , 2, 5, 10 and 25 mg subcutaneously OD after overnight fasting.

Plan III - Tablet ZYD1 2/5 mg subcutaneously OD after overnight fasting depending on results of Plan I.

Other Name: Selective GLP-1 agonist

Placebo Comparator: Placebo
Tablet Placebo 5 to 50 mg subcutaneously OD or BID depending upon the pharmacokinetic profile obtained in Plan I (Single dose study)
Drug: Placebo

Plan I - Tablet Placebo - 0.5, 1 , 2, 5, 10, 25 and 50 mg subcutaneously OD after overnight fasting.

Plan II - Tablet Placebo - 0.5, 1 , 2, 5, 10 and 25 mg subcutaneously OD after overnight fasting.

Plan III - Tablet Placebo 2/5 mg subcutaneously OD after overnight fasting depending on results of Plan I.





Primary Outcome Measures :
  1. To evaluate Safety and tolerability of ZYD1 [ Time Frame: 21 days ]
    The safety and tolerability shall be evaluated using physical examinations, standard laboratory tests (hematology, biochemistry and urine examination), and electrocardiogram (ECG). Spontaneously reported and solicited adverse events will also be used for safety parameters.


Secondary Outcome Measures :
  1. Pharmacokinetics (PK) and Pharmacodynamic (PD) effect after single and multiple subcutaneous dose administrations in healthy adult male volunteers Gender effect study. [ Time Frame: 1. For Plan I and III - Pre-dose (before dosing), 0.5, 1, 2, 3, 4, 6 ,8, 10, 12, 24, 48, 72 and 120 hrs post dose 2. Plan II - Day 01 - Pre-dose, 1, 2, 3, 4 and 8 hours following first dosing. Day 02 to 06 - Pre-dose of each . Day 07 - Pre-dose, 1, 2, 3, ]

    PK parameters evaluated for Plan I and Plan III: Cmax, Tmax, Area Under Curve (AUC)0-t, AUC 0-inf, T1/2, z, Clearance(CL), Volume of distribution (Vd) Plan II: Cmin, Tmin, Cavg, % Fluctuation, Accumulation Index, Clss, Cmax, Vd or Vss

    For urine data (Plans I, II, and III):

    Amount recovered, % recovered

    The following PD parameters (Plan I-III) will be evaluated: Plasma glucose, Serum insulin, C-Peptide, Glucagon

    Gender effects: PK and PD effect in female volunteers at preselected single dose will be compared with the results of single-dose study in male volunteers.




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Ages Eligible for Study:   18 Years to 45 Years   (Adult)
Sexes Eligible for Study:   All
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 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 1 year menopause or use of long acting nonhormonal contraceptive measures (e.g., intrauterine device) will be recruited.

Exclusion Criteria:

  1. Presence or history of hypersensitivity to any of the active or inactive ingredients of ZYD1 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 above the upper limit of the reference range)
  5. Active liver disease and/or liver transaminases greater than 1.5 X UNL
  6. Subject with personal or family history of medullary thyroid cancer
  7. Subject with personal or family history of multiple endocrine neoplasia syndrome type 2
  8. Subject with serum calcitonin >50 ng/L
  9. 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)
  10. Abnormal bleeding time (BT), clotting time (CT), prothrombin time (PT), and activated partial prothrombin time (APTT) tests on the day of check in
  11. History or presence of any medication in the last 14 days including any medication known to interact with the Cytochrome P (CYP) 450 system
  12. History or presence of significant alcoholism or drug abuse within the past 1 year
  13. History or presence of significant smoking (more than 10 cigarettes per day) or consumption of tobacco products (more than 10 times per day)
  14. Difficulty with donating blood
  15. 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
  16. Pulse rate less than 60/minute and more than 100/minute
  17. Any clinically significant abnormal X-ray or laboratory findings during screening
  18. History or presence of any clinically significant electrocardiogram (ECG) abnormalities during screening
  19. Major illness and/or major surgery in last 3 months
  20. Volunteers who have participated in any drug research study other than the present trial within past 3 months
  21. Volunteers who have donated one unit (350 ml) of blood in the past 3 months
  22. 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 device or history of less than 1 year of menopause
    • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01972893


Locations
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India
Zydus Research Centre, Survey No. 396/403, Opp. Sarvotam Hotel, Nr. Nova Petrochemicals, Sarkhej-Bavla N.H. No. 8A, Village : Moraiya,
Ahmedabad, Gujarat, India, 382213
Sponsors and Collaborators
Cadila Healthcare Limited
Investigators
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Study Director: Rajendrakumar H Jani, PhD(Medical) Senior Vice President - Cadila Healthcare Limited
Principal Investigator: Kevinkumar Kansagra, MD Zydus Research Centre

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Responsible Party: Cadila Healthcare Limited
ClinicalTrials.gov Identifier: NCT01972893     History of Changes
Other Study ID Numbers: ZYD1/1001
CTRI/2011/04/001684 ( Other Identifier: Clinical Trial Registration India )
First Posted: October 31, 2013    Key Record Dates
Last Update Posted: October 31, 2013
Last Verified: October 2013

Keywords provided by Cadila Healthcare Limited:
Selective GLP-1 agonist

Additional relevant MeSH terms:
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Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases